Using proliferation risk as a design metric in the development of nuclear systems

International Nuclear Information System (INIS)

Beard, C.; Lebouf, R.

2001-01-01

The necessity has arisen for newly proposed nuclear systems to be evaluated with regard to their potential aid to any proliferation. Thus, a mechanism is needed to introduce nonproliferation as a measure in the design phase of a new nuclear system. To accomplish this, a methodology for quantifying and measuring the proliferation risk of proposed system options is required. Such quantification has its difficulties due to inherent uncertainty, e.g. what is the probability that a quantity of material will be stolen in a given situation? Also, the lack of data on such occurrences makes the task of quantification nearly insurmountable. A systematic approach is necessary to estimate the proliferation risk. Currently, an advanced nuclear power system, the Accelerator Transmutation of Waste (ATW) program has been initiated to develop a system that will concurrently generate electricity while destroying long-lived radioactive isotopes. Therefore, because of the issues noted above, an effort to introduce proliferation risk into the design phase has been started. The purpose of this paper is to review previous work in quantification of proliferation risk in an effort to develop the proper basis for the current work. It should be noted that while proliferation on a national level has been studied extensively, efforts to quantify proliferation risk of individual nuclear systems or processes have been limited. Consequently, the available literature base is relatively sparse. (author)

Using proliferation risk as a design metric in the development of nuclear systems

Energy Technology Data Exchange (ETDEWEB)

Beard, C.; Lebouf, R. [Texas Univ., Austin, TX (United States). Nuclear Engineering Teaching Lab.

2001-07-01

The necessity has arisen for newly proposed nuclear systems to be evaluated with regard to their potential aid to any proliferation. Thus, a mechanism is needed to introduce nonproliferation as a measure in the design phase of a new nuclear system. To accomplish this, a methodology for quantifying and measuring the proliferation risk of proposed system options is required. Such quantification has its difficulties due to inherent uncertainty, e.g. what is the probability that a quantity of material will be stolen in a given situation? Also, the lack of data on such occurrences makes the task of quantification nearly insurmountable. A systematic approach is necessary to estimate the proliferation risk. Currently, an advanced nuclear power system, the Accelerator Transmutation of Waste (ATW) program has been initiated to develop a system that will concurrently generate electricity while destroying long-lived radioactive isotopes. Therefore, because of the issues noted above, an effort to introduce proliferation risk into the design phase has been started. The purpose of this paper is to review previous work in quantification of proliferation risk in an effort to develop the proper basis for the current work. It should be noted that while proliferation on a national level has been studied extensively, efforts to quantify proliferation risk of individual nuclear systems or processes have been limited. Consequently, the available literature base is relatively sparse. (author)

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.

North-East Asia: a risk of nuclear proliferation; Un risque de proliferation nucleaire en Asie du Nord-Est?

Energy Technology Data Exchange (ETDEWEB)

Courmont, B. [Centre d' Etudes Transatlantiques, 75 - Paris (France)

2009-04-15

North-East Asia is distinguished by being potentially one of the world's most nuclearised regions. It includes two nuclear powers recognised by the Non-Proliferation Treaty (Russia and China), a proliferating state (North Korea) and three countries that could very quickly complete nuclear programmes (Japan, South Korea and Taiwan). Now that the question of nuclear proliferation has again surfaced on the international strategic scene, and that North Korea's test of October 2006 has introduced a new security paradigm into the region, how real is the risk of nuclear proliferation in North-East Asia? (author)

Proliferation Risks of Fusion Energy: Clandestine Production, Covert Production, and Breakout

International Nuclear Information System (INIS)

Goldston, R.J.; Glaser, A.; Ross, A.F.

2009-01-01

Nuclear proliferation risks from fusion associated with access to weapon-usable material can be divided into three main categories: (1) clandestine production of fissile material in an undeclared facility, (2) covert production of such material in a declared and safeguarded facility, and (3) use of a declared facility in a breakout scenario, in which a state begins production of fissile material without concealing the effort. In this paper we address each of these categories of risk from fusion. For each case, we find that the proliferation risk from fusion systems can be much lower than the equivalent risk from fission systems, if commercial fusion systems are designed to accommodate appropriate safeguards

IPSN and the mastery of proliferation risks; L'IPSN et la maitrise des risques de proliferation

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-04-14

Since 20 years, the French Institute of Nuclear Protection and Safety (IPSN) works for the reinforcement of the efficiency of the actions against nuclear proliferation. This dossier takes stock of the means and action developed by the IPSN in this domain: nuclear and chemical proliferation: towards a reinforced mastery of risks (status of proliferation during the last 10 years, the aim of the international and national controls, the role of IPSN); nuclear proliferation: the technical control means of the IPSN (inspection, containment/surveillance of nuclear materials (PLUM and FUNE apparatuses), the cooperation between the IPSN and the Kurchatov institute (Russia)); the action of the IPSN in the application of international controls: example of chemistry (conventions, negotiations and expertise, inspections); appendixes: nuclear materials (declaration and permission thresholds), the different steps of the nuclear weapons non-proliferation policy. (J.S.)

Risk assessment of alternative proliferation routes

International Nuclear Information System (INIS)

Ahmed, S.; Husseiny, A.A.

1982-01-01

Multi-Attribute Decision Theory is applied to rank II alternative routes to nuclear proliferation in order of difficulty in acquiring nuclear weapons by nonnuclear countries. The method is based on reducing the various variables affecting the decision to a single function providing a measure for the proliferation route. The results indicate that the most difficult route to obtain atomic weapons is through nuclear power reactors, specifically the liquid-metal fast breeder reactor, heavy water Canada deuterium uranium reactor, and light water reactors such as boiling water and pressurized water reactors. The easiest routes are supercritical centrifuge isotope separation, laser isotope separation, and research reactor. However, nonnuclear routes available that result in substantial damage to life and property are easier than any nuclear route

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

Does interdependence alleviate proliferation risks in Asia?

International Nuclear Information System (INIS)

Yoshida, Osamu

1997-01-01

As the extension Conference of the Non-Proliferation Treaty ended with its unlimited extension without any modification of the treaty obligation of the nuclear-weapon states to nuclear disarmament, the prospect of the regime to incorporate those suspected nuclear powers in Asia, namely India, Pakistan and Israel, has become dark. In this paper the problem of proliferation risk centred in India is analysed. It is well known that India was the first to criticize the Non-Proliferation Treaty regime as highly discriminating between the five nuclear haves and the rest. As was always the case, India's point is logically persuasive and consistent. However, it is also true that the logical or legal point of view does not always solve the problem. Therefore, we look at the regional and international political constellation in which any assertion has to be constructed. At present there is very little possibility that this region will become nuclear-free. This is because the horizontal proliferation, that has seemingly taken place here, is the result of a 'nuclear chain reaction', starting with a minor nuclear-weapon state, China. However, the economic upsurge in the region now throws the nuclear chain-reactions into the background. It has come to a standstill and the future of nuclear proliferation here will have to be decided by global nuclear disarmament, as there is no motivation on the side of the two Asian giants to agree on the reduction in their nuclear arsenals, though under American pressure, another suspected nuclear power, Pakistan, may have to give up its nuclear development plan

Perspectives and benefits of the non-proliferating fuel cycle

International Nuclear Information System (INIS)

Parker, F.

2012-01-01

The world community has faced the issues of nuclear non-proliferation for decades. Frank Parker, Emeritus Distinguished Professor at Vanderbilt University, has proposed a non-proliferating fuel cycle, which greatly reduces the risk of use of nuclear materials for military purpose. A simplified fuel cycle with reduced opportunities for proliferation of nuclear weapons and permanent disposal of radioactive wastes as well as a reference sub-seabed HLW disposal system are described [ru

Evaluating the Cost, Safety, and Proliferation Risks of Small Floating Nuclear Reactors.

Science.gov (United States)

Ford, Michael J; Abdulla, Ahmed; Morgan, M Granger

2017-11-01

It is hard to see how our energy system can be decarbonized if the world abandons nuclear power, but equally hard to introduce the technology in nonnuclear energy states. This is especially true in countries with limited technical, institutional, and regulatory capabilities, where safety and proliferation concerns are acute. Given the need to achieve serious emissions mitigation by mid-century, and the multidecadal effort required to develop robust nuclear governance institutions, we must look to other models that might facilitate nuclear plant deployment while mitigating the technology's risks. One such deployment paradigm is the build-own-operate-return model. Because returning small land-based reactors containing spent fuel is infeasible, we evaluate the cost, safety, and proliferation risks of a system in which small modular reactors are manufactured in a factory, and then deployed to a customer nation on a floating platform. This floating small modular reactor would be owned and operated by a single entity and returned unopened to the developed state for refueling. We developed a decision model that allows for a comparison of floating and land-based alternatives considering key International Atomic Energy Agency plant-siting criteria. Abandoning onsite refueling is beneficial, and floating reactors built in a central facility can potentially reduce the risk of cost overruns and the consequences of accidents. However, if the floating platform must be built to military-grade specifications, then the cost would be much higher than a land-based system. The analysis tool presented is flexible, and can assist planners in determining the scope of risks and uncertainty associated with different deployment options. © 2017 Society for Risk Analysis.

Proliferation risks from nuclear power infrastructure

Science.gov (United States)

Squassoni, Sharon

2017-11-01

Certain elements of nuclear energy infrastructure are inherently dual-use, which makes the promotion of nuclear energy fraught with uncertainty. Are current restraints on the materials, equipment, and technology that can be used either to produce fuel for nuclear electricity generation or material for nuclear explosive devices adequate? Technology controls, supply side restrictions, and fuel market assurances have been used to dissuade countries from developing sensitive technologies but the lack of legal restrictions is a continued barrier to permanent reduction of nuclear proliferation risks.

Exercise reduces adipose tissue via cannabinoid receptor type 1 which is regulated by peroxisome proliferator-activated receptor-delta

DEFF Research Database (Denmark)

Yan, Zhen Cheng; Liu, Dao Yan; Zhang, Li Li

2007-01-01

Obesity is one major cardiovascular risk factor. We tested effects of endurance exercise on cannabinoid receptor type 1 (CB1) and peroxisome proliferator-activated receptor-delta (PPAR-delta)-dependent pathways in adipose tissue. Male Wistar rats were randomly assigned to standard laboratory chow...... or a high-fat diet without and with regular endurance exercise. Exercise in rats on high-fat diet significantly reduced visceral fat mass, blood pressure, and adipocyte size (each p...

Approach to proliferation risk assessment based on multiple objective analysis framework

Energy Technology Data Exchange (ETDEWEB)

Andrianov, A.; Kuptsov, I. [Obninsk Institute for Nuclear Power Engineering of NNRU MEPhI (Russian Federation); Studgorodok 1, Obninsk, Kaluga region, 249030 (Russian Federation)

2013-07-01

The approach to the assessment of proliferation risk using the methods of multi-criteria decision making and multi-objective optimization is presented. The approach allows the taking into account of the specifics features of the national nuclear infrastructure, and possible proliferation strategies (motivations, intentions, and capabilities). 3 examples of applying the approach are shown. First, the approach has been used to evaluate the attractiveness of HEU (high enriched uranium)production scenarios at a clandestine enrichment facility using centrifuge enrichment technology. Secondly, the approach has been applied to assess the attractiveness of scenarios for undeclared production of plutonium or HEU by theft of materials circulating in nuclear fuel cycle facilities and thermal reactors. Thirdly, the approach has been used to perform a comparative analysis of the structures of developing nuclear power systems based on different types of nuclear fuel cycles, the analysis being based on indicators of proliferation risk.

Approach to proliferation risk assessment based on multiple objective analysis framework

International Nuclear Information System (INIS)

Andrianov, A.; Kuptsov, I.

2013-01-01

The approach to the assessment of proliferation risk using the methods of multi-criteria decision making and multi-objective optimization is presented. The approach allows the taking into account of the specifics features of the national nuclear infrastructure, and possible proliferation strategies (motivations, intentions, and capabilities). 3 examples of applying the approach are shown. First, the approach has been used to evaluate the attractiveness of HEU (high enriched uranium)production scenarios at a clandestine enrichment facility using centrifuge enrichment technology. Secondly, the approach has been applied to assess the attractiveness of scenarios for undeclared production of plutonium or HEU by theft of materials circulating in nuclear fuel cycle facilities and thermal reactors. Thirdly, the approach has been used to perform a comparative analysis of the structures of developing nuclear power systems based on different types of nuclear fuel cycles, the analysis being based on indicators of proliferation risk

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.

An approach to quantitative assessment of relative proliferation risks from nuclear fuel cycles

International Nuclear Information System (INIS)

Silvennoinen, P.; Vira, J.

1981-01-01

Feasibility of quantitative assessments of the risk of nuclear weapons proliferation is discussed in this paper. The proliferation risk is defined as a combined utility of the different fuel cycle processes or materials for the proscribed acquisition of a nuclear weapon. Based on a set of selected weighted criteria, the process utilities are calculated employing utility functions or fuzzy expectation values. The methods are compared to each other. The scheme appears feasible in relative comparisons while certain leeway must still be retained for political judgement. (author)

Intent, Capability and Opportunity: A Holistic Approach to Addressing Proliferation as a Risk Management Issue

International Nuclear Information System (INIS)

Rynes, Amanda; Bjornard, Trond

2011-01-01

Currently, proliferation risk assessment models are designed to evaluate only a portion of the overall risk, focusing exclusively on either technological or social factors to determine the extent of a threat. Many of these models are intended to act as a means of predicting proliferation potential rather than assessing the system as a whole, ignoring the ability to enhance mitigating factors and manage, rather just establish the presence of, the threat. While the information garnered through these forms of analysis is necessary, it remains incomplete. By incorporating political, social, economic and technical capabilities as well as human factors such as intent into a single, multi-faceted risk management model, proliferation risk can be evaluated more effectively. Framing this information around how to improve and expand the Regime already in place and establishing where there are gaps in the system allows for a more complete approach to risk management, mitigation and resource allocation. The research conducted here seeks to combine all three elements (intent, capability and opportunity) in a comprehensive evaluation which incorporates an assessment of state-level variables, possible proliferation pathways and technical capability. Each portion of the analysis is carried out independently then combined to illustrate the full scope of a State's nuclear infrastructure while showing areas of weakness in the institutional framework.

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

radiation as well as a detection risk to would-be proliferators. However, countries with proliferation ambitions could give the U-mixture to terrorist groups directly after chemical separation, before significant build-up of the radioactive decay chain, which would significantly reduce the proliferation resistance of the mixture. A roadmap for overcoming some of these barriers to market entry is suggested.

Priorities for technology development and policy to reduce the risk from radioactive materials

International Nuclear Information System (INIS)

Duggan, Ruth Ann

2010-01-01

The Standing Committee on International Security of Radioactive and Nuclear Materials in the Nonproliferation and Arms Control Division conducted its fourth annual workshop in February 2010 on Reducing the Risk from Radioactive and Nuclear Materials. This workshop examined new technologies in real-time tracking of radioactive materials, new risks and policy issues in transportation security, the best practices and challenges found in addressing illicit radioactive materials trafficking, industry leadership in reducing proliferation risk, and verification of the Nuclear Nonproliferation Treaty, Article VI. Technology gaps, policy gaps, and prioritization for addressing the identified gaps were discussed. Participants included academia, policy makers, radioactive materials users, physical security and safeguards specialists, and vendors of radioactive sources and transportation services. This paper summarizes the results of this workshop with the recommendations and calls to action for the Institute of Nuclear Materials Management (INMM) membership community.

The Power of Integrators, Financiers, and Insurers to Reduce Proliferation Risks: Nuclear Dual-Use Goods

Energy Technology Data Exchange (ETDEWEB)

Weise, Rachel A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hund, Gretchen [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2015-05-01

Globalization of manufacturing supply chains has changed the nature of nuclear proliferation. Before 1991, nonproliferation efforts focused almost exclusively on limiting the spread of materials and equipment specifically designed for nuclear use -- reactors, centrifuges, and fissile material. Dual-use items, those items with both nuclear and non-nuclear applications, were not closely scrutinized or controlled. However, in 1991 the international community discovered that Iraq had developed a fairly sophisticated nuclear weapons program by importing dual-use items; this discovery spurred the international community to increase controls on dual-use technologies. Despite these international efforts, dual-use items are still a challenge for those seeking to limit proliferation.

The Power of Integrators, Financiers, and Insurers to Reduce Proliferation Risks: Nuclear Dual-Use Goods

International Nuclear Information System (INIS)

Weise, Rachel A.; Hund, Gretchen

2015-01-01

Globalization of manufacturing supply chains has changed the nature of nuclear proliferation. Before 1991, nonproliferation efforts focused almost exclusively on limiting the spread of materials and equipment specifically designed for nuclear use -- reactors, centrifuges, and fissile material. Dual-use items, those items with both nuclear and non-nuclear applications, were not closely scrutinized or controlled. However, in 1991 the international community discovered that Iraq had developed a fairly sophisticated nuclear weapons program by importing dual-use items; this discovery spurred the international community to increase controls on dual-use technologies. Despite these international efforts, dual-use items are still a challenge for those seeking to limit proliferation.

Intent, Capability and Opportunity: A Holistic Approach to Addressing Proliferation as a Risk Management Issue

Energy Technology Data Exchange (ETDEWEB)

Amanda Rynes; Trond Bjornard

2011-07-01

Currently, proliferation risk assessment models are designed to evaluate only a portion of the overall risk, focusing exclusively on either technological or social factors to determine the extent of a threat. Many of these models are intended to act as a means of predicting proliferation potential rather than assessing the system as a whole, ignoring the ability to enhance mitigating factors and manage, rather just establish the presence of, the threat. While the information garnered through these forms of analysis is necessary, it remains incomplete. By incorporating political, social, economic and technical capabilities as well as human factors such as intent into a single, multi-faceted risk management model, proliferation risk can be evaluated more effectively. Framing this information around how to improve and expand the Regime already in place and establishing where there are gaps in the system allows for a more complete approach to risk management, mitigation and resource allocation. The research conducted here seeks to combine all three elements (intent, capability and opportunity) in a comprehensive evaluation which incorporates an assessment of state-level variables, possible proliferation pathways and technical capability. Each portion of the analysis is carried out independently then combined to illustrate the full scope of a State's nuclear infrastructure while showing areas of weakness in the institutional framework.

Exports and experts:proliferation risks from the new Commonwealth

International Nuclear Information System (INIS)

Potter, W.C.

1992-01-01

Ironically, given the Cold War history and Western stereotypes about Soviet misbehavior, the long-standing experience of US-Soviet cooperation on nonproliferation may have made US policy-makers less attentive to, and less concerned about, signs of change in Soviet nuclear export policy. The breakup of the Soviet Union and the nuclear inheritance of its successor states belatedly focused Western attention on the proliferation risks posed by the disintegration of central authority. Most concern to date, however, has continued to emphasize the problems of nuclear command and control. But the nonproliferation threats associated with the unregulated export of sensitive nuclear material, technology, and equipment may be equally great, and present problems that are already real. At the same time, the new nation-building process in the Soviet successor states presents opportunities for expanding the NPT and international safeguards, containing the nuclear brain drain, promoting the cleanup of hazardous nuclear waste, enhancing international capabilities for monitoring proliferation, and building new communities of nonproliferation specialists. A rare occasion now exists for Western policy-makers to have a direct impact on the long-term nuclear export and non-proliferation behavior of the successor states to the Soviet Union. The speed and seriousness with which the West undertakes this task will largely determine how much ground, if any, will be lost from its decades-long effort to stop the proliferation of nuclear weapons

Assessing the optimism-pessimism debate: Nuclear proliferation, nuclear risks, and theories of state action

International Nuclear Information System (INIS)

Busch, Nathan Edward

2001-01-01

This dissertation focuses on the current debate in international relations literature over the risks associated with the proliferation of nuclear weapons. On this subject, IR scholars are divided into roughly two schools: proliferation 'optimists,' who argue that proliferation can be beneficial and that its associated hazards are at least surmountable, and proliferation 'pessimists,' who believe the opposite. This debate centers upon a theoretical disagreement about how best to explain and predict the behavior of states. Optimists generally ground their arguments on rational deterrence theory and maintain that nuclear weapons can actually increase stability among states, while pessimists often ground their arguments on 'organization theory,' which contends that organizational, bureaucratic, and other factors prevent states from acting rationally. A major difficulty with the proliferation debate, however, is that both sides tend to advance their respective theoretical positions without adequately supporting them with solid empirical evidence. This dissertation detailed analyses of the nuclear programs in the United States, Russia, China, India, and Pakistan to determine whether countries with nuclear weapons have adequate controls over their nuclear arsenals and tissue material stockpiles (such as highly enriched uranium and plutonium). These case studies identify the strengths and weaknesses of different systems of nuclear controls and help predict what types of controls proliferating states are likely to employ. On the basis of the evidence gathered from these cases, this dissertation concludes that a further spread of nuclear weapons would tend to have seriously negative effects on international stability by increasing risks of accidental, unauthorized, or inadvertent use of nuclear weapons and risks of thefts of fissile materials for use in nuclear or radiological devices by aspiring nuclear states or terrorist groups. (author)

Cellular Proliferation by Multiplex Immunohistochemistry Identifies High-Risk Multiple Myeloma in Newly Diagnosed, Treatment-Naive Patients.

