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.

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

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

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.

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

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

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.

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.

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.)

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

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.

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

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)

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

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

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

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

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

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

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)

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)

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

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

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.

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

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.

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

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

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

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.

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

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

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

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

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.)

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

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.

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)

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)

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

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

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

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.

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.

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

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.

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.

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.

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

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

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.

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)

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

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)

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.

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

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)

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...

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)

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)

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

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

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

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)

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.

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.)

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

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.)

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.)

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

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

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

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

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

[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.

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

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.

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

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.

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

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.

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

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

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

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.

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.

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

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)

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.

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)

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

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.

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

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.

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

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

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

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)

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...

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

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.

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

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)

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

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

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

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

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

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

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.

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.

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

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.

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.

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)

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.

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.

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

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.)

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.

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.)

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.

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

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

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

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�

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

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

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

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.

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.)

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.

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)

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.

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.

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.

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.

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)

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)

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)

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)

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, ...

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 ...

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.

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)

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)

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, ...

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.

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)

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)

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.

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.

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

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

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

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

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

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…

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 ...

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

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

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

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.

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.)

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

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)

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

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

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.

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.

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

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.

Thorium-based fuel cycles: Reassessment of fuel economics and proliferation risk

Energy Technology Data Exchange (ETDEWEB)

Serfontein, Dawid E., E-mail: Dawid.Serfontein@nwu.ac.za [Senior Lecturer at the School of Mechanical and Nuclear Engineering, North West University (PUK-Campus), PRIVATE BAG X6001, Internal Post Box 360, Potchefstroom 2520 (South Africa); Mulder, Eben J. [Professor at the School of Mechanical and Nuclear Engineering, North West University (South Africa)

2014-05-01

At current consumption and current prices, the proven reserves for natural uranium will last only about 100 years. However, the more abundant thorium, burned in breeder reactors, such as large High Temperature Gas-Cooled Reactors, and followed by chemical reprocessing of the spent fuel, could stretch the 100 years for uranium supply to 15,000 years. Thorium-based fuel cycles are also viewed as more proliferation resistant compared to uranium. However, several barriers to entry caused all countries, except India and Russia, to abandon their short term plans for thorium reactor projects, in favour of uranium/plutonium fuel cycles. In this article, based on the theory of resonance integrals and original analysis of fast fission cross sections, the breeding potential of {sup 232}Th is compared to that of {sup 238}U. From a review of the literature, the fuel economy of thorium-based fuel cycles is compared to that of natural uranium-based cycles. This is combined with a technical assessment of the proliferation resistance of thorium-based fuel cycles, based on a review of the literature. Natural uranium is currently so cheap that it contributes only about 10% of the cost of nuclear electricity. Chemical reprocessing is also very expensive. Therefore conservation of natural uranium by means of the introduction of thorium into the fuel is not yet cost effective and will only break even once the price of natural uranium were to increase from the current level of about $70/pound yellow cake to above about $200/pound. However, since fuel costs constitutes only a small fraction of the total cost of nuclear electricity, employing reprocessing in a thorium cycle, for the sake of its strategic benefits, may still be a financially viable option. The most important source of the proliferation resistance of {sup 232}Th/{sup 233}U fuel cycles is denaturisation of the {sup 233}U in the spent fuel by {sup 232}U, for which the highly radioactive decay chain potentially poses a large

Adrenaline promotes cell proliferation and increases chemoresistance in colon cancer HT29 cells through induction of miR-155

International Nuclear Information System (INIS)

Pu, Jun; Bai, Danna; Yang, Xia; Lu, Xiaozhao; Xu, Lijuan; Lu, Jianguo

2012-01-01

Highlights: ► Adrenaline increases colon cancer cell proliferation and its resistance to cisplatin. ► Adrenaline activates NFκB in a dose dependent manner. ► NFκB–miR-155 pathway contributes to cell proliferation and resistance to cisplatin. -- Abstract: Recently, catecholamines have been described as being involved in the regulation of cancer genesis and progression. Here, we reported that adrenaline increased the cell proliferation and decreased the cisplatin induced apoptosis in HT29 cells. Further study found that adrenaline increased miR-155 expression in an NFκB dependent manner. HT29 cells overexpressing miR-155 had a higher cell growth rate and more resistance to cisplatin induced apoptosis. In contrast, HT29 cells overexpressing miR-155 inhibitor displayed decreased cell proliferation and sensitivity to cisplatin induced cell death. In summary, our study here revealed that adrenaline–NFκB–miR-155 pathway at least partially contributes to the psychological stress induced proliferation and chemoresistance in HT29 cells, shedding light on increasing the therapeutic strategies of cancer chemotherapy.

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

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)

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

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

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

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

Connection between Proliferation Rate and Temozolomide Sensitivity of Primary Glioblastoma Cell Culture and Expression of YB-1 and LRP/MVP.

Science.gov (United States)

Moiseeva, N I; Susova, O Yu; Mitrofanov, A A; Panteleev, D Yu; Pavlova, G V; Pustogarov, N A; Stavrovskaya, A A; Rybalkina, E Yu

2016-06-01

Glioblastomas (GBL) are the most common and aggressive brain tumors. They are distinguished by high resistance to radiation and chemotherapy. To find novel approaches for GBL classification, we obtained 16 primary GBL cell cultures and tested them with real-time PCR for mRNA expression of several genes (YB-1, MGMT, MELK, MVP, MDR1, BCRP) involved in controlling cell proliferation and drug resistance. The primary GBL cultures differed in terms of proliferation rate, wherein a group of GBL cell cultures with low proliferation rate demonstrated higher resistance to temozolomide. We found that GBL primary cell cultures characterized by high proliferation rate and lower resistance to temozolomide expressed higher mRNA level of the YB-1 and MDR1 genes, whereas upregulated expression of MVP/LRP mRNA was a marker in the group of GBL with low proliferation rate and high resistance. A moderate correlation between expression of YB-1 and MELK as well as YB-1 and MDR1 was found. In the case of YB-1 and MGMT expression, no correlation was found. A significant negative correlation was revealed between mRNA expression of MVP/LRP and MELK, MDR1, and BCRP. No correlation in expression of YB-1 and MVP/LRP genes was observed. It seems that mRNA expression of YB-1 and MVP/LRP may serve as a marker for GBL cell cultures belonging to distinct groups, each of which is characterized by a unique pattern of gene activity.

Adrenaline promotes cell proliferation and increases chemoresistance in colon cancer HT29 cells through induction of miR-155

Energy Technology Data Exchange (ETDEWEB)

Pu, Jun [Department of General Surgery, Tangdu Hospital of the Fourth Military Medical University, Xi' an 710038 (China); Bai, Danna [Department of Cardiology, 323 Hospital of PLA, Xi' an 710054 (China); Yang, Xia [Department of Teaching and Medical Administration, Tangdu Hospital of the Fourth Military Medical University, Xi' an 710038 (China); Lu, Xiaozhao [Department of Nephrology, The 323 Hospital of PLA, Xi' an 710054 (China); Xu, Lijuan, E-mail: 13609296272@163.com [Department of Nephrology, The 323 Hospital of PLA, Xi' an 710054 (China); Lu, Jianguo, E-mail: lujianguo029@yahoo.com.cn [Department of General Surgery, Tangdu Hospital of the Fourth Military Medical University, Xi' an 710038 (China)

2012-11-16

Highlights: Black-Right-Pointing-Pointer Adrenaline increases colon cancer cell proliferation and its resistance to cisplatin. Black-Right-Pointing-Pointer Adrenaline activates NF{kappa}B in a dose dependent manner. Black-Right-Pointing-Pointer NF{kappa}B-miR-155 pathway contributes to cell proliferation and resistance to cisplatin. -- Abstract: Recently, catecholamines have been described as being involved in the regulation of cancer genesis and progression. Here, we reported that adrenaline increased the cell proliferation and decreased the cisplatin induced apoptosis in HT29 cells. Further study found that adrenaline increased miR-155 expression in an NF{kappa}B dependent manner. HT29 cells overexpressing miR-155 had a higher cell growth rate and more resistance to cisplatin induced apoptosis. In contrast, HT29 cells overexpressing miR-155 inhibitor displayed decreased cell proliferation and sensitivity to cisplatin induced cell death. In summary, our study here revealed that adrenaline-NF{kappa}B-miR-155 pathway at least partially contributes to the psychological stress induced proliferation and chemoresistance in HT29 cells, shedding light on increasing the therapeutic strategies of cancer chemotherapy.

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

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

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.

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.

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

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 ...

TET1-GPER-PI3K/AKT pathway is involved in insulin-driven endometrial cancer cell proliferation

International Nuclear Information System (INIS)

Xie, Bing-ying; Lv, Qiao-ying; Ning, Cheng-cheng; Yang, Bing-yi; Shan, Wei-wei; Cheng, Ya-li; Gu, Chao; Luo, Xue-zhen; Zhang, Zhen-bo; Chen, Xiao-jun; Xi, Xiao-wei; Feng, You-ji

2017-01-01

Large amount of clinical evidence has demonstrated that insulin resistance is closely related to oncogenesis of endometrial cancer (EC). Despite recent studies showed the up-regulatory role of insulin in G protein-coupled estrogen receptor (GPER/GPR30) expression, GPER expression was not decreased compared to control when insulin receptor was blocked even in insulin treatment. The purpose of this study was to explore the possible mechanism by which insulin up-regulates GPER that drives EC cell proliferation. For this purpose, we first investigated the GPER expression in tissues of endometrial lesions, further explored the effect of GPER on EC cell proliferation in insulin resistance context. Then we analyzed the role of Ten-Eleven Translocation 1 (TET1) in insulin-induced GEPR expression and EC cell proliferation. The results showed that GPER was highly expressed in endometrial atypical hyperplasia and EC tissues. Mechanistically, insulin up-regulated TET1 expression and the latter played an important role in up-regulating GPER expression and activating PI3K/AKT signaling pathway. TET1 mediated GPER up-regulation was another mechanism that insulin promotes EC cell proliferation. - Highlights: • GPER acts as an oncogene to drive EC cell growth in insulin resistance context. • TET1 is associated with insulin-induced GPER expression. • Insulin resistance contributed to EC through TET1-GPER-PI3K/AKT pathway.

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.

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.

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.

Assessment and reduction of proliferation risk of reactor-grade plutonium regarding construction of ‘fizzle bombs’ by terrorists

International Nuclear Information System (INIS)

Serfontein, Dawid E.; Mulder, Eben J.; Reitsma, Frederik

2014-01-01

The approximately 23.7 wt% 240 Pu in reactor-grade plutonium denatures the 239 Pu to the extent that it cannot fuel high yield nuclear weapons. 240 Pu has a high spontaneous fission rate, which increases the spontaneous neutron flux within the fuel. When such a nuclear weapon is triggered, these neutrons cause the nuclear fission chain reaction to pre-detonate which blows the imploding fuel shell apart before the designed level of compression and reactivity could be attained, thereby greatly reducing the average energy yield of such “fizzle” bombs. Therefore reactor-grade plutonium is normally viewed as highly proliferation resistant. In this article the literature on the proliferation resistance of reactor-grade plutonium and on the mechanism and effect of fizzle bombs is reviewed in order to test this view. It is shown that even very low yield fizzle bombs, exploded in urban areas, would still cause serious blast damage as well as radioactive contamination. Combined with the high levels of induced terror, fizzle bombs might thus be attractive psychological weapons for terrorists. Therefore reactor-grade plutonium may not be sufficiently proliferation resistant against nuclear terrorism. However, denaturisation with more than 9% 238 Pu produces high levels of decay heat which will melt or explode the high explosives around uncooled implosion type weapons, rendering them useless. Unfortunately, reactor-grade Pu contains only 2.7% 238 Pu and is thus not sufficiently proliferation resistant in this respect. It is also shown that the associated neptunium poses a substantial proliferation risk. In the present study strong improvement of the proliferation resistance was demonstrated by simulation of incineration of reactor-grade plutonium in the 400 MW th Pebble Bed Modular Reactor Demonstration Power Plant. Results for modified fuel cycles, aimed at transmutating 237 Np to 238 Pu are also reported. However, these modifications increased the disloaded heavy metal

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

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)

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

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.

High-temperature Gas Reactor (HTGR)

Science.gov (United States)

Abedi, Sajad

2011-05-01

General Atomics (GA) has over 35 years experience in prismatic block High-temperature Gas Reactor (HTGR) technology design. During this period, the design has recently involved into a modular have been performed to demonstrate its versatility. This versatility is directly related to refractory TRISO coated - particle fuel that can contain any type of fuel. This paper summarized GA's fuel cycle studies individually and compares each based upon its cycle sustainability, proliferation-resistance capabilities, and other performance data against pressurized water reactor (PWR) fuel cycle data. Fuel cycle studies LEU-NV;commercial HEU-Th;commercial LEU-Th;weapons-grade plutonium consumption; and burning of LWR waste including plutonium and minor actinides in the MHR. results show that all commercial MHR options, with the exception of HEU-TH, are more sustainable than a PWR fuel cycle. With LEU-NV being the most sustainable commercial options. In addition, all commercial MHR options out perform the PWR with regards to its proliferation-resistance, with thorium fuel cycle having the best proliferation-resistance characteristics.

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

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.

International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO). Introduction and status

International Nuclear Information System (INIS)

2002-01-01

INPRO is a response to the invitation of the IAEA General Conference to combine efforts in considering the issues of the nuclear fuel cycle, in particular by examining innovative and proliferation resistant nuclear technology. The objective if INPRO is to support the safe, sustainable, economic and proliferation-resistant use of nuclear technology to meet the global energy needs of the 21st century

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

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

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

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.

Assessment and reduction of proliferation risk of reactor-grade plutonium regarding construction of ‘fizzle bombs’ by terrorists

Energy Technology Data Exchange (ETDEWEB)

Serfontein, Dawid E., E-mail: Dawid.Serfontein@nwu.ac.za [School for Mechanical and Nuclear Engineering, North West University (PUK-Campus), PRIVATE BAG X6001 (Internal Post Box 360), Potchefstroom 2520 (South Africa); Mulder, Eben J. [School for Mechanical and Nuclear Engineering, North West University (South Africa); Reitsma, Frederik [Calvera Consultants (South Africa)

2014-05-01

The approximately 23.7 wt% {sup 240}Pu in reactor-grade plutonium denatures the {sup 239}Pu to the extent that it cannot fuel high yield nuclear weapons. {sup 240}Pu has a high spontaneous fission rate, which increases the spontaneous neutron flux within the fuel. When such a nuclear weapon is triggered, these neutrons cause the nuclear fission chain reaction to pre-detonate which blows the imploding fuel shell apart before the designed level of compression and reactivity could be attained, thereby greatly reducing the average energy yield of such “fizzle” bombs. Therefore reactor-grade plutonium is normally viewed as highly proliferation resistant. In this article the literature on the proliferation resistance of reactor-grade plutonium and on the mechanism and effect of fizzle bombs is reviewed in order to test this view. It is shown that even very low yield fizzle bombs, exploded in urban areas, would still cause serious blast damage as well as radioactive contamination. Combined with the high levels of induced terror, fizzle bombs might thus be attractive psychological weapons for terrorists. Therefore reactor-grade plutonium may not be sufficiently proliferation resistant against nuclear terrorism. However, denaturisation with more than 9% {sup 238}Pu produces high levels of decay heat which will melt or explode the high explosives around uncooled implosion type weapons, rendering them useless. Unfortunately, reactor-grade Pu contains only 2.7% {sup 238}Pu and is thus not sufficiently proliferation resistant in this respect. It is also shown that the associated neptunium poses a substantial proliferation risk. In the present study strong improvement of the proliferation resistance was demonstrated by simulation of incineration of reactor-grade plutonium in the 400 MW{sub th} Pebble Bed Modular Reactor Demonstration Power Plant. Results for modified fuel cycles, aimed at transmutating {sup 237}Np to {sup 238}Pu are also reported. However, these

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.

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.

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

Nuclear non-proliferation and disarmament: A long-term perspective

International Nuclear Information System (INIS)

Haeckel, E.

1990-01-01

International nuclear policy has been determined for a long time by the exigencies of the status quo. The non-proliferation regime draws its legitimacy from the continuation of extant patterns of power in world politics. Such a static policy cannot succeed forever. Overcoming the threat of nuclear proliferation will require innovative strategy that reaches beyond the status quo. It calls for structural change in the international system to be accomodated instead of resisted. If the Non-Proliferation Treaty is to hold, nuclear weapon states will finally have to forgo their privileged status. This cannot, however, be accomplished simply through the abolition or renunciation of nuclear weapons since nuclear weapons themselves continue to be instrumental for war prevention and international stability. Rather, what is needed is a new approach to the management of the nuclear world system under international responsibility. Nonproliferation and disarmament objectives together call for a concept of global security in which multilateral institutions assume an increasingly important role of nuclear diplomacy. (orig.) [de

Transcriptional Control of Vascular Smooth Muscle Cell Proliferation by Peroxisome Proliferator-Activated Receptor-γ: Therapeutic Implications for Cardiovascular Diseases

Directory of Open Access Journals (Sweden)

Florence Gizard

2008-01-01

Full Text Available Proliferation of vascular smooth muscle cells (SMCs is a critical process for the development of atherosclerosis and complications of procedures used to treat atherosclerotic diseases, including postangioplasty restenosis, vein graft failure, and transplant vasculopathy. Peroxisome proliferator-activated receptor (PPAR γ is a member of the nuclear hormone receptor superfamily and the molecular target for the thiazolidinediones (TZD, used clinically to treat insulin resistance in patients with type 2 diabetes. In addition to their efficacy to improve insulin sensitivity, TZD exert a broad spectrum of pleiotropic beneficial effects on vascular gene expression programs. In SMCs, PPARγ is prominently upregulated during neointima formation and suppresses the proliferative response to injury of the arterial wall. Among the molecular target genes regulated by PPARγ in SMCs are genes encoding proteins involved in the regulation of cell-cycle progression, cellular senescence, and apoptosis. This inhibition of SMC proliferation is likely to contribute to the prevention of atherosclerosis and postangioplasty restenosis observed in animal models and proof-of-concept clinical studies. This review will summarize the transcriptional target genes regulated by PPARγ in SMCs and outline the therapeutic implications of PPARγ activation for the treatment and prevention of atherosclerosis and its complications.

Microbial-based evaluation of anaerobic membrane bioreactors (AnMBRs) for the sustainable and efficient treatment of municipal wastewater

KAUST Repository

Harb, Moustapha

2017-03-01

Conventional activated sludge-based wastewater treatment is an energy and resource-intensive process. Historically it has been successful at producing safely treated wastewater effluents in the developed world, specifically in places that have the infrastructure and space to support its operation. However, with a growing need for safe and efficient wastewater treatment across the world in both urban and rural settings, a paradigm shift in waste treatment is proving to be necessary. The sustainability of the future of wastewater treatment, in a significant way, hinges on moving towards energy neutrality and wastewater effluent reuse. This potential for reuse is threatened by the recent emergence and study of contaminants that have not been previously taken into consideration, such as antibiotics and other organic micropollutants (OMPs), antibiotic resistance genes, and persistent pathogenic bacteria. This dissertation focuses on investigating the use of anaerobic membrane bioreactor (AnMBR) technology for the sustainable treatment of municipal-type wastewaters. Specifically, a microbial approach to understanding biofouling and methane recovery potential in anaerobic MBR systems has been employed to assess different reactor systems’ efficiency. This dissertation further compares AnMBRs to their more widely used aerobic counterparts. This comparison specifically focuses on the removal and biodegradation of OMPs and antibiotics in both anaerobic and aerobic MBRs, while also investigating their effect on the proliferation of antibiotic resistance genes. Due to rising interest in wastewater effluent reuse and the lack of a comprehensive understanding of MBR systems’ effects on pathogen proliferation, this dissertation also investigates the presence of pathogens in both aerobic and anaerobic MBR effluents by using molecularbased detection methods. The findings of this dissertation demonstrate that membrane-associated anaerobic digestion processes have significant

MHR fuel cycle options for future sustainability of nuclear power

International Nuclear Information System (INIS)

Baxter, Alan; Venneri, Francesco; Rodriguez, Carmelo; Fikani, Michael

2005-01-01

The future sustainability of the nuclear option is not significantly tied to the level of resources. For example, current high quality uranium reserves (∼3.34x10 6 tons) are enough for more than 55 years at present consumption rates (IAEA estimate). Doubling of the present uranium ore price (∼$26/kg) could create about a tenfold increase in resources, providing more than 550 years of supply at present rates (World Nuclear Association estimate). There are also thorium reserves which are estimated to be about three times those of uranium, and would allow for a significant increase in annual consumption levels. The key to a sustainable nuclear future is really tied to the political and technical problems of long term waste disposal, and the perceived risks of nuclear weapons proliferation. Thus fuel cycle options for a sustainable nuclear future must address and solve these issues. High temperature, Gas-Cooled, Graphite Moderated, reactors (MHRs) have nuclear and operational characteristics to provide multiple fuel cycle options to solve these issues. Three fuel cycles for the MHD are described in this paper, and their capabilities for meeting a sustainable nuclear future in terms of nuclear waste minimization and destruction, and reduction of proliferation risk, are discussed. (author)

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.

Effects of nicotinamide N-methyltransferase on PANC-1 cells proliferation, metastatic potential and survival under metabolic stress.

Science.gov (United States)

Yu, Tao; Wang, Yong-Tao; Chen, Pan; Li, Yu-Hua; Chen, Yi-Xin; Zeng, Hang; Yu, Ai-Ming; Huang, Min; Bi, Hui-Chang

2015-01-01

Aberrant expression of Nicotinamide N-methyltransferase (NNMT) has been reported in pancreatic cancer. However, the role of NNMT in pancreatic cancer development remains elusive. Therefore, the present study was to investigate the impact of NNMT on pancreatic cancer cell proliferation, metastatic potential and survival under metabolic stress. Pancreatic cancer cell line PANC-1 was transfected with NNMT expression plasmid or small interfering RNA of NNMT to overexpress or knockdown intracellular NNMT expression, respectively. Rate of cell proliferation was monitored. Transwell migration and matrigel invasion assays were conducted to assess cell migration and invasion capacity. Resistance to glucose deprivation, sensitivity to glycolytic inhibition, mitochondrial inhibtion and resistance to rapamycin were examined to evaluate cell survival under metabolic stress. NNMT silencing markedly reduced cell proliferation, whereas NNMT overexpression promoted cell growth moderately. Knocking down NNMT also significantly suppressed the migration and invasion capacities of PANC-1 cells. Conversely, NNMT upregulation enhanced cell migration and invasion capacities. In addition, NNMT knockdown cells were much less resistant to glucose deprivation and rapamycin as well as glycolytic inhibitor 2-deoxyglucose whereas NNMT-expressing cells showed opposite effects although the effects were not so striking. These data sugguest that NNMT plays an important role in PANC-1 cell proliferation, metastatic potential and survival under metabolic stress. © 2015 S. Karger AG, Basel.