Science.gov (United States)

Ely, Scott; Forsberg, Peter; Ouansafi, Ihsane; Rossi, Adriana; Modin, Alvin; Pearse, Roger; Pekle, Karen; Perry, Arthur; Coleman, Morton; Jayabalan, David; Di Liberto, Maurizio; Chen-Kiang, Selina; Niesvizky, Ruben; Mark, Tomer M

2017-12-01

Therapeutic options for multiple myeloma (MM) are growing, yet clinical outcomes remain heterogeneous. Cytogenetic analysis and disease staging are mainstays of risk stratification, but data suggest a complex interplay between numerous abnormalities. Myeloma cell proliferation is a metric shown to predict outcomes, but available methods are not feasible in clinical practice. Multiplex immunohistochemistry (mIHC), using multiple immunostains simultaneously, is universally available for clinical use. We tested mIHC as a method to calculate a plasma cell proliferation index (PCPI). By mIHC, marrow trephine core biopsy samples were costained for CD138, a plasma cell-specific marker, and Ki-67. Myeloma cells (CD138 + ) were counted as proliferating if coexpressing Ki-67. Retrospective analysis was performed on 151 newly diagnosed, treatment-naive patients divided into 2 groups on the basis of myeloma cell proliferation: low (PCPI ≤ 5%, n = 87), and high (PCPI > 5%, n = 64). Median overall survival (OS) was not reached versus 78.9 months (P = .0434) for the low versus high PCPI groups. Multivariate analysis showed that only high-risk cytogenetics (hazard ratio [HR] = 2.02; P = .023), International Staging System (ISS) stage > I (HR = 2.30; P = .014), and PCPI > 5% (HR = 1.70; P = .041) had independent effects on OS. Twenty-three (36%) of the 64 patients with low-risk disease (ISS stage 1, without high-risk cytogenetics) were uniquely reidentified as high risk by PCPI. PCPI is a practical method that predicts OS in newly diagnosed myeloma and facilitates broader use of MM cell proliferation for risk stratification. Copyright © 2017 Elsevier Inc. All rights reserved.

Interferon-γ Reduces the Proliferation of Primed Human Renal Tubular Cells

Directory of Open Access Journals (Sweden)

Omar García-Sánchez

2014-01-01

Full Text Available Background/Aims: Chronic kidney disease (CKD is a progressive deterioration of the kidney function, which may eventually lead to renal failure and the need for dialysis or kidney transplant. Whether initiated in the glomeruli or the tubuli, CKD is characterized by progressive nephron loss, for which the process of tubular deletion is of key importance. Tubular deletion results from tubular epithelial cell death and defective repair, leading to scarring of the renal parenchyma. Several cytokines and signaling pathways, including transforming growth factor-β (TGF-β and the Fas pathway, have been shown to participate in vivo in tubular cell death. However, there is some controversy about their mode of action, since a direct effect on normal tubular cells has not been demonstrated. We hypothesized that epithelial cells would require specific priming to become sensitive to TGF-β or Fas stimulation and that this priming would be brought about by specific mediators found in the pathological scenario. Methods: Herein we studied whether the combined effect of several stimuli known to take part in CKD progression, namely TGF-β, tumor necrosis factor-α, interferon-γ (IFN-γ, and Fas stimulation, on primed resistant human tubular cells caused cell death or reduced proliferation. Results: We demonstrate that these cytokines have no synergistic effect on the proliferation or viability of human kidney (HK2 cells. We also demonstrate that IFN-γ, but not the other stimuli, reduces the proliferation of cycloheximide-primed HK2 cells without affecting their viability. Conclusion: Our results point at a potentially important role of IFN-γ in defective repair, leading to nephron loss during CKD.

A perspective on the proliferation risks of plutonium mines

Energy Technology Data Exchange (ETDEWEB)

Lyman, E.S. [Nuclear Control Institute, Washington, DC (United States)

1996-05-01

The program of geologic disposal of spent fuel and other plutonium-containing materials is increasingly becoming the target of criticism by individuals who argue that in the future, repositories may become low-cost sources of fissile material for nuclear weapons. This paper attempts to outline a consistent framework for analyzing the proliferation risks of these so-called {open_quotes}plutonium mines{close_quotes} and putting them into perspective. First, it is emphasized that the attractiveness of plutonium in a repository as a source of weapons material depends on its accessibility relative to other sources of fissile material. Then, the notion of a {open_quotes}material production standard{close_quotes} (MPS) is proposed: namely, that the proliferation risks posed by geologic disposal will be acceptable if one can demonstrate, under a number of reasonable scenarios, that the recovery of plutonium from a repository is likely to be as difficult as new production of fissile material. A preliminary analysis suggests that the range of circumstances under which current mined repository concepts would fail to meet this standard is fairly narrow. Nevertheless, a broad application of the MPS may impose severe restrictions on repository design. In this context, the relationship of repository design parameters to easy of recovery is discussed.

A perspective on the proliferation risks of plutonium mines

International Nuclear Information System (INIS)

Lyman, E.S.

1996-01-01

The program of geologic disposal of spent fuel and other plutonium-containing materials is increasingly becoming the target of criticism by individuals who argue that in the future, repositories may become low-cost sources of fissile material for nuclear weapons. This paper attempts to outline a consistent framework for analyzing the proliferation risks of these so-called open-quotes plutonium minesclose quotes and putting them into perspective. First, it is emphasized that the attractiveness of plutonium in a repository as a source of weapons material depends on its accessibility relative to other sources of fissile material. Then, the notion of a open-quotes material production standardclose quotes (MPS) is proposed: namely, that the proliferation risks posed by geologic disposal will be acceptable if one can demonstrate, under a number of reasonable scenarios, that the recovery of plutonium from a repository is likely to be as difficult as new production of fissile material. A preliminary analysis suggests that the range of circumstances under which current mined repository concepts would fail to meet this standard is fairly narrow. Nevertheless, a broad application of the MPS may impose severe restrictions on repository design. In this context, the relationship of repository design parameters to easy of recovery is discussed

Central fuel banking to reduce the number of proliferation sensitive enrichment activities

International Nuclear Information System (INIS)

Cserhati, A.

2008-01-01

Central fuel banking is a complex international political, economic and technical concept that aims to reduce uncontrolled spreading of uranium enrichment technology in the world in order to prevent proliferation of nuclear weapons. This paper first gives an outline of the notions: 'non-proliferation', the 'front-end' of the fuel cycle, the scope of fuel baking, nuclear fuel and the 60 years of enrichment technology. Enrichment technology is highly concentrated in the nuclear weapon states and other developed countries, but this is not exclusive any more. The technology is spreading. The global demand for enrichment services - parallel to massive nuclear investments in the civil sector and the ageing of older facilities - is constantly growing. Proliferation sensitivity calls for an effective and comprehensive non-proliferation regime. The solution may be multilateralizing the nuclear fuel cycle. After a historical overview, the proposals on multilateral nuclear approaches are presented. The assessment of the proposals is complex in the dimensions of: the non-proliferation aim, the assurance of supply aspect and other variables such as legal issues and non-nuclear inducements. A general evaluation and the recommendations of the Expert Panel of the IAEA are introduced outlining a plan on a middle- and long-term basis. The conclusion of the paper stresses the importance and challenge in finding the 'new balance' between obligations and interests of the members of the global community stating that the answers will have a significant impact on the nuclear indus- try, world wide economics and security policy. (orig.)

Lymphocyte Redox Imbalance and Reduced Proliferation after a Single Session of High Intensity Interval Exercise.

Science.gov (United States)

Tossige-Gomes, Rosalina; Costa, Karine Beatriz; Ottone, Vinícius de Oliveira; Magalhães, Flávio de Castro; Amorim, Fabiano Trigueiro; Rocha-Vieira, Etel

2016-01-01

This study investigated whether an acute session of high-intensity interval training (HIIT) is sufficient to alter lymphocyte function and redox status. Sixteen young healthy men underwent a HIIT session on a cycloergometer, consisting of eight bouts of 1 min at 90-100% of peak power, with 75 seconds of active recovery at 30 W between bouts. Venous blood was collected before, immediately after, and 30 minutes after the HIIT session. In response to Staphylococcus aureus superantigen B (SEB) stimulation, lymphocyte proliferation decreased and the IL-2 concentration increased after the HIIT session. However, the HIIT session had no effect on lymphocyte proliferation or IL-2 response to phytohemagglutinin stimulation. The HIIT session also induced lymphocyte redox imbalance, characterized by an increase in the concentration of thiobarbituric acid reactive substances and a decrease in the activity of the antioxidant enzyme catalase. Lymphocyte viability was not affected by the HIIT session. The frequencies of CD25+ and CD69+ T helper and B lymphocytes in response to superantigen stimulation were lower after exercise, suggesting that superantigen-induced lymphocyte activation was reduced by HIIT. However, HIIT also led to a reduction in the frequency of CD4+ and CD19+ cells, so the frequencies of CD25+ and CD69+ cells within the CD4 and CD19 cell populations were not affected by HIIT. These data indicate that the reduced lymphocyte proliferation observed after HIIT is not due to reduced early lymphocyte activation by superantigen. Our findings show that an acute HIIT session promotes lymphocyte redox imbalance and reduces lymphocyte proliferation in response to superantigenic, but not to mitogenic stimulation. This observation cannot be explained by alteration of the early lymphocyte activation response to superantigen. The manner in which lymphocyte function modulation by an acute HIIT session can affect individual immunity and susceptibility to infection is important

Solution Monitoring Evaluated by Proliferation Risk Assessment and Fuzzy Optimization Analysis for Safeguards in a Reprocessing Process

Directory of Open Access Journals (Sweden)

Mitsutoshi Suzuki

2013-01-01

Full Text Available Solution monitoring (SM has been used in a nuclear reprocessing plant as an additional measure to provide assurance that the plant is operated as declared. The inline volume and density monitoring equipment with dip tubes is important for safety and safeguards purposes and is a typical example of safeguards by design (SBD. Recently safety, safeguards, and security by design (3SBD are proposed to promote an efficient and effective generation of nuclear energy. In 3SBD, proliferation risk assessment has the potential to consider likelihood of the incidence and proliferation risk in safeguards. In this study, risk assessment methodologies for safeguards and security are discussed and several mathematical methods are presented to investigate risk notion applied to intentional acts of facility misuse in an uncertainty environment. Proliferation risk analysis with the Markov model, deterrence effect with the game model, and SBD with fuzzy optimization are shown in feasibility studies to investigate the potential application of the risk and uncertainty analyses in safeguards. It is demonstrated that the SM is an effective measurement system using risk-informed and cost-effective SBD, even though there are inherent difficulties related to the possibility of operator’s falsification.

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

Shikonin Inhibits the Proliferation of Human Breast Cancer Cells by Reducing Tumor-Derived Exosomes

Directory of Open Access Journals (Sweden)

Yao Wei

2016-06-01

Full Text Available Shikonin is a naphthoquinone isolated from the traditional Chinese medicine Lithospermum. It has been used in the treatment of various tumors. However, the effects of shikonin on such diseases have not been fully elucidated. In the present study, we detected the exosome release of a breast cancer cell line (MCF-7 with shikonin treatment and found a positive relationship between the level of secreted exosomes and cell proliferation. We next analyzed miRNA profiles in MCF-7 cells and exosomes and found that some miRNAs are specifically sorted and abundant in exosomes. Knockdown of the most abundant miRNAs in exosomes and the MCF-7 proliferation assay showed that miR-128 in exosomes negatively regulates the level of Bax in MCF-7 recipient cells and inhibits cell proliferation. These results show that shikonin inhibits the proliferation of MCF-7 cells through reducing tumor-derived exosomal miR-128. The current study suggests that shikonin suppresses MCF-7 growth by the inhibition of exosome release.

NME2 reduces proliferation, migration and invasion of gastric cancer cells to limit metastasis.

Directory of Open Access Journals (Sweden)

Yan-fei Liu

Full Text Available Gastric cancer is one of the most common malignancies and has a high rate of metastasis. We hypothesize that NME2 (Nucleoside Diphosphate Kinase 2, which has previously been considered as an anti-metastatic gene, plays a role in the invasiveness of gastric cancer cells. Using a tissue chip technology and immunohistochemistry, we demonstrated that NME2 expression was associated with levels of differentiation of gastric cancer cells and their metastasis into the lymph nodes. When the NME2 gene product was over-expressed by ;in vitro stable transfection, cells from BGC823 and MKN45 gastric cancer cell lines had reduced rates of proliferation, migration, and invasion through the collagen matrix, suggesting an inhibitory activity of NME2 in the propagation and invasion of gastric cancer. NME2 could, therefore, severe as a risk marker for gastric cancer invasiveness and a potential new target for gene therapy to enhance or induce NME2 expression.

Reduced proliferation of endothelial colony-forming cells in unprovoked venous thromboembolic disease as a consequence of endothelial dysfunction

Science.gov (United States)

Hernandez-Lopez, Rubicel; Chavez-Gonzalez, Antonieta; Torres-Barrera, Patricia; Moreno-Lorenzana, Dafne; Lopez-DiazGuerrero, Norma; Santiago-German, David; Isordia-Salas, Irma; Smadja, David; C. Yoder, Mervin; Majluf-Cruz, Abraham

2017-01-01

Background Venous thromboembolic disease (VTD) is a public health problem. We recently reported that endothelial colony-forming cells (ECFCs) derived from endothelial cells (EC) (ECFC-ECs) from patients with VTD have a dysfunctional state. For this study, we proposed that a dysfunctional status of these cells generates a reduction of its proliferative ability, which is also associated with senescence and reactive oxygen species (ROS). Methods and results Human mononuclear cells (MNCs) were obtained from peripheral blood from 40 healthy human volunteers (controls) and 50 patients with VTD matched by age (20−50 years) and sex to obtain ECFCs. We assayed their proliferative ability with plasma of patients and controls and supernatants of cultures from ECFC-ECs, senescence-associated β-galactosidase (SA-β-gal), ROS, and expression of ephrin-B2/Eph-B4 receptor. Compared with cells from controls, cells from VTD patients showed an 8-fold increase of ECFCs that emerged 1 week earlier, reduced proliferation at long term (39%) and, in passages 4 and 10, a highly senescent rate (30±1.05% vs. 91.3±15.07%, respectively) with an increase of ROS and impaired expression of ephrin-B2/Eph-4 genes. Proliferation potential of cells from VTD patients was reduced in endothelial medium [1.4±0.22 doubling population (DP)], control plasma (1.18±0.31 DP), or plasma from VTD patients (1.65±0.27 DP). Conclusions As compared with controls, ECFC-ECs from individuals with VTD have higher oxidative stress, proliferation stress, cellular senescence, and low proliferative potential. These findings suggest that patients with a history of VTD are ECFC-ECs dysfunctional that could be associated to permanent risk for new thrombotic events. PMID:28910333

Laser isotope separation and proliferation risks

Energy Technology Data Exchange (ETDEWEB)

Fuss, Werner

2015-02-15

There is an ongoing discussion on the proliferation danger of laser enrichment of uranium by the Silex process. Here this risk is compared to that of other processes, in particular centrifuges. The two methods need a similar size of the plant for a comparable production rate (in separative work units per year) and the time and costs for their construction do not differ much. This conclusion from published material does not depend on technical details of Silex. But enough details are known to allow for additional conclusions: Whereas the selectivity (enrichment factor) in the Silex process seems higher, the energy consumption is probably larger. Due to the laser's repetition rate being insufficient for the molecular beam, the method has probably a low depletion factor; this is a serious disadvantage for cascading for high enrichment such as for bomb uranium, although it may be acceptable for low enrichment without cascading for reactor purposes.

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

Exercise reduces adipose tissue via cannabinoid receptor type 1 which is regulated by peroxisome proliferator-activated receptor-δ

International Nuclear Information System (INIS)

Yan Zhencheng; Liu Daoyan; Zhang Lili; Shen Chenyi; Ma Qunli; Cao Tingbing; Wang Lijuan; Nie Hai; Zidek, Walter; Tepel, Martin; Zhu Zhiming

2007-01-01

Obesity is one major cardiovascular risk factor. We tested effects of endurance exercise on cannabinoid receptor type 1 (CB1) and peroxisome proliferator-activated receptor-δ (PPAR-δ)-dependent pathways in adipose tissue. Male Wistar rats were randomly assigned to standard laboratory chow or a high-fat diet without and with regular endurance exercise. Exercise in rats on high-fat diet significantly reduced visceral fat mass, blood pressure, and adipocyte size (each p < 0.05). Adipocyte hypertrophy induced by high-fat diet was accompanied by increased CB1 expression in adipose tissue, whereas exercise significantly reduced CB1 expression (each p < 0.05). CB1 receptor expression and adipocyte differentiation were directly regulated by PPAR-δ. Adipocyte hypertrophy induced by high-fat diet was accompanied by reduced PPAR-δ. Furthermore, selective silencing of PPAR-δ by RNA interference in 3T3-L1-preadipocyte cells significantly increased CB1 expression from 1.00 ± 0.06 (n = 3) to 1.91 ± 0.06 (n = 3; p < 0.01) and increased adipocyte differentiation, whereas adenovirus-mediated overexpression of PPAR-δ significantly reduced CB1 expression to 0.39 ± 0.03 (n = 3; p < 0.01) and reduced adipocyte differentiation. In the presence of the CB1 antagonist rimonabant adipocyte differentiation in stimulated 3T3 L1 preadipocyte cells was significantly reduced. The study indicates that high-fat diet-induced hypertrophy of adipocytes is associated with increased CB1 receptor expression which is directly regulated by PPAR-δ. Both CB1 and PPAR-δ are intimately involved in therapeutic interventions against a most important cardiovascular risk factor

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

Nuclear power and nuclear-weapons proliferation

International Nuclear Information System (INIS)

Moniz, E.J.; Neff, T.L.

1978-01-01

Concern over the risk of nuclear proliferation has led to extensive reexamination of the technical, economic, and political assumptions underlying both national and international nuclear policies. An attempt is made in the present article to clarify the basic technical and political issues. The connections between various fuel cycles and their possible proliferation risks are discussed. As the resolution of the existing differing views on proliferation risks will be largely a political process, solutions to the problem are not proposed

Psoriatic T cells reduce epidermal turnover time and affect cell proliferation contributed from differential gene expression.

Science.gov (United States)

Li, Junqin; Li, Xinhua; Hou, Ruixia; Liu, Ruifeng; Zhao, Xincheng; Dong, Feng; Wang, Chunfang; Yin, Guohua; Zhang, Kaiming

2015-09-01

Psoriasis is mediated primarily by T cells, which reduce epidermal turnover time and affect keratinocyte proliferation. We aimed to identify differentially expressed genes (DEG) in T cells from normal, five pairs of monozygotic twins concordant or discordant for psoriasis, to determine whether these DEG may account for the influence to epidermal turnover time and keratinocyte proliferation. The impact of T cells on keratinocyte proliferation and epidermal turnover time were investigated separately by immunohistochemistry and cultured with (3) H-TdR. mRNA expression patterns were investigated by RNA sequencing and verified by real-time reverse transcription polymerase chain reaction. After co-culture with psoriatic T cells, the expression of Ki-67, c-Myc and p53 increased, while expression of Bcl-2 and epidermal turnover time decreased. There were 14 DEG which were found to participate in the regulation of cell proliferation or differentiation. Psoriatic T cells exhibited the ability to decrease epidermal turnover time and affect keratinocyte proliferation because of the differential expression of PPIL1, HSPH1, SENP3, NUP54, FABP5, PLEKHG3, SLC9A9 and CHCHD4. © 2015 Japanese Dermatological Association.

Nuclear energy and nuclear weapons proliferation

International Nuclear Information System (INIS)

1989-01-01

A summary of the report dispatched in the middle of 1978 by the Atlantic Council of United States, organized by North American citizens, is presented. The report considers the relation between the production of nucleoelectric energy and the capacity of proliferation of nuclear weapons. The factors which affect the grade of proliferation risk represented by the use of nuclear energy in the world comparing this risk with the proliferation risks independently of nuclear energy, are examined. (M.C.K.) [pt

Andrographolide reduces proliferation and migration of lens epithelial cells by modulating PI3K/Akt pathway.

Science.gov (United States)

Kayastha, Forum; Madhu, Hardik; Vasavada, Abhay; Johar, Kaid

2014-11-01

Lens epithelial cell proliferation, migration, and transdifferentiation are involved in the development of subcapsular cataracts and postoperative capsular opacification (PCO). PI3K/Akt pathway is involved in the proliferation and migration of lens epithelial cells. Andrographolide is the main bioactive component of Andrographis paniculata and is known to possess anti-proliferative and anti-migratory activities. The purpose of this study is to evaluate the effect of andrographolide on proliferation and migration induced by growth factors (TGF-β and bFGF) in the lens epithelial cell line, FHL 124. We have also evaluated the role of the PI3K/Akt pathway and its alteration by andrographolide during proliferation and migration of lens epithelial cells. The results showed that andrographolide significantly inhibited proliferation in a dose and time dependent manner. The growth factors, TGF-β and bFGF, induced migration of lens epithelial cells, which was lowered by andrographolide. The growth factors also up regulated phosphorylated Akt (Ser473) and Akt (Thr308), which was abolished by simultaneous treatment of andrographolide. Similar changes were also observed with the PI3K inhibitor, LY290042. Our findings suggest that andrographolide reduces proliferation, migration, and phosphorylated Akt levels in lens epithelial cells. Hence andrographolide can be utilized for the prevention of PCO. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

Downregulation of MMP1 in MDS-derived mesenchymal stromal cells reduces the capacity to restrict MDS cell proliferation.

Science.gov (United States)

Zhao, Sida; Zhao, Youshan; Guo, Juan; Fei, Chengming; Zheng, Qingqing; Li, Xiao; Chang, Chunkang

2017-03-06

The role of mesenchymal stromal cells (MSCs) in the pathogenesis of myelodysplastic syndromes (MDS) has been increasingly addressed, but has yet to be clearly elucidated. In this investigation, we found that MDS cells proliferated to a greater extent on MDS-derived MSCs compared to normal MSCs. Matrix metalloproteinase 1(MMP1), which was downregulated in MDS-MSCs, was identified as an inhibitory factor of MDS cell proliferation, given that treatment with an MMP1 inhibitor or knock-down of MMP1 in normal MSCs resulted in increased MDS cell proliferation. Further investigations indicated that MMP1 induced apoptosis of MDS cells by interacting with PAR1 and further activating the p38 MAPK pathway. Inhibition of either PAR1 or p38 MAPK can reverse the apoptosis-inducing effect of MMP1. Taken together, these data indicate that downregulation of MMP1 in MSCs of MDS patients may contribute to the reduced capacity of MSCs to restrict MDS cell proliferation, which may account for the malignant proliferation of MDS cells.

Simulated predator stimuli reduce brain cell proliferation in two electric fish species, Brachyhypopomus gauderio and Apteronotus leptorhynchus.