Effects of Nicotinamide N-Methyltransferase on PANC-1 Cells Proliferation, Metastatic Potential and Survival Under Metabolic Stress

Directory of Open Access Journals (Sweden)

Tao Yu

2015-01-01

Full Text Available Background: Aberrant expression of Nicotinamide N-methyltransferase (NNMT has been reported in pancreatic cancer. However, the role of NNMT in pancreatic cancer development remains elusive. Therefore, the present study was to investigate the impact of NNMT on pancreatic cancer cell proliferation, metastatic potential and survival under metabolic stress. Methods: Pancreatic cancer cell line PANC-1 was transfected with NNMT expression plasmid or small interfering RNA of NNMT to overexpress or knockdown intracellular NNMT expression, respectively. Rate of cell proliferation was monitored. Transwell migration and matrigel invasion assays were conducted to assess cell migration and invasion capacity. Resistance to glucose deprivation, sensitivity to glycolytic inhibition, mitochondrial inhibtion and resistance to rapamycin were examined to evaluate cell survival under metabolic stress. Results: NNMT silencing markedly reduced cell proliferation, whereas NNMT overexpression promoted cell growth moderately. Knocking down NNMT also significantly suppressed the migration and invasion capacities of PANC-1 cells. Conversely, NNMT upregulation enhanced cell migration and invasion capacities. In addition, NNMT knockdown cells were much less resistant to glucose deprivation and rapamycin as well as glycolytic inhibitor 2-deoxyglucose whereas NNMT-expressing cells showed opposite effects although the effects were not so striking. Conclusions: These data sugguest that NNMT plays an important role in PANC-1 cell proliferation, metastatic potential and survival under metabolic stress.

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 ...

Novel nanostructured enoxaparin sodium-PLGA hybrid carriers overcome tumor multidrug resistance of doxorubicin hydrochloride.

Science.gov (United States)

Wang, Jia; Wu, Lei; Kou, Longfa; Xu, Meng; Sun, Jin; Wang, Yongjun; Fu, Qiang; Zhang, Peng; He, Zhonggui

2016-11-20

Novel enoxaparin sodium-PLGA hybrid nanocarries (EPNs) were successfully designed for sustained delivery of hydrophilic cationic doxorubicin hydrochloride (DOX) and to overcome multidrug resistance (MDR). By incorporation of the negative polymer of enoxaparin sodium (ES), DOX was highly encapsulated into EPNs with an encapsulation efficiency of 92.49%, and ES effectively inhibited the proliferation of HUVEC cell lines. The in vivo pharmacokinetics study after intravenous injection indicated that DOX-loaded EPNs (DOX-EPNs) exhibited a higher area under the curve (AUC) and a longer half-life (t 1/2 ) in comparison with DOX solution (DOX-Sol). The biodistribution study demonstrated that DOX-EPNs increased the DOX level in plasma and decreased the accumulation of DOX in liver and spleen. Compared with DOX-Sol, DOX-EPNs increased the cytotoxicity in P-gp over-expressing MCF-7/Adr cells, attributed to the higher intracellular efficiency of DOX produced by the EPNs. DOX-EPNs entered into resistant tumor cells by multiple endocytosis pathways, which resulted in overcoming the multidrug resistance of MCF-7/Adr cells by escaping the efflux induced by P-gp transporters. Copyright © 2016 Elsevier B.V. All rights reserved.

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)

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 ...

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.

Pathophysiological mechanisms of death resistance in colorectal carcinoma.

Science.gov (United States)

Huang, Ching-Ying; Yu, Linda Chia-Hui

2015-11-07

Colon cancers develop adaptive mechanisms to survive under extreme conditions and display hallmarks of unlimited proliferation and resistance to cell death. The deregulation of cell death is a key factor that contributes to chemoresistance in tumors. In a physiological context, balance between cell proliferation and death, and protection against cell damage are fundamental processes for maintaining gut epithelial homeostasis. The mechanisms underlying anti-death cytoprotection and tumor resistance often bear common pathways, and although distinguishing them would be a challenge, it would also provide an opportunity to develop advanced anti-cancer therapeutics. This review will outline cell death pathways (i.e., apoptosis, necrosis, and necroptosis), and discuss cytoprotective strategies in normal intestinal epithelium and death resistance mechanisms of colon tumor. In colorectal cancers, the intracellular mechanisms of death resistance include the direct alteration of apoptotic and necroptotic machinery and the upstream events modulating death effectors such as tumor suppressor gene inactivation and pro-survival signaling pathways. The autocrine, paracrine and exogenous factors within a tumor microenvironment can also instigate resistance against apoptotic and necroptotic cell death in colon cancers through changes in receptor signaling or transporter uptake. The roles of cyclooxygenase-2/prostaglandin E2, growth factors, glucose, and bacterial lipopolysaccharides in colorectal cancer will be highlighted. Targeting anti-death pathways in the colon cancer tissue might be a promising approach outside of anti-proliferation and anti-angiogenesis strategies for developing novel drugs to treat refractory tumors.

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.

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.

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

Better, but good enough? Indicators for absolute environmental sustainability in a life cycle perspective

DEFF Research Database (Denmark)

Bjørn, Anders; Richardson, Katherine

An increasing focus on sustainability has led to proliferation of the use of environmental indicators to guide various types of decisions, from individual consumer choices to policy making at the national, regional and global scale. Most environmental indicators are relative, meaning that quantif......An increasing focus on sustainability has led to proliferation of the use of environmental indicators to guide various types of decisions, from individual consumer choices to policy making at the national, regional and global scale. Most environmental indicators are relative, meaning...... that quantified environmental interferences of a studied anthropogenic system (a product, a company, a city, etc.) are compared to those of chosen anthropogenic systems of reference. The use of relative indicators can give the impression that societies are moving towards environmental sustainability when...... that society-nature interactions in many cases are environmentally unsustainable and that the level of unsustainability may be increasing over time. A clear rationale therefore exists for developing and using absolute environmental sustainability indicators (AESI) that not only can identify the anthropogenic...

Proliferation attractiveness of nuclear material in a small modular pressure tube SCWR

Energy Technology Data Exchange (ETDEWEB)

McDonald, M.; Pencer, J., E-mail: mcdonamh@aecl.ca, E-mail: pencerj@aecl.ca [Atomic Energy of Canada Limited, Chalk River, Ontario (Canada)

2013-07-01

The SuperSafe© Reactor (SSR), has been recently proposed as a small modular version of the Canadian supercritical water cooled reactor (SCWR). This reactor is a heavy water moderated, pressure tube reactor using supercritical light water as coolant. The current SSR design is to generate 300 MWe taking advantage of the expected high thermal efficiency (assumed 45%). As one of the reactor types being considered by the Generation-IV International Forum, it is expected that this SCWR design will feature enhanced proliferation resistance over current generation technologies. Proliferation resistance assessments are wide-ranging, multidisciplinary efforts that are typically performed at a number of levels, from a state level down to a specific facility level. One small, but particularly important, sub-assessment is that of nuclear material attractiveness, that is, assessing the quality of nuclear materials throughout the fuel cycle for use in making a nuclear explosive device. The attractiveness of materials for three different SSR fuel options is examined in this work. (author)

A critical analysis of hazard resilience measures within sustainability assessment frameworks

International Nuclear Information System (INIS)

Matthews, Elizabeth C.; Sattler, Meredith; Friedland, Carol J.

2014-01-01

Today, numerous sustainability assessment frameworks (SAFs) exist to guide designers in achieving sustainable performance in the design of structures and communities. SAFs are beneficial in educating users and are useful tools for incorporating sustainability strategies into planning, design, and construction; however, there is currently a substantial gap in the ability of existing SAFs to incorporate hazard resistance and hazard mitigation in the broader context of sustainable design. This paper analyzes the incorporation of hazard resistant design and hazard mitigation strategies within SAFs via a multi-level analysis of eleven SAFs. The SAFs analyzed range in scale of application (i.e. building, site, community). Three levels of analysis are presented: (1) macro-level analysis comparing the number of measures strictly addressing resilience versus sustainability, (2) meso-level analysis of the coverage of types of hazards within SAFs (e.g. flood, fire), and (3) micro-level analysis of SAF measures connected to flood-related hazard resilience. The results demonstrate that hazard resistance and hazard mitigation do not figure prominently in the intent of SAFs and that weaknesses in resilience coverage exist that have the potential to lead to the design of structures and communities that are still highly vulnerable to the impacts of extreme events. - Highlights: • Sustainability assessment frameworks (SAFs) were analyzed for resilience coverage • Hazard resistance and mitigation do not figure prominently in the intent of SAFs • Approximately 75% of SAFs analyzed address three or fewer hazards • Lack of economic measures within SAFs could impact resilience and sustainability • Resilience measures for flood hazards are not consistently included in SAFs

A critical analysis of hazard resilience measures within sustainability assessment frameworks

Energy Technology Data Exchange (ETDEWEB)

Matthews, Elizabeth C., E-mail: echiso1@lsu.edu [Louisiana State University, Baton Rouge, LA (United States); Sattler, Meredith, E-mail: msattler@lsu.edu [School of Architecture, Louisiana State University, Baton Rouge, LA (United States); Friedland, Carol J., E-mail: friedland@lsu.edu [Bert S. Turner Department of Construction Management, Louisiana State University, Baton Rouge, LA (United States)

2014-11-15

Today, numerous sustainability assessment frameworks (SAFs) exist to guide designers in achieving sustainable performance in the design of structures and communities. SAFs are beneficial in educating users and are useful tools for incorporating sustainability strategies into planning, design, and construction; however, there is currently a substantial gap in the ability of existing SAFs to incorporate hazard resistance and hazard mitigation in the broader context of sustainable design. This paper analyzes the incorporation of hazard resistant design and hazard mitigation strategies within SAFs via a multi-level analysis of eleven SAFs. The SAFs analyzed range in scale of application (i.e. building, site, community). Three levels of analysis are presented: (1) macro-level analysis comparing the number of measures strictly addressing resilience versus sustainability, (2) meso-level analysis of the coverage of types of hazards within SAFs (e.g. flood, fire), and (3) micro-level analysis of SAF measures connected to flood-related hazard resilience. The results demonstrate that hazard resistance and hazard mitigation do not figure prominently in the intent of SAFs and that weaknesses in resilience coverage exist that have the potential to lead to the design of structures and communities that are still highly vulnerable to the impacts of extreme events. - Highlights: • Sustainability assessment frameworks (SAFs) were analyzed for resilience coverage • Hazard resistance and mitigation do not figure prominently in the intent of SAFs • Approximately 75% of SAFs analyzed address three or fewer hazards • Lack of economic measures within SAFs could impact resilience and sustainability • Resilience measures for flood hazards are not consistently included in SAFs.

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

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

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.

Extensively Drug-Resistant Tuberculosis: Principles of Resistance, Diagnosis, and Management.

Science.gov (United States)

Wilson, John W; Tsukayama, Dean T

2016-04-01

Extensively drug-resistant (XDR) tuberculosis (TB) is an unfortunate by-product of mankind's medical and pharmaceutical ingenuity during the past 60 years. Although new drug developments have enabled TB to be more readily curable, inappropriate TB management has led to the emergence of drug-resistant disease. Extensively drug-resistant TB describes Mycobacterium tuberculosis that is collectively resistant to isoniazid, rifampin, a fluoroquinolone, and an injectable agent. It proliferates when established case management and infection control procedures are not followed. Optimized treatment outcomes necessitate time-sensitive diagnoses, along with expanded combinations and prolonged durations of antimicrobial drug therapy. The challenges to public health institutions are immense and most noteworthy in underresourced communities and in patients coinfected with human immunodeficiency virus. A comprehensive and multidisciplinary case management approach is required to optimize outcomes. We review the principles of TB drug resistance and the risk factors, diagnosis, and managerial approaches for extensively drug-resistant TB. Treatment outcomes, cost, and unresolved medical issues are also discussed. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

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

Pressure tube reactors and a sustainable energy future: the ultra development path

International Nuclear Information System (INIS)

Duffey, R.

2008-01-01

Nuclear energy must be made available, freely and readily, to help meet world energy needs, concerns over energy price and security of supply, and alleviating the uncertainties over potential climate change. The perspective offered here is a model for others to consider, adopting and adapting using whatever elements fit their own strategies and needs. The underlying philosophy is to retain flexibility in the reactor development, deployment and fuel cycle, while ensuring the principle that customer, energy market, safety, non-proliferation and sustainability needs are all addressed. Canada is the world's largest exporter of uranium, providing about one-third of the world supply for nuclear power reactors. Pressure tube reactors (PTRs), of which CANDU is a prime example, have a major role to play in a sustainable energy future. The inherent fuel cycle flexibility of the PTR offers many technical, resource and sustainability, and economic advantages over other reactor technologies and is the subject of this paper. The design evolution and development intent is to be consistent with improved or enhanced safety, licensing and operating limits, global proliferation concerns, and waste stream reduction, thus enabling sustainable energy futures. The limits are simply those placed by safety, economics and resource availability. (author)

Pressure tube reactors and a sustainable energy future: the ultra development path

International Nuclear Information System (INIS)

Duffey, R.

2008-01-01

Nuclear energy must be made available, freely and readily, to help meet world energy needs, concerns over energy price and security of supply, and alleviating the uncertainties over potential climate change. The perspective offered here is a model for others to consider, adopting and adapting using whatever elements fit their own strategies and needs. The underlying philosophy is to retain flexibility in the reactor development, deployment and fuel cycle, while ensuring the principle that customer, energy market, safety, non-proliferation and sustainability needs are all addressed. Canada is the world's largest exporter of uranium, providing about one-third of the world supply for nuclear power reactors. Pressure tube reactors (PTRs), of which CANDU, is a prime example, have a major role to play in a sustainable energy future. The inherent fuel cycle flexibility of the PTR offers many technical, resource and sustainability and economic advantages over other reactor technologies and is the subject of this paper. The design evolution and development intent is to be consistent with improved or enhanced safety, licensing and operating limits, global proliferation concerns, and waste stream reduction, thus enabling sustainable energy futures. The limits are simply those placed by safety, economics and resource availability. (author)

Role of varieties in sustainable rice production in Malaysia

International Nuclear Information System (INIS)

Othman Omar; Saad Abdullah

2002-01-01

Rice is the staple food of Malaysians. Rice production in Malaysia is concentrated in granary areas, which are provided with irrigation facilities. There is no plan to increase the size or the number of these granary areas, thus productivity per unit area must be increased to sustain the current level of self-sufficiency. Variety determines the potential productivity; environment and crop management determine how much of this potential is realized. Crop management is very important, as any drop in the level of management will effect productivity. However there are characteristics / factors that can be incorporated into varieties which can buffer the effect of environment and crop management. Pests and diseases can result in severe yield loss and lead to non-sustainable production. Varietal resistance to some of these diseases can be incorporated into rice varieties. Active breeding to incorporate rice resistance to blast, PMV (tungro), bacterial blight and brown planthopper is being currently carried out Factors that determine or justify the active breeding status are: importance of Oe pests diseases, resistance sources and the availability of efficient screening procedure. Sheath blight is also an important disease in direct seeded crops as it can cause severe yield loss, but good resistant sources are not available for incorporation and the screening procedure is also not very efficient. Biotechnologists are working hard to introduce resistance from other crops and also develop other resistance mechanisms for sheath blight. Water, shortage or excess, is a major cause of non-sustainable production. The breeding of short-term varieties can overcome water problems or shortages. Negative interaction between varietal characteristics and environment do occur. Finally farmers have to decide which factors of the environment cannot be easily controlled, and choose the correct varieties in order to achieve sustainable production. (Author)

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

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...

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....

Andrographolide Suppresses MV4-11 Cell Proliferation through the Inhibition of FLT3 Signaling, Fatty Acid Synthesis and Cellular Iron Uptake

Directory of Open Access Journals (Sweden)

Xiao Chen

2017-08-01

Full Text Available Background: Andrographolide (ADR, the main active component of Andrographis paniculata, displays anticancer activity in various cancer cell lines, among which leukemia cell lines exhibit the highest sensitivity to ADR. In particular, ADR was also reported to have reduced drug resistance in multidrug resistant cell lines. However, the mechanism of action (MOA of ADR’s anticancer and anti-drug-resistance activities remain elusive. Methods: In this study, we used the MV4-11 cell line, a FLT3 positive acute myeloid leukemia (AML cell line that displays multidrug resistance, as our experimental system. We first evaluated the effect of ADR on MV4-11 cell proliferation. Then, a quantitative proteomics approach was applied to identify differentially expressed proteins in ADR-treated MV4-11 cells. Finally, cellular processes and signal pathways affected by ADR in MV4-11 cell were predicted with proteomic analysis and validated with in vitro assays. Results: ADR inhibits MV4-11 cell proliferation in a dose- and time-dependent manner. With a proteomic approach, we discovered that ADR inhibited fatty acid synthesis, cellular iron uptake and FLT3 signaling pathway in MV4-11 cells. Conclusions: ADR inhibits MV4-11 cell proliferation through inhibition of fatty acid synthesis, iron uptake and protein synthesis. Furthermore, ADR reduces drug resistance by blocking FLT3 signaling.

Nuclear Fuel Cycle System Analysis (I)

Energy Technology Data Exchange (ETDEWEB)

Ko, Won Il; Kwon, Eun Ha; Kim, Ho Dong; Yoon, Ji Sup; Park, Seong Won

2006-12-15

As a nation develops strategies that provide nuclear energy while meeting its various objectives, it must begin with identification of a fuel cycle option that can be best suitable for the country. For such a purpose, this paper takes four different fuel cycle options - Once-through Cycle, DUPIC Recycle, Thermal Reactor Recycle and GEN-IV Recycle, and evaluates each option in terms of sustainability, environment-friendliness, proliferation-resistance and economics. The analysis shows that the GEN-IV Recycle appears to have an advantage in terms of sustainability, environment-friendliness and long-term proliferation-resistance, while it is expected to be more economically competitive, if uranium ore prices increase or costs of pyroprocessing and fuel fabrication decrease.

CyclinG1 Amplification Enhances Aurora Kinase Inhibitor-Induced Polyploid Resistance and Inhibition of Bcl-2 Pathway Reverses the Resistance

Directory of Open Access Journals (Sweden)

Wenfeng Zhang

2017-08-01

Full Text Available Background/Aims: CyclinG1 (CycG1 is frequently overexpressed in solid tumors and overexpression of CycG1 promotes cell survival upon paclitaxel exposure by inducing polyploidy. Whether and how CycG1 regulates polyploidization caused by small molecular targeted inhibitors remains unclear. Methods: Immunohistochemistry and immunoblotting were utilized to examine protein expression. Cell proliferation was measured by ATPlite assay, and cell cycle distribution and apoptosis were measured by flow cytometry and/or DNA fragmentation assays. Results: Overexpression of CycG1 in breast cancer cells caused apoptosis-resistant polyploidy upon treatment with Aurora kinase inhibitor, ZM447439 (ZM. Addition of ABT-263, a small-molecule BH3 mimetic, to ZM, produced a synergistic loss of cell viability with greater sustained tumor growth inhibition in breast cancer cell lines. Decrease of Mcl-1 and increase of NOXA caused by ZM treatment, were responsible for the synergy. Furthermore, CycG1 was highly expressed in Triple-Negative-Breast-Cancer patients treated with paclitaxel and was paralleled by decreased cell survival. Conclusion: CycG1 is a crucial factor in ZM-induced polyploidy resistance, and ABT-263/ZM combination hold therapeutic utility in the CycG1-amplified subset of breast cancer and CycG1, thus, is a promising target in breast cancer.

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.

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.)

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

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

MicroRNA-21 Increases Proliferation and Cisplatin Sensitivity of Osteosarcoma-Derived Cells.

Directory of Open Access Journals (Sweden)

Vanita Vanas

Full Text Available Osteosarcoma is the most common primary bone tumor and poor prognosis for osteosarcoma patients is mainly due to chemotherapy resistance. MicroRNAs are important to maintain pathophysiological mechanisms of cancer and influence cell sensitivity to chemotherapy. In this study, we tested the functions of microRNA-21 for malignant features as well as for drug resistance of osteosarcoma. We used Northern blot to measure microRNA-21 levels in osteosarcoma-derived cell lines. MicroRNA-21 activity was modulated by either expressing a sponge to decrease its activity in an osteosarcoma-derived cell line expressing high levels of microRNA-21 or by introducing pri-microRNA-21 in a cell line with low endogenous levels. Cell migration was determined in a scratch assay and cell proliferation was measured by performing growth curve analysis. Sensitivity of the cells towards chemotherapeutics was investigated by performing cell viability assays and calculating the IC50 values. While cell migration was unaffected by modulated microRNA-21 levels, microRNA-21 inhibition slowed proliferation and exogenously expressed microRNA-21 promoted this process. Modulated microRNA-21 activity failed to effect sensitivity of osteosarcoma-derived cell lines to doxorubicin or methotrexate. Contrarily, reduction of microRNA-21 activity resulted in enhanced resistance towards cisplatin while ectopic expression of microRNA-21 showed the opposite effect. Increased microRNA-21 levels repressed the expression of Sprouty2 and ectopic expression of Sprouty2 was able to largely rescue the observed effects of microRNA-21 in osteosarcoma. In summary, our data indicate that in osteosarcoma microRNA-21 expression is an important component for regulation of cell proliferation and for determining sensitivity to cisplatin.

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

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.