Science.gov (United States)

Dunlap, Kent D; Keane, Geoffrey; Ragazzi, Michael; Lasky, Elise; Salazar, Vielka L

2017-07-01

The brain structure of many animals is influenced by their predators, but the cellular processes underlying this brain plasticity are not well understood. Previous studies showed that electric fish ( Brachyhypopomus occidentalis ) naturally exposed to high predator ( Rhamdia quelen ) density and tail injury had reduced brain cell proliferation compared with individuals facing few predators and those with intact tails. However, these field studies described only correlations between predator exposure and cell proliferation. Here, we used a congener Brachyhypopomus gauderio and another electric fish Apteronotus leptorhynchus to experimentally test the hypothesis that exposure to a predator stimulus and tail injury causes alterations in brain cell proliferation. To simulate predator exposure, we either amputated the tail followed by short-term (1 day) or long-term (17-18 days) recovery or repeatedly chased intact fish with a plastic rod over a 7 day period. We measured cell proliferation (PCNA+ cell density) in the telencephalon and diencephalon, and plasma cortisol, which commonly mediates stress-induced changes in brain cell proliferation. In both species, either tail amputation or simulated predator chase decreased cell proliferation in the telencephalon in a manner resembling the effect of predators in the field. In A. leptorhynchus , cell proliferation decreased drastically in the short term after tail amputation and partially rebounded after long-term recovery. In B. gauderio , tail amputation elevated cortisol levels, but repeated chasing had no effect. In A. leptorhynchus , tail amputation elevated cortisol levels in the short term but not in the long term. Thus, predator stimuli can cause reductions in brain cell proliferation, but the role of cortisol is not clear. © 2017. Published by The Company of Biologists Ltd.

Reducing the risk of nuclear terrorism

International Nuclear Information System (INIS)

Hibbs, R.

2005-01-01

Full text: The March 2005 'International conference on nuclear security, global directions for the future' noted that nuclear terrorism is one of the greatest threats to society. Eminent members of a multi-national panel stated that there is no one principal activity to reduce the risk of nuclear terrorism and that a combination of activities is required. This paper seeks to identify those activities by analyzing the elements that comprise the risk of nuclear terrorism. For the purpose of the analysis, risk is the product of the probability of a terrorist attack (A p ), the success of a terrorist act (S p ) and the consequence (C) of the attack: R=A p * S p * C. The paper examines each of these three elements of risk with the objective of identifying what we are doing and what else we could be doing to reduce risk. It takes into consideration some historic catastrophes, examines how they might have been prevented or their consequences reduced, and if there are lessons that are applicable to reducing the risk of nuclear terrorism. The paper demonstrates that we have concentrated on only one of the three elements of risk and offer suggestions for diminishing the risk of nuclear terrorism by addressing all the elements. (author)

Should We Use PPAR Agonists to Reduce Cardiovascular Risk?

Directory of Open Access Journals (Sweden)

Jennifer G. Robinson

2008-01-01

Full Text Available Trials of peroxisome proliferator-activated receptor (PPAR agonists have shown mixed results for cardiovascular prevention. Fibrates are PPAR- agonists that act primarily to improve dyslipidemia. Based on low- and high-density lipoprotein cholesterol (LDL and HDL effects, gemfibrozil may be of greater cardiovascular benefit than expected, fenofibrate performed about as expected, and bezafibrate performed worse than expected. Increases in both cardiovascular and noncardiovascular serious adverse events have been observed with some fibrates. Thiazolidinediones (TZDs are PPAR- agonists used to improve impaired glucose metabolism but also influence lipids. Pioglitazone reduces atherosclerotic events in diabetic subjects, but has no net cardiovascular benefit due to increased congestive heart failure risk. Rosiglitazone may increase the risk of atherosclerotic events, and has a net harmful effect on the cardiovascular system when congestive heart failure is included. The primary benefit of TZDs appears to be the prevention of diabetic microvascular complications. Dual PPAR-/ agonists have had unacceptable adverse effects but more selective agents are in development. PPAR- and pan-agonists are also in development. It will be imperative to prove that future PPAR agonists not only prevent atherosclerotic events but also result in a net reduction on total cardiovascular events without significant noncardiovascular adverse effects with long-term use.

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.

Reduced proliferation and osteocalcin expression in osteoblasts of male idiopathic osteoporosis.

Science.gov (United States)

Ruiz-Gaspà, Sílvia; Blanch-Rubió, Josep; Ciria-Recasens, Manuel; Monfort, Jordi; Tío, Laura; Garcia-Giralt, Natàlia; Nogués, Xavier; Monllau, Joan C; Carbonell-Abelló, Jordi; Pérez-Edo, Lluis

2010-03-01

Osteoporosis is characterized by low bone mineral density (BMD), resulting in increasing susceptibility to bone fractures. In men, it has been related to some diseases and toxic habits, but in some instances the cause of the primary--or idiopathic--osteoporosis is not apparent. In a previous study, our group compared histomorphometric measurements in cortical and cancellous bones from male idiopathic osteoporosis (MIO) patients to those of control subjects and found reduced bone formation without major differences in bone resorption. To confirm these results, this study analyzed the etiology of this pathology, examining the osteoblast behavior in vitro. We compared two parameters of osteoblast activity in MIO patients and controls: osteoblastic proliferation and gene expression of COL1A1 and osteocalcin, in basal conditions and with vitamin D(3) added. All these experiments were performed from a first-passage osteoblastic culture, obtained from osteoblasts that had migrated from the transiliac explants to the plate. The results suggested that the MIO osteoblast has a slower proliferation rate and decreased expression of genes related to matrix formation, probably due to a lesser or slower response to some stimulus. We concluded that, contrary to female osteoporosis, in which loss of BMD is predominantly due to increased resorption, low BMD in MIO seems to be due to an osteoblastic defect.

Thorium fuel for light water reactors - reducing proliferation potential of nuclear power fuel cycle

Energy Technology Data Exchange (ETDEWEB)

Galperin, A; Radkowski, A [Ben-Gurion Univ. of the Negev, Beersheba (Israel)

1996-12-01

The proliferation potential of the light water reactor fuel cycle may be significantly reduced by utilization of thorium as a fertile component of the nuclear fuel. The main challenge of Th utilization is to design a core and a fuel cycle, which would be proliferation-resistant and economically feasible. This challenge is met by the Radkowsky Thorium Reactor (RTR) concept. So far the concept has been applied to a Russian design of a 1,000 MWe pressurized water reactor, known as a WWER-1000, and designated as VVERT. The following are the main results of the preliminary reference design: * The amount of Pu contained in the RTR spent fuel stockpile is reduced by 80% in comparison with a VVER of a current design. * The isotopic composition of the RTR-Pu greatly increases the probability of pre-initiation and yield degradation of a nuclear explosion. An extremely large Pu-238 content causes correspondingly large heat emission, which would complicate the design of an explosive device based on RTR-Pu. The economic incentive to reprocess and reuse the fissile component of the RTR spent fuel is decreased. The once-through cycle is economically optimal for the RTR core and cycle. To summarize all the items above: the replacement of a standard (U-based) fuel for nuclear reactors of current generation by the RTR fuel will provide an inherent barrier for nuclear weapon proliferation. This inherent barrier, in combination with existing safeguard measures and procedures is adequate to unambiguously disassociate civilian nuclear power from military nuclear power. * The RTR concept is applied to existing power plants to assure its economic feasibility. Reductions in waste disposal requirements, as well as in natural U and fabrication expenses, as compared to a standard WWER fuel, provide approximately 20% reduction in fuel cycle (authors).

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

C2C12 myotubes inhibit the proliferation and differentiation of 3T3-L1 preadipocytes by reducing the expression of glucocorticoid receptor gene

Energy Technology Data Exchange (ETDEWEB)

Chu, Weiwei; Wei, Wei; Yu, Shigang; Han, Haiyin; Shi, Xiaoli [College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095 (China); Sun, Wenxing [College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095 (China); College of Public Health, Nantong University, Nantong 226019 (China); Gao, Ying [College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095 (China); Zhang, Lifan [College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095 (China); Chen, Jie, E-mail: jiechen@njau.edu.cn [College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095 (China)

2016-03-25

Obesity is a well-established risk factor to health for its relationship with insulin resistance, diabetes and metabolic syndrome. Myocyte-adipocyte crosstalk model plays a significant role in studying the interaction of muscle and adipose development. Previous related studies mainly focus on the effects of adipocytes on the myocytes activity, however, the influence of myotubes on the preadipocytes development remains unclear. The present study was carried out to settle this issue. Firstly, the co-culture experiment showed that the proliferation, cell cycle, and differentiation of 3T3-L1 preadipocytes were arrested, and the apoptosis was induced, by differentiated C2C12 myotubes. Next, the sensitivity of 3T3-L1 preadipocytes to glucocorticoids (GCs), which was well known as cell proliferation, differentiation, apoptosis factor, was decreased after co-cultured with C2C12 myotubes. What's more, our results showed that C2C12 myotubes suppressed the mRNA and protein expression of glucocorticoid receptor (GR) in 3T3-L1 preadipocytes, indicating the potential mechanism of GCs sensitivity reduction. Taken together, we conclude that C2C12 myotubes inhibited 3T3-L1 preadipocytes proliferation and differentiation by reducing the expression of GR. These data suggest that decreasing GR by administration of myokines may be a promising therapy for treating patients with obesity or diabetes. - Highlights: • C2C12 myotubes inhibited proliferation and differentiation of 3T3-L1 preadipocytes. • C2C12 myotubes arrested cell cycle of 3T3-L1 preadipocytes. • C2C12 myotubes induced apoptosis of 3T3-L1 preadipocytes. • C2C12 inhibit 3T3-L1 cells by reducing the expression of glucocorticoid receptor gene.

Mercury induces proliferation and reduces cell size in vascular smooth muscle cells through MAPK, oxidative stress and cyclooxygenase-2 pathways

Energy Technology Data Exchange (ETDEWEB)

Aguado, Andrea; Galán, María; Zhenyukh, Olha; Wiggers, Giulia A.; Roque, Fernanda R. [Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), 28029, Madrid (Spain); Redondo, Santiago [Departamento de Farmacología, Facultad de Medicina, Universidad Complutense, 28040, Madrid (Spain); Peçanha, Franck [Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), 28029, Madrid (Spain); Martín, Angela [Departamento de Bioquímica, Fisiología y Genética Molecular, Universidad Rey Juan Carlos, 28922, Alcorcón (Spain); Fortuño, Ana [Área de Ciencias Cardiovasculares, Centro de Investigación Médica Aplicada, Universidad de Navarra, 31008, Pamplona (Spain); Cachofeiro, Victoria [Departamento de Fisiología, Facultad de Medicina, Universidad Complutense, 28040, Madrid (Spain); Tejerina, Teresa [Departamento de Farmacología, Facultad de Medicina, Universidad Complutense, 28040, Madrid (Spain); Salaices, Mercedes, E-mail: mercedes.salaices@uam.es [Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), 28029, Madrid (Spain); and others

2013-04-15

Mercury exposure is known to increase cardiovascular risk but the underlying cellular mechanisms remain undetermined. We analyzed whether chronic exposure to HgCl{sub 2} affects vascular structure and the functional properties of vascular smooth muscle cells (VSMC) through oxidative stress/cyclooxygenase-2 dependent pathways. Mesenteric resistance arteries and aortas from Wistar rats treated with HgCl{sub 2} (first dose 4.6 mg kg{sup −1}, subsequent doses 0.07 mg kg{sup −1} day{sup −1}, 30 days) and cultured aortic VSMC stimulated with HgCl{sub 2} (0.05–5 μg/ml) were used. Treatment of rats with HgCl{sub 2} decreased wall thickness of the resistance and conductance vasculature, increased the number of SMC within the media and decreased SMC nucleus size. In VSMCs, exposure to HgCl{sub 2}: 1) induced a proliferative response and a reduction in cell size; 2) increased superoxide anion production, NADPH oxidase activity, gene and/or protein levels of the NADPH oxidase subunit NOX-1, the EC- and Mn-superoxide dismutases and cyclooxygenase-2 (COX-2); 3) induced activation of ERK1/2 and p38 MAPK. Both antioxidants and COX-2 inhibitors normalized the proliferative response and the altered cell size induced by HgCl{sub 2}. Blockade of ERK1/2 and p38 signaling pathways abolished the HgCl{sub 2}-induced Nox1 and COX-2 expression and normalized the alterations induced by mercury in cell proliferation and size. In conclusion, long exposure of VSMC to low doses of mercury activates MAPK signaling pathways that result in activation of inflammatory proteins such as NADPH oxidase and COX-2 that in turn induce proliferation of VSMC and changes in cell size. These findings offer further evidence that mercury might be considered an environmental risk factor for cardiovascular disease. - Highlights: ► Chronic HgCl{sub 2} exposure induces vascular remodeling. ► HgCl{sub 2} induces proliferation and decreased cell size in vascular smooth muscle cells. ► HgCl{sub 2} induces

The impact of 27-hydroxycholesterol on endometrial cancer proliferation.

Science.gov (United States)

Gibson, Douglas A; Collins, Frances; Cousins, Fiona L; Esnal Zufiaurre, Arantza; Saunders, Philippa T K

2018-04-01

Endometrial cancer (EC) is the most common gynaecological malignancy. Obesity is a major risk factor for EC and is associated with elevated cholesterol. 27-hydroxycholesterol (27HC) is a cholesterol metabolite that functions as an endogenous agonist for Liver X receptor (LXR) and a selective oestrogen receptor modulator (SERM). Exposure to oestrogenic ligands increases risk of developing EC; however, the impact of 27HC on EC is unknown. Samples of stage 1 EC ( n  = 126) were collected from postmenopausal women undergoing hysterectomy. Expression of LXRs ( NR1H3 , LXRα; NR1H2 , LXRβ) and enzymes required for the synthesis ( CYP27A1 ) or breakdown ( CYP7B1 ) of 27HC were detected in all grades of EC. Cell lines originating from well-, moderate- and poorly-differentiated ECs (Ishikawa, RL95, MFE 280 respectively) were used to assess the impact of 27HC or the LXR agonist GW3965 on proliferation or expression of a luciferase reporter gene under the control of LXR- or ER-dependent promoters (LXRE, ERE). Incubation with 27HC or GW3965 increased transcription via LXRE in Ishikawa, RL95 and MFE 280 cells ( P  MFE 280 cells, 27HC did not alter proliferation but selective targeting of LXR with GW3965 significantly reduced cell proliferation ( P  < 0.0001). These novel results suggest that 27HC can contribute to risk of EC by promoting proliferation of endometrial cancer epithelial cells and highlight LXR as a potential therapeutic target in the treatment of advanced disease. © 2018 The authors.

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

Non-proliferation of nuclear weapons

International Nuclear Information System (INIS)

Fischer, D.; Haeckel, E.; Haefele, W.; Lauppe, W.D.; Mueller, H.; Ungerer, W.

1991-01-01

During the turbulant transitional events in world politics in the nineties, the control of nuclear weapons plays a major role. While the superpowers are reducing their nuclear arsenal, the danger of nuclear anarchy in the world remains virulent. The NPT of 1968 is up for review soon. The falling apart of the former communist sphere of power, and the regions of conflict in the Third World present new risks for the proliferation of nuclear arms. For unified Germany, which explicitly renounced nuclear weapons, this situation presents difficult questions concerning national safety policies and international responsibility. This volume presents contributions which take a new look at topical and long-term problems of nuclear NP politics. The authors evaluate the conditions under which the NP regime came into being, and assess short- and long-term possibilities and risks. The following papers are included: 1.) Basic controversies during the negotiations concerning the Treaty on non-proliferation of nuclear weapons (Ungerer); 2.) Prologation of the NPT 1995 and appropriate problems concerning safety and control (Haefele/Lauppe); 3.) Consequences of the Iraq case for NP policy (Ficher); 4.) Problems of nuclear technology control (Mueller); 5.) Framework conditions of a nuclear world system (Haeckel). (orig./HP) [de

Autopoiesis of the techno-social systems as a factor of social risks proliferation

Directory of Open Access Journals (Sweden)

D E Orlov

2015-12-01

Full Text Available The article describes the problem of the unpredictable proliferation and complication of techno-social systems (such as Internet and financial markets. The authors try to explicate the social risks generated by these systems with the theoretical resources of the system theory of communication (N. Luhmann, which is based on the concepts of ‘recursion’, ‘process’ (‘operation’, ‘operationally closed system’, ‘autopoiesis’, etc. The authors believe that the autopoietic system response to external stimuli cannot be predicted by classical means of sociology and cybernetics. Turbulence and continuous complication of techno-social objects let the authors suggest that the dynamics of the systems under consideration contains some features of autopoiesis. Thus, the analysis of the financial market as a complex techno-social object based on the ideas of G. Akerlof (theory of irrational economic behavior and K. Knorr Cetina (object-centric sociology allows to better understand the phenomenon of unpredictable market dynamics (the risk of proliferation of market expectations, inability to capture the control level by any of the participants, etc. The authors believe that such a conceptualization helps to bring together sociological practices of the techno-social objects research and perspective methods of applied mathematics (fractal geometry, theory of reflexive relations, ‘soft’ models, etc., as well as contributes to the search of effective tools for modeling complex techno-social objects, and, thus, social risks accompanying them.

Review of nuclear fuel cycle alternatives including certain features pertaining to weapon proliferation

International Nuclear Information System (INIS)

Williams, D.C.; Rosenstroch, B.

1978-01-01

Largely as a result of concerns over nuclear weapon proliferation, the U.S. program to develop and commercialize the plutonium-fueled breeder reactor has been slowed down; interest in alternative fuel cycles has increased. The report offers an informal review of the various nuclear fuel cycle options including some aspects relevant to weapon proliferation, although no complete review of the latter subject is attempted. Basic principles governing breeding, reactor safety, and efficient utilization of fission energy resources (thorium and uranium) are discussed. The controversial problems of weapon proliferation and its relation to fuel reprocessing (which is essential for efficient fuel cycles) are reviewed and a number of proposed approaches to reducing proliferation risks are noted. Some representative specific reactor concepts are described, with emphasis on their development status, their potentials for resource utilization, and their implications for proliferation

Proliferation: does the peaceful use of nuclear energy have to lead to proliferation of nuclear weapons

International Nuclear Information System (INIS)

Muench, E.; Stein, G.

The question of whether the proliferation of nuclear weapons is promoted by an increasing use of peaceful nuclear energy can be answered with a well-founded no. Even a regional renouncing of the peaceful use of nuclear energy would not reduce the worldwide problem of nuclear weapons' proliferation. Therefore, joint efforts must be aimed at promoting trust between peoples in the nuclear sphere and the political reasons for the proliferation of nuclear weapons must be reduced in order also to promote international harmony

Risk Reducing Effect of AIS Implementation on Collision Risk

DEFF Research Database (Denmark)

Lützen, Marie; Friis-Hansen, Peter

2003-01-01

AIS (Automatic Identification System) is a transponder system developed for sea traffic purposes. The system sends and receives important ship information and other safety-related information between other ships and shore-based AIS stations. The implementation of AIS has now been initiated and......, as a result, the community will undoubtedly observe an increase in navigational safety. However, to the authors? knowledge, no study has so far rigorously quantified the risk reducing effect of using AIS as an integrated part of the navigational system. The objective of this study is to fill this gap....... The risk reducing effect of AIS is quantified by building a Bayesian network facilitating an evaluation of the effect of AIS on the navigational officer?s reaction ability in a potential, critical collision situation. The time-dependent change in the risk reducing effect on ship collisions is analysed...

Proliferation resistance of small modular reactors fuels

Energy Technology Data Exchange (ETDEWEB)

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

2013-07-01

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

Effect of Interlukin-1β on proliferation of gastric epithelial cells in culture

Directory of Open Access Journals (Sweden)

Beales Ian LP

2002-04-01

Full Text Available Abstract Background Helicobacter pylori is the main risk factor for the development of non-cardia gastric cancer. Increased proliferation of the gastric mucosa is a feature of H. pylori infection. Mucosal interkeukin-1β production is increased in H. pylori infection and IL-1β genotypes associated with increased pro-inflammatory activity are risk factors for the development of gastric cancer. The effect of IL-1β on gastric epithelial cell proliferation has been examined in this study. Methods AGS cells were cultured with IL-1β. DNA synthesis was assed by [3H]thymidine incorporation and total viable cell numbers by MTT assay. Results IL-1β dose dependently increased DNA synthesis and cell numbers. The enhanced proliferation was blocked by interleukin-1 receptor antagonist. Addition of neutralising antibody to GM-CSF reduced IL-1β-stimulated proliferation by 31 ± 4 %. GM-CSF alone significantly stimulated proliferation. Addition or neutralisation of IL-8 had no effect on basal or IL-1β-stimulated proliferation. The tyrosine kinase inhibitor genistein completely blocked IL-1β-stimulated proliferation and inhibition of the extracellular signal related kinase pathway with PD 98059 inhibited IL-1β stimulated proliferation by 58 ± 5 %. Conclusions IL-1β stimulates proliferation in gastric epithelial cells. Autocrine stimulation by GM-CSF contributes to this proliferative response. Signalling via tyrosine kinase activity is essential to the mitogenic response to IL-1β. The extracellular signal related kinase pathway is involved in, but not essential to downstream signalling. IL-1β may contribute to the hyperproliferation seen in H. pylori- infected gastric mucosa, and be involved in the carcinogenic process.

Inhibition of lectin-like oxidized low-density lipoprotein receptor-1 reduces cardiac fibroblast proliferation by suppressing GATA Binding Protein 4

Energy Technology Data Exchange (ETDEWEB)

Liu, Bin; Liu, Ning-Ning; Liu, Wei-Hua; Zhang, Shuang-Wei; Zhang, Jing-Zhi; Li, Ai-Qun [Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou (China); Guangzhou Institute of Cardiovascular Disease, Guangzhou (China); Liu, Shi-Ming, E-mail: gzliushiming@126.com [Department of Cardiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou (China); Guangzhou Institute of Cardiovascular Disease, Guangzhou (China)

2016-07-08

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and GATA Binding Protein 4 (GATA4) are important for the growth of cardiac fibroblasts (CFs). When deregulated, LOX-1 and GATA4 can cause cardiac remodeling. In the present study, we found novel evidence that GATA4 was required for the LOX-1 regulation of CF proliferation. The inhibition of LOX-1 by RNA interference LOX-1 lentivirus resulted in the loss of PI3K/Akt activation and GATA4 protein expression. The overexpression of LOX-1 by lentivirus rescued CF proliferation, PI3K/Akt activation, and GATA4 protein expression. Moreover, GATA4 overexpression enhanced CF proliferation with LOX-1 inhibition. We also found that the inhibition of PI3K/Akt activation by LY294002, a PI3K inhibitor, reduced cell proliferation and protein level of GATA4. In summary, GATA4 may play an important role in the LOX-1 and PI3K/Akt regulation of CF proliferation. -- Highlights: •GATA4 is regulated by LOX-1 signaling in CFs. •GATA4 is involved in LOX-1 regulating CF proliferation. •GATA4 is regulated by PI3K/Akt signaling in CFs.

Nuclear proliferation. II. Monopoly or cartel

International Nuclear Information System (INIS)

Baker, S.J.

1976-01-01

Increasing competition between a growing number of nations exporting nuclear technology and recent exporting of full fuel-cycle facilities raise fears of nuclear proliferation and widespread nuclear weapons. As a result of the 1973 oil crisis, industrial nations seeking a share in the international nuclear market in order to protect their economic interests must also cooperate to protect these same interests from nuclear risks. Disagreement over the form of cooperation centers on the competing exporters' tactics of undercutting safeguards and political restrictions. Monopoly was never an option for even the United States. Government intervention in the international nuclear market in the form of subsidies and financial incentives is a more practical approach than a free market. A cartel arrangement is appropriate to nuclear energy in the sense of reducing economic uncertainties, but political objections would be strong and there would be some risk of independent nuclear development. As a strategy to forestall proliferation, however, the cartel can control exports of enrichment and reprocessing facilities and make it more expensive for nations to independently develop nuclear weapons. An enlargement of safeguards arrangements by nuclear suppliers will require nations to trade some of their economic interests in order to achieve international political objectives

Stabilization and immobilization of military plutonium: A non-proliferation perspective

Energy Technology Data Exchange (ETDEWEB)

Leventhal, P. [Nuclear Control Institute, Washington, DC (United States)

1996-05-01

The Nuclear Control Institute welcomes this DOE-sponsored technical workshop on stabilization and immobilization of weapons plutonium (W Pu) because of the significant contribution it can make toward the ultimate non-proliferation objective of eliminating weapons-usable nuclear material, plutonium and highly enriched uranium (HEU), from world commerce. The risk of theft or diversion of these materials warrants concern, as only a few kilograms in the hands of terrorists or threshold states would give them the capability to build nuclear weapons. Military plutonium disposition questions cannot be addressed in isolation from civilian plutonium issues. The National Academy of Sciences has urged that {open_quotes}further steps should be taken to reduce the proliferation risks posed by all of the world`s plutonium stocks, military and civilian, separated and unseparated...{close_quotes}. This report discusses vitrification and a mixed oxide fuels option, and the effects of disposition choices on civilian plutonium fuel cycles.

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.

Orlistat Reduces Proliferation and Enhances Apoptosis in Human Pancreatic Cancer Cells (PANC-1).

Science.gov (United States)

Sokolowska, Ewa; Presler, Malgorzata; Goyke, Elzbieta; Milczarek, Ryszard; Swierczynski, Julian; Sledzinski, Tomasz

2017-11-01

Pancreatic cancer is a disease with very poor prognosis, and none of currently available pharmacotherapies have proven to be efficient in this indication. The aim of this study was to analyze the expression of fatty acid synthase (FASN) gene as a potential therapeutic target in proliferating human pancreatic cancer cells (PANC-1), and verify if orlistat, originally developed as an anti-obesity drug, inhibits PANC-1 proliferation. The effects of orlistat on gene expression, lipogenesis, proliferation and apoptosis was studied in PANC-1 cell culture. Expression of FASN increased during proliferation of PANC-1. Inhibition of FASN by orlistat resulted in a significant reduction of PANC-1 proliferation and enhanced apoptosis of these cells. This study showed, to our knowledge for the first time, that orlistat exhibits significant antitumor activity against PANC-1 cells. This implies that orlistat analogs with good oral bioavailability may find application in pharmacotherapy of pancreatic cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Coilin phosphomutants disrupt Cajal body formation, reduce cell proliferation and produce a distinct coilin degradation product.

Directory of Open Access Journals (Sweden)

Zunamys I Carrero

Full Text Available Coilin is a nuclear phosphoprotein that accumulates in Cajal bodies (CBs. CBs participate in ribonucleoprotein and telomerase biogenesis, and are often found in cells with high transcriptional demands such as neuronal and cancer cells, but can also be observed less frequently in other cell types such as fibroblasts. Many proteins enriched within the CB are phosphorylated, but it is not clear what role this modification has on the activity of these proteins in the CB. Coilin is considered to be the CB marker protein and is essential for proper CB formation and composition in mammalian cells. In order to characterize the role of coilin phosphorylation on CB formation, we evaluated various coilin phosphomutants using transient expression. Additionally, we generated inducible coilin phosphomutant cell lines that, when used in combination with endogenous coilin knockdown, allow for the expression of the phosphomutants at physiological levels. Transient expression of all coilin phosphomutants except the phosphonull mutant (OFF significantly reduces proliferation. Interestingly, a stable cell line induced to express the coilin S489D phosphomutant displays nucleolar accumulation of the mutant and generates a N-terminal degradation product; neither of which is observed upon transient expression. A N-terminal degradation product and nucleolar localization are also observed in a stable cell line induced to express a coilin phosphonull mutant (OFF. The nucleolar localization of the S489D and OFF coilin mutants observed in the stable cell lines is decreased when endogenous coilin is reduced. Furthermore, all the phosphomutant cells lines show a significant reduction in CB formation when compared to wild-type after endogenous coilin knockdown. Cell proliferation studies on these lines reveal that only wild-type coilin and the OFF mutant are sufficient to rescue the reduction in proliferation associated with endogenous coilin depletion. These results emphasize

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.

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

The 'polypill' to reduce cardiovascular risk

DEFF Research Database (Denmark)

Patel, Vinod; Pedersen, Oluf; Morrissey, John

2004-01-01

This article considers data from the Steno-2 multifactorial intervention study in type 2 diabetes to which are applied the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. Mathematical analyses support the use of a 'polypill' to reduce cardiovascular risk in type 2 diabetes. It is s...

Benefits from reducing risk of death

Energy Technology Data Exchange (ETDEWEB)

Krupnick, A

1994-07-01

Of the categories of benefits to individuals, reductions in the risk of premature mortality are of central. concern to the public and environmental policy makers. These benefits can include those from reductions in own- risk, for example, an individual's valuation of reducing his or her own mortality risks; reductions in risk to an individual's family, friends, or co-workers (i.e., of people known to the individual); and reductions in risks to unknown individuals. The last type would be an example of altruistic value. The overall goal is to measure the welfare change from a change in the current and/or future probability of dying. The willingness to pay (WTP) reflects the amount of income taken from a person that would leave him or her indifferent to a decrease in risk, whenever it occurs. When this value is divided by the risk change, the resulting value is called the 'value of a statistical life'. Another relevant measure appearing in the literature is the value of life-years saved. A final issue concerns the type of premature mortality risks one is valuing when environmental pollution is at issue. While most effort has gone into estimating the welfare effects of a change in current probability of death of healthy workers on the job, this is more relevant for characterizing the benefits of reducing accidental death risks than death from environmental causes. Exposure to pollutants raises risks of developing cancer, chronic heart, respiratory, and other diseases that raise mortality risks in the future. Such exposure also may raise current death risks for the very old and the sick. But, surely the pollution effect that is analogous to occupational health risks-pollution exposures high enough to raise current risks of death for the healthy, prime-age person-is insignificant in the United States.

Benefits from reducing risk of death

International Nuclear Information System (INIS)

Krupnick, A.

1994-01-01

Of the categories of benefits to individuals, reductions in the risk of premature mortality are of central. concern to the public and environmental policy makers. These benefits can include those from reductions in own- risk, for example, an individual's valuation of reducing his or her own mortality risks; reductions in risk to an individual's family, friends, or co-workers (i.e., of people known to the individual); and reductions in risks to unknown individuals. The last type would be an example of altruistic value. The overall goal is to measure the welfare change from a change in the current and/or future probability of dying. The willingness to pay (WTP) reflects the amount of income taken from a person that would leave him or her indifferent to a decrease in risk, whenever it occurs. When this value is divided by the risk change, the resulting value is called the 'value of a statistical life'. Another relevant measure appearing in the literature is the value of life-years saved. A final issue concerns the type of premature mortality risks one is valuing when environmental pollution is at issue. While most effort has gone into estimating the welfare effects of a change in current probability of death of healthy workers on the job, this is more relevant for characterizing the benefits of reducing accidental death risks than death from environmental causes. Exposure to pollutants raises risks of developing cancer, chronic heart, respiratory, and other diseases that raise mortality risks in the future. Such exposure also may raise current death risks for the very old and the sick. But, surely the pollution effect that is analogous to occupational health risks-pollution exposures high enough to raise current risks of death for the healthy, prime-age person-is insignificant in the United States

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.

Relationship Between Perceived Risk of Falling and Adoption of Precautions to Reduce Fall Risk.

Science.gov (United States)

Blalock, Susan J; Gildner, Paula L; Jones, Jennifer L; Bowling, James M; Casteel, Carri H

2016-06-01

To better understand the relationship between perceived risk of falling and awareness and adoption of four specific precautions that older adults have taken to reduce this risk. Cross-sectional. Data were collected in in-person interviews conducted in the homes of study participants. Interviews conducted between March 2011 and September 2013 and lasted an average of 60-90 minutes. A stratified sampling strategy designed to enroll an equal number of homebound and nonhomebound participants was used. All participants (N = 164) were recruited from central North Carolina. Participants were asked about 1-year fall history, perceived risk of falling, restriction of activities because of fear of falling, awareness of four recommended fall prevention behaviors (exercise, annual medication review, bathroom grab bars, safe footwear), and current practice of these behaviors. In bivariate analyses, individuals who were aware of two behaviors recommended to reduce the risk of falling (exercise, use of safe footwear) and had adopted these behaviors perceived their risk of falling as lower than individuals who were aware of the recommended behaviors but had not adopted them. Moreover, in multivariate analyses, individuals who did not know that exercise is recommended to reduce the risk of falling perceived their risk of falling as lower than those who were aware of this recommendation and had adopted it. Individuals were least likely to be aware that medication reviews and exercise are recommended to reduce fall risk. Awareness of behaviors recommended to reduce fall risk appears necessary for adoption of these behaviors to reduce perceived risk. Fall-prevention campaigns should emphasize behaviors where awareness is low. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

High relative humidity pre-harvest reduces post-harvest proliferation of Salmonella in tomatoes.

Science.gov (United States)

Devleesschauwer, Brecht; Marvasi, Massimiliano; Giurcanu, Mihai C; Hochmuth, George J; Speybroeck, Niko; Havelaar, Arie H; Teplitski, Max

2017-09-01

Outbreaks of human illness caused by enteric pathogens such as Salmonella are increasingly linked to the consumption of fruits and vegetables. Knowledge on the factors affecting Salmonella proliferation on fresh produce therefore becomes increasingly important to safeguard public health. Previous experiments showed a limited impact of pre-harvest production practices on Salmonella proliferation on tomatoes, but suggested a significant effect of harvest time. We explored the data from two previously published and one unpublished experiment using regression trees, which allowed overcoming the interpretational difficulties of classical statistical models with higher order interactions. We assessed the effect of harvest time by explicitly modeling the climatic conditions at harvest time and by performing confirmatory laboratory experiments. Across all datasets, regression trees confirmed the dominant effect of harvest time on Salmonella proliferation, with humidity-related factors emerging as the most important underlying climatic factors. High relative humidity the week prior to harvest was consistently associated with lower Salmonella proliferation. A controlled lab experiment confirmed that tomatoes containing their native epimicrobiota supported significantly lower Salmonella proliferation when incubated at higher humidity prior to inoculation. The complex interactions between environmental conditions and the native microbiota of the tomato crop remain to be fully understood. Copyright © 2017 Elsevier Ltd. All rights reserved.

Functional neural correlates of reduced physiological falls risk

Directory of Open Access Journals (Sweden)

Hsu Chun

2011-08-01

Full Text Available Abstract Background It is currently unclear whether the function of brain regions associated with executive cognitive processing are independently associated with reduced physiological falls risk. If these are related, it would suggest that the development of interventions targeted at improving executive neurocognitive function would be an effective new approach for reducing physiological falls risk in seniors. Methods We performed a secondary analysis of 73 community-dwelling senior women aged 65 to 75 years old who participated in a 12-month randomized controlled trial of resistance training. Functional MRI data were acquired while participants performed a modified Eriksen Flanker Task - a task of selective attention and conflict resolution. Brain volumes were obtained using MRI. Falls risk was assessed using the Physiological Profile Assessment (PPA. Results After accounting for baseline age, experimental group, baseline PPA score, and total baseline white matter brain volume, baseline activation in the left frontal orbital cortex extending towards the insula was negatively associated with reduced physiological falls risk over the 12-month period. In contrast, baseline activation in the paracingulate gyrus extending towards the anterior cingulate gyrus was positively associated with reduced physiological falls risk. Conclusions Baseline activation levels of brain regions underlying response inhibition and selective attention were independently associated with reduced physiological falls risk. This suggests that falls prevention strategies may be facilitated by incorporating intervention components - such as aerobic exercise - that are specifically designed to induce neurocognitive plasticity. Trial Registration ClinicalTrials.gov Identifier: NCT00426881

Does Metformin Reduce Cancer Risks? Methodologic Considerations.

Science.gov (United States)

Golozar, Asieh; Liu, Shuiqing; Lin, Joeseph A; Peairs, Kimberly; Yeh, Hsin-Chieh

2016-01-01

The substantial burden of cancer and diabetes and the association between the two conditions has been a motivation for researchers to look for targeted strategies that can simultaneously affect both diseases and reduce their overlapping burden. In the absence of randomized clinical trials, researchers have taken advantage of the availability and richness of administrative databases and electronic medical records to investigate the effects of drugs on cancer risk among diabetic individuals. The majority of these studies suggest that metformin could potentially reduce cancer risk. However, the validity of this purported reduction in cancer risk is limited by several methodological flaws either in the study design or in the analysis. Whether metformin use decreases cancer risk relies heavily on the availability of valid data sources with complete information on confounders, accurate assessment of drug use, appropriate study design, and robust analytical techniques. The majority of the observational studies assessing the association between metformin and cancer risk suffer from methodological shortcomings and efforts to address these issues have been incomplete. Future investigations on the association between metformin and cancer risk should clearly address the methodological issues due to confounding by indication, prevalent user bias, and time-related biases. Although the proposed strategies do not guarantee a bias-free estimate for the association between metformin and cancer, they will reduce synthesis of and reporting of erroneous results.

Reduced RAC1 activity inhibits cell proliferation and induces apoptosis in neurofibromatosis type 2(NF2)-associated schwannoma.

Science.gov (United States)

Wang, Ying; Wang, Bo; Li, Peng; Zhang, Qi; Liu, Pinan

2017-12-01

Objective To study the function and potential mechanism of RAC1 inhibitors in NF2-associated schwannoma. Methods In this study, we the downregulation of RAC1 activity and tumor cell phenotypes by RAC1 inhibitor NSC23766 in vitro. And we further validated the anti-proliferation effect by this RAC1 inhibitor in subcutaneous xenograft tumor model and sciatic nerve model. Results Pharmacological inhibition of RAC1 could significantly inhibit the proliferation of both RT4 cells and human NF2-associated primary schwannoma cells by inducing apoptosis. Pharmacological inhibition of RAC1 effectively reduced Rac1 activity and down-regulated the pathway downstream of Rac. Moreover, pharmacological inhibition of RAC1 showed a potential antitumor effect, with low toxicity in vivo. Conclusion RAC1 inhibitors may play a therapeutic role in patients with schwannoma.

Mechanisms underlying the dualistic mode of action of major soy isoflavones in relation to cell proliferation and cancer risks

NARCIS (Netherlands)

Rietjens, I.M.C.M.; Sotoca, A.M.; Vervoort, J.; Louisse, J.

2013-01-01

Isoflavones are phytoestrogens that have been linked to both beneficial as well as adverse effects in relation to cell proliferation and cancer risks. The present article presents an overview of these seemingly contradicting health effects and of mechanisms that could be involved in this dualistic

Reducing cancer risk in rural communities through supermarket interventions.

Science.gov (United States)

McCool, Barent N; Lyford, Conrad P; Hensarling, Natalie; Pence, Barbara; McCool, Audrey C; Thapa, Janani; Belasco, Eric; Carter, Tyra M

2013-09-01

Cancer risk is high, and prevention efforts are often minimal in rural communities. Feasible means of encouraging lifestyles that will reduce cancer risk for residents of rural communities are needed. This project developed and tested a model that could be feasibly adopted by rural communities to reduce cancer risk. This model focuses on incorporating multi-faceted cancer risk education in the local supermarket. As the supermarket functions both as the primary food source and an information source in small rural communities, the supermarket focus encourages the development of a community environment supportive of lifestyles that should reduce residents' risk for cancer. The actions taken to implement the model and the challenges that communities would have in implementing the model are identified.

Nuclear exports and non-proliferation

International Nuclear Information System (INIS)

Courteix, Simone.

1978-01-01

Increased preoccupation in present times with the risk of proliferation of nuclear weapons is reflected in the multiplication of international agreements such as the Non-proliferation Treaty and in the strengthening of consultations between industrialised countries (London Club). After analysing the IAEA safeguards system under the Non-proliferation Treaty and its shortcomings both technically and otherwise, the author considers how this situation can be remedied in the light of the London Agreements and in view of the position of the main countries concerned. The annex to the book contains the texts of many international agreements and relevant national regulations as well as nuclear policy statements. It also includes a detailed bibliograaphy. (NEA) [fr

Evaluation of the Administration's proposed nuclear non-proliferation strategy. Report to the Congress

International Nuclear Information System (INIS)

1977-01-01

Dwindling supplies of fossil fuels are causing countries to turn increasingly to nuclear power as a major source of energy. Although nuclear power holds out the promise of energy independence, it has a formidable drawback--it can also lead to the proliferation of nuclear weapons. In April, the President announced a new policy designed to curb nuclear proliferation and the executive branch proposed legislation entitled 'The Nuclear Non-Proliferation Policy Act of 1977.' The strategy outlined in these documents calls for stricter export controls and safeguards as well as actions affecting uranium enrichment services, reprocessing, storing of spent fuel, and disposing of radioactive nuclear wastes. GAO analyzed this non-proliferation strategy as it relates to: Improving nuclear export controls; Strengthening international nuclear safeguards; Maintaining U.S. reliability as a supplier of uranium enrichment services; Deferring U.S. reprocessing of spent fuel as an example for others; Reducing risk of proliferation by controlling spent reactor fuel. In general, GAO concluded that the administration's strategy is constructive but noted some weaknesses which should be addressed. Some of the problems noted in this report may already have been addressed by congressional committees in their markup of the legislation

Cell proliferation of Paramecium tetraurelia under simulated microgravity

Science.gov (United States)

Sawai, S.; Mogami, Y.; Baba, S. A.

Paramecium is known to proliferate faster under microgravity in space and slower under hypergravity Experiments using axenic culture medium have demonstrated that the hypergravity affected directly on the proliferation of Paramecium itself Kato et al 2003 In order to assess the mechanisms underlying the physiological effects of gravity on cell proliferation Paramecium tetraurelia was grown under simulated microgravity performed by clinorotation and the time course of the proliferation was investigated in detail on the basis of the logistic analysis P tetraurelia was cultivated in a closed chamber in which cells were confined without air babbles reducing the shear stresses and turbulence under the rotation The chamber is made of quartz and silicone rubber film the former is for the optically-flat walls for the measurement of cell density by means of a non-invasive laser optical-slice method and the latter for gas exchange Because the closed chamber has an inner dimension of 3 times 3 times 60 mm Paramecium does not accumulate at the top of the chamber despite its negative gravitactic behavior We measured the cell density at regular time intervals without breaking the configuration of the chamber and analyzed the proliferation parameters by fitting the data to a logistic equation Clinorotation had the effects of reducing the proliferation of P tetraurelia It reduced both the saturation cell density and the maximum proliferation rate although it had little effect on the

Nutritional strategies to reduce falls risk in older people.

Science.gov (United States)

Nash, Louise; Bergin, Nick

2018-03-23

A literature review found an association between increased falls risk and malnutrition, sarcopenia, vitamin D deficiency and dehydration. Strategies to identify, prevent and treat these conditions can help to reduce falls risk in at-risk groups such as frail, older people. Nurses can reduce falls risk in older people by raising awareness of risk factors and embedding nutritional strategies in local falls reduction strategies. ©2018 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

Intermittent pressure decreases human keratinocyte proliferation in vitro.

Science.gov (United States)

Nasca, Maria R; Shih, Alan T; West, Dennis P; Martinez, Wanda M; Micali, Giuseppe; Landsman, Adam S

2007-01-01

The aim of this study was to investigate the correlation between pressure changes and keratinocyte proliferation by determining whether keratinocytes exposed to altered mechanical pressures would proliferate at different rates compared to control cells not subjected to pressure changes. Tissue culture flasks of human keratinocytes plated at an approximate density of 15,000 cells/cm(2) undergoing an intermittent cyclic pressure of 362 mm Hg at a frequency of 2.28 or 5.16 cycles/min (0.038 or 0.086 Hz) for 8 h were compared to control flasks grown at ambient room pressure. An in-line pressure transducer was used to monitor and adjust pressure within the cell chambers, using a solenoid valve. A thymidine incorporation assay assessed the amount of cell proliferation in each set of experiments. Differences in proliferation between keratinocytes subjected to cyclic pressure changes and control cells were found to be statistically significant (p < 0.05) in 4 out of 5 proliferation assays. Also, a higher frequency of pressure changes consistently generated a reduced proliferation rate compared to that seen in cells exposed to a lower frequency of pressure changes. These data indicate that keratinocytes undergoing intermittent pressure changes exhibit decreased proliferation rates compared to controls. Furthermore, an increased frequency rate seems to have a greater effect on proliferation than low-frequency rate pressure changes, suggesting that the stress caused by frequently changed pressure may play a greater role in reducing keratinocyte proliferation than the actual magnitude of load applied to the cells. Our results support the current treatment protocol of reducing speed and duration of walking on the site of the wound to promote healing of foot ulcers. (c) 2007 S. Karger AG, Basel.