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)

PNIPAAM modified mesoporous hydroxyapatite for sustained osteogenic drug release and promoting cell attachment

Energy Technology Data Exchange (ETDEWEB)

Wu, Tao [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China); Tan, Lei [Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Science, Wuhan University, Wuhan 430072 (China); Cheng, Ning; Yan, Qi; Zhang, Yu-Feng [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China); Liu, Chuan-Jun, E-mail: cjliu@whu.edu.cn [Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Science, Wuhan University, Wuhan 430072 (China); Shi, Bin, E-mail: shibin_dentist@126.com [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China)

2016-05-01

This work presented a sustained release system of simvastatin (SIM) based on the mesoporous hydroxyapatite (MHA) capped with poly(N-isopropylacrylamide) (PNIPAAM). The MHA was prepared by using cetyltrimethylammonium bromide (CTAB) as a template and the modified PNIPAAM layer on the surface of MHA was fabricated through surface-initiated atom transfer radical polymerization (SI-ATRP). The SIM loaded MHA-PNIPAAM showed a sustained release of SIM at 37 °C over 16 days. The bone marrow mesenchymal stem cell (BMSC) proliferation was assessed by cell counting kit-8 (CCK-8) assay, and the osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity and Alizarin Red staining. The release profile showed that the release of SIM from MHA-SIM-PNIPAAM lasted 16 days and the cumulative amount of released SIM was almost seven-fold than MHA-SIM. Besides, SIM loaded MHA-PNIPAAM exhibited better performance on cell proliferation, ALP activity, and calcium deposition than pure MHA due to the sustained release of SIM. The quantity of ALP in MHA-SIM-PNIPAAM group was more than two fold than pure MHA group at 7 days. Compared to pure MHA, better BMSC attachment on PNIPAAM modified MHA was observed using fluorescent microscopy, indicating the better biocompatibility of MHA-PNIPAAM. - Highlights: • PNIPAAM modified mesoporous hydroxyapatite (MHA) was fabricated by SI-ATRP. • SIM loaded MHA-PNIPAAM continually released SIM in effect concentration for 16 days. • MHA-SIM-PNIPAAM behaved well on cell proliferation, ALP activity and calcium deposition.

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.

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.

Loss of TRPV2 Homeostatic Control of Cell Proliferation Drives Tumor Progression

Directory of Open Access Journals (Sweden)

Sonia Liberati

2014-02-01

Full Text Available Herein we evaluate the involvement of the TRPV2 channel, belonging to the Transient Receptor Potential Vanilloid channel family (TRPVs, in development and progression of different tumor types. In normal cells, the activation of TRPV2 channels by growth factors, hormones, and endocannabinoids induces a translocation of the receptor from the endosomal compartment to the plasma membrane, which results in abrogation of cell proliferation and induction of cell death. Consequently, loss or inactivation of TRPV2 signaling (e.g., glioblastomas, induces unchecked proliferation, resistance to apoptotic signals and increased resistance to CD95-induced apoptotic cell death. On the other hand, in prostate cancer cells, Ca2+-dependent activation of TRPV2 induced by lysophospholipids increases the invasion of tumor cells. In addition, the progression of prostate cancer to the castration-resistant phenotype is characterized by de novo TRPV2 expression, with higher TRPV2 transcript levels in patients with metastatic cancer. Finally, TRPV2 functional expression in tumor cells can also depend on the presence of alternative splice variants of TRPV2 mRNA that act as dominant-negative mutant of wild-type TRPV2 channels, by inhibiting its trafficking and translocation to the plasma membrane. In conclusion, as TRP channels are altered in human cancers, and their blockage impair tumor progression, they appear to be a very promising targets for early diagnosis and chemotherapy.

Ginger Phytochemicals Inhibit Cell Growth and Modulate Drug Resistance Factors in Docetaxel Resistant Prostate Cancer Cell.

Science.gov (United States)

Liu, Chi-Ming; Kao, Chiu-Li; Tseng, Yu-Ting; Lo, Yi-Ching; Chen, Chung-Yi

2017-09-05

Ginger has many bioactive compounds with pharmacological activities. However, few studies are known about these bioactive compounds activity in chemoresistant cells. The aim of the present study was to investigate the anticancer properties of ginger phytochemicals in docetaxel-resistant human prostate cancer cells in vitro. In this study, we isolated 6-gingerol, 10-gingerol, 4-shogaol, 6-shogaol, 10-shogaol, and 6-dehydrogingerdione from ginger. Further, the antiproliferation activity of these compounds was examined in docetaxel-resistant (PC3R) and sensitive (PC3) human prostate cancer cell lines. 6-gingerol, 10-gingerol, 6-shogaol, and 10-shogaol at the concentration of 100 μM significantly inhibited the proliferation in PC3R but 6-gingerol, 6-shogaol, and 10-shogaol displayed similar activity in PC3. The protein expression of multidrug resistance associated protein 1 (MRP1) and glutathione-S-transferase (GSTπ) is higher in PC3R than in PC3. In summary, we isolated the bioactive compounds from ginger. Our results showed that 6-gingerol, 10-gingerol, 6-shogaol, and 10-shogaol inhibit the proliferation of PC3R cells through the downregulation of MRP1 and GSTπ protein expression.

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.

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.

Peroxisome Proliferator-Activated Receptor Ligands and Their Role in Chronic Myeloid Leukemia: Therapeutic Strategies.

Science.gov (United States)

Yousefi, Bahman; Samadi, Nasser; Baradaran, Behzad; Shafiei-Irannejad, Vahid; Zarghami, Nosratollah

2016-07-01

Imatinib therapy remains the gold standard for treatment of chronic myeloid leukemia; however, the acquired resistance to this therapeutic agent in patients has urged the scientists to devise modalities for overcoming this chemoresistance. For this purpose, initially therapeutic agents with higher tyrosine kinase activity were introduced, which had the potential for inhibiting even mutant forms of Bcr-Abl. Furthermore, coupling imatinib with peroxisome proliferator-activated receptor ligands also showed beneficial effects in chronic myeloid leukemia cell proliferation. These combination protocols inhibited cell growth and induced apoptosis as well as differentiation in chronic myeloid leukemia cell lines. In addition, peroxisome proliferator-activated receptors ligands increased imatinib uptake by upregulating the expression of human organic cation transporter 1. Taken together, peroxisome proliferator-activated receptors ligands are currently being considered as novel promising therapeutic candidates for chronic myeloid leukemia treatment, because they can synergistically enhance the efficacy of imatinib. In this article, we reviewed the potential of peroxisome proliferator-activated receptors ligands for use in chronic myeloid leukemia treatment. The mechanism of action of these therapeutics modalities are also presented in detail. © 2016 John Wiley & Sons A/S.

Nitrous Oxide Induces Prominent Cell Proliferation in Adult Rat Hippocampal Dentate Gyrus

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Farah Chamaa

2018-05-01

Full Text Available The identification of distinct and more efficacious antidepressant treatments is highly needed. Nitrous oxide (N2O is an N-methyl-D-aspartic acid (NMDA antagonist that has been reported to exhibit antidepressant effects in treatment-resistant depression (TRD patients. Yet, no studies have investigated the effects of sub-anesthetic dosages of N2O on hippocampal cell proliferation and neurogenesis in adult brain rats. In our study, adult male Sprague-Dawley rats were exposed to single or multiple exposures to mixtures of 70% N2O and 30% oxygen (O2. Sham groups were exposed to 30% O2 and the control groups to atmospheric air. Hippocampal cell proliferation was assessed by bromodeoxyuridine (BrdU incorporation, and BrdU-positive cells were counted in the dentate gyrus (DG using confocal microscopy. Results showed that while the rates of hippocampal cell proliferation were comparable between the N2O and sham groups at day 1, levels increased by 1.4 folds at day 7 after one session exposure to N2O. Multiple N2O exposures significantly increased the rate of hippocampal cell proliferation to two folds. Therefore, sub-anesthetic doses of N2O, similar to ketamine, increase hippocampal cell proliferation, suggesting that there will ultimately be an increase in neurogenesis. Future studies should investigate added N2O exposures and their antidepressant behavioral correlates.

Somaclonal variation in hybrid poplars for resistance to Septoria leaf spot

Science.gov (United States)

M.E. Ostry; D. D. Skilling

1987-01-01

Tissue culture techniques have been used to obtain hybrid poplars with putative resistance to leaf spot caused by Septoria musiva from clones previously susceptible to the disease. Stem internode explants were used to obtain proliferating callus cultures. Adventitious bud formation and shoot proliferation were then induced. Elongated shoots were excised and rooted in a...

Toward Sustainable Brownfield Redevelopment Using Life-Cycle Thinking

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I-Chun Chen

2016-10-01

Full Text Available The redevelopment of brownfields has become an important issue, as the number of contaminated sites has been increasing. However, a comprehensive regulatory framework is lacking that includes urban planning and a sustainability plan at the national level to support brownfield redevelopment in Taiwan. Few studies have explored sustainable management objectives to reduce the environmental impact of increasing economic value of the proliferating redeveloped brownfields. This study proposes a feasible definition for “brownfield” in Taiwan and analyzes the remediation goals to enable their inclusion in future land-use categories for urban planning. In order to rank the various options for brownfield development by sustainability, this study evaluates the external costs and benefits based on the environmental impact. Finally, the brownfield sustainability index (BSI was developed to determine the feasibility of sustainable redevelopment relevant to the different land reuse scenarios. For the selected study site, the option of green land with solar energy (ground P-Si panels was determined to be the best choice compared with the commercial, residential, and industrial scenarios. This study provides a framework for planning brownfield assessment strategies to address the current soil and groundwater remediation and land use policy issues in Taiwan.

Peroxisome proliferator-activated receptor-gamma (PPARgamma) Pro12Ala polymorphism and risk for pediatric obesity

NARCIS (Netherlands)

Dedoussis, George V; Vidra, Nikoleta; Butler, Johannah; Papoutsakis, Constantina; Yannakoulia, Mary; Hirschhorn, Joel N; Lyon, Helen N; Vidra, Nikoletta

BACKGROUND: Variation in the peroxisome-proliferator-activated receptor gamma (PPARgamma) gene has been reported to alter the risk for adiposity in adults. METHODS: We investigated the gender related association between the Pro12Ala variant (rs1801282) in obesity and insulin resistance traits in 794

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

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

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

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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.

Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor α signalling and results in tamoxifen insensitive proliferation

International Nuclear Information System (INIS)

Moerkens, Marja; Zhang, Yinghui; Wester, Lynn; Water, Bob van de; Meerman, John HN

2014-01-01

Tamoxifen resistance is a major problem in the treatment of estrogen receptor (ER) α -positive breast cancer patients. Although the mechanisms behind tamoxifen resistance are still not completely understood, clinical data suggests that increased expression of receptor tyrosine kinases is involved. Here, we studied the estrogen and anti-estrogen sensitivity of human breast cancer MCF7 cells that have a moderate, retroviral-mediated, ectopic expression of epidermal growth factor receptor (MCF7-EGFR). Proliferation of MCF7-EGFR and parental cells was induced by 17β-estradiol (E2), epidermal growth factor (EGF) or a combination of these. Inhibition of proliferation under these conditions was investigated with 4-hydroxy-tamoxifen (TAM) or fulvestrant at 10 -12 to 10 -6 M. Cells were lysed at different time points to determine the phosphorylation status of EGFR, MAPK 1/3 , AKT and the expression of ERα. Knockdown of target genes was established using smartpool siRNAs. Transcriptomics analysis was done 6 hr after stimulation with growth factors using Affymetrix HG-U133 PM array plates. While proliferation of parental MCF7 cells could only be induced by E2, proliferation of MCF7-EGFR cells could be induced by either E2 or EGF. Treatment with TAM or fulvestrant did significantly inhibit proliferation of MCF7-EGFR cells stimulated with E2 alone. EGF treatment of E2/TAM treated cells led to a marked cell proliferation thereby overruling the anti-estrogen-mediated inhibition of cell proliferation. Under these conditions, TAM however did still inhibit ERα- mediated transcription. While siRNA-mediated knock-down of EGFR inhibited the EGF- driven proliferation under TAM/E2/EGF condition, knock down of ERα did not. The TAM resistant cell proliferation mediated by the conditional EGFR-signaling may be dependent on the PI3K/Akt pathway but not the MEK/MAPK pathway, since a MEK inhibitor (U0126), did not block the proliferation. Transcriptomic analysis under the various E2/TAM

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.

Metformin Antagonizes Cancer Cell Proliferation by Suppressing Mitochondrial-Dependent Biosynthesis.

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Takla Griss

2015-12-01

Full Text Available Metformin is a biguanide widely prescribed to treat Type II diabetes that has gained interest as an antineoplastic agent. Recent work suggests that metformin directly antagonizes cancer cell growth through its actions on complex I of the mitochondrial electron transport chain (ETC. However, the mechanisms by which metformin arrests cancer cell proliferation remain poorly defined. Here we demonstrate that the metabolic checkpoint kinases AMP-activated protein kinase (AMPK and LKB1 are not required for the antiproliferative effects of metformin. Rather, metformin inhibits cancer cell proliferation by suppressing mitochondrial-dependent biosynthetic activity. We show that in vitro metformin decreases the flow of glucose- and glutamine-derived metabolic intermediates into the Tricarboxylic Acid (TCA cycle, leading to reduced citrate production and de novo lipid biosynthesis. Tumor cells lacking functional mitochondria maintain lipid biosynthesis in the presence of metformin via glutamine-dependent reductive carboxylation, and display reduced sensitivity to metformin-induced proliferative arrest. Our data indicate that metformin inhibits cancer cell proliferation by suppressing the production of mitochondrial-dependent metabolic intermediates required for cell growth, and that metabolic adaptations that bypass mitochondrial-dependent biosynthesis may provide a mechanism of tumor cell resistance to biguanide activity.

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

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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.

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

Sustainability and the Fixed Bed Nuclear Reactor (FBNR

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Farhang Sefidvash

2012-08-01

Full Text Available Sustainability as a multifaceted and holistic concept is analyzed. Sustainability involves human relationship with elements such as natural environment, economy, power, governance, education and technology with the ultimate purpose of carrying forward an ever-advancing civilization. The Fixed Bed Nuclear Reactor (FBNR is an innovative, small, simple in design, inherently safe, non-proliferating, and environmentally friendly concept that its deployment can generate energy in a sustainable manner contributing to the prosperity of humanity. The development of FBNR will provide electricity as well as desalinated water through a simple but advanced technology for the developing, as well as developed countries. FBNR is environmentally friendly due to its inherent safety and the convenience of using its spent fuel as the source of radiation for irradiation purposes in agriculture, industry, and medicine. Politically, if a ping pong game brought peace between China and USA, a program of development of FBNR supported by the peace loving international community can become a more mature means to bring peace among certain apparently hostile nations who crave sustainable energy, desalinated water and simple advanced technology.

Central proliferation and neurogenesis is impaired in type 2 diabetes and prediabetes animal models.

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Juan Jose Ramos-Rodriguez

Full Text Available Type 2 diabetes (T2D is an important risk factor to suffer dementia, including Alzheimer's disease (AD, and some neuropathological features observed in dementia could be mediated by T2D metabolic alterations. Since brain atrophy and impaired neurogenesis have been observed both T2D and AD we analyzed central nervous system (CNS morphological alterations in the db/db mice (leptin receptor KO mice, as a model of long-term insulin resistance and T2D, and in C57Bl6 mice fed with high fat diet (HFD, as a model of diet induced insulin resistance and prediabetes. Db/db mice showed an age-dependent cortical and hippocampal atrophy, whereas in HFD mice cortex and hippocampus were preserved. We also detected increased neurogenesis and cell proliferation rates in young db/db mice when compared with control littermates. Our study shows that metabolic parameters serve as predictors of both atrophy and altered proliferation and neurogenesis in the CNS. Moreover in the cortex, atrophy, cell proliferation and neurogenesis were significantly correlated. Our data suggest that T2D may underline some of the pathological features observed in the dementia process. They also support that blood glucose control in elderly patients could help to slow down dementia evolution and maybe, improve its prognosis.

Dedifferentiation, Proliferation, and Redifferentiation of Adult Mammalian Cardiomyocytes After Ischemic Injury.

Science.gov (United States)

Wang, Wei Eric; Li, Liangpeng; Xia, Xuewei; Fu, Wenbin; Liao, Qiao; Lan, Cong; Yang, Dezhong; Chen, Hongmei; Yue, Rongchuan; Zeng, Cindy; Zhou, Lin; Zhou, Bin; Duan, Dayue Darrel; Chen, Xiongwen; Houser, Steven R; Zeng, Chunyu

2017-08-29

Adult mammalian hearts have a limited ability to generate new cardiomyocytes. Proliferation of existing adult cardiomyocytes (ACMs) is a potential source of new cardiomyocytes. Understanding the fundamental biology of ACM proliferation could be of great clinical significance for treating myocardial infarction (MI). We aim to understand the process and regulation of ACM proliferation and its role in new cardiomyocyte formation of post-MI mouse hearts. β-Actin-green fluorescent protein transgenic mice and fate-mapping Myh6-MerCreMer-tdTomato/lacZ mice were used to trace the fate of ACMs. In a coculture system with neonatal rat ventricular myocytes, ACM proliferation was documented with clear evidence of cytokinesis observed with time-lapse imaging. Cardiomyocyte proliferation in the adult mouse post-MI heart was detected by cell cycle markers and 5-ethynyl-2-deoxyuridine incorporation analysis. Echocardiography was used to measure cardiac function, and histology was performed to determine infarction size. In vitro, mononucleated and bi/multinucleated ACMs were able to proliferate at a similar rate (7.0%) in the coculture. Dedifferentiation proceeded ACM proliferation, which was followed by redifferentiation. Redifferentiation was essential to endow the daughter cells with cardiomyocyte contractile function. Intercellular propagation of Ca 2+ from contracting neonatal rat ventricular myocytes into ACM daughter cells was required to activate the Ca 2+ -dependent calcineurin-nuclear factor of activated T-cell signaling pathway to induce ACM redifferentiation. The properties of neonatal rat ventricular myocyte Ca 2+ transients influenced the rate of ACM redifferentiation. Hypoxia impaired the function of gap junctions by dephosphorylating its component protein connexin 43, the major mediator of intercellular Ca 2+ propagation between cardiomyocytes, thereby impairing ACM redifferentiation. In vivo, ACM proliferation was found primarily in the MI border zone. An ischemia-resistant

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

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

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.

Molecular imaging of proliferation with [{sup 18}F]FLT-PET; Molekulare Bildgebung der Proliferation mit [{sup 18}F]FLT-PET

Energy Technology Data Exchange (ETDEWEB)

Buck, A.K.; Herrmann, K.; Schwaiger, M.; Wester, H.J. [Klinikum rechts der Isar, Technische Univ. Muenchen (Germany). Nuklearmedizinische Klinik und Poliklinik; Dechow, T.; Graf, N. [Klinikum rechts der Isar, Technische Univ. Muenchen (Germany). Medizinische Klinik III, Haematologi/Onkologie

2009-06-15

An increased proliferation fraction is a hallmark of malignant cells and a specific feature of malignant tumors which potentially allows more specific tumor imaging compared to increased glucose consumption (FDG-PET). The majority of therapeutic approaches aim at inhibition of proliferation or induction of apoptosis. Accordingly, non-invasive assessment of the proliferation fraction is also of interest for monitoring response to treatment and to early detect resistance to a specific kind of therapy. In clinical studies it has been demonstrated that the radiotracer 3'-deoxy-3'-[{sup 18}F]fluorothymidine (FLT) accumulates specifically in malignant tumors. Regression analysis of tumoral FLT-uptake and immunohistochemically detected proliferation fraction (PCNA, Ki-67) resulted in a significant correlation (e.g., in lung cancer, correlation coefficient r=0.87, p<0.0001). The possibility to non-invasively assess the proliferation fraction with FLT-PET has been shown in a variety of solid cancers. Compared to the standard radiotracer FDG, superior demonstration of the proliferative activity using FLT as the tracer has been demonstrated. On the other hand, accumulation of FLT was significantly lower compared to FDG. Malignant tumors with low proliferation rates did not present with increased FLT-uptake resulting in a reduced sensitivity. In lung cancer for example, the sensitivity was 86% of FLT-PET compared to 100% of FDG-PET. Also, regarding detection of locoregional lymph node metastases or distant metastases, FDG-PET was shown to have a higher sensitivity. Due to the reduced sensitivity, there is no advantage of specific imaging of tumor proliferation regarding tumor staging. In malignant lymphoma, FLT was similar effective for tumor staging as compared to FDG-PET. In a pilot study comprising 34 patients, both tracers showed a similar sensitivity regarding detection of lymphoma. An observed specificity of 100% indicates that FLT-PET represents a diagnostic

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

Nuclear non proliferation and disarmament; Non-proliferation nucleaire et desarmement

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-07-01

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.)

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

Expression of a novel non-coding mitochondrial RNA in human proliferating cells.

Science.gov (United States)

Villegas, Jaime; Burzio, Veronica; Villota, Claudio; Landerer, Eduardo; Martinez, Ronny; Santander, Marcela; Martinez, Rodrigo; Pinto, Rodrigo; Vera, María I; Boccardo, Enrique; Villa, Luisa L; Burzio, Luis O

2007-01-01

Previously, we reported the presence in mouse cells of a mitochondrial RNA which contains an inverted repeat (IR) of 121 nucleotides (nt) covalently linked to the 5' end of the mitochondrial 16S RNA (16S mtrRNA). Here, we report the structure of an equivalent transcript of 2374 nt which is over-expressed in human proliferating cells but not in resting cells. The transcript contains a hairpin structure comprising an IR of 815 nt linked to the 5' end of the 16S mtrRNA and forming a long double-stranded structure or stem and a loop of 40 nt. The stem is resistant to RNase A and can be detected and isolated after digestion with the enzyme. This novel transcript is a non-coding RNA (ncRNA) and several evidences suggest that the transcript is synthesized in mitochondria. The expression of this transcript can be induced in resting lymphocytes stimulated with phytohaemagglutinin (PHA). Moreover, aphidicolin treatment of DU145 cells reversibly blocks proliferation and expression of the transcript. If the drug is removed, the cells re-assume proliferation and over-express the ncmtRNA. These results suggest that the expression of the ncmtRNA correlates with the replicative state of the cell and it may play a role in cell proliferation.

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...