Does retirement reduce the risk of myocardial infarction?

DEFF Research Database (Denmark)

Olesen, Kasper; Rugulies, Reiner; Rod, Naja Hulvej

2014-01-01

BACKGROUND: Recent studies have suggested that retirement may have beneficial effects on health outcomes. In this study we examined whether the risk of myocardial infarction (MI) was reduced following retirement in a Danish population sample. METHODS: Participants were 617 511 Danish workers, born...... of 1.11 (95% confidence interval: 1.06, 1.16) when comparing retirees with active workers of the same age. CONCLUSIONS: This study does not support the hypothesis that retirement reduces risk of MI. On the contrary, we find that retirement is associated with a modestly increased risk of MI....

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.

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 on 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 bum 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 nonproliferation 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

The diabetes medication Canagliflozin reduces cancer cell proliferation by inhibiting mitochondrial complex-I supported respiration

Directory of Open Access Journals (Sweden)

Linda A. Villani

2016-10-01

Full Text Available Objective: The sodium-glucose transporter 2 (SGLT2 inhibitors Canagliflozin and Dapagliflozin are recently approved medications for type 2 diabetes. Recent studies indicate that SGLT2 inhibitors may inhibit the growth of some cancer cells but the mechanism(s remain unclear. Methods: Cellular proliferation and clonogenic survival were used to assess the sensitivity of prostate and lung cancer cell growth to the SGLT2 inhibitors. Oxygen consumption, extracellular acidification rate, cellular ATP, glucose uptake, lipogenesis, and phosphorylation of AMP-activated protein kinase (AMPK, acetyl-CoA carboxylase, and the p70S6 kinase were assessed. Overexpression of a protein that maintains complex-I supported mitochondrial respiration (NDI1 was used to establish the importance of this pathway for mediating the anti-proliferative effects of Canagliflozin. Results: Clinically achievable concentrations of Canagliflozin, but not Dapagliflozin, inhibit cellular proliferation and clonogenic survival of prostate and lung cancer cells alone and in combination with ionizing radiation and the chemotherapy Docetaxel. Canagliflozin reduced glucose uptake, mitochondrial complex-I supported respiration, ATP, and lipogenesis while increasing the activating phosphorylation of AMPK. The overexpression of NDI1 blocked the anti-proliferative effects of Canagliflozin indicating reductions in mitochondrial respiration are critical for anti-proliferative actions. Conclusion: These data indicate that like the biguanide metformin, Canagliflozin not only lowers blood glucose but also inhibits complex-I supported respiration and cellular proliferation in prostate and lung cancer cells. These observations support the initiation of studies evaluating the clinical efficacy of Canagliflozin on limiting tumorigenesis in pre-clinical animal models as well epidemiological studies on cancer incidence relative to other glucose lowering therapies in clinical populations. Keywords: AMP

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

The Natural Compound Dansameum Reduces foam Cell Formation by Downregulating CD36 and Peroxisome Proliferator-activated Receptor-gamma; Expression.

Science.gov (United States)

Park, Kang-Seo; Ahn, Sang Hyun; Lee, Kang Pa; Park, Sun-Young; Cheon, Jin Hong; Choi, Jun-Yong; Kim, Kibong

2018-01-01

Atherosclerosis-induced vascular disorders are major causes of death in most western countries. During the development of atherosclerotic lesions, foam cell formation is essential and formed through the expression of CD36 and the peroxisome proliferator-activated receptor gamma (PPAR-γ). To investigate whether dansameum extract (DSE) could show anti-atherosclerotic effect through down-regulating cellular redox state including CD36 and PARP-γ expression in oxidative low-density lipoprotein (oxLDL)-treated RAW264.7 cells and on differentiated foam cells in ApoE Knockout (ApoE-/-) mice. The Korean polyherbal medicine DSE was prepared from three plants in the following proportions: 40 g of Salvia miltiorrhiza root, 4 g of Amomumxanthioides fruit, and 4 g of Santalum album lignum. The immunohistochemistry and reverse transcription-polymerase chain reaction was used for analysis of protein and mRNA involved in foam cell formation. We first showed that effects of DSE on foam cell formation in both oxLDL-induced RAW264.7 cells and in blood vessels from apolipoprotein E deficientApoE-/- mice with high fat diet-fed. DSE treatment significantly reduced the expression of CD36 and PPAR-γ in oxLDL-stimulated RAW264.7 cells and ApoE-/-mice, in the latter case by regulating heme oxygenase-1. Furthermore, DSE treatment also reduced cellular lipid content in vitro and in vivo experiments. Our data suggest that DSE may have anti-atherosclerotic properties through regulating foam cell formation. Dansameum extract (DSE) Regulates the expression of CD36 and peroxisome proliferator-activated receptor gamma in oxidative low-density lipoprotein-stimulated RAW264.7 Cells and ApoE Knockout (ApoE Knockout [ApoE-/-]) miceDSE Regulates Cholesterol Levels in the Serum of ApoE-deficient (ApoE-/-) miceDSE Reduced the Formation of Foam Cells by Regulating heme oxygenase-1 in ApoE-/- mice with high fat diet-fed. Abbreviations used: DSE: Dansameum extract, PPAR-γ: Peroxisome proliferator

Breast cancer after bilateral risk-reducing mastectomy

DEFF Research Database (Denmark)

Skytte, A-B; Crüger, Dorthe Gylling; Gerster, M

2011-01-01

This study aims to evaluate the incidence of breast cancer after risk-reducing mastectomy (RRM) in healthy BRCA mutation carriers. This study is a long-term follow-up of 307 BRCA mutation carriers of whom 96 chose RRM. None of the study participants had a previous history of breast or ovarian...... cancer nor had they undergone RRM or risk-reducing bilateral salpingo-oophorectomy (BSO) prior to the time of BRCA testing. The annual incidence of post-mastectomy breast cancer was 0.8% compared with 1.7% in the non-operated group. Implications of these findings in relation to genetic counseling...

Advanced Nuclear Measurements - Sensitivity Analysis Emerging Safeguards, Problems and Proliferation Risk

International Nuclear Information System (INIS)

Dreicer, J.S.

1999-01-01

During the past year this component of the Advanced Nuclear Measurements LDRD-DR has focused on emerging safeguards problems and proliferation risk by investigating problems in two domains. The first is related to the analysis, quantification, and characterization of existing inventories of fissile materials, in particular, the minor actinides (MA) formed in the commercial fuel cycle. Understanding material forms and quantities helps identify and define future measurement problems, instrument requirements, and assists in prioritizing safeguards technology development. The second problem (dissertation research) has focused on the development of a theoretical foundation for sensor array anomaly detection. Remote and unattended monitoring or verification of safeguards activities is becoming a necessity due to domestic and international budgetary constraints. However, the ability to assess the trustworthiness of a sensor array has not been investigated. This research is developing an anomaly detection methodology to assess the sensor array

Low physiologic oxygen tensions reduce proliferation and differentiation of human multipotent mesenchymal stromal cells

Directory of Open Access Journals (Sweden)

Handgretinger Rupert

2010-01-01

Full Text Available Abstract Background Human multipotent mesenchymal stromal cells (MSC can be isolated from various tissues including bone marrow. Here, MSC participate as bone lining cells in the formation of the hematopoietic stem cell niche. In this compartment, the oxygen tension is low and oxygen partial pressure is estimated to range from 1% to 7%. We analyzed the effect of low oxygen tensions on human MSC cultured with platelet-lysate supplemented media and assessed proliferation, morphology, chromosomal stability, immunophenotype and plasticity. Results After transferring MSC from atmospheric oxygen levels of 21% to 1%, HIF-1α expression was induced, indicating efficient oxygen reduction. Simultaneously, MSC exhibited a significantly different morphology with shorter extensions and broader cell bodies. MSC did not proliferate as rapidly as under 21% oxygen and accumulated in G1 phase. The immunophenotype, however, was unaffected. Hypoxic stress as well as free oxygen radicals may affect chromosomal stability. However, no chromosomal abnormalities in human MSC under either culture condition were detected using high-resolution matrix-based comparative genomic hybridization. Reduced oxygen tension severely impaired adipogenic and osteogenic differentiation of human MSC. Elevation of oxygen from 1% to 3% restored osteogenic differentiation. Conclusion Physiologic oxygen tension during in vitro culture of human MSC slows down cell cycle progression and differentiation. Under physiological conditions this may keep a proportion of MSC in a resting state. Further studies are needed to analyze these aspects of MSC in tissue regeneration.

Breastfeeding Reduces Childhood Obesity Risks.

Science.gov (United States)

Wang, Liang; Collins, Candice; Ratliff, Melanie; Xie, Bin; Wang, Youfa

2017-06-01

The present study examined the effects of breastfeeding and its duration on the development of childhood obesity from 24 months through grade 6. U.S. longitudinal data collected from 1234 children were analyzed using logistic regression models and generalized estimating equation (GEE). Child height and weight were measured six times at ages of 24 months, 36 months, 54 months, grade 1, grade 3, and grade 6. During the early 1990s, prevalence of breastfeeding was low in the United States, 60% and 48% at 1 and 6 months, respectively. Nonsmoking, white, married mothers with both parents in the household, and with income above the poverty line, were more likely to breastfeed at 1 month of age of their babies. Obesity rate of the children increased with age from 24 months to grade 6. Logistic regression showed that breastfeeding at month 1 was associated with 53% (odds ratio [OR]: 0.47, 95% confidence interval [CI]: 0.30-0.73) and 47% (OR: 0.53, 95% CI: 0.36-0.78) decreased risks for childhood obesity at grades 1 and 6, respectively. GEE analysis showed that breastfeeding at 1 month reduced risk for childhood obesity by 36% (95% CI: 0.47-0.88) from ages 24 months through grade 6. Regarding breastfeeding duration, more than 6 months (vs. never) was associated with a decreased risk for childhood obesity by 42% (OR: 0.58, 95% CI: 0.36-0.94). Breastfeeding at 1 month and more than 6 months reduced the risk of childhood obesity. Rate of breastfeeding was low in the United States in the 1990s, which may have had long-term implications on children.

Non-proliferation, safeguards, and security for the fissile materials disposition program immobilization alternatives

Energy Technology Data Exchange (ETDEWEB)

Duggan, R.A.; Jaeger, C.D.; Tolk, K.M. [Sandia National Labs., Albuquerque, NM (United States); Moore, L.R. [Lawrence Livermore National Lab., CA (United States)

1996-05-01

The Department of Energy is analyzing long-term storage and disposition alternatives for surplus weapons-usable fissile materials. A number of different disposition alternatives are being considered. These include facilities for storage, conversion and stabilization of fissile materials, immobilization in glass or ceramic material, fabrication of fissile material into mixed oxide (MOX) fuel for reactors, use of reactor based technologies to convert material into spent fuel, and disposal of fissile material using geologic alternatives. This paper will focus on how the objectives of reducing security and proliferation risks are being considered, and the possible facility impacts. Some of the areas discussed in this paper include: (1) domestic and international safeguards requirements, (2) non-proliferation criteria and measures, (3) the threats, and (4) potential proliferation, safeguards, and security issues and impacts on the facilities. Issues applicable to all of the possible disposition alternatives will be discussed in this paper. However, particular attention is given to the plutonium immobilization alternatives.

Aspirin therapy reduces the ability of platelets to promote colon and pancreatic cancer cell proliferation: Implications for the oncoprotein c-MYC

Science.gov (United States)

Sylman, Joanna L.; Ngo, Anh T. P.; Pang, Jiaqing; Sears, Rosalie C.; Williams, Craig D.; McCarty, Owen J. T.

2017-01-01

Aspirin, an anti-inflammatory and antithrombotic drug, has become the focus of intense research as a potential anticancer agent owing to its ability to reduce tumor proliferation in vitro and to prevent tumorigenesis in patients. Studies have found an anticancer effect of aspirin when used in low, antiplatelet doses. However, the mechanisms through which low-dose aspirin works are poorly understood. In this study, we aimed to determine the effect of aspirin on the cross talk between platelets and cancer cells. For our study, we used two colon cancer cell lines isolated from the same donor but characterized by different metastatic potential, SW480 (nonmetastatic) and SW620 (metastatic) cancer cells, and a pancreatic cancer cell line, PANC-1 (nonmetastatic). We found that SW480 and PANC-1 cancer cell proliferation was potentiated by human platelets in a manner dependent on the upregulation and activation of the oncoprotein c-MYC. The ability of platelets to upregulate c-MYC and cancer cell proliferation was reversed by an antiplatelet concentration of aspirin. In conclusion, we show for the first time that inhibition of platelets by aspirin can affect their ability to induce cancer cell proliferation through the modulation of the c-MYC oncoprotein. PMID:27903583

Maslinic acid inhibits proliferation of renal cell carcinoma cell lines and suppresses angiogenesis of endothelial cells

Directory of Open Access Journals (Sweden)

Parth Thakor

2017-03-01

Full Text Available Despite the introduction of many novel therapeutics in clinical practice, metastatic renal cell carcinoma (RCC remains a treatment-re-sistant cancer. As red and processed meat are considered risk factors for RCC, and a vegetable-rich diet is thought to reduce this risk, research into plant-based therapeutics may provide valuable complementary or alternative therapeutics for the management of RCC. Herein, we present the antiproliferative and antiangiogenic effects of maslinic acid, which occurs naturally in edible plants, particularly in olive fruits, and also in a variety of medicinal plants. Human RCC cell lines (ACHN, Caki-1, and SN12K1, endothelial cells (human umbilical vein endothelial cell line [HUVEC], and primary cultures of kidney proximal tubular epithelial cells (PTEC were treated with maslinic acid. Maslinic acid was relatively less toxic to PTEC when compared with RCC under similar experimental conditions. In RCC cell lines, maslinic acid induced a significant reduction in proliferation, proliferating cell nuclear antigen, and colony formation. In HUVEC, maslinic acid induced a significant reduction in capillary tube formation in vitro and vascular endothelial growth factor. This study provides a rationale for incorporating a maslinic acid–rich diet either to reduce the risk of developing kidney cancer or as an adjunct to existing antiangiogenic therapy to improve efficacy.

Reducing cardiovascular risk : protecting the kidney

NARCIS (Netherlands)

Dobre, Daniela; Lambers Heerspink, Hiddo J.; de Zeeuw, Dick

2009-01-01

Progressive decline of renal function in chronic kidney disease (CKD), measured by a reduced glomerular filtration rate or albuminuria, is linked to an increased risk of cardiovascular (CV) disease. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), most

Future non-proliferation challenges

International Nuclear Information System (INIS)

Yelchenko, Volodymyr

2008-01-01

Having chaired the Second Session of the Preparatory Committee Mr. Volodymyr Yelchenko noted that the NPT States parties reaffirmed the important role of the Treaty as the cornerstone of the global non-proliferation regime. They stressed that non-compliance with the Treaty provisions by States parties undermined non-proliferation and placed emphasis on the mutually reinforcing nature of disarmament and non-proliferation, and due respect for the right of States parties to the peaceful use of nuclear energy in conformity with the treaty. They reaffirmed the importance of promoting the peaceful uses of nuclear energy and international nuclear cooperation for peaceful purposes in ways consistent with the non-proliferation goal of the Treaty. The universality aspect was brought to the front with the lack of progress in this area. States parties called upon India, Israel and Pakistan to accede to the Treaty as non-nuclear-weapons states, promptly and without conditions and to bring into force comprehensive safeguards agreements, together with Additional Protocols, for ensuring non-proliferation. There is concern that non-States actors could gain access to weapons of mass destruction. One of the underlying themes at the Second Prepcom was the total elimination of nuclear weapons as the only absolute guarantee against their proliferation. Negative consequences to nuclear non-proliferation were also mentioned in the context of the abrogation of the Anti-Ballistic Missile Treaty and the development of missile defense systems, with the risk of a new arms race on Earth and in outer space. The importance of the immediate commencement of negotiations in the Conference of Disarmament on a treaty concerning fissile material for nuclear weapons or other nuclear explosive devices and the urgent conclusion of such a treaty as a beneficial step towards non-proliferation was stressed. The NPT states parties reaffirmed the role of the IAEA as the sole competent authority responsible for

Chemical Activation of the Hypoxia-Inducible Factor Reversibly Reduces Tendon Stem Cell Proliferation, Inhibits Their Differentiation, and Maintains Cell Undifferentiation.

Science.gov (United States)

Menon, Alessandra; Creo, Pasquale; Piccoli, Marco; Bergante, Sonia; Conforti, Erika; Banfi, Giuseppe; Randelli, Pietro; Anastasia, Luigi

2018-01-01

Adult stem cell-based therapeutic approaches for tissue regeneration have been proposed for several years. However, adult stem cells are usually limited in number and difficult to be expanded in vitro, and they usually tend to quickly lose their potency with passages, as they differentiate and become senescent. Culturing stem cells under reduced oxygen tensions (below 21%) has been proposed as a tool to increase cell proliferation, but many studies reported opposite effects. In particular, cell response to hypoxia seems to be very stem cell type specific. Nonetheless, it is clear that a major role in this process is played by the hypoxia inducible factor (HIF), the master regulator of cell response to oxygen deprivation, which affects cell metabolism and differentiation. Herein, we report that a chemical activation of HIF in human tendon stem cells reduces their proliferation and inhibits their differentiation in a reversible and dose-dependent manner. These results support the notion that hypoxia, by activating HIF, plays a crucial role in preserving stem cells in an undifferentiated state in the "hypoxic niches" present in the tissue in which they reside before migrating in more oxygenated areas to heal a damaged tissue.

Chemical Activation of the Hypoxia-Inducible Factor Reversibly Reduces Tendon Stem Cell Proliferation, Inhibits Their Differentiation, and Maintains Cell Undifferentiation

Directory of Open Access Journals (Sweden)

Alessandra Menon

2018-01-01

Full Text Available Adult stem cell-based therapeutic approaches for tissue regeneration have been proposed for several years. However, adult stem cells are usually limited in number and difficult to be expanded in vitro, and they usually tend to quickly lose their potency with passages, as they differentiate and become senescent. Culturing stem cells under reduced oxygen tensions (below 21% has been proposed as a tool to increase cell proliferation, but many studies reported opposite effects. In particular, cell response to hypoxia seems to be very stem cell type specific. Nonetheless, it is clear that a major role in this process is played by the hypoxia inducible factor (HIF, the master regulator of cell response to oxygen deprivation, which affects cell metabolism and differentiation. Herein, we report that a chemical activation of HIF in human tendon stem cells reduces their proliferation and inhibits their differentiation in a reversible and dose-dependent manner. These results support the notion that hypoxia, by activating HIF, plays a crucial role in preserving stem cells in an undifferentiated state in the “hypoxic niches” present in the tissue in which they reside before migrating in more oxygenated areas to heal a damaged tissue.

Bauhinia bauhinioides cruzipain inhibitor reduces endothelial proliferation and induces an increase of the intracellular Ca2+ concentration.

Science.gov (United States)

Bilgin, Mehmet; Neuhof, Christiane; Doerr, Oliver; Benscheid, Utz; Andrade, Sheila S; Most, Astrid; Abdallah, Yaser; Parahuleva, Mariana; Guenduez, Dursun; Oliva, Maria L; Erdogan, Ali

2010-12-01

Proteinase inhibitors, isolated from different types of Bauhinia, have an effect on apoptosis, angiogenesis and inflammation. The Bauhinia bauhinioides cruzipain inhibitor (BbCI) is a Kunitz-type inhibitor and inactivates the cysteine proteinases cruzipain and cruzain from Trypanosoma cruzi. Cruzipain and tissue kallikrein have similar biochemical properties, e.g. the proteolytic cleavage of the kininogen precursor of lys-bradykinin. Tissue kallikrein stimulation in endothelial cells causes migration and capillary tube formation. The aim of this study was to examine whether the antiproliferative effect of BbCI is dependent on changes of the intracellular calcium concentration and membrane hyperpolarization. Endothelial cells were isolated from human umbilical cord veins (HUVEC). For proliferation experiments, HUVEC were incubated with BbCI (10-100 μmol/L) for 48 h. The proliferation was detected by cell counting with a Neubauer chamber. The effect of BbCI (10-100 μM) on the membrane potential was measured with the fluorescence dye DiBAC4(3) and the effect on [Ca+2]i with the fluorescence probe Fluo-3 AM. The change of the fluorescence intensity was determined with a GENios plate reader (Tecan). The experiments showed that BbCI (10-100 μmol/L) reduces the endothelial cell proliferation significantly in a concentration-dependent manner with a maximum effect at 100 μmol/L (35.1±1.8% as compared to control (p≤0.05; n=45)). As compared to the control, the addition of BbCI (100 μmol/L) caused a significant increase of systolic Ca2+ of 28.4±5.0% after 30 min incubation. HUVEC treatment with BbCI (100 μmol/L) showed a weak but significant decrease of the membrane potential of 9.5±0.9% as compared to control (p≤0.05; n=80). BbCI influenced significantly the endothelial proliferation, the intracellular Ca2+ concentration and the membrane potential.

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

Akt1 deficiency diminishes skeletal muscle hypertrophy by reducing satellite cell proliferation.