Tumour resistance to cisplatin: a modelling approach

Energy Technology Data Exchange (ETDEWEB)

Marcu, L [School of Chemistry and Physics, University of Adelaide, North Terrace, SA 5000 (Australia); Bezak, E [School of Chemistry and Physics, University of Adelaide, North Terrace, SA 5000 (Australia); Olver, I [Faculty of Medicine, University of Adelaide, North Terrace, SA 5000 (Australia); Doorn, T van [School of Chemistry and Physics, University of Adelaide, North Terrace, SA 5000 (Australia)

2005-01-07

Although chemotherapy has revolutionized the treatment of haematological tumours, in many common solid tumours the success has been limited. Some of the reasons for the limitations are: the timing of drug delivery, resistance to the drug, repopulation between cycles of chemotherapy and the lack of complete understanding of the pharmacokinetics and pharmacodynamics of a specific agent. Cisplatin is among the most effective cytotoxic agents used in head and neck cancer treatments. When modelling cisplatin as a single agent, the properties of cisplatin only have to be taken into account, reducing the number of assumptions that are considered in the generalized chemotherapy models. The aim of the present paper is to model the biological effect of cisplatin and to simulate the consequence of cisplatin resistance on tumour control. The 'treated' tumour is a squamous cell carcinoma of the head and neck, previously grown by computer-based Monte Carlo techniques. The model maintained the biological constitution of a tumour through the generation of stem cells, proliferating cells and non-proliferating cells. Cell kinetic parameters (mean cell cycle time, cell loss factor, thymidine labelling index) were also consistent with the literature. A sensitivity study on the contribution of various mechanisms leading to drug resistance is undertaken. To quantify the extent of drug resistance, the cisplatin resistance factor (CRF) is defined as the ratio between the number of surviving cells of the resistant population and the number of surviving cells of the sensitive population, determined after the same treatment time. It is shown that there is a supra-linear dependence of CRF on the percentage of cisplatin-DNA adducts formed, and a sigmoid-like dependence between CRF and the percentage of cells killed in resistant tumours. Drug resistance is shown to be a cumulative process which eventually can overcome tumour regression leading to treatment failure.

Tumour resistance to cisplatin: a modelling approach

International Nuclear Information System (INIS)

Marcu, L; Bezak, E; Olver, I; Doorn, T van

2005-01-01

Although chemotherapy has revolutionized the treatment of haematological tumours, in many common solid tumours the success has been limited. Some of the reasons for the limitations are: the timing of drug delivery, resistance to the drug, repopulation between cycles of chemotherapy and the lack of complete understanding of the pharmacokinetics and pharmacodynamics of a specific agent. Cisplatin is among the most effective cytotoxic agents used in head and neck cancer treatments. When modelling cisplatin as a single agent, the properties of cisplatin only have to be taken into account, reducing the number of assumptions that are considered in the generalized chemotherapy models. The aim of the present paper is to model the biological effect of cisplatin and to simulate the consequence of cisplatin resistance on tumour control. The 'treated' tumour is a squamous cell carcinoma of the head and neck, previously grown by computer-based Monte Carlo techniques. The model maintained the biological constitution of a tumour through the generation of stem cells, proliferating cells and non-proliferating cells. Cell kinetic parameters (mean cell cycle time, cell loss factor, thymidine labelling index) were also consistent with the literature. A sensitivity study on the contribution of various mechanisms leading to drug resistance is undertaken. To quantify the extent of drug resistance, the cisplatin resistance factor (CRF) is defined as the ratio between the number of surviving cells of the resistant population and the number of surviving cells of the sensitive population, determined after the same treatment time. It is shown that there is a supra-linear dependence of CRF on the percentage of cisplatin-DNA adducts formed, and a sigmoid-like dependence between CRF and the percentage of cells killed in resistant tumours. Drug resistance is shown to be a cumulative process which eventually can overcome tumour regression leading to treatment failure

Indirubin inhibits cell proliferation, migration, invasion and angiogenesis in tumor-derived endothelial cells

Directory of Open Access Journals (Sweden)

Li Z

2018-05-01

Full Text Available Zhuohong Li, Chaofu Zhu, Baiping An, Yu Chen, Xiuyun He, Lin Qian, Lan Lan, Shijie Li Department of Oncology, The Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China Purpose: Hepatocellular carcinoma is one of the most predominant malignancies with high fatality rate and its incidence is rising at an alarming rate because of its resistance to radio- and chemotherapy. Indirubin is the major active anti-tumor ingredient of a traditional Chinese herbal medicine. The present study aimed to analyze the effects of indirubin on cell proliferation, migration, invasion, and angiogenesis of tumor-derived endothelial cells (Td-EC. Methods: Td-EC were derived from human umbilical vein endothelial cells (HUVEC by treating HUVEC with the conditioned medium of human liver cancer cell line HepG2. Cell proliferation, migration, invasion, and angiogenesis were assessed by MTT, wound healing, in vitro cell invasion, and in vitro tube formation assay. Results: Td-EC were successfully obtained from HUVEC cultured with 50% culture supernatant from serum-starved HepG2 cells. Indirubin significantly inhibited Td-EC proliferation in a dose- and time-dependent manner. Indirubin also inhibited Td-EC migration, invasion, and angiogenesis. However, indirubin’s effects were weaker on HUVEC than Td-EC. Conclusion: Indirubin significantly inhibited Td-EC proliferation, migration, invasion, and angiogenesis. Keywords: indirubin, Td-EC, proliferation, migration, invasion, angiogenesis

Sustainable development - a role for nuclear power? 2nd scientific forum

International Nuclear Information System (INIS)

2000-03-01

economically in deep geologic formations. However, the necessary political decisions to select sites for repositories need public support and understanding about what the industry is doing and what can be done. As to nuclear weapons proliferation, the existing safeguards system must be fully maintained and strengthened and inherently proliferation-resistant fuel cycles should be explored. Overviews of the future global energy demand and of the prospects for nuclear power in various economic regions of the world indicate that, in the case of the OECD countries, the dominant issue is economics in an increasingly free market system for electricity. For the so-called transition economies, countries of the Former Soviet Union and Central and Eastern Europe, the issue is one of managing nuclear power plant operations safely. In the case of developing countries, the dominant concern is effective management of technology, in addition to economics and finance. The prospects for nuclear power depend on the resolution of two cardinal issues. The first is economic competitiveness, and in particular, reduced capital cost. The second is public confidence in the ability of the industry to manage plant operations and its high level waste safely. There is a continuing need for dialogue and communication with all sectors of the public: economists, investors, social scientists, politicians, regulators, unions, and environmentalists. Of help in this dialogue would be nuclear power's relevance to and comparative advantages in addressing environmental issues, such as global climate change, local air quality, and regional acidification. Suggestions have been made for a globalized approach to critical nuclear power issues, such as waste management, innovative and proliferation-resistant reactors and fuel cycles, and international standards for new generation nuclear reactor designs.The conclusion seems to be that there is a role for nuclear energy in sustainable development, especially if greenhouse

Intermittent hypoxia induces the proliferation of rat vascular smooth muscle cell with the increases in epidermal growth factor family and erbB2 receptor

International Nuclear Information System (INIS)

Kyotani, Yoji; Ota, Hiroyo; Itaya-Hironaka, Asako; Yamauchi, Akiyo; Sakuramoto-Tsuchida, Sumiyo; Zhao, Jing; Ozawa, Kentaro; Nagayama, Kosuke; Ito, Satoyasu; Takasawa, Shin; Kimura, Hiroshi; Uno, Masayuki; Yoshizumi, Masanori

2013-01-01

Obstructive sleep apnea is characterized by intermittent hypoxia (IH), and associated with cardiovascular diseases, such as stroke and heart failure. These cardiovascular diseases have a relation to atherosclerosis marked by the proliferation of vascular smooth muscle cells (VSMCs). In this study, we investigated the influence of IH on cultured rat aortic smooth muscle cell (RASMC). The proliferation of RASMC was significantly increased by IH without changing the level of apoptosis. In order to see what induces RASMC proliferation, we investigated the influence of normoxia (N)-, IH- and sustained hypoxia (SH)-treated cell conditioned media on RASMC proliferation. IH-treated cell conditioned medium significantly increased RASMC proliferation compared with N-treated cell conditioned medium, but SH-treated cell conditioned medium did not. We next investigated the epidermal growth factor (EGF) family as autocrine growth factors. Among the EGF family, we found significant increases in mRNAs for epiregulin (ER), amphiregulin (AR) and neuregulin-1 (NRG1) in IH-treated cells and mature ER in IH-treated cell conditioned medium. We next investigated the changes in erbB family receptors that are receptors for ER, AR and NRG1, and found that erbB2 receptor mRNA and protein expressions were increased by IH, but not by SH. Phosphorylation of erbB2 receptor at Tyr-1248 that mediates intracellular signaling for several physiological effects including cell proliferation was increased by IH, but not by SH. In addition, inhibitor for erbB2 receptor suppressed IH-induced cell proliferation. These results provide the first demonstration that IH induces VSMC proliferation, and suggest that EGF family, such as ER, AR and NRG1, and erbB2 receptor could be involved in the IH-induced VSMC proliferation. - Highlights: ●In vitro system for intermittent hypoxia (IH) and sustained hypoxia (SH). ●IH, but not SH, induces the proliferation of rat vascular smooth muscle cell. ●Epiregulin m

Intermittent hypoxia induces the proliferation of rat vascular smooth muscle cell with the increases in epidermal growth factor family and erbB2 receptor

Energy Technology Data Exchange (ETDEWEB)

Kyotani, Yoji, E-mail: cd147@naramed-u.ac.jp [Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Department of Pharmacy, Nara Medical University Hospital, Kashihara 634-8522 (Japan); Ota, Hiroyo [Second Department of Internal Medicine, Nara Medical University School of Medicine, Kashihara 634-8522 (Japan); Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Itaya-Hironaka, Asako; Yamauchi, Akiyo; Sakuramoto-Tsuchida, Sumiyo [Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Zhao, Jing; Ozawa, Kentaro; Nagayama, Kosuke; Ito, Satoyasu [Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Takasawa, Shin [Department of Biochemistry, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan); Kimura, Hiroshi [Second Department of Internal Medicine, Nara Medical University School of Medicine, Kashihara 634-8522 (Japan); Uno, Masayuki [Department of Pharmacy, Nara Medical University Hospital, Kashihara 634-8522 (Japan); Yoshizumi, Masanori [Department of Pharmacology, Nara Medical University School of Medicine, Kashihara 634-8521 (Japan)

2013-11-15

Obstructive sleep apnea is characterized by intermittent hypoxia (IH), and associated with cardiovascular diseases, such as stroke and heart failure. These cardiovascular diseases have a relation to atherosclerosis marked by the proliferation of vascular smooth muscle cells (VSMCs). In this study, we investigated the influence of IH on cultured rat aortic smooth muscle cell (RASMC). The proliferation of RASMC was significantly increased by IH without changing the level of apoptosis. In order to see what induces RASMC proliferation, we investigated the influence of normoxia (N)-, IH- and sustained hypoxia (SH)-treated cell conditioned media on RASMC proliferation. IH-treated cell conditioned medium significantly increased RASMC proliferation compared with N-treated cell conditioned medium, but SH-treated cell conditioned medium did not. We next investigated the epidermal growth factor (EGF) family as autocrine growth factors. Among the EGF family, we found significant increases in mRNAs for epiregulin (ER), amphiregulin (AR) and neuregulin-1 (NRG1) in IH-treated cells and mature ER in IH-treated cell conditioned medium. We next investigated the changes in erbB family receptors that are receptors for ER, AR and NRG1, and found that erbB2 receptor mRNA and protein expressions were increased by IH, but not by SH. Phosphorylation of erbB2 receptor at Tyr-1248 that mediates intracellular signaling for several physiological effects including cell proliferation was increased by IH, but not by SH. In addition, inhibitor for erbB2 receptor suppressed IH-induced cell proliferation. These results provide the first demonstration that IH induces VSMC proliferation, and suggest that EGF family, such as ER, AR and NRG1, and erbB2 receptor could be involved in the IH-induced VSMC proliferation. - Highlights: ●In vitro system for intermittent hypoxia (IH) and sustained hypoxia (SH). ●IH, but not SH, induces the proliferation of rat vascular smooth muscle cell. ●Epiregulin m

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)

The neuropeptide catestatin promotes vascular smooth muscle cell proliferation through the Ca{sup 2+}-calcineurin-NFAT signaling pathway

Energy Technology Data Exchange (ETDEWEB)

Guo, Xiaoxia [Department of Cardiology, People' s Hospital, Peking University, No. 11 South Avenue, Xi Zhi Men Xicheng District, Beijing 100044 (China); Zhou, Chunyan, E-mail: chunyanzhou@bjmu.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191 (China); Sun, Ningling, E-mail: nlsun@263.net [Department of Cardiology, People' s Hospital, Peking University, No. 11 South Avenue, Xi Zhi Men Xicheng District, Beijing 100044 (China)

2011-04-22

Highlights: {yields} Catestatin stimulates proliferation of vascular smooth muscle cells in a dose-dependent manner. {yields} Catestatin provokes sustained increase in intracellular Ca{sup 2+}. {yields} Catestatin produces increased activation of calcineurin and promotes NFATc1 translocation into the nucleus. -- Abstract: The Chromogranin A-derived neuropeptide catestatin is an endogenous nicotinic cholinergic antagonist that acts as a pleiotropic hormone. Since catestatin shares several functions with other members derived from the chromogranin/secretogranin protein family and other neuropeptides which exert proliferative effects on vascular smooth muscle cells (VSMCs), we therefore hypothesized that catestatin would regulate VSMC proliferation. The present study demonstrates that catestatin caused a dose-dependent induction of proliferation in rat aortic smooth muscle cells and furthermore evoked a sustained increase in intracellular calcium. This subsequently leaded to enhanced activation of the Ca{sup 2+}/calmodulin-dependent phosphatase, calcineurin and resulted in an activation of the Ca{sup 2+}-dependent transcription factor, nuclear factor of activated T cells (NFAT), initiating transcription of proliferative genes. In addition, cyclosporin A (CsA), a potent inhibitor of calcineurin, abrogated catestatin-mediated effect on VSMCs, indicating that the calcineurin-NFAT signaling is strongly required for catestatin-induced growth of VSMCs. The present study establishes catestatin as a novel proliferative cytokine on vascular smooth muscle cells and this effect is mediated by the Ca{sup 2+}-calcineurin-NFAT signaling pathway.

On the future of civilian plutonium: An assessment of technological impediments to nuclear terrorism and proliferation

Science.gov (United States)

Avedon, Roger Edmond

This dissertation addresses the value of developing diversion- and theft-resistant nuclear power technology, given uncertain future demand for nuclear power, and uncertain risks of nuclear terrorism and of proliferation from the reprocessing of civilian plutonium. The methodology comprises four elements: Economics. An economic growth model coupled with market penetration effects for plutonium and for the hypothetical new technology provides a range of estimates for future nuclear demand. A flow model accounts for the longevity of capital assets (nuclear plants) over time. Terrorism. The commercial nuclear fuel cycle may provide a source of fissile material for terrorists seeking to construct a crude nuclear device. An option value model is used to estimate the effects of the hypothetical new technology on reducing the probability of theft. A game theoretic model is used to explore the deterrence value of physical security and then to draw conclusions about how learning on the part of terrorists or security forces might affect the theft estimate. The principal uncertainties in the theft model can be updated using Bayesian techniques as new data emerge. Proliferation. Access to fissile material is the principal technical impediment to a state's acquisition of nuclear weapons. A game theoretic model is used to determine the circumstances under which a state may proliferate via diversion. The model shows that the hypothetical new technology will have little value for counter-proliferation if diversion is not a preferred proliferation method. A technology policy analysis of the choice of proliferation method establishes that diversion is unlikely to be used because it has no constituency among the important parties to the decision, namely the political leadership, the scientific establishment, and the military. Value. The decision whether to develop a diversion- and theft-resistant fuel cycle depends on the perceived value of avoiding nuclear terrorism and proliferation

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.)

[Targeting of the AKT/m-TOR Pathway: Biomarkers of Resistance to Cancer Therapy--
AKT/m-TOR Pathway and Resistance to Cancer Therapy].

Science.gov (United States)

Spirina, Liudmila V; Kondakova, Irina V; Tarasenko, Natalia V; Slonimskaya, Elena M; Usynin, Evgeny A; Gorbunov, Alexey K; Yurmazov, Zahar A; Chigevskaya, Svetlana Yu

2018-01-20

Resistance to cancer therapy continues to be a major limitation for the successful treatment of cancer. There are many published studies on therapy resistance in breast and prostate cancers; however, there are currently no data on molecular markers associated with resistance. The conflicting data were reported regarding the AKT/m-TOR signaling pathway components as markers predicting resistance. The AKT/m-TOR signaling pathway is involved in the development of many human cancers; its activation is related to cell proliferation, angiogenesis, apoptosis, as well as to therapy resistance. Molecular alterations in the AKT/m-TOR signaling pathway provide a platform to identify universal markers associated with the development of resistance to cancer therapy.

Nuclear energy and sustainability in Latin America

International Nuclear Information System (INIS)

Sterner, Thomas

1991-01-01

The concept of sustainability has been given numerous interpretations, some overlapping or complementary, some contradictory. Thus it is difficult to judge whether the nuclear industry does, or does not, meet sustainability criteria; particularly as the present nuclear technologies are not renewable. Uranium resources appear to be of the same order of magnitude as oil and gas resources. This implies that they are a transitional source of energy. There are also other potential arguments against the sustainability of nuclear power: its pollution, risks and costs. Environmental damage may come from various parts of the nuclear fuel cycle. Two types of risk will be discussed: first the risk of major accidents and thereby exceptional environmental damage, and second the risks associated with the proliferation of nuclear weapons. Each of these factors, as well as the pure economic cost of nuclear electricity, ought to be compared to the environmental damage, risks and costs of the available alternatives. Only the Latin American experience will be considered. For example, the need for Mexico to use nuclear power when it has large oil and gas supplies, is considered. (author)

Sustainability Education in Indian Business Schools: A Status Review

Directory of Open Access Journals (Sweden)

PD JOSE

Full Text Available Sustainability issues, given their potential scale of impact and urgency, have captured the imagination of both corporations and academic institutions everywhere. This paper examines how such problems and their potential solutions have been incorporated into higher education, particularly business school education in India. With over 3,600 business schools in the public and private sector, business education in India has proliferated. However, students by and large still remain unexposed to sustainability and disaster management concepts in their curriculum. The underlying factors for this include, lack of institutional capacity, issues related to faculty motivation and incentives, lack of recruiter interest and limited availability to high quality resource material. Further, while several schools in India focus on sectors relevant to sustainability, inter-organizational linkages have not developed and business school generally operate independently. This paper examines the way forward to deeply integrate sustainability principles into the core curriculum of business schools. Measures suggested include creating communities of practice among academia and industry, building a resource base of teaching materials for easy access by faculty, and several measures to strengthen institutional capacity.

Phosphorylation at tyrosine 114 of Proliferating Cell Nuclear Antigen (PCNA) is required for adipogenesis in response to high fat diet

Energy Technology Data Exchange (ETDEWEB)

Lo, Yuan-Hung; Ho, Po-Chun; Chen, Min-Shan; Hugo, Eric; Ben-Jonathan, Nira [Department of Cancer Biology, University of Cincinnati College of Medicine, 3125 Eden Avenue, Cincinnati, OH 45267-0521 (United States); Department of Environmental Health, University of Cincinnati College of Medicine, 3223 Eden Avenue, Kettering Laboratory, Cincinnati, OH 45267-0056 (United States); Wang, Shao-Chun, E-mail: shao-chun.wang@uc.edu [Department of Cancer Biology, University of Cincinnati College of Medicine, 3125 Eden Avenue, Cincinnati, OH 45267-0521 (United States); Department of Environmental Health, University of Cincinnati College of Medicine, 3223 Eden Avenue, Kettering Laboratory, Cincinnati, OH 45267-0056 (United States)

2013-01-04

Highlights: Black-Right-Pointing-Pointer Proliferating Cell Nuclear Antigen (PCNA) is phosphorylated at Y114. Black-Right-Pointing-Pointer Phospho-Y114 of PCNA is not required for cell proliferation for normal growth. Black-Right-Pointing-Pointer MCE during adipogenesis is abolished in the lack of the phosphorylation. Black-Right-Pointing-Pointer Homozygous Y114F mice are resistant to high fat diet induced obesity. Black-Right-Pointing-Pointer Our results shed light on the interface between proliferation and differentiation. -- Abstract: Clonal proliferation is an obligatory component of adipogenesis. Although several cell cycle regulators are known to participate in the transition between pre-adipocyte proliferation and terminal adipocyte differentiation, how the core DNA synthesis machinery is coordinately regulated in adipogenesis remains elusive. PCNA (Proliferating Cell Nuclear Antigen) is an indispensable component for DNA synthesis during proliferation. Here we show that PCNA is subject to phosphorylation at the highly conserved tyrosine residue 114 (Y114). Replacing the Y114 residue with phenylalanine (Y114F), which is structurally similar to tyrosine but cannot be phosphorylated, does not affect normal animal development. However, when challenged with high fat diet, mice carrying homozygous Y114F alleles (PCNA{sup F/F}) are resistant to adipose tissue enlargement in comparison to wild-type (WT) mice. Mouse embryonic fibroblasts (MEFs) harboring WT or Y114F mutant PCNA proliferate at similar rates. However, when subjected to adipogenesis induction in culture, PCNA{sup F/F} MEFs are not able to re-enter the cell cycle and fail to form mature adipocytes, while WT MEFs undergo mitotic clonal expansion in response to the adipogenic stimulation, accompanied by enhanced Y114 phosphorylation of PCNA, and differentiate to mature adipocytes. Consistent with the function of Y114 phosphorylation in clonal proliferation in adipogenesis, fat tissues isolated from WT

Toward a sustainability label for food products: an analysis of experts' and consumers' acceptance.

Science.gov (United States)

Engels, Stéphanie V; Hansmann, Ralf; Scholz, Roland W

2010-01-01

The recent proliferation of standards and labels for organic, fair-trade, locally produced, and healthy food products risks creating confusion among consumers. This study presents a standardized approach to developing a comprehensive sustainability label that incorporates ecological, economic, and social values. The methodology is based on an extension of modular life-cycle assessment to non-environmental sustainability criteria. Interviews with a wide range of experts (n=65) and a consumer survey (n=233) were conducted to analyze the feasibility and potential effectiveness of the approach. Responses indicated that a comprehensive sustainability label could considerably influence consumption patterns and facilitate cross-product comparisons. Copyright © Taylor & Francis Group, LLC

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...

Effects of Vitamin K3 and K5 on Daunorubicin-resistant Human T Lymphoblastoid Leukemia Cells.

Science.gov (United States)

Nakaoka, Eri; Tanaka, Sachiko; Onda, Kenji; Sugiyama, Kentaro; Hirano, Toshihiko

2015-11-01

Anticancer efficacy of vitamin K derivatives on multidrug-resistant cancer cells has been scarcely investigated. The effects of vitamins K3 and K5 on proliferation of human leukemia MOLT-4 cells and on daunorubicin-resistant MOLT-4/DNR cells were estimated by a WST assay. Apoptotic cells were detected by Annexin V and propidium iodide staining, followed by flow cytometry. Vitamins K3 and K5 significantly inhibited proliferation of leukemic cells at 10 and 100 μM (pVitamin K3 induced cell apoptosis at 10 and 100 μM in both MOLT-4 and MOLT-4/DNR cells (pVitamin K5 also increased apoptotic cells, while rather inducing necrotic cell death. Vitamins K3 and K5 suppress MOLT-4 and MOLT-4/DNR cell-proliferation partially through induction of apoptosis, and these vitamin derivatives can overcome drug resistance due to P-glycoprotein expression. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

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

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

Towards the just and sustainable use of antibiotics.

Science.gov (United States)

Merrett, Gemma L Buckland; Bloom, Gerald; Wilkinson, Annie; MacGregor, Hayley

2016-01-01

The emergence and spread of antibiotic resistant pathogens poses a big challenge to policy-makers, who need to oversee the transformation of health systems that evolved to provide easy access to these drugs into ones that encourage appropriate use of antimicrobials, whilst reducing the risk of resistance. This is a particular challenge for low and middle-income countries with pluralistic health systems where antibiotics are available in a number of different markets. This review paper considers access and use of antibiotics in these countries from a complex adaptive system perspective. It highlights the main areas of intervention that could provide the key to addressing the sustainable long term use and availability of antibiotics. A focus on the synergies between interventions addressing access strategies, antibiotic quality, diagnostics for low-resource settings, measures to encourage just and sustainable decision making and help seeking optimal therapeutic and dosing strategies are key levers for the sustainable future of antibiotic use. Successful integration of such strategies will be dependent on effective governance mechanisms, effective partnerships and coalition building and accurate evaluation systems at national, regional and global levels.

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

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

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

Increased keratinocyte proliferation initiated through downregulation of desmoplakin by RNA interference

International Nuclear Information System (INIS)

Wan Hong; South, Andrew P.; Hart, Ian R.

2007-01-01

The intercellular adhesive junction desmosomes are essential for the maintenance of tissue structure and integrity in skin. Desmoplakin (Dp) is a major obligate plaque protein which plays a fundamental role in anchoring intermediate filaments to desmosomal cadherins. Evidence from hereditary human disease caused by mutations in the gene encoding Dp, e.g. Dp haploinsufficiency, suggests that alterations in Dp expression result not only in the disruption of tissue structure and integrity but also could evoke changes in keratinocyte proliferation. We have used transient RNA interference (RNAi) to downregulate Dp specifically in HaCaT keratinocytes. We showed that this Dp downregulation also caused reduced expression of several other desmosomal proteins. Increased cell proliferation and enhanced G 1 -to-S-phase entry in the cell cycle, as monitored by colonial cellular density and BrdU incorporation, were seen in Dp RNAi-treated cells. These proliferative changes were associated with elevated phospho-ERK1/2 and phospho-Akt levels. Furthermore, this increase in phospho-ERK/1/2 and phospho-Akt levels was sustained in Dp RNAi-treated cells at confluence whereas in control cells there was a significant reduction in phosphorylation of ERK1/2. This study indicates that Dp may participate in the regulation of keratinocyte cell proliferation by, in part at least, regulating cell cycle progression

Role of MXD3 in proliferation of DAOY human medulloblastoma cells.

Directory of Open Access Journals (Sweden)

Gustavo A Barisone

Full Text Available A subset of medulloblastomas, the most common brain tumor in children, is hypothesized to originate from granule neuron precursors (GNPs in which the sonic hedgehog (SHH pathway is over-activated. MXD3, a basic helix-look-helix zipper transcription factor of the MAD family, has been reported to be upregulated during postnatal cerebellar development and to promote GNP proliferation and MYCN expression. Mxd3 is upregulated in mouse models of medulloblastoma as well as in human medulloblastomas. Therefore, we hypothesize that MXD3 plays a role in the cellular events that lead to medulloblastoma biogenesis. In agreement with its proliferative role in GNPs, MXD3 knock-down in DAOY cells resulted in decreased proliferation. Sustained overexpression of MXD3 resulted in decreased cell numbers due to increased apoptosis and cell cycle arrest. Structure-function analysis revealed that the Sin3 interacting domain, the basic domain, and binding to E-boxes are essential for this activity. Microarray-based expression analysis indicated up-regulation of 84 genes and down-regulation of 47 genes. Potential direct MXD3 target genes were identified by ChIP-chip. Our results suggest that MXD3 is necessary for DAOY medulloblastoma cell proliferation. However, increased level and/or duration of MXD3 expression ultimately reduces cell numbers via increased cell death and cell cycle arrest.

Which future for nuclear counter-proliferation?; Quel avenir pour la contre-proliferation nucleaire?

Energy Technology Data Exchange (ETDEWEB)

Duval, M.

2010-07-15

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

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...

Physics of reversed-field pinch profile sustainment

International Nuclear Information System (INIS)

Moses, R.W.

1984-01-01

A description of the Reversed-Field Pinch (RFP) is given, emphasizing the necessity of a magnetohydrodynamic (MHD) or kinetic process to sustain field reversal. Three sustainment mechanisms are reviewed: the MHD dynamo, the tangled discharge model, and nonlocal resistivity. A slab model of steady (ohmic) states is described. A relationship between ohmic state wave numbers and the minimum amplitude of nonsymmetric field components is given. If ohmic states are the sole source of the sustainment process, their wave lengths are probably much longer than the minor diameter of the plasma. Otherwise field asymmetries would exceed those observed in experiments. It is noted that internal field data are still limited, restricting the generality of our comments

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

Wine Tourism and Sustainability: A Review

Directory of Open Access Journals (Sweden)

Marta Maria Montella

2017-01-01

Full Text Available The literature on tourism and events is endless; a niche in this wide research field is represented by food and wine research. The growing interest shown by wine tourists has nurtured the proliferation of wine events and the growth of the wine tourism business; as a consequence, academicians’ interest in this issue has increased. At the same time, research on tourism and events is an evolving field and it has moved from a main economic focus to a broader perspective: some scholars have highlighted how the growing interest towards green and sustainable practices has stimulated academic research and a lot has been done on the management of environmental issues. Given the resonance of wine tourism and the role it has for local and rural development, the interest towards the issue of sustainability in wine is more than warranted. Thus, this paper aims to provide some useful insights about where research has gone and where it is going; a thorough literature review has been performed.

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

TC-1 Overexpression Promotes Cell Proliferation in Human Non-Small Cell Lung Cancer that Can Be Inhibited by PD173074

Science.gov (United States)

Zhang, Na; Bai, Guangzhen; Zhong, Daixing; Su, Kai; Liu, Boya; Li, Xiaofei; Wang, Yunjie; Wang, Xiaoping

2014-01-01

Thyroid cancer-1 (TC-1), a natively disordered protein, is widely expressed in vertebrates and overexpressed in many kinds of tumors. However, its exact role and regulation mechanism in human non-small cell lung cancer (NSCLC) are still unclear. In the present study, we found that TC-1 is highly expressed in NSCLC and that its aberrant expression is strongly associated with NSCLC cell proliferation. Exogenous TC-1 overexpression promotes cell proliferation, accelerates the cell G1-to-S-phase transition, and reduces apoptosis in NSCLC. The knockdown of TC-1, however, inhibits NSCLC cell proliferation, cycle transition, and apoptosis resistance. Furthermore, we also demonstrated that PD173074, which functions as an inhibitor of the TC-1 in NSCLC, decreases the expression of TC-1 and inhibits TC-1 overexpression mediated cell proliferation in vitro and in vivo. Nevertheless, the inhibition function of PD173074 on NSCLC cell proliferation was eliminated in cells with TC-1 knockdown. These results suggest that PD173074 plays a significant role in TC-1 overexpression mediated NSCLC cell proliferation and may be a potential intervention target for the prevention of cell proliferation in NSCLC. PMID:24941347

Co-induction of glucose regulated proteins and adriamycin resistance in Chinese hamster cells

International Nuclear Information System (INIS)

Shen, J.; Hughes, C.; Cai, J.; Bartels, C.; Gessner, T.; Subjeck, J.

1987-01-01

Glucose deprivation, anoxia, calcium ionophore A23187 or 2-deoxyglucose all inducers of glucose regulated proteins (grps), also lead to a significant induction of resistance to the drug adriamycin. In the case of anoxia, A23187 and 2-deoxyglucose, the induction of resistance correlates with both the application of the inducing stress and the induction of grps. In the case of glucose deprivation, the onset of resistance correlates with the onset of glucose deprivation and precedes grp induction. Removal of each grp including condition results in the rapid disappearance of this resistance in a manner which correlates with the repression of the grps. This drug resistance can be induced in confluent cells or in actively proliferating cells, although the effect is greater in the more sensitive proliferating cells. Induction of heat shock proteins (hsps) does not appear to lead to any major change in adriamycin resistance. Grp induced cells retain less adriamycin than do controls with the greatest reduction occurring during anoxia, which is also the strongest inducer of grps and resistance. The authors propose that the application of a grp inducing stress leads to a concurrent induction in drug resistance, possibly via the translocation of grps in the cell. Finally, they also observed that adriamycin itself can induce both hsps and grps. It is possible that adriamycin exposure may correspondingly induce auto-resistance

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

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

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

New concepts for small power reactors without on-site refuelling for non-proliferation

International Nuclear Information System (INIS)

Brown, N.W.; Hasberger, J.A.

2000-01-01

The report discusses the preliminary requirements and a technical approach for developing small reactors and the rationale for selecting them. It then discusses the four nuclear system technologies and how they might proceed to meet the requirements. Brief discussions are provided on the approaches to stimulating the appropriate international and industrial participation necessary to finance development of a design with improved proliferation resistance that is useful to the developing countries. (author)

Antibiotic sensitivity and resistance in children with urinary tract infection in Sanliurfa.

Science.gov (United States)

Abuhandan, Mahmut; Güzel, Bülent; Oymak, Yeşim; Çiftçi, Halil

2013-06-01

This study aimed to evaluate antibiotic resistance in the province of Şanliurfa and to observe any difference between antibiotic resistance rates. The study comprised 107 children who presented at the pediatric polyclinic with complaints of urinary tract infection with the diagnosis of urinary tract infection and whose urine cultures exhibited bacterial growth. The patients were analyzed with respect to the frequency of proliferating pathogens, sensitivity to the antibiotics used and the rates of developed resistance to the antibiotics. A total of 107 patients aged between 1 year and 15 years were included in the study, encompassing 14 (13.1%) males and 93 (86.9%) females. According to the urine culture results, proliferation of Escherichia coli (E. coli) was observed in 69 (64.5%), Klebsiella spp. in 13 (12.1%), Proteus mirabilis in 9 (8.4%), Staphylococcus aureus in 5 (4.7%), Pseudomonas aeruginosa in 5 (4.7%), Acinetobacter spp. in 3 (2.8%) and Enterococcus spp. in 3 (2.8%) patients. For proliferating E. coli, high resistance rates to ceftriaxone (39.5%), nitrofurantoin (19.7%), ampicillin-sulbactam (64.1%), co-trimoxazole (41.5%), amoxicillinclavulanate (51.7%) and cefuroxime (38.1%) were observed. All of isolated microorganisms were resistant to ampicillin-sulbactam, amoxicillin-clavulanate, co-trimoxazole, ceftriaxone, cefuroxime and cefoxitin in decreasing frequencies. The most effective antimicrobial agents were determined to be imipenem, sulpera-zone, quinolone and aminoglycosides. In our region, parenteral antibiotics that should be selected for the empirical treatment of UTIs in all age groups are the aminoglycosides and 3(rd) generation cephalosporines. In contrast to other studies, these results suggest that co-trimoxazole should be used for children aged 0-1, and 2(nd) generation cephalosporins should be used for the oral treatment of children aged 1-5 due to the low rate of resistance to nitrofurantoin in patients aged over 5 years.

New reactor concepts for new generation of nuclear power plants: an overview, invited paper

International Nuclear Information System (INIS)

Vujic, J.; Greenspan, E.; Milosevic, M.

2006-01-01

The outlook for energy demand underscores the need to increase the share of nuclear energy production. Achieving the vision of sustainable growth of nuclear energy will require development of both advanced nuclear fuel cycles and next generation reactor technologies and advanced reprocessing and fuel treatment technologies. To achieve this vision, the US department of energy (DOE) has adopted new strategy, the Global Nuclear Energy Partnership (GNEP), which integrates earlier programs: the Generation IV Nuclear Energy Systems Initiative (Generation IV), Nuclear Hydrogen Initiative (NHI), and the Advanced Fuel Cycle Initiative (AFCI) with proliferation-resistant spent fuel reprocessing to minimize nuclear waste. Generation IV furthers this vision beyond previous energy systems, such as Generation III+, through incremental improvements in economic competitiveness, sustainability, development of passively safe systems, and breakthrough methods to reduce the routes of nuclear proliferation. This paper summarizes the main characteristics of the six most promising nuclear energy systems identified by the Generation IV Roadmap and reviews some Generation IV system designs for small-side proliferation resistant reactors being developed by University of California at Berkeley. (author)

Sustained co-delivery of BIO and IGF-1 by a novel hybrid hydrogel system to stimulate endogenous cardiac repair in myocardial infarcted rat hearts.

Science.gov (United States)

Fang, Rui; Qiao, Shupei; Liu, Yi; Meng, Qingyuan; Chen, Xiongbiao; Song, Bing; Hou, Xiaolu; Tian, Weiming

2015-01-01

Dedifferentiation and proliferation of endogenous cardiomyocytes in situ can effectively improve cardiac repair following myocardial infarction (MI). 6-Bromoindirubin-3-oxime (BIO) and insulin-like growth factor 1 (IGF-1) are two potent factors that promote cardiomyocyte survival and proliferation. However, their delivery for sustained release in MI-affected areas has proved to be challenging. In the current research, we present a study on the sustained co-delivery of BIO and IGF-1 in a hybrid hydrogel system to simulate endogenous cardiac repair in an MI rat model. Both BIO and IGF-1 were efficiently encapsulated in gelatin nanoparticles, which were later cross-linked with the oxidized alginate to form a novel hybrid hydrogel system. The in vivo results indicated that the hybrid system could enhance the proliferation of cardiomyocytes in situ and could promote revascularization around the MI sites, allowing improved cardiac function. Taken together, we concluded that the hybrid hydrogel system can co-deliver BIO and IGF-1 to areas of MI and thus improve cardiac function by promoting the proliferation of cardiomyocytes and revascularization.

Sustained co-delivery of BIO and IGF-1 by a novel hybrid hydrogel system to stimulate endogenous cardiac repair in myocardial infarcted rat hearts

Science.gov (United States)

Fang, Rui; Qiao, Shupei; Liu, Yi; Meng, Qingyuan; Chen, Xiongbiao; Song, Bing; Hou, Xiaolu; Tian, Weiming

2015-01-01

Dedifferentiation and proliferation of endogenous cardiomyocytes in situ can effectively improve cardiac repair following myocardial infarction (MI). 6-Bromoindirubin-3-oxime (BIO) and insulin-like growth factor 1 (IGF-1) are two potent factors that promote cardiomyocyte survival and proliferation. However, their delivery for sustained release in MI-affected areas has proved to be challenging. In the current research, we present a study on the sustained co-delivery of BIO and IGF-1 in a hybrid hydrogel system to simulate endogenous cardiac repair in an MI rat model. Both BIO and IGF-1 were efficiently encapsulated in gelatin nanoparticles, which were later cross-linked with the oxidized alginate to form a novel hybrid hydrogel system. The in vivo results indicated that the hybrid system could enhance the proliferation of cardiomyocytes in situ and could promote revascularization around the MI sites, allowing improved cardiac function. Taken together, we concluded that the hybrid hydrogel system can co-deliver BIO and IGF-1 to areas of MI and thus improve cardiac function by promoting the proliferation of cardiomyocytes and revascularization. PMID:26251592

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.)

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.

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

Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) promotes lung fibroblast proliferation, survival and differentiation to myofibroblasts.

Science.gov (United States)

Hasaneen, Nadia A; Cao, Jian; Pulkoski-Gross, Ashleigh; Zucker, Stanley; Foda, Hussein D

2016-02-17

Idiopathic pulmonary fibrosis (IPF) is a chronic progressively fatal disease. Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) is a glycosylated transmembrane protein that induces the expression of some matrix metalloproteinase (MMP) in neighboring stromal cells through direct epithelial-stromal interactions. EMMPRIN is highly expressed in type II alveolar epithelial cells at the edges of the fibrotic areas in IPF lung sections. However, the exact role of EMMPRIN in IPF is unknown. To determine if EMMPRIN contributes to lung fibroblast proliferation, resistance to apoptosis, and differentiation to myofibroblasts, normal Human lung fibroblasts (NHLF) transiently transfected with either EMMPRIN/GFP or GFP were treated with TGF- β1 from 0 to 10 ng/ml for 48 h and examined for cell proliferation (thymidine incorporation), apoptosis (FACS analysis and Cell Death Detection ELISA assay), cell migration (Modified Boyden chamber) and differentiation to myofibroblasts using Western blot for α-smooth actin of cell lysates. The effect of EMMPRIN inhibition on NHLF proliferation, apoptosis, migration and differentiation to myofibroblasts after TGF- β1 treatment was examined using EMMPRIN blocking antibody. We examined the mechanism by which EMMPRIN induces its effects on fibroblasts by studying the β-catenin/canonical Wnt signaling pathway using Wnt luciferase reporter assays and Western blot for total and phosphorylated β-catenin. Human lung fibroblasts overexpressing EMMPRIN had a significant increase in cell proliferation and migration compared to control fibroblasts. Furthermore, EMMPRIN promoted lung fibroblasts resistance to apoptosis. Lung fibroblasts overexpressing EMMPRIN showed a significantly increased expression of α- smooth muscle actin, a marker of differentiation to myofibroblasts compared to control cells. TGF-β1 increased the expression of EMMPRIN in lung fibroblasts in a dose-dependent manner. Attenuation of EMMPRIN expression with the use of an

17β-estradiol exerts anticancer effects in anoikis-resistant hepatocellular carcinoma cell lines by targeting IL-6/STAT3 signaling

Energy Technology Data Exchange (ETDEWEB)

Lee, Seulki, E-mail: sl10f@naver.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Lee, Minjong, E-mail: minjonglee2@naver.com [Division of Gastroenterology, Department of Internal Medicine, Kangwon National University Hospital, 156 Baengnyeong-ro, Chuncheon-si, Gangwon-do (Korea, Republic of); Kim, Jong Bin, E-mail: kkimjp@hanmail.net [Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN, 55912 (United States); Jo, Ara, E-mail: loveara0315@naver.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Cho, Eun Ju, E-mail: creatioex@gmail.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Yu, Su Jong, E-mail: ydoctor2@hanmail.net [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Lee, Jeong-Hoon, E-mail: pindra@empal.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Yoon, Jung-Hwan, E-mail: yoonjh@snu.ac.kr [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Kim, Yoon Jun, E-mail: yoonjun@snu.ac.kr [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of)

2016-05-13

17β-Estradiol (E2) has been proven to exert protective effects against HCC; however, its mechanism on HCC proliferation and suppression of invasion remains to be further explored. Because HCC up-regulates serum Interleukin-6 (IL-6) levels and Signal Transducer and Activator of Transcription 3 (STAT3), molecular agents that attenuate IL-6/STAT3 signaling can potentially suppress HCC development. In this study, we examined involvement of E2 in anoikis resistance that induces invasion capacities and chemo-resistance. Huh-BAT and HepG2 cells grown under anchorage-independent condition were selected. The anoikis-resistant (AR) cells showed stronger chemo-resistance against sorafenib, doxorubicin, 5-fluorouracil and cisplatin compared to adherent HCC cells. AR HCC cells exhibited decreased expression of E-cadherin and increased expression of the N-cadherin and vimentin compared to adherent HCC cells. We then demonstrated that E2 suppressed cell proliferation in AR HCC cells. IL-6 treatment enhanced invasive characteristics, and E2 reversed it. Regarding mechanism of E2, it decreased in the phosphorylation of STAT3 that overexpressed on AR HCC cells. The inhibitory effect of E2 on cell growth was accompanied with cell cycle arrest at G2/M phase and caspase-3/9/PARP activation through c-Jun N-terminal Kinase (JNK) phosphorylation. Taken together, these findings suggested that E2 inhibited the proliferation of AR HCC cells through down-regulation of IL-6/STAT3 signaling. Thus, E2 can be a potential therapeutic drug for treatment of metastatic or chemo-resistant HCC. -- Highlights: •Anoikis-resistant HCC cells characterized chemo-resistant and metastatic potentials. •17β-Estradiol down-regulated IL-6/STAT3 signaling in anoikis-resistant HCC cells. •17β-Estradiol suppressed cell proliferation by inducing G2/M phase arrest and apoptosis though JNK phosphorylation.

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.

Taraxacum officinale dandelion extract efficiently inhibited the breast cancer stem cell proliferation

OpenAIRE

Ngu Van Trinh; Nghi Doan-Phuong Dang; Diem Hong Tran; Phuc Van Pham

2016-01-01

Background: Breast cancer stem cells (BCSCs) play an important role in breast cancer initiation, metastasis, recurrence, and drug resistance. Therefore, targeting BCSCs is an essential strategy to suppress cancer growth. This study aimed to evaluate the effects of dandelion Taraxacum officinale extracts on BCSC proliferation in vitro in 2D and 3D cell culture platforms. Materials and Methods: The BCSCs were maintained under standard conditions, verified for expression of CD44 and CD24 surface...