Science.gov (United States)

Moriya, Nobuki; Miyazaki, Mitsunori

2018-02-14

Skeletal muscle mass is determined by the net dynamic balance between protein synthesis and degradation. Although the Akt/mechanistic target of rapamycin (mTOR)-dependent pathway plays an important role in promoting protein synthesis and subsequent skeletal muscle hypertrophy, the precise molecular regulation of mTOR activity by the upstream protein kinase Akt is largely unknown. In addition, the activation of satellite cells has been indicated as a key regulator of muscle mass. However, the requirement of satellite cells for load-induced skeletal muscle hypertrophy is still under intense debate. In this study, female germline Akt1 knockout (KO) mice were used to examine whether Akt1 deficiency attenuates load-induced skeletal muscle hypertrophy through suppressing mTOR-dependent signaling and satellite cell proliferation. Akt1 KO mice showed a blunted hypertrophic response of skeletal muscle, with a diminished rate of satellite cell proliferation following mechanical overload. In contrast, Akt1 deficiency did not affect the load-induced activation of mTOR signaling and the subsequent enhanced rate of protein synthesis in skeletal muscle. These observations suggest that the load-induced activation of mTOR signaling occurs independently of Akt1 regulation and that Akt1 plays a critical role in regulating satellite cell proliferation during load-induced muscle hypertrophy.

Business risks, functions, methods of assessment and ways to reduce risk

Directory of Open Access Journals (Sweden)

A.V. Mihalchuk

2015-06-01

Full Text Available For successful existence in a market economy entrepreneur have to take bold actions, and this increases the risk. The article describes the concept of entrepreneurship and business risk, positive and negative aspects of functions of risk in business. Therefore, it is necessary to assess the risk properly and be able to manage it to achieve the most effective results in the market. In market conditions the problem of assessing and accounting market becomes independent theoretical and practical significance as an important component of the theory and practice of management. Risk - a key element of business activities. Development of risk situations can lead to both the occurrence of adverse effects (losses, lost profits, and positive results for a company in the form of increased profit. This article describes: the concept of entrepreneurship, risk and business risks, characteristic of positive and negative aspects of risk functions in business, methods of assessment and risk reduction, shows formulae and examples you can use to assess risk in an enterprise. Analyzing already established methods of risk assessment a number of rules were proposed in order to reduce business risk.

Colon cancer proliferating desulfosinigrin in wasabi (Wasabia japonica).

Science.gov (United States)

Weil, Marvin J; Zhang, Yanjun; Nair, Muraleedharan G

2004-01-01

A reduced incidence of different types of cancer has been linked to consumption of Brassica vegetables, and there is evidence that glucosinolates (GSLs) and their hydrolysis products play a role in reducing cancer risk. Wasabi (Wasabia japonica) and horseradish (Armoracia rusticana), both Brassica vegetables, are widely used condiments both in Japanese cuisine and in the United States. Desulfosinigrin (DSS) (1) was isolated from a commercially available wasabi powder and from fresh wasabi roots. Sinigrin (2) was isolated from horseradish roots. DSS and sinigrin were evaluated for their inhibitory effects on cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes, on lipid peroxidation, and on the proliferation of human colon (HCT-116), breast (MCF-7), lung (NCIH460), and central nervous system (CNS, SF-268) cancer cell lines. DSS did not inhibit COX enzymes or lipid peroxidation at 250 microg/ml. Sinigrin inhibited lipid peroxidation by 71% at 250 microg/ml. However, DSS promoted the growth of HCT-116 (colon) and NCI H460 (lung) human cancer cells as determined by the MTT assay in a concentration-dependent manner. At 3.72 microg/ml, a 27% increase in the number of viable human HCT-116 colon cancer cells was observed; the corresponding increases at 7.50 and 15 microg/ml were 42 and 69%, respectively. At 60 microg/ml, DSS doubled the number of HCT-16 colon cancer cells. For NCI H460 human lung cancer cells, DSS at 60 microg/ml increased the cell number by 20%. Sinigrin showed no proliferating effect on the tumor cells tested. This is the first report of the tumor cell-proliferating activity by a desulfoglucosinolate, the biosynthetic precursor of GSLs found in Brassica spp.

Metformin Induces Cell Cycle Arrest, Reduced Proliferation, Wound Healing Impairment In Vivo and Is Associated to Clinical Outcomes in Diabetic Foot Ulcer Patients.

Science.gov (United States)

Ochoa-Gonzalez, Fatima; Cervantes-Villagrana, Alberto R; Fernandez-Ruiz, Julio C; Nava-Ramirez, Hilda S; Hernandez-Correa, Adriana C; Enciso-Moreno, Jose A; Castañeda-Delgado, Julio E

2016-01-01

Several epidemiological studies in diabetic patients have demonstrated a protective effect of metformin to the development of several types of cancer. The underlying mechanisms of such phenomenon is related to the effect of metformin on cell proliferation among which, mTOR, AMPK and other targets have been identified. However, little is known about the role that metformin treatment have on other cell types such as keratinocytes and whether exposure to metformin of these cells might have serious repercussions in wound healing delay and in the development of complications in diabetic patients with foot ulcers or in their exacerbation. HaCaT Cells were exposed to various concentrations of metformin and cell viability was evaluated by a Resazurin assay; Proliferation was also evaluated with a colony formation assay and with CFSE dilution assay by flow cytometry. Cell cycle was also evaluated by flow cytometry by PI staining. An animal model of wound healing was used to evaluate the effect of metformin in wound closure. Also, an analysis of patients receiving metformin treatment was performed to determine the effect of metformin treatment on the outcome and wound area. Statistical analysis was performed on SPSS v. 18 and GraphPad software v.5. Metformin treatment significantly reduces cell proliferation; colony formation and alterations of the cell cycle are observed also in the metformin treated cells, particularly in the S phase. There is a significant increase in the area of the wound of the metformin treated animals at different time points (Pdiabetic foot ulcers at the time of hospitalization. A protective effect of metformin was observed for amputation, probably associated with the anti inflammatory effects reported of metformin. Metformin treatment reduces cell proliferation and reduces wound healing in an animal model and affects clinical outcomes in diabetic foot ulcer patients. Chronic use of this drug should be further investigated to provide evidence of

Periodontal disease with treatment reduces subsequent cancer risks.

Science.gov (United States)

Hwang, Ing-Ming; Sun, Li-Min; Lin, Cheng-Li; Lee, Chun-Feng; Kao, Chia-Hung

2014-10-01

The aim of our study was to evaluate the relationship between routine treatment of periodontal disease (PD) and the subsequent risks for cancers in Taiwan. Study participants were selected from the Taiwan National Health Insurance (NHI) system database. The PD with a routine treatment cohort contained 38 902 patients. For each treatment cohort participant, two age- and sex-matched comparison (control) cohort participants were randomly selected. Cox's proportional hazards regression analysis was used to estimate the effects of PD with treatment on the subsequent risk of cancer. The overall risk of developing cancer was significantly lower in the treatment cohort than in the patients without treatment (adjusted Hazard ratio = 0.72, 95% confidence interval = 0.68-0.76). The risks of developing most gastrointestinal tract, lung, gynecological and brain malignancies were significantly lower in the treatment cohort than in the comparison cohort. In contrast, the risks of prostate and thyroid cancers were significantly higher in the treatment cohort than in the comparison cohort. Our findings suggest that PD with treatment is associated with a significantly reduced overall risk of cancer and reduced risks of certain types of cancers. © The Author 2014. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Mechanical unloading reduces microtubule actin crosslinking factor 1 expression to inhibit β-catenin signaling and osteoblast proliferation.

Science.gov (United States)

Yin, Chong; Zhang, Yan; Hu, Lifang; Tian, Ye; Chen, Zhihao; Li, Dijie; Zhao, Fan; Su, Peihong; Ma, Xiaoli; Zhang, Ge; Miao, Zhiping; Wang, Liping; Qian, Airong; Xian, Cory J

2018-07-01

Mechanical unloading was considered a major threat to bone homeostasis, and has been shown to decrease osteoblast proliferation although the underlying mechanism is unclear. Microtubule actin crosslinking factor 1 (MACF1) is a cytoskeletal protein that regulates cellular processes and Wnt/β-catenin pathway, an essential signaling pathway for osteoblasts. However, the relationship between MACF1 expression and mechanical unloading, and the function and the associated mechanisms of MACF1 in regulating osteoblast proliferation are unclear. This study investigated effects of mechanical unloading on MACF1 expression levels in cultured MC3T3-E1 osteoblastic cells and in femurs of mice with hind limb unloading; and it also examined the role and potential action mechanisms of MACF1 in osteoblast proliferation in MACF1-knockdown, overexpressed or control MC3T3-E1 cells treated with or without the mechanical unloading condition. Results showed that the mechanical unloading condition inhibited osteoblast proliferation and MACF1 expression in MC3T3-E1 osteoblastic cells and mouse femurs. MACF1 knockdown decreased osteoblast proliferation, while MACF1 overexpression increased it. The inhibitory effect of mechanical unloading on osteoblast proliferation also changed with MACF1 expression levels. Furthermore, MACF1 was found to enhance β-catenin expression and activity, and mechanical unloading decreased β-catenin expression through MACF1. Moreover, β-catenin was found an important regulator of osteoblast proliferation, as its preservation by treatment with its agonist lithium attenuated the inhibitory effects of MACF1-knockdown or mechanical unloading on osteoblast proliferation. Taken together, mechanical unloading decreases MACF1 expression, and MACF1 up-regulates osteoblast proliferation through enhancing β-catenin signaling. This study has thus provided a mechanism for mechanical unloading-induced inhibited osteoblast proliferation. © 2017 Wiley Periodicals, Inc.

A novel transgenic mouse model of growth plate dysplasia reveals that decreased chondrocyte proliferation due to chronic ER stress is a key factor in reduced bone growth

Directory of Open Access Journals (Sweden)

Benedetta Gualeni

2013-11-01

Disease mechanisms leading to different forms of chondrodysplasia include extracellular matrix (ECM alterations and intracellular stress resulting in abnormal changes to chondrocyte proliferation and survival. Delineating the relative contribution of these two disease mechanisms is a major challenge in understanding disease pathophysiology in genetic skeletal diseases and a prerequisite for developing effective therapies. To determine the influence of intracellular stress and changes in chondrocyte phenotype to the development of chondrodysplasia, we targeted the expression of the G2320R mutant form of thyroglobulin to the endoplasmic reticulum (ER of resting and proliferating chondrocytes. Previous studies on this mutant protein have shown that it induces intracellular aggregates and causes cell stress and death in the thyroid gland. The expression and retention of this exogenous mutant protein in resting and proliferating chondrocytes resulted in a chronic cell stress response, growth plate dysplasia and reduced bone growth, without inducing any alterations to the architecture and organization of the cartilage ECM. More significantly, the decreased bone growth seemed to be the direct result of reduced chondrocyte proliferation in the proliferative zone of growth plates in transgenic mice, without transcriptional activation of a classical unfolded protein response (UPR or apoptosis. Overall, these data show that mutant protein retention in the ER of resting and proliferative zone chondrocytes is sufficient to cause disrupted bone growth. The specific disease pathways triggered by mutant protein retention do not necessarily involve a prototypic UPR, but all pathways impact upon chondrocyte proliferation in the cartilage growth plate.

Nuclear proliferation: motivations, capabilities, and strategies for control

International Nuclear Information System (INIS)

Greenwood, T.; Feiveson, H.A.; Taylor, T.B.

1977-01-01

Two possible patterns of proliferation appear to involve the greatest risks for nuclear use or war. The first is proliferation to particular categories of states and the second dangerous possibility is proliferation at a rapid rate. But rapid proliferation could cause instabilities that might be too great for political systems and institutions to handle, making nuclear use of nuclear war more likely. Thus, any strategy for nonproliferation should especially attempt to prevent a rapid spread of nuclear weapons and to avert acquisition by states in the high-risk categories. Nuclear proliferation will also have important effects on world and regional stability for reasons not directly related to nuclear use. The mere possession of nuclear weapons by certain states could radically alter international perceptions and threaten global arrangements. The main concern in this discussion is to analyze the various incentives and disincentives--involving both security and political considerations--that will affect states' decisions about whether or not to acquire nuclear weapons. The discussion then turns to the means by which individual states and the international community can influence nuclear incentives and disincentives. The particularly important subject of the management of the international nuclear industry is addressed separately, followed by an analysis of nuclear acquisition, use, and threat by non-state entities. Finally, a general strategy for decreasing incentives and increasing disincentives is proposed and applied to four special categories of states

Criteria for proliferation resistance of nuclear fuel cycle options

International Nuclear Information System (INIS)

Kiriyama, Eriko; Pickett, Susan; Suzuki, Tatsujiro

2000-01-01

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

The efficiency of asset management strategies to reduce urban flood risk.

Science.gov (United States)

ten Veldhuis, J A E; Clemens, F H L R

2011-01-01

In this study, three asset management strategies were compared with respect to their efficiency to reduce flood risk. Data from call centres at two municipalities were used to quantify urban flood risks associated with three causes of urban flooding: gully pot blockage, sewer pipe blockage and sewer overloading. The efficiency of three flood reduction strategies was assessed based on their effect on the causes contributing to flood risk. The sensitivity of the results to uncertainty in the data source, citizens' calls, was analysed through incorporation of uncertainty ranges taken from customer complaint literature. Based on the available data it could be shown that increasing gully pot blockage is the most efficient action to reduce flood risk, given data uncertainty. If differences between cause incidences are large, as in the presented case study, call data are sufficient to decide how flood risk can be most efficiently reduced. According to the results of this analysis, enlargement of sewer pipes is not an efficient strategy to reduce flood risk, because flood risk associated with sewer overloading is small compared to other failure mechanisms.

The REDUCE metagram: a comprehensive prediction tool for determining the utility of dutasteride chemoprevention in men at risk for prostate cancer

Directory of Open Access Journals (Sweden)

Carvell eNguyen

2012-10-01

Full Text Available Introduction: 5-alpha reductase inhibitors can reduce the risk of prostate cancer but can be associated with significant side effects. A library of nomograms which predict the risk of clinical endpoints relevant to dutasteride treatment may help determine if chemoprevention is suited to the individual patient. Methods: Data from the REDUCE trial was used to identify predictive factors for nine endpoints relevant to dutasteride treatment. Using the treatment and placebo groups from the biopsy cohort, Cox proportional hazards and competing risks regression models were used to build 18 nomograms, whose predictive ability was measured by concordance index and calibration plots. Results: A total of 18 nomograms assessing the risks of cancer, high-grade cancer, high grade prostatic intraepithelial neoplasia (HGPIN, atypical small acinar proliferation (ASAP, erectile dysfunction (ED, acute urinary retention (AUR, gynecomastia, urinary tract infection (UTI and BPH-related surgery either on or off dutasteride were created. The nomograms for cancer, high grade cancer, ED, AUR, and BPH-related surgery demonstrated good discrimination and calibration while those for gynecomastia, UTI, HGPIN, and ASAP predicted no better than random chance. Conclusions: To aid patients in determining whether the benefits of dutasteride use outweigh the risks, we have developed a comprehensive metagram that can generate individualized risks of 9 outcomes relevant to men considering chemoprevention. Better models based on more predictive markers are needed for some of the endpoints but the current metagram demonstrates potential as a tool for patient counseling and decision making that is accessible, intuitive, and clinically relevant.

The REDUCE metagram: a comprehensive prediction tool for determining the utility of dutasteride chemoprevention in men at risk for prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Nguyen, Carvell T.; Isariyawongse, Brandon [Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH (United States); Yu, Changhong; Kattan, Michael W., E-mail: kattanm@ccf.org [Department of Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, OH (United States)

2012-10-11

Introduction: 5-alpha reductase inhibitors can reduce the risk of prostate cancer (PCa) but can be associated with significant side effects. A library of nomograms which predict the risk of clinical endpoints relevant to dutasteride treatment may help determine if chemoprevention is suited to the individual patient. Methods: Data from the REDUCE trial was used to identify predictive factors for 9 endpoints relevant to dutasteride treatment. Using the treatment and placebo groups from the biopsy cohort, Cox proportional hazards (PH) and competing risks regression (CRR) models were used to build 18 nomograms, whose predictive ability was measured by concordance index (CI) and calibration plots. Results: A total of 18 nomograms assessing the risks of cancer, high grade cancer, high grade prostatic intraepithelial neoplasia (HGPIN), atypical small acinar proliferation (ASAP), erectile dysfunction (ED), acute urinary retention (AUR), gynecomastia, urinary tract infection (UTI) and BPH-related surgery either on or off dutasteride were created. The nomograms for cancer, high grade cancer, ED, AUR, and BPH-related surgery demonstrated good discrimination and calibration while those for gynecomastia, UTI, HGPIN, and ASAP predicted no better than random chance. Conclusions: To aid patients in determining whether the benefits of dutasteride use outweigh the risks, we have developed a comprehensive metagram that can generate individualized risks of 9 outcomes relevant to men considering chemoprevention. Better models based on more predictive markers are needed for some of the endpoints but the current metagram demonstrates potential as a tool for patient counseling and decision-making that is accessible, intuitive, and clinically relevant.

The REDUCE metagram: a comprehensive prediction tool for determining the utility of dutasteride chemoprevention in men at risk for prostate cancer

International Nuclear Information System (INIS)

Nguyen, Carvell T.; Isariyawongse, Brandon; Yu, Changhong; Kattan, Michael W.

2012-01-01

Introduction: 5-alpha reductase inhibitors can reduce the risk of prostate cancer (PCa) but can be associated with significant side effects. A library of nomograms which predict the risk of clinical endpoints relevant to dutasteride treatment may help determine if chemoprevention is suited to the individual patient. Methods: Data from the REDUCE trial was used to identify predictive factors for 9 endpoints relevant to dutasteride treatment. Using the treatment and placebo groups from the biopsy cohort, Cox proportional hazards (PH) and competing risks regression (CRR) models were used to build 18 nomograms, whose predictive ability was measured by concordance index (CI) and calibration plots. Results: A total of 18 nomograms assessing the risks of cancer, high grade cancer, high grade prostatic intraepithelial neoplasia (HGPIN), atypical small acinar proliferation (ASAP), erectile dysfunction (ED), acute urinary retention (AUR), gynecomastia, urinary tract infection (UTI) and BPH-related surgery either on or off dutasteride were created. The nomograms for cancer, high grade cancer, ED, AUR, and BPH-related surgery demonstrated good discrimination and calibration while those for gynecomastia, UTI, HGPIN, and ASAP predicted no better than random chance. Conclusions: To aid patients in determining whether the benefits of dutasteride use outweigh the risks, we have developed a comprehensive metagram that can generate individualized risks of 9 outcomes relevant to men considering chemoprevention. Better models based on more predictive markers are needed for some of the endpoints but the current metagram demonstrates potential as a tool for patient counseling and decision-making that is accessible, intuitive, and clinically relevant.

MicroRNA-27a promotes myoblast proliferation by targeting myostatin

International Nuclear Information System (INIS)

Huang, Zhiqing; Chen, Xiaoling; Yu, Bing; He, Jun; Chen, Daiwen

2012-01-01

Highlights: ► We identified a myogenic role for miR-27a and a new target, myostatin. ► The miR-27a was confirmed to target myostatin 3′UTR. ► miR-27a is upregulated and myostatin is downregulated during myoblast proliferation. ► miR-27a promotes myoblast proliferation by reducing the expression of myostatin. -- Abstract: MicroRNAs (miRNAs) are a class of endogenous non-coding RNAs that play critical roles in skeletal muscle development as well as in regulation of muscle cell proliferation and differentiation. However, the role of miRNAs in myoblast proliferation remains poorly understood. Here we found that the expression of miR-27a was increased during proliferation of C2C12 myoblasts. Moreover, overexpression of miR-27a in C2C12 cells promoted myoblast proliferation by reducing the expression of myostatin, a critical inhibitor of skeletal myogenesis. In addition, the miR-27a was confirmed to target myostatin 3′UTR by a luciferase reporter analysis. Together, these results suggest that miR-27a promotes myoblast proliferation through targeting myostatin.

MicroRNA-27a promotes myoblast proliferation by targeting myostatin

Energy Technology Data Exchange (ETDEWEB)

Huang, Zhiqing; Chen, Xiaoling; Yu, Bing; He, Jun [Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Yaan, Sichuan 625014 (China); Chen, Daiwen, E-mail: dwchen@sicau.edu.cn [Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Yaan, Sichuan 625014 (China)

2012-06-29

Highlights: Black-Right-Pointing-Pointer We identified a myogenic role for miR-27a and a new target, myostatin. Black-Right-Pointing-Pointer The miR-27a was confirmed to target myostatin 3 Prime UTR. Black-Right-Pointing-Pointer miR-27a is upregulated and myostatin is downregulated during myoblast proliferation. Black-Right-Pointing-Pointer miR-27a promotes myoblast proliferation by reducing the expression of myostatin. -- Abstract: MicroRNAs (miRNAs) are a class of endogenous non-coding RNAs that play critical roles in skeletal muscle development as well as in regulation of muscle cell proliferation and differentiation. However, the role of miRNAs in myoblast proliferation remains poorly understood. Here we found that the expression of miR-27a was increased during proliferation of C2C12 myoblasts. Moreover, overexpression of miR-27a in C2C12 cells promoted myoblast proliferation by reducing the expression of myostatin, a critical inhibitor of skeletal myogenesis. In addition, the miR-27a was confirmed to target myostatin 3 Prime UTR by a luciferase reporter analysis. Together, these results suggest that miR-27a promotes myoblast proliferation through targeting myostatin.