Culture Medium Supplements Derived from Human Platelet and Plasma: Cell Commitment and Proliferation Support

Directory of Open Access Journals (Sweden)

Anita Muraglia

2017-11-01

Full Text Available Present cell culture medium supplements, in most cases based on animal sera, are not fully satisfactory especially for the in vitro expansion of cells intended for human cell therapy. This paper refers to (i an heparin-free human platelet lysate (PL devoid of serum or plasma components (v-PL and (ii an heparin-free human serum derived from plasma devoid of PL components (Pl-s and to their use as single components or in combination in primary or cell line cultures. Human mesenchymal stem cells (MSC primary cultures were obtained from adipose tissue, bone marrow, and umbilical cord. Human chondrocytes were obtained from articular cartilage biopsies. In general, MSC expanded in the presence of Pl-s alone showed a low or no proliferation in comparison to cells grown with the combination of Pl-s and v-PL. Confluent, growth-arrested cells, either human MSC or human articular chondrocytes, treated with v-PL resumed proliferation, whereas control cultures, not supplemented with v-PL, remained quiescent and did not proliferate. Interestingly, signal transduction pathways distinctive of proliferation were activated also in cells treated with v-PL in the absence of serum, when cell proliferation did not occur, indicating that v-PL could induce the cell re-entry in the cell cycle (cell commitment, but the presence of serum proteins was an absolute requirement for cell proliferation to happen. Indeed, Pl-s alone supported cell growth in constitutively activated cell lines (U-937, HeLa, HaCaT, and V-79 regardless of the co-presence of v-PL. Plasma- and plasma-derived serum were equally able to sustain cell proliferation although, for cells cultured in adhesion, the Pl-s was more efficient than the plasma from which it was derived. In conclusion, the cells expanded in the presence of the new additives maintained their differentiation potential and did not show alterations in their karyotype.

Breast cancers radiation-resistance: key role of the cancer stem cells marker CD24

International Nuclear Information System (INIS)

Bensimon, Julie

2013-01-01

This work focuses on the characterization of radiation-resistant breast cancer cells, responsible for relapse after radiotherapy. The 'Cancer Stem Cells' (CSC) theory describes a radiation-resistant cellular sub-population, with enhanced capacity to induce tumors and proliferate. In this work, we show that only the CSC marker CD24-/low defines a radiation resistant cell population, able to transmit the 'memory' of irradiation, expressed as long term genomic instability in the progeny of irradiated cells. We show that CD24 is not only a marker, but is an actor of radiation-response. So, CD24 expression controls cell proliferation in vitro and in vivo, and ROS level before and after irradiation. As a result, CD24-/low cells display enhanced radiation-resistance and genomic stability. For the first time, our results attribute a role to CD24-/low CSCs in the transmission of genomic instability. Moreover, by providing informations on tumor intrinsic radiation-sensitivity, CD24- marker could help to design new radiotherapy protocols. (author)

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

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

HCV core protein promotes hepatocyte proliferation and chemoresistance by inhibiting NR4A1

Energy Technology Data Exchange (ETDEWEB)

Tan, Yongsheng, E-mail: yongshengtanwhu@126.com; Li, Yan, E-mail: liyansd2@163.com

2015-10-23

This study investigated the effect of HCV core protein on the proliferation of hepatocytes and hepatocellular carcinoma cells (HCC), the influence of HCV core protein on HCC apoptosis induced by the chemotherapeutic agent cisplatin, and the mechanism through which HCV core protein acts as a potential oncoprotein in HCV-related HCC by measuring the levels of NR4A1 and Runt-related transcription factor 3 (RUNX3), which are associated with tumor suppression and chemotherapy resistance. In the present study, PcDNA3.1-core and RUNX3 siRNA were transfected into LO2 and HepG2 cells using Lipofectamine 2000. LO2-core, HepG2-core, LO2-RUNX3 {sup low} and control cells were treated with different concentrations of cisplatin for 72 h, and cell proliferation and apoptosis were assayed using the CellTiter 96{sup ®}Aqueous Non-Radioactive Cell Proliferation Assay Kit. Western blot and real time PCR analyses were used to detect NR4A1, RUNX3, smad7, Cyclin D1 and BAX. Confocal microscopy was used to determine the levels of NR4A1 in HepG2 and HepG2-core cells. The growth rate of HepG2-core cells was considerably greater than that of HepG2 cells. HCV core protein increased the expression of cyclin D1 and decreased the expressions of NR4A1 and RUNX3. In LO2 – RUNX3 {sup low}, the rate of cell proliferation and the level of cisplatin resistance were the same as in the LO2 -core. These results suggest that HCV core protein decreases the sensitivity of hepatocytes to cisplatin by inhibiting the expression of NR4A1 and promoting the expression of smad7, which negatively regulates the TGF-β pathway. This effect results in down regulation of RUNX3, a target of the TGF-β pathway. Taken together, these findings indicate that in hepatocytes, HCV core protein increases drug resistance and inhibits cell apoptosis by inhibiting the expressions of NR4A1 and RUNX3. - Highlights: • HCV core protein inhibits HepG2 cell sensitivity to cisplatin. • Core expression in HepG2 decreases

HCV core protein promotes hepatocyte proliferation and chemoresistance by inhibiting NR4A1

International Nuclear Information System (INIS)

Tan, Yongsheng; Li, Yan

2015-01-01

This study investigated the effect of HCV core protein on the proliferation of hepatocytes and hepatocellular carcinoma cells (HCC), the influence of HCV core protein on HCC apoptosis induced by the chemotherapeutic agent cisplatin, and the mechanism through which HCV core protein acts as a potential oncoprotein in HCV-related HCC by measuring the levels of NR4A1 and Runt-related transcription factor 3 (RUNX3), which are associated with tumor suppression and chemotherapy resistance. In the present study, PcDNA3.1-core and RUNX3 siRNA were transfected into LO2 and HepG2 cells using Lipofectamine 2000. LO2-core, HepG2-core, LO2-RUNX3 "l"o"w and control cells were treated with different concentrations of cisplatin for 72 h, and cell proliferation and apoptosis were assayed using the CellTiter 96"®Aqueous Non-Radioactive Cell Proliferation Assay Kit. Western blot and real time PCR analyses were used to detect NR4A1, RUNX3, smad7, Cyclin D1 and BAX. Confocal microscopy was used to determine the levels of NR4A1 in HepG2 and HepG2-core cells. The growth rate of HepG2-core cells was considerably greater than that of HepG2 cells. HCV core protein increased the expression of cyclin D1 and decreased the expressions of NR4A1 and RUNX3. In LO2 – RUNX3 "l"o"w, the rate of cell proliferation and the level of cisplatin resistance were the same as in the LO2 -core. These results suggest that HCV core protein decreases the sensitivity of hepatocytes to cisplatin by inhibiting the expression of NR4A1 and promoting the expression of smad7, which negatively regulates the TGF-β pathway. This effect results in down regulation of RUNX3, a target of the TGF-β pathway. Taken together, these findings indicate that in hepatocytes, HCV core protein increases drug resistance and inhibits cell apoptosis by inhibiting the expressions of NR4A1 and RUNX3. - Highlights: • HCV core protein inhibits HepG2 cell sensitivity to cisplatin. • Core expression in HepG2 decreases expression of NR4A1

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.)

Regulatory Lymphocytes Are Key Factors in MHC-Independent Resistance to EAE

Science.gov (United States)

Marín, Nieves; Mecha, Miriam; Espejo, Carmen; Mestre, Leyre; Eixarch, Herena; Montalban, Xavier; Álvarez-Cermeño, José C.; Guaza, Carmen; Villar, Luisa M.

2014-01-01

Background and Objectives. Resistant and susceptible mouse strains to experimental autoimmune encephalomyelitis (EAE), an inducible demyelinating experimental disease serving as animal model for multiple sclerosis, have been described. We aimed to explore MHC-independent mechanisms inducing resistance to EAE. Methods. For EAE induction, female C57BL/6 (susceptible strain) and CD1 (resistant outbred strain showing heterogeneous MHC antigens) mice were immunized with the 35–55 peptide of myelin oligodendrocyte glycoprotein (MOG35−55). We studied T cell proliferation, regulatory and effector cell subpopulations, intracellular and serum cytokine patterns, and titers of anti-MOG serum antibodies. Results. Upon immunization with MOG35−55, T lymphocytes from susceptible mice but not that of resistant strain were capable of proliferating when stimulated with MOG35−55. Accordingly, resistant mice experienced a rise in regulatory B cells (P = 0.001) and, to a lower extent, in regulatory T cells (P = 0.02) compared with C57BL/6 susceptible mice. As a consequence, MOG35−55-immunized C57BL/6 mice showed higher percentages of CD4+ T cells producing both IFN-gamma (P = 0.02) and IL-17 (P = 0.009) and higher serum levels of IL-17 (P = 0.04) than resistant mice. Conclusions. Expansion of regulatory B and T cells contributes to the induction of resistance to EAE by an MHC-independent mechanism. PMID:24868560

Regulatory Lymphocytes Are Key Factors in MHC-Independent Resistance to EAE

Directory of Open Access Journals (Sweden)

Nieves Marín

2014-01-01

Full Text Available Background and Objectives. Resistant and susceptible mouse strains to experimental autoimmune encephalomyelitis (EAE, an inducible demyelinating experimental disease serving as animal model for multiple sclerosis, have been described. We aimed to explore MHC-independent mechanisms inducing resistance to EAE. Methods. For EAE induction, female C57BL/6 (susceptible strain and CD1 (resistant outbred strain showing heterogeneous MHC antigens mice were immunized with the 35–55 peptide of myelin oligodendrocyte glycoprotein (MOG35−55. We studied T cell proliferation, regulatory and effector cell subpopulations, intracellular and serum cytokine patterns, and titers of anti-MOG serum antibodies. Results. Upon immunization with MOG35−55, T lymphocytes from susceptible mice but not that of resistant strain were capable of proliferating when stimulated with MOG35−55. Accordingly, resistant mice experienced a rise in regulatory B cells (P=0.001 and, to a lower extent, in regulatory T cells (P=0.02 compared with C57BL/6 susceptible mice. As a consequence, MOG35−55-immunized C57BL/6 mice showed higher percentages of CD4+ T cells producing both IFN-gamma (P=0.02 and IL-17 (P=0.009 and higher serum levels of IL-17 (P=0.04 than resistant mice. Conclusions. Expansion of regulatory B and T cells contributes to the induction of resistance to EAE by an MHC-independent mechanism.

Microarray-based apoptosis gene screening technique in trichostatin A-induced drug-resisted lung cancer A549/CDDP cells

Directory of Open Access Journals (Sweden)

Ya-jun WANG

2016-09-01

Full Text Available Objective 　To detect the expression profile changes of apoptosis-related genes in trichostatin A (TSA-induced drug-resisted lung cancer cells A549/CDDP by microarray, in order to screen the target genes in TSA treating cisplatin-resisted lung cancer. Methods 　A549/CDDP cells were treated by TSA for 24 hours. Total RNA was extracted and reversely transcribed into cDNA. Gene expression levels were detected by the NimbleGen whole genome microarray. Differences of expression profiles between TSA-treated and control group were measured by NimbleScan 2.5 software and GO analysis. Apoptosis and proliferation related genes were screened from the expression changed genes. Results 　Compared with the control group, 85 apoptosis-related genes were up-regulated and 43 growth or proliferation related genes were down-regulated in the TSA-treated group. GO analysis showed that the functions of these genes are mainly regulating apoptosis, cell resistance to chem ical stimuli protein, as well as regulating cell growth, proliferation and the biological process of maintaining the cell biological quality. TSA-activated not only the mitochondrial apoptotic pathways, but also the death receptor related apoptosis pathway, and down-regulated the drug resistance related genes BAG3 and ABCC2. Conclusion 　TSA may cause the expression changes of apoptotic and proliferation genes in A549/CDDP cells, these genes may play a role in TSA treating cisplatin-resisted lung cancer. DOI: 10.11855/j.issn.0577-7402.2016.08.07

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....

TRPM8 ion channels differentially modulate proliferation and cell cycle distribution of normal and cancer prostate cells.

Directory of Open Access Journals (Sweden)

María Ll Valero

Full Text Available Overexpression of the cation-permeable channel TRPM8 in prostate cancers might represent a novel opportunity for their treatment. Inhibitors of TRPM8 reduce the growth of prostate cancer cells. We have used two recently described and highly specific blockers, AMTB and JNJ41876666, and RNAi to determine the relevance of TRPM8 expression in the proliferation of non-tumor and tumor cells. Inhibition of the expression or function of the channel reduces proliferation rates and proliferative fraction in all tumor cells tested, but not of non-tumor prostate cells. We observed no consistent acceleration of growth after stimulation of the channel with menthol or icilin, indicating that basal TRPM8 expression is enough to sustain growth of prostate cancer cells.

TRPM8 ion channels differentially modulate proliferation and cell cycle distribution of normal and cancer prostate cells.

Science.gov (United States)

Valero, María Ll; Mello de Queiroz, Fernanda; Stühmer, Walter; Viana, Félix; Pardo, Luis A

2012-01-01

Overexpression of the cation-permeable channel TRPM8 in prostate cancers might represent a novel opportunity for their treatment. Inhibitors of TRPM8 reduce the growth of prostate cancer cells. We have used two recently described and highly specific blockers, AMTB and JNJ41876666, and RNAi to determine the relevance of TRPM8 expression in the proliferation of non-tumor and tumor cells. Inhibition of the expression or function of the channel reduces proliferation rates and proliferative fraction in all tumor cells tested, but not of non-tumor prostate cells. We observed no consistent acceleration of growth after stimulation of the channel with menthol or icilin, indicating that basal TRPM8 expression is enough to sustain growth of prostate cancer cells.

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 ...

Sustainable Use of Tepetate Composite in Earthen Structure

Directory of Open Access Journals (Sweden)

T. López-Lara

2013-01-01

Full Text Available One of the best indicators for construction sustainability is the use of earthy local materials which are completely recyclables and savers of energy during their life cycle. Tepetate is an underestimated earth-natural material, vast and economic, used only in a compacted form in backfills for layers of low resistance in pavements and platforms of buildings. This volcanic soil, named in different ways in several countries, is found in the central region of Mexico. Its resistance as compacted material is very low, of the order of 0.08 MPa. In this work, an improved sustainable-tepetate composite, using CaOH, is presented. This research includes the determination of mechanical properties as well as the physicochemical characterization of the sustainable-tepetate composite behavior. It can be concluded that the strength of the proposed composite increases significantly, immediately after treatment and with time. X-Ray Diffraction shows that all the mineralogical phases prevail in the natural tepetate and only a new phase appeared (calcite, which increases with time. This and the reaction of CaOH with clay content are very likely associated with the continuous strength increase of the composite.

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)

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...

Leptin deficiency unmasks the deleterious effects of impaired peroxisome proliferator-activated receptor γ function (P465L PPARγ) in mice

NARCIS (Netherlands)

Gray, S.L.; Dalla Nora, E.; Grosse, J.; Manieri, M.; Stoeger, T.; Medina-Gomez, G.; Burling, K.; Wattler, S.; Russ, A.; Yeo, G.S.H.; Chatterjee, V.K.; O'Rahilly, S.; Voshol, P.J.; Cinti, S.; Vidal-Puig, A.

2006-01-01

Peroxisome proliferator-activated receptor (PPAR)γ is a key transcription factor facilitating fat deposition in adipose tissue through its proadipogenic and lipogenic actions. Human patients with dominant-negative mutations in PPARγ display lipodystrophy and extreme insulin resistance. For this

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

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.

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

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.

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

Residual characteristic properties of ternary blended steel fibre reinforced concrete subjected to sustained elevated temperature

Directory of Open Access Journals (Sweden)

Sinha Deepa A.

2013-09-01

Full Text Available To study the behavior of ternary blended steel fibre reinforced concrete when subjected to 800 Deg.C and 1000 Deg.C for 3 hours. It has been found that the ternary blended steel fibre reinforced concrete containing (FA+GGBFS and (FA+MK offer higher resistance to sustained elevated temperatures upto 800 Deg.C, where as the blend containing (FA+SF does not offer any resistance at this temperature. The study reveals that the blend containing (FA+GGBFS and (FA+MK gives highest resistance at replacement levels of (10+20 and (15+15 respectively at sustained exposure to 800 Deg.C.

Towards a remote sensing based indicator of rangeland ecosystem resistance and resilience

Science.gov (United States)

Understanding ecosystem resistance and resilience to disturbance and invasive species is critical to the sustainable management of rangeland systems. In this context, resistance refers to the inherent ability of an ecosystem to resist disturbance, while resilience refers to the capacity of an ecosys...

Essential variables help to focus sustainable development goals monitoring

CSIR Research Space (South Africa)

Reyers, B

2017-06-01

Full Text Available indicators [1], each one of which relies on existing and new multiple data streams for its development (Figure 1a). Under this current proliferation logic, the process of developing an SDG monitoring system inexorably results in an ever-expanding set....sciencedirect.com Essential Sustainable Development Goal Variables Reyers et al. 99abstraction provides a degree of independence from observations, thus accommodating multiple diverse pri- mary data streams across regions and sections, as well as the flexibility to meet...

Sustainable use of winter Durum wheat landraces under ...

African Journals Online (AJOL)

... the two checks cultivars. Bi- plot analysis showed that some promising lines with reasonable grain yields, good quality parameters, winter hardiness and drought tolerances among yellow rust resistance durum wheat landraces can be selected for semiarid conditions of Mediterranean countries for sustainable production.

Second annual report on nuclear non-proliferation: supplement to Secretary's Annual Report to Congress

International Nuclear Information System (INIS)

1980-01-01

This document covers: goals of US nonproliferation policy, agreements for cooperation, technical exchange, US as a reliable supplier of nuclear fuels, IAEA Expert Group on International Plutonium Storage, implementation of US nonproliferation policy, classification, cooperation in strengthening international safeguards and physical security, the US-IAEA voluntary offer safeguards agreement, US spent fuel storage policy, development of proliferation-resistant fuel cycle technologies, and the International Nuclear Fuel Cycle Evaluation

Thermodynamic characterization of salt components for Molten Salt Reactor fuel

NARCIS (Netherlands)

Capelli, E.

2016-01-01

The Molten Salt Reactor (MSR) is a promising future nuclear fission reactor technology with excellent performance in terms of safety and reliability, sustainability, proliferation resistance and economics. For the design and safety assessment of this concept, it is extremely important to have a

Low-power critical facilities: their role in the nuclear renaissance

International Nuclear Information System (INIS)

Didsbury, R.

2011-01-01

This paper discusses the role of low power critical facilities and their role in the nuclear renaissance. It outline the role of human capital in some detail. sufficient conditions for the renaissance are that nuclear power is safe, sustainable, economical and proliferation resistant.

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

Trehalose improves cell proliferation and dehydration tolerance of human HaCaT cells

Directory of Open Access Journals (Sweden)

Lee Kyung Eun

2015-01-01

Full Text Available Trehalose is a disaccharide molecule that serves as a natural osmotic regulator in halophilic microorganisms and plants but not in mammals. We observed that human HaCaT cells supplied with trehalose improved cell proliferation and extended viability under dehydration. In HaCaT cells, in response to increasing concentrations of exogenous trehalose, the levels of heat shock protein (HSP 70 increased and matrix metalloproteinase (MMP 1 decreased. Proteome analysis of trehalose-treated HaCaT cells revealed remarkable increases in the levels of proteins involved in cell signaling and the cell cycle, including p21 activated kinase I, Sec I family domain protein and elongation factor G. Moreover, the proteins for cell stress resistance, tryptophan hydroxylase, serine/cysteine proteinase inhibitors and vitamin D receptors were also increased. In addition, the proteins responsible for the maintenance of the cytoskeleton and cellular structures including procollagen-lysine dioxygenase, vinculin and ezrin were increased. Proteomic data revealed that trehalose affected HaCaT cells by inducing the proteins involved in cell proliferation. These results suggest that trehalose improves the proliferation and dehydration tolerance of HaCaT cells by inducing proteins involved in cell growth and dehydration protection.

Insect-resistance and high-yield transgenic tobacco obtained by ...

African Journals Online (AJOL)

hope&shola

2010-10-04

Oct 4, 2010 ... had great significance for agricultural sustained develop- ment. Significant advances have been made in insect- resistant gene cry engineering (Cui and Guo, 1998; Ni et al., 1998; Yan, 2003). Insect-resistant trangenic cotton, harbouring the modified, synthesized gene cry, has already been commercialized ...

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.

RhoA-Rho kinase and platelet-activating factor stimulation of ovine foetal pulmonary vascular smooth muscle cell proliferation.

Science.gov (United States)

Renteria, L S; Austin, M; Lazaro, M; Andrews, M A; Lustina, J; Raj, J U; Ibe, B O

2013-10-01

Platelet-activating factor (PAF) is produced by pulmonary vascular smooth muscle cells (PVSMC). We studied effects of Rho kinase on PAF stimulation of PVSMC proliferation in an attempt to understand the role of RhoA/Rho kinase on PAF-induced ovine foetal pulmonary vascular remodelling. Our hypothesis is that PAF acts through Rho kinase, as one of its downstream signals, to induce arterial (SMC-PA) and venous (SMC-PV) cell proliferation in the hypoxic lung environment of the foetus, in utero. Rho kinase and MAPK effects on PAF receptor (PAFR)-mediated cell population expansion, and PAFR expression, were studied by DNA synthesis, western blot analysis and immunocytochemistry. Effects of constructs T19N and G14V on PAF-induced cell proliferation were also investigated. Hypoxia increased PVSMC proliferation and Rho kinase inhibitors, Y-27632 and Fasudil (HA-1077) as well as MAPK inhibitors PD 98059 and SB 203580 attenuated PAF stimulation of cell proliferation. RhoA T19N and G14V stimulated cell proliferation, but co-incubation with PAF did not affect proliferative effects of the constructs. PAFR protein expression was significantly downregulated in both cell types by both Y-27632 and HA-1077, with comparable profiles. Also, cells treated with Y-27632 had less PAF receptor fluorescence with significant disruption of cell morphology. Our results show that Rho kinase non-specifically modulated PAFR-mediated responses by a translational modification of PAFR protein, and suggest that, in vivo, activation of Rho kinase by PAF may be a further pathway to sustain PAFR-mediated PVSMC proliferation. © 2013 John Wiley & Sons Ltd.

Sustainability of a Compartmentalized Host-Parasite Replicator System under Periodic Washout-Mixing Cycles

Directory of Open Access Journals (Sweden)

Taro Furubayashi

2018-01-01

Full Text Available The emergence and dominance of parasitic replicators are among the major hurdles for the proliferation of primitive replicators. Compartmentalization of replicators is proposed to relieve the parasite dominance; however, it remains unclear under what conditions simple compartmentalization uncoupled with internal reaction secures the long-term survival of a population of primitive replicators against incessant parasite emergence. Here, we investigate the sustainability of a compartmentalized host-parasite replicator (CHPR system undergoing periodic washout-mixing cycles, by constructing a mathematical model and performing extensive simulations. We describe sustainable landscapes of the CHPR system in the parameter space and elucidate the mechanism of phase transitions between sustainable and extinct regions. Our findings revealed that a large population size of compartments, a high mixing intensity, and a modest amount of nutrients are important factors for the robust survival of replicators. We also found two distinctive sustainable phases with different mixing intensities. These results suggest that a population of simple host–parasite replicators assumed before the origin of life can be sustained by a simple compartmentalization with periodic washout-mixing processes.

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....

Non-proliferation issues for the disposition of fissile materials using reactor alternatives

International Nuclear Information System (INIS)

Jaeger, C.D.; Duggan, R.A.; Tolk, K.M.

1996-01-01

The Department of Energy (DOE) is analyzing long-term storage imposition options for excess weapons-usable fissile materials. A number of the disposition alternatives are being considered which involve the use of reactors. The various reactor alternatives are all very similar and include front-end processes that could convert plutonium to a usable form for fuel fabrication, a MOX fuel fab facility, reactors to burn the MOX fuel and ultimate disposal of spent fuel in some geologic repository. They include existing, partially completed, advanced or evolutionary light water reactors and Canadian deuterium uranium (CANDU) reactors. In addition to the differences in the type of reactors, other variants on these alternatives are being evaluated to include the location and number of the reactors, the location of the mixed oxide (MOX) fabrication facility, the ownership of the facilities (private or government) and the colocation and/or separation of these facilities. All of these alternatives and their variants must be evaluated with respect to non-proliferation resistance. Both domestic and international safeguards support are being provided to DOE's Fissile Materials Disposition Program (FMDP) and includes such areas as physical protection, nuclear materials accountability and material containment and surveillance. This paper will focus on how the non-proliferation objective of reducing security risks and strengthening arms reduction will be accomplished and what some of the non-proliferation issues are for the reactor alternatives. Proliferation risk has been defined in terms of material form, physical environment, and the level of security and safeguards that is applied to the material. Metrics have been developed for each of these factors. The reactor alternatives will be evaluated with respect to these proliferation risk factors at each of the unit process locations in the alternative

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...

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.

An antitubulin agent BCFMT inhibits proliferation of cancer cells and induces cell death by inhibiting microtubule dynamics.

Directory of Open Access Journals (Sweden)

Ankit Rai

Full Text Available Using cell based screening assay, we identified a novel anti-tubulin agent (Z-5-((5-(4-bromo-3-chlorophenylfuran-2-ylmethylene-2-thioxothiazolidin-4-one (BCFMT that inhibited proliferation of human cervical carcinoma (HeLa (IC(50, 7.2 ± 1.8 µM, human breast adenocarcinoma (MCF-7 (IC(50, 10.0 ± 0.5 µM, highly metastatic breast adenocarcinoma (MDA-MB-231 (IC(50, 6.0 ± 1 µM, cisplatin-resistant human ovarian carcinoma (A2780-cis (IC(50, 5.8 ± 0.3 µM and multi-drug resistant mouse mammary tumor (EMT6/AR1 (IC(50, 6.5 ± 1 µM cells. Using several complimentary strategies, BCFMT was found to inhibit cancer cell proliferation at G2/M phase of the cell cycle apparently by targeting microtubules. In addition, BCFMT strongly suppressed the dynamics of individual microtubules in live MCF-7 cells. At its half maximal proliferation inhibitory concentration (10 µM, BCFMT reduced the rates of growing and shortening phases of microtubules in MCF-7 cells by 37 and 40%, respectively. Further, it increased the time microtubules spent in the pause (neither growing nor shortening detectably state by 135% and reduced the dynamicity (dimer exchange per unit time of microtubules by 70%. In vitro, BCFMT bound to tubulin with a dissociation constant of 8.3 ± 1.8 µM, inhibited tubulin assembly and suppressed GTPase activity of microtubules. BCFMT competitively inhibited the binding of BODIPY FL-vinblastine to tubulin with an inhibitory concentration (K(i of 5.2 ± 1.5 µM suggesting that it binds to tubulin at the vinblastine site. In cultured cells, BCFMT-treatment depolymerized interphase microtubules, perturbed the spindle organization and accumulated checkpoint proteins (BubR1 and Mad2 at the kinetochores. BCFMT-treated MCF-7 cells showed enhanced nuclear accumulation of p53 and its downstream p21, which consequently activated apoptosis in these cells. The results suggested that BCFMT inhibits proliferation of several types of cancer cells including drug

Effects of o-aminoazotoluene on liver regeneration and p53 activation in mice susceptible and resistant to hepatocarcinogenesis

International Nuclear Information System (INIS)

Timofeeva, Olga A.; Eremeev, Artem V.; Goloshchapov, Andrey; Kalashnikova, Eugenia; Ilnitskaya, Svetlana; Setkov, Nikolai A.; Kobzev, Victor; Buzard, Gregory S.; Filipenko, Maxim L.; Kaledin, Vasily I.; Merkulova, Tatyana I.

2008-01-01

The susceptibility to hepatocellular carcinoma (HCC) varies greatly within human populations in response to environmental risk agents. The mechanisms underlying differential susceptibility are still largely unknown and need to be clarified to improve HCC chemoprevention and therapeutic treatment. Inbred rodent strains with established predispositions for hepatocarcinogenesis offer the opportunity to identify intrinsic susceptibility and resistance factors. Previously, we have characterized mouse strains showing differential susceptibility to o-aminoazotoluene (OAT) and established that susceptibility does not result from OAT metabolism or genotoxicity in the livers of resistant and susceptible mice. In this study we have found that OAT differently affects hepatocyte proliferation in mice after partial hepatectomy (PH). OAT inhibited hepatocyte proliferation by 60-80% in the livers of susceptible mice, whereas resistant mice showed less than 15% inhibition. The inhibition resulted in significant delay of hepatic mass recovery in susceptible mice. OAT induced p53 stabilization and transcriptional activation in response to carcinogen treatment to the same degree in both, susceptible and resistant mice. Taken together, our data support inhibition of hepatocyte proliferation as a major cause for increased mouse susceptibility to hepatocarcinogenesis, and acceleration of functional liver recovery may offer a way to increase resistance to hepatic neoplasms. These results may have relevance to clinical observations of HCCs and implications for HCC chemoprevention and treatment

Corrosion resistance and cytocompatibility of tantalum-surface-functionalized biomedical ZK60 Mg alloy

International Nuclear Information System (INIS)

Jin, Weihong; Wang, Guomin; Lin, Zhengjie; Feng, Hongqing; Li, Wan; Peng, Xiang; Qasim, Abdul Mateen; Chu, Paul K.

2017-01-01

Highlights: • Films comprising Ta_2O_5, Ta suboxide, and Ta are sputter-deposited on ZK60 Mg alloy. • The Ta-containing film significantly mitigates degradation of ZK60. • The modified ZK60 exhibits notably enhanced cell adhesion and proliferation. - Abstract: Tantalum (Ta) is introduced to the surface of the ZK60 Mg alloy by reactive magnetron sputtering to enhance the corrosion resistance and cytocompatibility. The film thickness and composition, corrosion behavior, and cytocompatibility are studied by various techniques systematically. The surface layer composed of Ta_2O_5, Ta suboxide, and Ta increases the corrosion resistance of ZK60 while simultaneously improving cell attachment, spreading, and proliferation in vitro. The enhancement mechanism is proposed and discussed.

Erlotinib is a viable treatment for tumors with acquired resistance to cetuximab

Science.gov (United States)

Brand, Toni M; Dunn, Emily F; Iida, Mari; Myers, Rebecca A; Kostopoulos, Kellie T; Li, Chunrong; Peet, Chimera R

2011-01-01

The epidermal growth factor receptor (EGFR) is an ubiquitously expressed receptor tyrosine kinase (RTK) and is recognized as a key mediator of tumorigenesis in many human tumors. Currently there are five EGFR inhibitors used in oncology, two monoclonal antibodies (panitumumab and cetuximab) and three tyrosine kinase inhibitors (erlotinib, gefitinib and lapatinib). Both strategies of EGFR inhibition have demonstrated clinical success; however, many tumors remain non-responsive or acquire resistance during therapy. To explore potential molecular mechanisms of acquired resistance to cetuximab we previously established a series of cetuximab-resistant clones by chronically exposing the NCI-H226 NSCLC cell line to escalating doses of cetuximab. Cetuximab-resistant clones exhibited a dramatic increase in the activation of EGFR, HER2 and HER3 receptors as well as increased signaling through the MAP K and AKT pathways. RNAi studies demonstrated dependence of cetuximab-resistant clones on the EGFR signaling network. These findings prompted investigation on whether or not cells with acquired resistance to cetuximab would be sensitive to the EGFR targeted TKI erlotinib. In vitro, erlotinib was able to decrease signaling through the EGFR axis, decrease cellular proliferation and induce apoptosis. To determine if erlotinib could have therapeutic benefit in vivo, we established cetuximab-resistant NCI-H226 mouse xenografts, and subsequently treated them with erlotinib. Mice harboring cetuximab-resistant tumors treated with erlotinib exhibited either a tumor regression or growth delay as compared with vehicle controls. Analysis of the erlotinib treated tumors demonstrated a decrease in cell proliferation and increased rates of apoptosis. The work presented herein suggests that (1) cells with acquired resistance to cetuximab maintain their dependence on EGFR and (2) tumors developing resistance to cetuximab can benefit from subsequent treatment with erlotinib, providing rationale

BMI-1 Promotes Self-Renewal of Radio- and Temozolomide (TMZ)-Resistant Breast Cancer Cells.

Science.gov (United States)

Yan, Yanfang; Wang, Ying; Zhao, Pengxin; Ma, Weiyuan; Hu, Zhigang; Zhang, Kaili

2017-12-01

Breast cancer is a hormone-dependent malignancy and is the most prevalent cause of cancer-related mortality among females. Radiation therapy and chemotherapy are common treatments of breast cancer. However, tumor relapse and metastasis following therapy are major clinical challenges. The importance of B-lymphoma Moloney murine leukemia virus insertion region-1 (BMI-1) was implicated in cell proliferation, stem cell maintenance, and tumor initiation. We established radio- and temozolomide (TMZ)-resistant (IRC-R) MCF-7 and MDA-MB-231 cell lines to investigate the mechanism involved in therapeutic resistance. Cell proliferation and sphere number were dramatically elevated, and BMI-1 was remarkably upregulated, in IRC-R cells compared to parental cells. Silencing BMI-1 by RNA interference only affected the cell proliferation of IRC-R but not parental cells, suggesting the critical role of BMI-1 in radio- and TMZ resistance. We used a xenograft mice model to elucidate that BMI-1 was necessary in tumor development by assessing tumor volume and Ki67 expression. We found that Hedgehog (Hhg) signaling exerted synergized functions together with BMI-1, implicating the importance of BMI-1 in Hhg signaling. Downregulation of BMI-1 could be an effective strategy to suppress tumor growth, which supports the potential clinical use of targeting BMI-1 in breast cancer treatment.

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

Finding synergy between local competitiveness and global sustainability to provide a future to nuclear energy

International Nuclear Information System (INIS)

Van Den Durpel, Luc; Yacout, Abdellatif; Wade, Dave

2008-01-01

The world's future energy needs will require a mix of energy conversion technologies matched to the local energy market needs while also responding to both local and global socio-political concerns, e.g. energy security, environmental impact, safety and non-proliferation. There is growing recognition worldwide that nuclear energy should not only be part of the solution but maybe as well play a larger share in future's energy supply. The sustainability of future nuclear energy systems is hereby important and a variety of studies have already shown that sustainability of nuclear energy from a resource perspective is achievable via the nuclear fuel cycle though where economic sustainability is essentially defined by the nuclear power plants. The main challenge in deploying sustainable nuclear energy systems will be to find synergies between this local competitiveness of nuclear power plants and the global resource sustainability defined via the nuclear fuel cycle. Both may go hand-in-hand in the long-term but may need government guidance in starting the transition towards such future sustainable nuclear energy systems. (authors)

How Fitness Reduced, Antimicrobial Resistant Bacteria Survive and Spread

DEFF Research Database (Denmark)

Græsbøll, Kaare; Nielsen, Søren Saxmose; Toft, Nils

2014-01-01

More than 30% of E. coli strains sampled from pig farms in Denmark over the last five years were resistant to the commonly used antimicrobial tetracycline. This raises a number of questions: How is this high level sustained if resistant bacteria have reduced growth rates? Given that there are mul...

Sustained release of sphingosine 1-phosphate for therapeutic arteriogenesis and bone tissue engineering.

Science.gov (United States)

Sefcik, Lauren S; Petrie Aronin, Caren E; Wieghaus, Kristen A; Botchwey, Edward A

2008-07-01

Sphingosine 1-phosphate (S1P) is a bioactive phospholipid that impacts migration, proliferation, and survival in diverse cell types, including endothelial cells, smooth muscle cells, and osteoblast-like cells. In this study, we investigated the effects of sustained release of S1P on microvascular remodeling and associated bone defect healing in vivo. The murine dorsal skinfold window chamber model was used to evaluate the structural remodeling response of the microvasculature. Our results demonstrated that 1:400 (w/w) loading and subsequent sustained release of S1P from poly(lactic-co-glycolic acid) (PLAGA) significantly enhanced lumenal diameter expansion of arterioles and venules after 3 and 7 days. Incorporation of 5-bromo-2-deoxyuridine (BrdU) at day 7 revealed significant increases in mural cell proliferation in response to S1P delivery. Additionally, three-dimensional (3D) scaffolds loaded with S1P (1:400) were implanted into critical-size rat calvarial defects, and healing of bony defects was assessed by radiograph X-ray, microcomputed tomography (muCT), and histology. Sustained release of S1P significantly increased the formation of new bone after 2 and 6 weeks of healing and histological results suggest increased numbers of blood vessels in the defect site. Taken together, these experiments support the use of S1P delivery for promoting microvessel diameter expansion and improving the healing outcomes of tissue-engineered therapies.

PKC-alpha modulation by miR-483-3p in platinum-resistant ovarian carcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Arrighetti, Noemi, E-mail: Noemi.Arrighetti@istitutotumori.mi.it [Molecular Pharmacology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, via Amadeo 42, Milan 20133 (Italy); Cossa, Giacomo, E-mail: Gia.Cossa@gmail.com [Molecular Pharmacology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, via Amadeo 42, Milan 20133 (Italy); De Cecco, Loris, E-mail: Loris.Dececco@istitutotumori.mi.it [Functional Genomics and Bioinformatics, Fondazione IRCCS Istituto Nazionale dei Tumori, via Amadeo 42, Milan 20133 (Italy); Stucchi, Simone, E-mail: Simone.Stucchi@istitutotumori.mi.it [Molecular Pharmacology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, via Amadeo 42, Milan 20133 (Italy); Carenini, Nives, E-mail: Nives.Carenini@istitutotumori.mi.it [Molecular Pharmacology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, via Amadeo 42, Milan 20133 (Italy); Corna, Elisabetta, E-mail: Elisabetta.Corna@istitutotumori.mi.it [Molecular Pharmacology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, via Amadeo 42, Milan 20133 (Italy); Gandellini, Paolo, E-mail: Paolo.Gandellini@istitutotumori.mi.it [Molecular Pharmacology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, via Amadeo 42, Milan 20133 (Italy); Zaffaroni, Nadia, E-mail: Nadia.Zaffaroni@istitutotumori.mi.it [Molecular Pharmacology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, via Amadeo 42, Milan 20133 (Italy); Perego, Paola, E-mail: paola.perego@istitutotumori.mi.it [Molecular Pharmacology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, via Amadeo 42, Milan 20133 (Italy); Gatti, Laura, E-mail: Laura.Gatti@istitutotumori.mi.it [Molecular Pharmacology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, via Amadeo 42, Milan 20133 (Italy)

2016-11-01

The occurrence of drug resistance limits the efficacy of platinum compounds in the cure of ovarian carcinoma. Since microRNAs (miRNAs) may contribute to this phenomenon by regulating different aspects of tumor cell response, the aim of this study was to exploit the analysis of expression of miRNAs in platinum sensitive/resistant cells in an attempt to identify potential regulators of drug response. MiR-483-3p, which may participate in apoptosis and cell proliferation regulation, was found up-regulated in 4 platinum resistant variants, particularly in the IGROV-1/Pt1 subline, versus parental cells. Transfection of a synthetic precursor of miR-483-3p in IGROV-1 parental cells elicited a marked up-regulation of the miRNA levels. Growth-inhibition and colony-forming assays indicated that miR-483-3p over-expression reduced cell growth and conferred mild levels of cisplatin resistance in IGROV-1 cells, by interference with their proliferative potential. Predicted targets of miR-483-3p included PRKCA (encoding PKC-alpha), previously reported to be associated to platinum-resistance in ovarian carcinoma. We found that miR-483-3p directly targeted PRKCA in IGROV-1 cells. In keeping with this finding, cisplatin sensitivity of IGROV-1 cells decreased upon molecular/pharmacological inhibition of PKC-alpha. Overall, our results suggest that overexpression of miR-483-3p by ovarian carcinoma platinum-resistant cells may interfere with their proliferation, thus protecting them from DNA damage induced by platinum compounds and ultimately representing a drug-resistance mechanism. The impairment of cell growth may account for low levels of drug resistance that could be relevant in the clinical setting. - Highlights: • miR-483-3p is up-regulated in ovarian carcinoma cells resistant to platinum drugs. • Ectopic expression of miR-483-3p in IGROV-1 confers mild levels of Pt-resistance. • Overexpression of miR-483-3p down-regulates PRKCA levels in ovarian carcinoma cells. • miR 483

Eosinophil peroxidase signals via epidermal growth factor-2 to induce cell proliferation.

LENUS (Irish Health Repository)

Walsh, Marie-Therese

2011-11-01

Eosinophils exert many of their inflammatory effects in allergic disorders through the degranulation and release of intracellular mediators, including a set of cationic granule proteins that include eosinophil peroxidase. Studies suggest that eosinophils are involved in remodeling. In previous studies, we showed that eosinophil granule proteins activate mitogen-activated protein kinase signaling. In this study, we investigated the receptor mediating eosinophil peroxidase-induced signaling and downstream effects. Human cholinergic neuroblastoma IMR32 and murine melanoma B16.F10 cultures, real-time polymerase chain reaction, immunoprecipitations, and Western blotting were used in the study. We showed that eosinophil peroxidase caused a sustained increase in both the expression of epidermal growth factor-2 (HER2) and its phosphorylation at tyrosine 1248, with the consequent activation of extracellular-regulated kinase 1\\/2. This, in turn, promoted a focal adhesion kinase-dependent egress of the cyclin-dependent kinase inhibitor p27(kip) from the nucleus to the cytoplasm. Eosinophil peroxidase induced a HER2-dependent up-regulation of cell proliferation, indicated by an up-regulation of the nuclear proliferation marker Ki67. This study identifies HER2 as a novel mediator of eosinophil peroxidase signaling. The results show that eosinophil peroxidase, at noncytotoxic levels, can drive cell-cycle progression and proliferation, and contribute to tissue remodeling and cell turnover in airway disease. Because eosinophils are a feature of many cancers, these findings also suggest a role for eosinophils in tumorigenesis.

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

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.

Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone reverses the adverse effects of diet-induced obesity on oocyte quality.

Science.gov (United States)

Minge, Cadence E; Bennett, Brenton D; Norman, Robert J; Robker, Rebecca L

2008-05-01

Obesity and its physiological consequences are increasingly prevalent among women of reproductive age and are associated with infertility. To investigate, female mice were fed a high-fat diet until the onset of insulin resistance, followed by assessments of ovarian gene expression, ovulation, fertilization, and oocyte developmental competence. We report defects to ovarian function associated with diet-induced obesity (DIO) that result in poor oocyte quality, subsequently reduced blastocyst survival rates, and abnormal embryonic cellular differentiation. To identify critical cellular mediators of ovarian responses to obesity induced insulin resistance, DIO females were treated for 4 d before mating with an insulin-sensitizing pharmaceutical: glucose and lipid-lowering AMP kinase activator, 5-aminoimidazole 4-carboxamide-riboside, 30 mg/kg.d; sodium salicylate, IkappaK inhibitor that reverses insulin resistance, 50 mg/kg.d; or peroxisome proliferator activated receptor-gamma agonist rosiglitazone, 10 mg/kg.d. 5-aminoimidazole 4-carboxamide-riboside or sodium salicylate treatment did not have significant effects on the reproductive parameters examined. However, embryonic development to the blastocyst stage was significantly improved when DIO mice were treated with rosiglitazone, effectively repairing development rates. Rosiglitazone also normalized DIO-associated abnormal blastomere allocation to the inner cell mass. Such improvements to oocyte quality were coupled with weight loss, improved glucose metabolism, and changes in ovarian mRNA expression of peroxisome proliferator activated receptor-regulated genes, Cd36, Scarb1, and Fabp4 cholesterol transporters. These studies demonstrate that peri-conception treatment with select insulin-sensitizing pharmaceuticals can directly influence ovarian functions and ultimately exert positive effects on oocyte developmental competence. Improved blastocyst quality in obese females treated with rosiglitazone before mating

MicroRNA-2400 promotes bovine preadipocyte proliferation

International Nuclear Information System (INIS)

Wei, Yao; Cui, Ya Feng; Tong, Hui Li; Zhang, Wei Wei; Yan, Yun Qin

2016-01-01

MicroRNAs (miRNAs) play critical roles in the proliferation of bovine preadipocytes. miR-2400 is a novel and unique miRNA from bovines. In the present study, we separated and identified preadipocytes from bovine samples. miR-2400 overexpression increased the rate of preadipocyte proliferation, which was analyzed with a combination of EdU and flow cytometry. Simultaneously, functional genes related to proliferation (PCNA, CCND2, CCNB1) were also increased, which was detected by real-time PCR. Furthermore, luciferase reporter assays showed that miR-2400 bound directly to the 3'untranslated regions (3′UTRs) of PRDM11 mRNA. These data suggested that miR-2400 could promote preadipocyte proliferation by targeting PRDM11. - Highlights: • miRNAs are important in bovine preadipocyte proliferation. • miR-2400 is a novel miRNA from bovines. • miR-2400 overexpression increased preadipocyte proliferation. • Functional genes related to preadipocyte proliferation were upregulated. • Preadipocyte proliferation was promoted by targeting PRDM11.