Cell proliferation and apoptosis in rat mammary glands following combinational exposure to bisphenol A and genistein

International Nuclear Information System (INIS)

Wang, Jun; Jenkins, Sarah; Lamartiniere, Coral A

2014-01-01

Humans are exposed to an array of both harmful and beneficial hormonally active compounds in the environment and through diet. Two such chemicals are Bisphenol A (BPA), a plasticizer, and genistein, a component of soy. Prepubertal exposure to BPA increased mammary carcinogenesis, while genistein suppressed cancer in a chemically-induced model of rodent mammary cancer. The purpose of this research was to determine the effects of combinational exposure to genistein and BPA on cell proliferation, apoptosis, and associated proteins as markers of cancer in mammary glands of rats exposed prepubertally to these environmental chemicals. Prepubertal rats (postpartum days (PND) 2–20) were exposed through lactation via nursing dams treated orally with sesame oil (SO), BPA, genistein, or a combination of BPA and genistein (BPA + Gen). Cell proliferation, apoptosis and protein expressions were investigated for mechanistic studies in mammary glands of rats exposed to these environmental chemicals. Prepubertal exposure to genistein increased cell proliferation in mammary glands of PND21 rats, while BPA increased cell proliferation in adult (PND50) rats. Prepubertal combinational exposure to BPA + Gen increased cell proliferation and reduced apoptosis in PND21 rats, but reduced cell proliferation and increased apoptosis in PND50 rats. The altered mechanisms behind these cellular responses appear to be centered on differential protein expression of caspases, PARP, Bad, p21, Akts, PTEN, ER-β and SRCs 1–3, in the rat mammary gland. Prepubertal BPA exposure resulted in increased cell proliferation in mammary glands of PND50 rats, a process associated with increased risk of cancer development in a chemically-induced mammary cancer. On the other hand, genistein stimulated cell proliferation at PND21, a process that correlates with mammary gland maturation and chemoprevention. In contrast to single chemical exposure, combinational exposure to BPA + Gen performed most similarly to

Aspirin-induced AMP-activated protein kinase activation regulates the proliferation of vascular smooth muscle cells from spontaneously hypertensive rats

International Nuclear Information System (INIS)

Sung, Jin Young; Choi, Hyoung Chul

2011-01-01

Highlights: → Aspirin-induced AMPK phosphorylation was greater in VSMC from SHR than WKY. → Aspirin-induced AMPK phosphorylation inhibited proliferation of VSMC from SHR. → Low basal AMPK phosphorylation in SHR elicits increased VSMC proliferation. → Inhibition of AMPK restored decreased VSMC proliferation by aspirin in SHR. → Aspirin exerts anti-proliferative effect through AMPK activation in VSMC from SHR. -- Abstract: Acetylsalicylic acid (aspirin), used to reduce risk of cardiovascular disease, plays an important role in the regulation of cellular proliferation. However, mechanisms responsible for aspirin-induced growth inhibition are not fully understood. Here, we investigated whether aspirin may exert therapeutic effects via AMP-activated protein kinase (AMPK) activation in vascular smooth muscle cells (VSMC) from wistar kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Aspirin increased AMPK and acetyl-CoA carboxylase phosphorylation in a time- and dose-dependent manner in VSMCs from WKY and SHR, but with greater efficacy in SHR. In SHR, a low basal phosphorylation status of AMPK resulted in increased VSMC proliferation and aspirin-induced AMPK phosphorylation inhibited proliferation of VSMCs. Compound C, an AMPK inhibitor, and AMPK siRNA reduced the aspirin-mediated inhibition of VSMC proliferation, this effect was more pronounced in SHR than in WKY. In VSMCs from SHR, aspirin increased p53 and p21 expression and inhibited the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. These results indicate that in SHR VSMCs aspirin exerts anti-proliferative effects through the induction of AMPK phosphorylation.

Aspirin-induced AMP-activated protein kinase activation regulates the proliferation of vascular smooth muscle cells from spontaneously hypertensive rats

Energy Technology Data Exchange (ETDEWEB)

Sung, Jin Young [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Choi, Hyoung Chul, E-mail: hcchoi@med.yu.ac.kr [Department of Pharmacology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of)

2011-05-06

Highlights: {yields} Aspirin-induced AMPK phosphorylation was greater in VSMC from SHR than WKY. {yields} Aspirin-induced AMPK phosphorylation inhibited proliferation of VSMC from SHR. {yields} Low basal AMPK phosphorylation in SHR elicits increased VSMC proliferation. {yields} Inhibition of AMPK restored decreased VSMC proliferation by aspirin in SHR. {yields} Aspirin exerts anti-proliferative effect through AMPK activation in VSMC from SHR. -- Abstract: Acetylsalicylic acid (aspirin), used to reduce risk of cardiovascular disease, plays an important role in the regulation of cellular proliferation. However, mechanisms responsible for aspirin-induced growth inhibition are not fully understood. Here, we investigated whether aspirin may exert therapeutic effects via AMP-activated protein kinase (AMPK) activation in vascular smooth muscle cells (VSMC) from wistar kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Aspirin increased AMPK and acetyl-CoA carboxylase phosphorylation in a time- and dose-dependent manner in VSMCs from WKY and SHR, but with greater efficacy in SHR. In SHR, a low basal phosphorylation status of AMPK resulted in increased VSMC proliferation and aspirin-induced AMPK phosphorylation inhibited proliferation of VSMCs. Compound C, an AMPK inhibitor, and AMPK siRNA reduced the aspirin-mediated inhibition of VSMC proliferation, this effect was more pronounced in SHR than in WKY. In VSMCs from SHR, aspirin increased p53 and p21 expression and inhibited the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. These results indicate that in SHR VSMCs aspirin exerts anti-proliferative effects through the induction of AMPK phosphorylation.

Evaluating shielding effectiveness for reducing space radiation cancer risks

International Nuclear Information System (INIS)

Cucinotta, Francis A.; Kim, Myung-Hee Y.; Ren, Lei

2006-01-01

We discuss calculations of probability distribution functions (PDF) representing uncertainties in projecting fatal cancer risk from galactic cosmic rays (GCR) and solar particle events (SPE). The PDFs are used in significance tests for evaluating the effectiveness of potential radiation shielding approaches. Uncertainties in risk coefficients determined from epidemiology data, dose and dose-rate reduction factors, quality factors, and physics models of radiation environments are considered in models of cancer risk PDFs. Competing mortality risks and functional correlations in radiation quality factor uncertainties are included in the calculations. We show that the cancer risk uncertainty, defined as the ratio of the upper value of 95% confidence interval (CI) to the point estimate is about 4-fold for lunar and Mars mission risk projections. For short-stay lunar missions ( 180d) or Mars missions, GCR risks may exceed radiation risk limits that are based on acceptable levels of risk. For example, the upper 95% CI exceeding 10% fatal risk for males and females on a Mars mission. For reducing GCR cancer risks, shielding materials are marginally effective because of the penetrating nature of GCR and secondary radiation produced in tissue by relativistic particles. At the present time, polyethylene or carbon composite shielding cannot be shown to significantly reduce risk compared to aluminum shielding based on a significance test that accounts for radiobiology uncertainties in GCR risk projection

Nuclear proliferation and the near-nuclear countries

International Nuclear Information System (INIS)

Marwah, O.; Schulz, A.

1975-01-01

The process of nuclear proliferation and its consequences for the international political system is examined by focusing on the issues in the nuclear-strategic debate that divide first and second order states. Information is included on: the US-USSR arms race; SALT agreement; the Non-Proliferation Treaty; the nuclear aspirations and policies of India, Middle Eastern countries, South Africa, Japan, Brazil, and Argentina; and assessment of the risks related to the nuclear fuel cycle and nuclear weapons

Perspectives of the nuclear non-proliferation regime

International Nuclear Information System (INIS)

Koungou, Leon

2004-01-01

To join traditional methods and new approaches of 'non-proliferation'. This is a technical method and the best way to fight against 'non-proliferation' which is facing few preoccupations: knowledge's disseminations; technologies; equipments and weapons that should be stopped. As it's important to note the return of nuclear danger as the end of confrontation between west-east which should be reduce. As the adaptation of mechanisms is necessary today, as it is important to react about states' incitations to violate international engagement of non-proliferation. Areas control allows finding out change and evolution, but more insufficient. Functional difficulties show that the IAEA (International Agency of Atomic Energy) does not work good. Safeguard system does not allow to respect 'non-proliferation' engagements; for instance 'junkies states' that they cannot dissuade traditional methods. The fight of 'non-proliferation' shows new progresses with fearing methods of prevention actions and heaviest international controls of exportation. The target of this is very ambitious. This new method is self-successful because it contributes to re-enforce international security when defeating acquisition of nuclear and mass destruction weapons by non-states factors. Therefore non-proliferation regime and especially 'non-proliferation treaty' remains delicate as long as some militaries state such USA will reject their 'non-proliferation' engagement. (author) [fr

Risk-reducing mastectomy for the prevention of primary breast cancer.

Science.gov (United States)

Carbine, Nora E; Lostumbo, Liz; Wallace, Judi; Ko, Henry

2018-04-05

Recent progress in understanding the genetic basis of breast cancer and widely publicized reports of celebrities undergoing risk-reducing mastectomy (RRM) have increased interest in RRM as a method of preventing breast cancer. This is an update of a Cochrane Review first published in 2004 and previously updated in 2006 and 2010. (i) To determine whether risk-reducing mastectomy reduces death rates from any cause in women who have never had breast cancer and in women who have a history of breast cancer in one breast, and (ii) to examine the effect of risk-reducing mastectomy on other endpoints, including breast cancer incidence, breast cancer mortality, disease-free survival, physical morbidity, and psychosocial outcomes. For this Review update, we searched Cochrane Breast Cancer's Specialized Register, MEDLINE, Embase and the WHO International Clinical Trials Registry Platform (ICTRP) on 9 July 2016. We included studies in English. Participants included women at risk for breast cancer in at least one breast. Interventions included all types of mastectomy performed for the purpose of preventing breast cancer. At least two review authors independently abstracted data from each report. We summarized data descriptively; quantitative meta-analysis was not feasible due to heterogeneity of study designs and insufficient reporting. We analyzed data separately for bilateral risk-reducing mastectomy (BRRM) and contralateral risk-reducing mastectomy (CRRM). Four review authors assessed the methodological quality to determine whether or not the methods used sufficiently minimized selection bias, performance bias, detection bias, and attrition bias. All 61 included studies were observational studies with some methodological limitations; randomized trials were absent. The studies presented data on 15,077 women with a wide range of risk factors for breast cancer, who underwent RRM.Twenty-one BRRM studies looking at the incidence of breast cancer or disease-specific mortality, or

Domestic Politics and Nuclear Proliferation

Energy Technology Data Exchange (ETDEWEB)

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

2016-05-15

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

Domestic Politics and Nuclear Proliferation

International Nuclear Information System (INIS)

Kim, Chul Min; Yim, Man Sung

2016-01-01

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

[Strategies for reducing risks in smoking: opportunity or threat].

Science.gov (United States)

Córdoba, Rodrigo; Nerín, Isabel

2009-12-01

The smoking control policies recommended by the World Health Organisation have achieved a slight decrease in smoking prevalence in the developed countries, although associated mortality is still very high. The use of tobacco products other than cigarettes and even medicinal nicotine (known as nicotine replacement therapy (NRT)) has been proposed as a risk reduction strategy. Among the tobacco products with less individual risk than cigarettes would be any type of tobacco without smoke (smokeless) with a low content in nitrosamines and modified cigarettes; both forms included under the PREP (Potentially Reduced Exposure Products) concept. The idea would be to promote these products among those who cannot quit smoking or wish to reduce their risk without giving up nicotine intake. The possible effects of risk reduction strategies, including PREP, on the decreased prevalence and morbidity and mortality are reviewed, and the possible implications that this measure could have in our country are analysed. Tobacco control measures in Spain are recent and still insufficient. Therefore, the current priority in Spain is the development of policies of control that have shown to more than effective. The marketing and advertising of new tobacco products, even with reduced potential risk, seems more a serious threat than an opportunity for the development of smoking control policies.

Paullinia cupana Mart var. sorbilis, guaraná, reduces cell proliferation and increases apoptosis of B16/F10 melanoma lung metastases in mice

Directory of Open Access Journals (Sweden)

H. Fukumasu

2008-04-01

Full Text Available We showed that guaraná (Paullinia cupana Mart var. sorbilis had a chemopreventive effect on mouse hepatocarcinogenesis and reduced diethylnitrosamine-induced DNA damage. In the present experiment, we evaluated the effects of guaraná in an experimental metastasis model. Cultured B16/F10 melanoma cells (5 x 10(5 cells/animal were injected into the tail vein of mice on the 7th day of guaraná treatment (2.0 mg P. cupana/g body weight, per gavage and the animals were treated with guaraná daily up to 14 days until euthanasia (total treatment time: 21 days. Lung sections were obtained for morphometric analysis, apoptotic bodies were counted to calculate the apoptotic index and proliferating cell nuclear antigen-positive cells were counted to determine the proliferation index. Guaraná-treated (GUA animals presented a 68.6% reduction in tumor burden area compared to control (CO animals which were not treated with guaraná (CO: 0.84 ± 0.26, N = 6; GUA: 0.27 ± 0.24, N = 6; P = 0.0043, a 57.9% reduction in tumor proliferation index (CO: 23.75 ± 20.54, N = 6; GUA: 9.99 ± 3.93, N = 6; P = 0.026 and a 4.85-fold increase in apoptotic index (CO: 66.95 ± 22.95, N = 6; GUA: 324.37 ± 266.74 AB/mm², N = 6; P = 0.0152. In this mouse model, guaraná treatment decreased proliferation and increased apoptosis of tumor cells, consequently reducing the tumor burden area. We are currently investigating the molecular pathways of the effects of guaraná in cultured melanoma cells, regarding principally the cell cycle inhibitors and cyclins.

Reducing the Risk of Methadone Overdose

Centers for Disease Control (CDC) Podcasts

2012-07-03

This podcast is based on the July 2012 CDC Vital Signs report. Approximately 14 people die every day of overdoses related to methadone. Listen to learn how to reduce your risk of an overdose.  Created: 7/3/2012 by Centers for Disease Control and Prevention (CDC).   Date Released: 7/3/2012.

RISK-INFORMED BALANCING OF SAFETY, NONPROLIFERATION, AND ECONOMICS FOR THE SFR

Energy Technology Data Exchange (ETDEWEB)

Apostolakis, George; Driscoll, Michael; Golay, Michael; Kadak, Andrew; Todreas, Neil; Aldmir, Tunc; Denning, Richard; Lineberry, Michael

2011-10-20

A substantial barrier to the implementation of Sodium-cooled Fast Reactor (SFR) technology in the short term is the perception that they would not be economically competitive with advanced light water reactors. With increased acceptance of risk-informed regulation, the opportunity exists to reduce the costs of a nuclear power plant at the design stage without applying excessive conservatism that is not needed in treating low risk events. In the report, NUREG-1860, the U.S. Nuclear Regulatory Commission describes developmental activities associated with a risk-informed, scenario-based technology neutral framework (TNF) for regulation. It provides quantitative yardsticks against which the adequacy of safety risks can be judged. We extend these concepts to treatment of proliferation risks. The objective of our project is to develop a risk-informed design process for minimizing the cost of electricity generation within constraints of adequate safety and proliferation risks. This report describes the design and use of this design optimization process within the context of reducing the capital cost and levelized cost of electricity production for a small (possibly modular) SFR. Our project provides not only an evaluation of the feasibility of a risk-informed design process but also a practical test of the applicability of the TNF to an actual advanced, non-LWR design. The report provides results of five safety related and one proliferation related case studies of innovative design alternatives. Applied to previously proposed SFR nuclear energy system concepts We find that the TNF provides a feasible initial basis for licensing new reactors. However, it is incomplete. We recommend improvements in terms of requiring acceptance standards for total safety risks, and we propose a framework for regulation of proliferation risks. We also demonstrate methods for evaluation of proliferation risks. We also suggest revisions to scenario-specific safety risk acceptance standards

Risk-Informed Balancing Of Safety, Nonproliferation, And Economics For The SFR

International Nuclear Information System (INIS)

Apostolakis, George; Driscoll, Michael; Golay, Michael; Kadak, Andrew; Todreas, Neil; Aldmir, Tunc; Denning, Richard; Lineberry, Michael

2011-01-01

A substantial barrier to the implementation of Sodium-cooled Fast Reactor (SFR) technology in the short term is the perception that they would not be economically competitive with advanced light water reactors. With increased acceptance of risk-informed regulation, the opportunity exists to reduce the costs of a nuclear power plant at the design stage without applying excessive conservatism that is not needed in treating low risk events. In the report, NUREG-1860, the U.S. Nuclear Regulatory Commission describes developmental activities associated with a risk-informed, scenario-based technology neutral framework (TNF) for regulation. It provides quantitative yardsticks against which the adequacy of safety risks can be judged. We extend these concepts to treatment of proliferation risks. The objective of our project is to develop a risk-informed design process for minimizing the cost of electricity generation within constraints of adequate safety and proliferation risks. This report describes the design and use of this design optimization process within the context of reducing the capital cost and levelized cost of electricity production for a small (possibly modular) SFR. Our project provides not only an evaluation of the feasibility of a risk-informed design process but also a practical test of the applicability of the TNF to an actual advanced, non-LWR design. The report provides results of five safety related and one proliferation related case studies of innovative design alternatives. Applied to previously proposed SFR nuclear energy system concepts We find that the TNF provides a feasible initial basis for licensing new reactors. However, it is incomplete. We recommend improvements in terms of requiring acceptance standards for total safety risks, and we propose a framework for regulation of proliferation risks. We also demonstrate methods for evaluation of proliferation risks. We also suggest revisions to scenario-specific safety risk acceptance standards

Communication in reducing facility siting risk

International Nuclear Information System (INIS)

Bisconti, A.S.

1992-01-01

Today, social considerations are as important as technical ones in siting new nuclear facilities. Siting any industrial facility has become extremely difficult in this era of not in my backyard (NIMBY). Even if NIMBY does not arise locally, well-organized national opposition groups can be counted on to step in to fan the flames, especially when the industrial facility has to do with anything nuclear. It is now generally recognized that the greatest risk of failure for new nuclear facilities is not technical but social. Applying lessons gained from past experience and social science research can help reduce that risk. From these lessons, six principles for public interaction and communication stand out: (1) create goodwill now; (2) involve the community early; (3) establish the need; (4) communicate controls, not risk; (5) avoid jargon; (6) understand your public

A surety engineering framework to reduce cognitive systems risks.

Energy Technology Data Exchange (ETDEWEB)

Caudell, Thomas P. (University of New Mexico, Albuquerque, NM); Peercy, David Eugene; Caldera, Eva O. (University of New Mexico, Albuquerque, NM); Shaneyfelt, Wendy L.

2008-12-01

Cognitive science research investigates the advancement of human cognition and neuroscience capabilities. Addressing risks associated with these advancements can counter potential program failures, legal and ethical issues, constraints to scientific research, and product vulnerabilities. Survey results, focus group discussions, cognitive science experts, and surety researchers concur technical risks exist that could impact cognitive science research in areas such as medicine, privacy, human enhancement, law and policy, military applications, and national security (SAND2006-6895). This SAND report documents a surety engineering framework and a process for identifying cognitive system technical, ethical, legal and societal risks and applying appropriate surety methods to reduce such risks. The framework consists of several models: Specification, Design, Evaluation, Risk, and Maturity. Two detailed case studies are included to illustrate the use of the process and framework. Several Appendices provide detailed information on existing cognitive system architectures; ethical, legal, and societal risk research; surety methods and technologies; and educing information research with a case study vignette. The process and framework provide a model for how cognitive systems research and full-scale product development can apply surety engineering to reduce perceived and actual risks.

Culture promotes transfer of thyroid epithelial cell hyperplasia and proliferation by reducing regulatory T cell numbers.

Science.gov (United States)

Kayes, Timothy D; Braley-Mullen, Helen

2013-01-01

IFN-γ(-/-) NOD.H-2h4 mice develop a spontaneous autoimmune thyroid disease, thyroid epithelial cell hyperplasia and proliferation (TEC H/P) when given NaI in their water for 7+ mo. TEC H/P can be transferred to IFN-γ(-/-) SCID mice by splenocytes from mice with severe (4-5+) disease, and transfer of TEC H/P is improved when splenocytes are cultured prior to transfer. Older (9+ mo) IFN-γ(-/-) NOD.H-2h4 mice have elevated numbers of FoxP3(+) T reg cells, up to 2-fold greater than younger (2 mo) mice. During culture, the number of T reg decreases and this allows the improved transfer of TEC H/P. Co-culture with IL-2 prior to transfer prevents the decrease of T reg and improves their in vitro suppressive ability resulting in reduced TEC H/P in recipient mice. Therefore, culturing splenocytes improves transfer of TEC H/P by reducing the number of T reg and IL-2 inhibits transfer by preserving T reg number and function. Copyright © 2013 Elsevier Inc. All rights reserved.

The fight against the weapons of mass destruction proliferation; La lutte contre la proliferation des armes de destruction massive

Energy Technology Data Exchange (ETDEWEB)

Boutherin, G. [Centre d' Etudes et de Recherches Internationales et Communautaires (CERIC), 13 - Aix-en-Provence (France)

2007-07-01

The author provides a stimulating analysis of the increasing risk of nuclear weapons proliferation, a major concern of the international community. This analysis is applied on juridical, strategical and political examinations. (A.L.B.)

Human cardiac-derived adherent proliferating cells reduce murine acute Coxsackievirus B3-induced myocarditis.

Directory of Open Access Journals (Sweden)

Kapka Miteva

Full Text Available BACKGROUND: Under conventional heart failure therapy, inflammatory cardiomyopathy typically has a progressive course, indicating a need for alternative therapeutic strategies to improve long-term outcomes. We recently isolated and identified novel cardiac-derived cells from human cardiac biopsies: cardiac-derived adherent proliferating cells (CAPs. They have similarities with mesenchymal stromal cells, which are known for their anti-apoptotic and immunomodulatory properties. We explored whether CAPs application could be a novel strategy to improve acute Coxsackievirus B3 (CVB3-induced myocarditis. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the safety of our approach, we first analyzed the expression of the coxsackie- and adenovirus receptor (CAR and the co-receptor CD55 on CAPs, which are both required for effective CVB3 infectivity. We could demonstrate that CAPs only minimally express both receptors, which translates to minimal CVB3 copy numbers, and without viral particle release after CVB3 infection. Co-culture of CAPs with CVB3-infected HL-1 cardiomyocytes resulted in a reduction of CVB3-induced HL-1 apoptosis and viral progeny release. In addition, CAPs reduced CD4 and CD8 T cell proliferation. All CAPs-mediated protective effects were nitric oxide- and interleukin-10-dependent and required interferon-γ. In an acute murine model of CVB3-induced myocarditis, application of CAPs led to a decrease of cardiac apoptosis, cardiac CVB3 viral load and improved left ventricular contractility parameters. This was associated with a decline in cardiac mononuclear cell activity, an increase in T regulatory cells and T cell apoptosis, and an increase in left ventricular interleukin-10 and interferon-γ mRNA expression. CONCLUSIONS: We conclude that CAPs are a unique type of cardiac-derived cells and promising tools to improve acute CVB3-induced myocarditis.