A method to define breeding goals for sustainable dairy cattle production.

Science.gov (United States)

Nielsen, H M; Christensen, L G; Odegård, J

2006-09-01

The objective of this study was to present a method to define breeding goals for sustainable dairy cattle production by adding nonmarket values to market economic values for functional traits in the breeding goal. A nonmarket value can represent the value of improved animal welfare or societal influences for animal production. The nonmarket value for mastitis resistance, conception rate, and stillbirth were derived based on how much farmers or breeding companies were willing to lose in selection response for milk yield to improve functional traits. The desired response for milk yield corresponding to a given percent loss was obtained using desired gain indices. By allowing a 5% loss in the selection response for milk yield, the nonmarket value was found to be 40.4 euro for mastitis resistance, 16.1 euro for conception rate, and 9.7 euro for stillbirth. The nonmarket value increased proportionally with increasing loss in the selection response for milk yield, but the selection response was lower for conception rate than for mastitis resistance because of differences in market economic value and heritability. To increase the response for conception rate, the nonmarket value was also derived for 2 situations, in which the desired responses for milk yield, mastitis resistance, and conception rate were specified. The method can be used to define breeding goals for sustainable production and to increase the response for traits that are at critically low levels. When defining breeding goals for sustainable production, breeding organizations should predict the selection response based on market economic value and add non-market value for traits with unacceptable selection responses.

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

Antimicrobial resistance, heavy metal resistance and integron content in bacteria isolated from a South African tilapia aquaculture system.

Science.gov (United States)

Chenia, Hafizah Y; Jacobs, Anelet

2017-11-21

Antibacterial compounds and metals co-select for antimicrobial resistance when bacteria harbour resistance genes towards both types of compounds, facilitating the proliferation and evolution of antimicrobial and heavy metal resistance. Antimicrobial and heavy metal resistance indices of 42 Gram-negative bacteria from a tilapia aquaculture system were determined to identify possible correlations between these phenotypes. Agar dilution assays were carried out to determine susceptibility to cadmium, copper, lead, mercury, chromate and zinc, while susceptibility to 21 antimicrobial agents was investigated by disk diffusion assays. Presence of merA, the mercury resistance gene, was determined by dot-blot hybridizations and PCR. Association of mercury resistance with integrons and transposon Tn21 was also investigated by PCR. Isolates displayed a high frequency of antimicrobial (erythromycin: 100%; ampicillin: 85%; trimethoprim: 78%) and heavy metal (Zn2+: 95%; Cd2+: 91%) resistance. No correlation was established between heavy metal and multiple antibiotic resistance indices. Significant positive correlations were observed between heavy metal resistance profiles, indices, Cu2+ and Cr3+ resistance with erythromycin resistance. Significant positive correlations were observed between merA (24%)/Tn21 (24%) presence and heavy metal resistance profiles and indices; however, significant negative correlations were obtained between integron-associated qacE∆1 (43%) and sulI (26%) gene presence and heavy metal resistance indices. Heavy metal and antimicrobial agents co-select for resistance, with fish-associated, resistant bacteria demonstrating simultaneous heavy metal resistance. Thus, care should be taken when using anti-fouling heavy metals as feed additives in aquaculture facilities.

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

Sustained antimicrobial activity and reduced toxicity of oxidative biocides through biodegradable microparticles.

Science.gov (United States)

Sofokleous, Panagiotis; Ali, Shanom; Wilson, Peter; Buanz, Asma; Gaisford, Simon; Mistry, Dharmit; Fellows, Adrian; Day, Richard M

2017-12-01

The spread of antibiotic-resistant pathogens requires new treatments. Small molecule precursor compounds that produce oxidative biocides with well-established antimicrobial properties could provide a range of new therapeutic products to combat resistant infections. The aim of this study was to investigate a novel biomaterials-based approach for the manufacture, targeted delivery and controlled release of a peroxygen donor (sodium percarbonate) combined with an acetyl donor (tetraacetylethylenediamine) to deliver local antimicrobial activity via a dynamic equilibrium mixture of hydrogen peroxide and peracetic acid. Entrapment of the pre-cursor compounds into hierarchically structured degradable microparticles was achieved using an innovative dry manufacturing process involving thermally induced phase separation (TIPS) that circumvented compound decomposition associated with conventional microparticle manufacture. The microparticles provided controlled release of hydrogen peroxide and peracetic acid that led to rapid and sustained killing of multiple drug-resistant organisms (methicillin-resistant Staphylococcus aureus and carbapenem-resistant Escherichia coli) without associated cytotoxicity in vitro nor intracutaneous reactivity in vivo. The results from this study demonstrate for the first time that microparticles loaded with acetyl and peroxygen donors retain their antimicrobial activity whilst eliciting no host toxicity. In doing so, it overcomes the detrimental effects that have prevented oxidative biocides from being used as alternatives to conventional antibiotics. The manuscript explores a novel approach to utilize the antimicrobial activity of oxidative species for sustained killing of multiple drug-resistant organisms without causing collateral tissue damage. The results demonstrate, for the first time, the ability to load pre-cursor compounds into porous polymeric structures that results in their release and conversion into oxidative species in a

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

Germ cell differentiation and proliferation in the developing testis of the South American plains viscacha, Lagostomus maximus (Mammalia, Rodentia).

Science.gov (United States)

Gonzalez, C R; Muscarsel Isla, M L; Fraunhoffer, N A; Leopardo, N P; Vitullo, A D

2012-08-01

Cell proliferation and cell death are essential processes in the physiology of the developing testis that strongly influence the normal adult spermatogenesis. We analysed in this study the morphometry, the expression of the proliferation cell nuclear antigen (PCNA), cell pluripotency marker OCT-4, germ cell marker VASA and apoptosis in the developing testes of Lagostomus maximus, a rodent in which female germ line develops through abolished apoptosis and unrestricted proliferation. Morphometry revealed an increment in the size of the seminiferous cords with increasing developmental age, arising from a significant increase of PCNA-positive germ cells and a stable proportion of PCNA-positive Sertoli cells. VASA showed a widespread cytoplasmic distribution in a great proportion of proliferating gonocytes that increased significantly at late development. In the somatic compartment, Leydig cells increased at mid-development, whereas peritubular cells showed a stable rate of proliferation. In contrast to other mammals, OCT-4 positive gonocytes increased throughout development reaching 90% of germ cells in late-developing testis, associated with a conspicuous increase in circulating FSH from mid- to late-gestation. TUNEL analysis was remarkable negative, and only a few positive cells were detected in the somatic compartment. These results show that the South American plains viscacha displays a distinctive pattern of testis development characterized by a sustained proliferation of germ cells throughout development, with no signs of apoptosis cell demise, in a peculiar endocrine in utero ambiance that seems to promote the increase of spermatogonial number as a primary direct effect of FSH.

Lung adenocarcinoma originates from retrovirus infection of proliferating type 2 pneumocytes during pulmonary post-natal development or tissue repair.

Science.gov (United States)

Murgia, Claudio; Caporale, Marco; Ceesay, Ousman; Di Francesco, Gabriella; Ferri, Nicola; Varasano, Vincenzo; de las Heras, Marcelo; Palmarini, Massimo

2011-03-01

Jaagsiekte sheep retrovirus (JSRV) is a unique oncogenic virus with distinctive biological properties. JSRV is the only virus causing a naturally occurring lung cancer (ovine pulmonary adenocarcinoma, OPA) and possessing a major structural protein that functions as a dominant oncoprotein. Lung cancer is the major cause of death among cancer patients. OPA can be an extremely useful animal model in order to identify the cells originating lung adenocarcinoma and to study the early events of pulmonary carcinogenesis. In this study, we demonstrated that lung adenocarcinoma in sheep originates from infection and transformation of proliferating type 2 pneumocytes (termed here lung alveolar proliferating cells, LAPCs). We excluded that OPA originates from a bronchioalveolar stem cell, or from mature post-mitotic type 2 pneumocytes or from either proliferating or non-proliferating Clara cells. We show that young animals possess abundant LAPCs and are highly susceptible to JSRV infection and transformation. On the contrary, healthy adult sheep, which are normally resistant to experimental OPA induction, exhibit a relatively low number of LAPCs and are resistant to JSRV infection of the respiratory epithelium. Importantly, induction of lung injury increased dramatically the number of LAPCs in adult sheep and rendered these animals fully susceptible to JSRV infection and transformation. Furthermore, we show that JSRV preferentially infects actively dividing cell in vitro. Overall, our study provides unique insights into pulmonary biology and carcinogenesis and suggests that JSRV and its host have reached an evolutionary equilibrium in which productive infection (and transformation) can occur only in cells that are scarce for most of the lifespan of the sheep. Our data also indicate that, at least in this model, inflammation can predispose to retroviral infection and cancer.

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

A UV-resistant mutant without an increased repair synthesis activity, established from a UV-sensitive human clonal cell line

International Nuclear Information System (INIS)

Suzuki, N.

1984-01-01

When cells of a human clonal cell line, RSa, with high sensitivity to UV lethality, were treated with the mutagen, ethyl methanesulfonate, a variant cell strain, UVr-1, was established as a mutant resistant to 254-nm far-ultraviolet radiation (UV). Cell proliferation studies showed that UVr-1 cells survived and actively proliferated at doses of UV-irradiation that greatly suppressed the proliferation of RSa cells. Colony-formation assays also confirmed the increased resistance of UVr-1 cells to UV. The recovery from a UV-induced inhibition in DNA synthesis, as [methyl- 3 H]thymidine uptake into cellular DNA, was more pronounced in UVr-1 cells than in RSa cells. Nevertheless, there was no significant difference in the activity of UV-induced DNA repair synthesis in either cell line, as estimated by the extent of unscheduled DNA synthesis and DNA repair replication. These characteristics of UVr-1 cells are discussed in the light of a previously reported UV-resistant variant, UVr-10, which had an increased DNA repair synthesis activity. (Auth.)

Functional ablation of pRb activates Cdk2 and causes antiestrogen resistance in human breast cancer cells.

Directory of Open Access Journals (Sweden)

Hemant Varma

2007-12-01

Full Text Available Estrogens are required for the proliferation of hormone dependent breast cancer cells, making estrogen receptor (ER positive tumors amenable to endocrine therapies such as antiestrogens. However, resistance to these agents remains a significant cause of treatment failure. We previously demonstrated that inactivation of the retinoblastoma protein (pRb family tumor suppressors causes antiestrogen resistance in MCF-7 cells, a widely studied model of estrogen responsive human breast cancers. In this study, we investigate the mechanism by which pRb inactivation leads to antiestrogen resistance. Cdk4 and cdk2 are two key cell cycle regulators that can phosphorylate and inactivate pRb, therefore we tested whether these kinases are required in cells lacking pRb function. pRb family members were inactivated in MCF-7 cells by expressing polyomavirus large tumor antigen (PyLT, and cdk activity was inhibited using the cdk inhibitors p16(INK4A and p21(Waf1/Cip1. Cdk4 activity was no longer required in cells lacking functional pRb, while cdk2 activity was required for proliferation in both the presence and absence of pRb function. Using inducible PyLT cell lines, we further demonstrated that pRb inactivation leads to increased cyclin A expression, cdk2 activation and proliferation in antiestrogen arrested cells. These results demonstrate that antiestrogens do not inhibit cdk2 activity or proliferation of MCF-7 cells in the absence of pRb family function, and suggest that antiestrogen resistant breast cancer cells resulting from pRb pathway inactivation would be susceptible to therapies that target cdk2.

Liver-derived systemic factors drive β-cell hyperplasia in insulin resistant states

Energy Technology Data Exchange (ETDEWEB)

El Ouaamari, Abdelfattah; Kawamori, Dan; Dirice, Ercument; Liew, Chong Wee; Shadrach, Jennifer L.; Hu, Jiang; Katsuta, Hitoshi; Hollister-Lock, Jennifer; Qian, Weijun; Wagers, Amy J.; Kulkarni, Rohit N.

2013-02-21

Integrative organ cross-talk regulates key aspects of energy homeostasis and its dysregulation may underlie metabolic disorders such as obesity and diabetes. To test the hypothesis that cross-talk between the liver and pancreatic islets modulates β-cell growth in response to insulin resistance, we used the Liver-specific Insulin Receptor Knockout (LIRKO) mouse, a unique model that exhibits dramatic islet hyperplasia. Using complementary in vivo parabiosis and transplantation assays, and in vitro islet culture approaches, we demonstrate that humoral, non-neural, non-cell autonomous factor(s) induce β-cell proliferation in LIRKO mice. Furthermore, we report that a hepatocyte-derived factor(s) stimulates mouse and human β-cell proliferation in ex vivo assays, independent of ambient glucose and insulin levels. These data implicate the liver as a critical source of β-cell growth factors in insulin resistant states.

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

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

Alpinetin inhibits lung cancer progression and elevates sensitization drug-resistant lung cancer cells to cis-diammined dichloridoplatium

Directory of Open Access Journals (Sweden)

Wu L

2015-11-01

Full Text Available Lin Wu, Wei Yang, Su-ning Zhang, Ji-bin Lu Department of Thoracic Surgery, Sheng Jing Hospital of China Medical University, Shenyang, People’s Republic of China Objective: Alpinetin is a novel flavonoid that has demonstrated potent antitumor activity in previous studies. However, the efficacy and mechanism of alpinetin in treating lung cancer have not been determined. Methods: We evaluated the impact of different doses and durations of alpinetin treatment on the cell proliferation, the apoptosis of lung cancer cells, as well as the drug-resistant lung cancer cells. Results: This study showed that the alpinetin inhibited the cell proliferation, enhanced the apoptosis, and inhibited the PI3K/Akt signaling in lung cancer cells. Moreover, alpinetin significantly increased the sensitivity of drug-resistant lung cancer cells to the chemotherapeutic effect of cis-diammined dichloridoplatium. Taken together, this study demonstrated that alpinetin significantly suppressed the development of human lung cancer possibly by influencing mitochondria and the PI3K/Akt signaling pathway and sensitized drug-resistant lung cancer cells. Conclusion: Alpinetin may be used as a potential compound for combinatorial therapy or as a complement to other chemotherapeutic agents when multiple lines of treatments have failed to reduce lung cancer. Keywords: alpinetin, cell proliferation and apoptosis, drug resistance reversal, PI3K/Akt, lung cancer

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...

Simulation study of self-sustainment mechanism in reversed-field pinch configuration

International Nuclear Information System (INIS)

Kusano, Kanya; Sato, Tetsuya.

1989-09-01

3D magnetohydrodynamic (MHD) simulations are carried out in order to reveal the fundamental mechanism of the self-sustainment process in the reversed-field pinch plasma. It is confirmed that the RFP configuration is sustained in a cyclic process, where the MHD relaxation phase and the resistive diffusion phase appear cyclically and alternatively. In the MHD relaxation process, the RFP plasma approaches a Taylor's minimum energy state, but it departs from there in the diffusion process. In other words, since MHD relaxation processes periodically release excess magnetic energy accumulated in the resistive diffusion phase, RFP plasma can stay in the neighborhood of the minimum energy state. The mechanism of this cyclic process is disclosed. Namely, when at least two ideal kink (m = 1) modes becomes unstable, MHD relaxation can take place. This is because the MHD relaxation progresses through nonlinear reconnection of the m = 0 mode, which is driven by nonlinear coupling between the unstable kink modes. Therefore, self-sustainment processes can be achieved by the nonlinear effects of essentially the m = 0 and 1 modes. The quantitative dependence of the relaxation-diffusion cycle on the aspect ratio of the device is considered along with its dependence on the magnetic Reynolds, number. These results are consistent with recent experiments and indicate that a coherent oscillation, which is often observed in experiments, is necessary for self-sustainment. The influence of self-sustainment processes on particle confinement is briefly discussed. (author)

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

Nicotine induces cell proliferation in association with cyclin D1 up-regulation and inhibits cell differentiation in association with p53 regulation in a murine pre-osteoblastic cell line

International Nuclear Information System (INIS)

Sato, Tsuyoshi; Abe, Takahiro; Nakamoto, Norimichi; Tomaru, Yasuhisa; Koshikiya, Noboru; Nojima, Junya; Kokabu, Shoichiro; Sakata, Yasuaki; Kobayashi, Akio; Yoda, Tetsuya

2008-01-01

Recent studies have suggested that nicotine critically affects bone metabolism. Many studies have examined the effects of nicotine on proliferation and differentiation, but the underlying molecular mechanisms remain unclear. We examined cell cycle regulators involved in the proliferation and differentiation of MC3T3-E1 cells. Nicotine induced cell proliferation in association with p53 down-regulation and cyclin D1 up-regulation. In differentiated cells, nicotine reduced alkaline phosphatase activity and mineralized nodule formation in dose-dependent manners. Furthermore, p53 expression was sustained in nicotine-treated cells during differentiation. These findings indicate that nicotine promotes the cell cycle and inhibits differentiation in association with p53 regulation in pre-osteoblastic cells

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

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.)

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

Dual effect of LPS on murine myeloid leukemia cells: Pro-proliferation and anti-proliferation

International Nuclear Information System (INIS)

Yu, Lingling; Zhao, Yingmin; Gu, Xin; Wang, Jijun; Pang, Lei; Zhang, Yanqing; Li, Yaoyao; Jia, Xiaoqin; Wang, Xin; Gu, Jian; Yu, Duonan

2016-01-01

Modification of the bone marrow microenvironment is considered as a promising strategy to control leukemic cell proliferation, diseases progression and relapse after treatment. However, due to the diversity and complexity of the cellular and molecular compartments in the leukemic microenvironment, it is extremely difficult to dissect the role of each individual molecule or cell type in vivo. Here we established an in vitro system to dissect the role of lipopolysaccharide (LPS), stromal cells and endothelial cells in the growth of mouse myeloid tumor cells and B-lymphoma cells. We found that either LPS or bone marrow stromal cells as a feeder layer in culture is required for the proliferation of myeloid tumor cells. Surprisingly, the growth of myeloid leukemic cells on stromal cells is strongly inhibited when coupled with LPS in culture. This opposing effect of LPS, a complete switch from pro-proliferation to antitumor growth is due, at least in part, to the rapidly increased production of interleukin 12, Fas ligand and tissue inhibitor of metalloproteinases-2 from stromal cells stimulated by LPS. These results demonstrate that LPS can either facilitate or attenuate tumor cell proliferation, thus changing the disease course of myeloid leukemias through its direct effect or modulation of the tumor microenvironment. - Highlights: • LPS alone in culture is required for the proliferation of murine myeloid tumor cells. • Bone marrow stromal cells as a feeder layer is also required for the proliferation of myeloid tumor cells. • However, the growth of myeloid tumor cells is inhibited when LPS and stromal cells are both available in culture. • Thus LPS can either facilitate or attenuate tumor growth through its direct effect or modulation of tumor microenvironment.

Dual effect of LPS on murine myeloid leukemia cells: Pro-proliferation and anti-proliferation

Energy Technology Data Exchange (ETDEWEB)

Yu, Lingling [Department of Pediatrics, Jingjiang People' s Hospital, Yangzhou University, Jingjiang 214500 (China); Noncoding RNA Center, Yangzhou University, Yangzhou 225001 (China); Zhao, Yingmin [Department of Pediatrics, Jingjiang People' s Hospital, Yangzhou University, Jingjiang 214500 (China); Gu, Xin; Wang, Jijun; Pang, Lei; Zhang, Yanqing; Li, Yaoyao; Jia, Xiaoqin; Wang, Xin [Noncoding RNA Center, Yangzhou University, Yangzhou 225001 (China); Gu, Jian [Department of Hematology, Yangzhou University School of Clinical Medicine, Yangzhou 225001 (China); Yu, Duonan, E-mail: duonan@yahoo.com [Department of Pediatrics, Jingjiang People' s Hospital, Yangzhou University, Jingjiang 214500 (China); Noncoding RNA Center, Yangzhou University, Yangzhou 225001 (China); Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Disease, Yangzhou 225001 (China); Institute of Comparative Medicine, Yangzhou University, Yangzhou 225001 (China); Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonosis, Yangzhou 225001 (China)

2016-06-10

Modification of the bone marrow microenvironment is considered as a promising strategy to control leukemic cell proliferation, diseases progression and relapse after treatment. However, due to the diversity and complexity of the cellular and molecular compartments in the leukemic microenvironment, it is extremely difficult to dissect the role of each individual molecule or cell type in vivo. Here we established an in vitro system to dissect the role of lipopolysaccharide (LPS), stromal cells and endothelial cells in the growth of mouse myeloid tumor cells and B-lymphoma cells. We found that either LPS or bone marrow stromal cells as a feeder layer in culture is required for the proliferation of myeloid tumor cells. Surprisingly, the growth of myeloid leukemic cells on stromal cells is strongly inhibited when coupled with LPS in culture. This opposing effect of LPS, a complete switch from pro-proliferation to antitumor growth is due, at least in part, to the rapidly increased production of interleukin 12, Fas ligand and tissue inhibitor of metalloproteinases-2 from stromal cells stimulated by LPS. These results demonstrate that LPS can either facilitate or attenuate tumor cell proliferation, thus changing the disease course of myeloid leukemias through its direct effect or modulation of the tumor microenvironment. - Highlights: • LPS alone in culture is required for the proliferation of murine myeloid tumor cells. • Bone marrow stromal cells as a feeder layer is also required for the proliferation of myeloid tumor cells. • However, the growth of myeloid tumor cells is inhibited when LPS and stromal cells are both available in culture. • Thus LPS can either facilitate or attenuate tumor growth through its direct effect or modulation of tumor microenvironment.