The catechin flavonoid reduces proliferation and induces apoptosis of murine lymphoma cells LB02 through modulation of antiapoptotic proteins

Directory of Open Access Journals (Sweden)

Daniela Laura Papademetrio

2013-06-01

Full Text Available Flavonoids are products of secondary metabolism of plants. They are present in herbs and trees and also act as natural chemopreventives and anticancer agents. Ligaria cuneifolia (Ruiz & Pav. Tiegh., Loranthaceae, is a hemiparasite species that belongs to Argentine flora. Phytochemical studies have disclosed the presence of quercetin, catechin-4β-ol and pro-anthocyanidine as polyphenolic compounds in the active extracts. We previously demonstrated that ethyl acetate extract was capable of reducing cell proliferation and inducing apoptotic death of lymphoid tumor cells. The aim of the current study is to determine whether or not catechin, isolated from L. cuneifolia extracts can induce leukemia cell death and to determine its effect on the cytoplasmatic proteins that modulate cell survival. Our results show that catechin can reduce proliferation of murine lymphoma cell line LB02. The effect is mediated by apoptosis at concentrations upper to 100 µg/mL. Cell death is related to the loss of mitochondrial membrane potential (ΔΨm and a down regulation of survivin and Bcl-2 together with the increase of pro-apoptotic protein Bax. In summary, the current study indicates that catechin present in the extract of L. cuneifolia is in part, responsible for the anti-proliferative activity of whole extracts by induction of ΔΨm disruption and modulation of the anti-apoptotic proteins over expressed in tumor cells. These results give new findings into the potential anticancer and chemopreventive activities of L. cuneifolia.

The catechin flavonoid reduces proliferation and induces apoptosis of murine lymphoma cells LB02 through modulation of antiapoptotic proteins

Directory of Open Access Journals (Sweden)

Daniela Laura Papademetrio

2013-03-01

Full Text Available Flavonoids are products of secondary metabolism of plants. They are present in herbs and trees and also act as natural chemopreventives and anticancer agents. Ligaria cuneifolia (Ruiz & Pav. Tiegh., Loranthaceae, is a hemiparasite species that belongs to Argentine flora. Phytochemical studies have disclosed the presence of quercetin, catechin-4β-ol and pro-anthocyanidine as polyphenolic compounds in the active extracts. We previously demonstrated that ethyl acetate extract was capable of reducing cell proliferation and inducing apoptotic death of lymphoid tumor cells. The aim of the current study is to determine whether or not catechin, isolated from L. cuneifolia extracts can induce leukemia cell death and to determine its effect on the cytoplasmatic proteins that modulate cell survival. Our results show that catechin can reduce proliferation of murine lymphoma cell line LB02. The effect is mediated by apoptosis at concentrations upper to 100 µg/mL. Cell death is related to the loss of mitochondrial membrane potential (ΔΨm and a down regulation of survivin and Bcl-2 together with the increase of pro-apoptotic protein Bax. In summary, the current study indicates that catechin present in the extract of L. cuneifolia is in part, responsible for the anti-proliferative activity of whole extracts by induction of ΔΨm disruption and modulation of the anti-apoptotic proteins over expressed in tumor cells. These results give new findings into the potential anticancer and chemopreventive activities of L. cuneifolia.

Reducing the Risks for Contrast-Induced Nephropathy

International Nuclear Information System (INIS)

Stacul, Fulvio

2005-01-01

Contrast-induced nephropathy (CIN) is one of the most serious adverse events associated with the use of contrast media (CM). Patients who develop this complication can have increased morbidity, higher rates of mortality, lengthy hospital stays, and poor long-term outcomes. Although CIN cannot be eliminated, the chances of developing this condition can be reduced by using appropriate prevention strategies. An important first step to reduce the chance of CIN is to identify risk factors associated with this condition. Patients with a previously elevated serum creatinine level, especially when secondary to diabetic nephropathy, are at great risk for developing CIN. Other patient-related risk factors include concurrent use of nephrotoxic medications, dehydration, congestive heart failure, age greater than 70 years, and probably the presence of diabetes mellitus even if serum creatinine is normal. Adequate hydration is widely accepted as an important prophylactic measure for preventing CIN, but the optimal hydration regimen is still debatable. The risk of CIN increases with greater doses of CM, as well as with the type of CM used. A high-osmolar CM poses a greater risk of CIN than does a low-osmolar CM and, as recent but limited data suggest, the use of an iso-osmolar CM is less nephrotoxic than a low-osmolar CM in patients with renal impairment following intra-arterial procedures, although this finding needs to be verified in future clinical studies. Pharmacologic agents such as calcium channel blockers, dopamine, atrial natriuretic peptide, fenoldopam, prostaglandin E1, and endothelin receptor antagonist have not been proven effective against CIN development. Controversies still exist on the possible effectiveness of theophylline and N-acetylcysteine. Simple strategies for the prevention of CIN in at-risk patients are reviewed and unproven interventions are discussed

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

Cell proliferation of Paramecium tetraurelia on a slow rotating clinostat

Science.gov (United States)

Sawai, Satoe; Mogami, Yoshihiro; Baba, Shoji A.

Paramecium is known to proliferate faster under microgravity conditions, and slower under hypergravity. Experiments using axenic culture medium have demonstrated that hypergravity affected directly on the proliferation of Paramecium itself. In order to assess the mechanisms underlying the physiological effects of gravity on cell proliferation, Paramecium tetraurelia was grown under clinorotation (2.5 rpm) and the time course of the proliferation was investigated in detail on the basis of the logistic analysis. On the basis of the mechanical properties of Paramecium, this slow rate of the rotation appears to be enough to simulate microgravity in terms of the randomization of the cell orientation with respect to gravity. P. tetraurelia was cultivated in a closed chamber in which cells were confined without air bubbles, reducing the shear forces and turbulences under clinorotation. The chamber is made of quartz and silicone rubber film; the former is for the optically-flat walls for the measurement of cell density by means of a non-invasive laser optical-slice method, and the latter for gas exchange. Because of the small dimension for culture space, Paramecium does not accumulate at the top of the chamber in spite of its known negative gravitactic behavior. We measured the cell density at regular time intervals without breaking the configuration of the chamber, and analyzed the proliferation parameters by fitting the data to a logistic equation. As a result, P. tetraurelia showed reduced proliferation under slow clinorotation. The saturation of the cell density as well as the maximum proliferation rate decreased, although we found no significant changes on the half maximal time for proliferation. We also found that the mean swimming velocity decreased under slow clinorotation. These results were not consistent with those under microgravity and fast rotating clinostat. This may suggest that randomization of the cell orientation performed by slow rotating clinostat has

Nuclear proliferation: prospects, problems, and proposals

International Nuclear Information System (INIS)

Anon.

1977-01-01

This issue of the ANNALS addresses itself to three aspects of nuclear proliferation: the prospect that new nuclear powers will come on the scene, the problems that their arrival may create, and ways of coping with those problems. In an introductory paper, ''Quo Vadimus,'' Joseph I. Coffey investigates the pros and cons of proliferation, concluding that it is not a question of whether there will be nuclear proliferation, but in what countries. Part I, Where We Are, contains five papers preceded by introductory comments by Joseph I. Coffey. The papers and their authors are: Why States Go--and Don't Go--Nuclear, William Epstein; How States Can ''Go Nuclear,'' Frank C. Barnaby; What Happens If. . .Terrorists, Revolutionaries, and Nuclear Weapons, David Kreiger; Safeguards Against Diversion of Nuclear Material: An Overview, Ryukichi Imai; and Reducing the Incentives to Proliferation, George H. Quester. Part II, And Where We May Go, again includes some introductory remarks by Joseph I. Coffey. The seven succeeding papers are: Nth Powers of the Future, Ashok Kapur; Nuclear Proliferation and World Politics, Lewis A. Dunn; Arms Control in a Nuclear Armed World, Colin Gray; The United Nations, the Superpowers, and Proliferation, Abraham Bargman; Proliferation and the Future: Destruction or Transformation, Frederick C. Thayer; Decision Making in a Nuclear Armed World, Michael Brenner; and The United States in a World of Nuclear Powers, Michael Nacht. This special report is concluded with a glossary

Improvement of endocytoscopic findings after per oral endoscopic myotomy (POEM) in esophageal achalasia; does POEM reduce the risk of developing esophageal carcinoma? Per oral endoscopic myotomy, endocytoscopy and carcinogenesis.

Science.gov (United States)

Minami, Hitomi; Yamaguchi, Naoyuki; Matsushima, Kayoko; Akazawa, Yuko; Ohnita, Ken; Takeshima, Fuminao; Nakayama, Toshiyuki; Hayashi, Tomayoshi; Inoue, Haruhiro; Nakao, Kazuhiko; Isomoto, Hajime

2013-01-30

Per oral endoscopic myotomy (POEM) has been reported to be a new therapeutic option for esophageal achalasia. The possibility that POEM could reduce the risk of developing esophageal squamous cell carcinoma was evaluated. This was a single-centre, retrospective study. Fifteen consecutive patients with esophageal achalasia who underwent POEM in our institution between August 2010 and January 2012 were enrolled. Ultra-high magnification with endocytoscopy was performed, and both histopathological and immunohistochemical evaluations for Ki-67 and p53 were assessed before and 3 months after POEM. POEM was successfully performed and effectively released the dysphagia symptom in all patients without severe complications. Subjective symptoms (mean Ekcardt score, before 7.4 vs. after 0.5, ptreatment of choice against achalasia and may reduce the risk of esophageal carcinogenesis. Endocytoscopy can be useful for the assessment of esophageal cellular proliferation.

Reducing the harms associated with risk assessments

International Nuclear Information System (INIS)

Montague, Peter

2004-01-01

Risk assessments are the intellectual products of dedicated public health and environmental professionals. Like many other products, risk assessments carry with them the potential for both good and harm. This paper briefly examines some of the harms to which risk assessments have contributed, and then suggests that the legal 'duty to warn' doctrine offers a logical and practical way to reduce some of these harms. The paper suggests concepts that could be incorporated into warnings accompanying every formal risk assessment as routine 'boiler plate' addenda, just as other potentially harmful products, such as lawn mowers and cook stoves, are accompanied by warnings. Finally, the paper briefly examines the 'Code of Ethics and Standards of Practice for Environmental Professionals' (promulgated by the National Association of Environmental Professionals) and shows that the suggested warnings are consistent with recommended practices for environmental professionals

Mitigating flood exposure: Reducing disaster risk and trauma signature.

Science.gov (United States)

Shultz, James M; McLean, Andrew; Herberman Mash, Holly B; Rosen, Alexa; Kelly, Fiona; Solo-Gabriele, Helena M; Youngs, Georgia A; Jensen, Jessica; Bernal, Oscar; Neria, Yuval

2013-01-01

Introduction. In 2011, following heavy winter snowfall, two cities bordering two rivers in North Dakota, USA faced major flood threats. Flooding was foreseeable and predictable although the extent of risk was uncertain. One community, Fargo, situated in a shallow river basin, successfully mitigated and prevented flooding. For the other community, Minot, located in a deep river valley, prevention was not possible and downtown businesses and one-quarter of the homes were inundated, in the city's worst flood on record. We aimed at contrasting the respective hazards, vulnerabilities, stressors, psychological risk factors, psychosocial consequences, and disaster risk reduction strategies under conditions where flood prevention was, and was not, possible. Methods . We applied the "trauma signature analysis" (TSIG) approach to compare the hazard profiles, identify salient disaster stressors, document the key components of disaster risk reduction response, and examine indicators of community resilience. Results . Two demographically-comparable communities, Fargo and Minot, faced challenging river flood threats and exhibited effective coordination across community sectors. We examined the implementation of disaster risk reduction strategies in situations where coordinated citizen action was able to prevent disaster impact (hazard avoidance) compared to the more common scenario when unpreventable disaster strikes, causing destruction, harm, and distress. Across a range of indicators, it is clear that successful mitigation diminishes both physical and psychological impact, thereby reducing the trauma signature of the event. Conclusion . In contrast to experience of historic flooding in Minot, the city of Fargo succeeded in reducing the trauma signature by way of reducing risk through mitigation.

Back-end of the fuel cycle and non-proliferation strategies

Energy Technology Data Exchange (ETDEWEB)

Chebeskov, A.N.; Oussanov, V.I.; Iougai, S.V.; Pshakin, G.M. [Institute of Physics and Power Engineering, State Scientific Center of Russian Federation, Obninsk (Russian Federation)

2001-07-01

The paper focuses on the problem of fissile materials proliferation risk estimation. Some methodological approaches to the solution of this task and results of their application for comparison of different nuclear fuel cycle strategies are discussed. The results of comparative assessment of non-proliferation aspects of plutonium utilization alternatives in Russia using system analysis approach are presented. (author)

Back-end of the fuel cycle and non-proliferation strategies

International Nuclear Information System (INIS)

Chebeskov, A.N.; Oussanov, V.I.; Iougai, S.V.; Pshakin, G.M.

2001-01-01

The paper focuses on the problem of fissile materials proliferation risk estimation. Some methodological approaches to the solution of this task and results of their application for comparison of different nuclear fuel cycle strategies are discussed. The results of comparative assessment of non-proliferation aspects of plutonium utilization alternatives in Russia using system analysis approach are presented. (author)

Nuclear proliferation in South Asia; La proliferation nucleaire en Asie du Sud

Energy Technology Data Exchange (ETDEWEB)

Lamballe, A

2007-07-15

Neither India nor Pakistan has signed the Nuclear Non-Proliferation Treaty or the Comprehensive Test Ban Treaty.By carrying out tests in 1998, they therefore violated no international agreement but dealt a severe blow to non-proliferation by inciting other countries, including Iran, to develop nuclear weapons. The purpose of India strike force is to deter China; Pakistan hopes that with a credible strike force it will be able to deter any major attack by India. The nuclear phenomenon is now firmly entrenched in the minds of all those on the subcontinent, where the arms race continues without let-up on all fronts: witness the many launches of ballistic and cruise missiles by both countries. And now that radical Islamist movements are showing an interest in nuclear weapons systems there is a risk of tipping from the rational to the irrational world, with all its attendant dangers. (author)

Eroding market stability by proliferation of financial instruments

Science.gov (United States)

Caccioli, F.; Marsili, M.; Vivo, P.

2009-10-01

We contrast Arbitrage Pricing Theory (APT), the theoretical basis for the development of financial instruments, with a dynamical picture of an interacting market, in a simple setting. The proliferation of financial instruments apparently provides more means for risk diversification, making the market more efficient and complete. In the simple market of interacting traders discussed here, the proliferation of financial instruments erodes systemic stability and it drives the market to a critical state characterized by large susceptibility, strong fluctuations and enhanced correlations among risks. This suggests that the hypothesis of APT may not be compatible with a stable market dynamics. In this perspective, market stability acquires the properties of a common good, which suggests that appropriate measures should be introduced in derivative markets, to preserve stability. in here

United States non-proliferation policy

International Nuclear Information System (INIS)

Scheinman, L.

1978-01-01

U.S. non-proliferation policy is aimed at slowing the spread of nuclear weapons capabilities, managing the destabilizing effects of nuclear technology for energy purposes, and fostering international standards and institutions to deal responsibly with global nuclear development. These goals assume that nuclear technology has not already precluded social control and recognize the social benefits offered by peaceful uses of atomic energy. Non-proliferation policies recognize that the motivation for possessing nuclear weapons is a more-difficult problem than technical ability and will concentrate on reducing those incentives through international agreements and safeguards and by maintaining the separation of commercial nuclear fuel cycles and military uses

More efficient integrated safeguards by applying a reasonable detection probability for maintaining low presence probability of undetected nuclear proliferating activities

International Nuclear Information System (INIS)

Otsuka, Naoto

2013-01-01

Highlights: • A theoretical foundation is presented for more efficient Integrated Safeguards (IS). • Probability of undetected nuclear proliferation activities should be maintained low. • For nations under IS, the probability to start proliferation activities is very low. • The fact can decrease the detection probability of IS by dozens of percentage points. • The cost of IS per nation can be cut down by reducing inspection frequencies etc. - Abstract: A theoretical foundation is presented for implementing more efficiently the present International Atomic Energy Agency (IAEA) integrated safeguards (ISs) on the basis of fuzzy evaluation of the probability that the evaluated nation will continue peaceful activities. It is shown that by determining the presence probability of undetected nuclear proliferating activities, nations under IS can be maintained at acceptably low proliferation risk levels even if the detection probability of current IS is decreased by dozens of percentage from the present value. This makes it possible to reduce inspection frequency and the number of collected samples, allowing the IAEA to cut costs per nation. This will contribute to further promotion and application of IS to more nations by the IAEA, and more efficient utilization of IAEA resources from the viewpoint of whole IS framework

Reducing risks, protecting people. A harmonized approach

International Nuclear Information System (INIS)

Foster, R.B.

2000-01-01

Risk training, education and communication usually refer to the responsibilities of those who generate risk (e.g. operators of nuclear power plants) towards those who are exposed to the risk (e.g. employees working in the plants and those living in the vicinity). In this context training, education and communication are intended to transfer information from risk professionals to a largely uninformed audience, with a view to improving standards or providing reassurance. However, with the growth of media such as the Internet those to whom such training, education and communication have traditionally been directed are now much better informed. In addition, increasing prosperity affects expectations and prompts questions, not only about the adequacy of the control measures intended to address specific hazards, but also about whether the hazardous activity is justified at all. Within the UK (and Europe) this is very evident for nuclear power, other applications of ionizing radiation, and in other areas such as genetically modified food. In consequence regulators of hazardous activities face considerable new challenges. Of course, regulators still have to formulate standards, communicate them to those responsible for risk reduction and see that the necessary controls are in place. But in addition regulators also have to be able to answer questions such as: - why is this hazardous activity (e.g. a nuclear power plant) allowed at all? - what level of risk is unacceptable? - is the approach to risk reduction sufficiently precautionary? - why shouldn't the risk be reduced further? - why are the risks from certain activities (e.g. those from ionizing radiation) controlled to much lower levels than those from other work activities? - how are decisions made, what criteria are applied and how are the stake holders involves? All this does not make life easy for regulators! The full paper will describe how the Health and Safety Executive (HSE) has responded to these challenges by

Managing Risk, Reducing Vulnerability and Enhancing Productivity ...

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

Managing Risk, Reducing Vulnerability and Enhancing Productivity under a Changing Climate. The countries of the Greater Horn of Africa are particularly vulnerable to drought, exacerbated by widespread poverty and dependence on rainfed agriculture. Even with normal rainfall, the region does not produce enough food to ...

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

Reducing Risk for the Next Generation Nuclear Plant

Energy Technology Data Exchange (ETDEWEB)

John M. Beck II; Harold J. Heydt; Emmanuel O. Opare; Kyle B. Oswald

2010-07-01

The Next Generation Nuclear Plant (NGNP) Project, managed by the Idaho National Laboratory (INL), is directed by the Energy Policy Act of 2005, to research, develop, design, construct, and operate a prototype forth generation nuclear reactor to meet the needs of the 21st Century. As with all large projects developing and deploying new technologies, the NGNP has numerous risks that need to be identified, tracked, mitigated, and reduced in order for successful project completion. A Risk Management Plan (RMP) was created to outline the process the INL is using to manage the risks and reduction strategies for the NGNP Project. Integral to the RMP is the development and use of a Risk Management System (RMS). The RMS is a tool that supports management and monitoring of the project risks. The RMS does not only contain a risk register, but other functionality that allows decision makers, engineering staff, and technology researchers to review and monitor the risks as the project matures.

Reducing Risk for the Next Generation Nuclear Plant

International Nuclear Information System (INIS)

Beck, John M. II; Heydt, Harold J.; Opare, Emmanuel O.; Oswald, Kyle B.

2010-01-01

The Next Generation Nuclear Plant (NGNP) Project, managed by the Idaho National Laboratory (INL), is directed by the Energy Policy Act of 2005, to research, develop, design, construct, and operate a prototype forth generation nuclear reactor to meet the needs of the 21st Century. As with all large projects developing and deploying new technologies, the NGNP has numerous risks that need to be identified, tracked, mitigated, and reduced in order for successful project completion. A Risk Management Plan (RMP) was created to outline the process the INL is using to manage the risks and reduction strategies for the NGNP Project. Integral to the RMP is the development and use of a Risk Management System (RMS). The RMS is a tool that supports management and monitoring of the project risks. The RMS does not only contain a risk register, but other functionality that allows decision makers, engineering staff, and technology researchers to review and monitor the risks as the project matures.

Prognostic value of proliferation in pleomorphic soft tissue sarcomas

DEFF Research Database (Denmark)

Seinen, Jojanneke M; Jönsson, Mats; Bendahl, Pär-Ola O

2012-01-01

= 1.6-12.1), Top2a (hazard ratio = 2.2, CI = 1.2-3.5) and high S-phase fraction (hazard ratio = 1.8, CI = 1.2-3.7) significantly correlated with risk for metastasis. When combined with currently used prognostic factors, Ki-67, S-phase fraction and Top2a fraction contributed to refined identification...... of prognostic risk groups. Proliferation, as assessed by expression of Ki-67 and Top2a and evaluation of S-phase fraction and applied to statistical decision-tree models, provides prognostic information in soft tissue sarcomas of the extremity and trunk wall. Though proliferation contributes independently...... to currently applied prognosticators, its role is particularly strong when few other factors are available, which suggests a role in preoperative decision-making related to identification of high-risk individuals who would benefit from neoadjuvant therapy....

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.)

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.

Entrapped Sediments as a Source of Phosphorus in Epilithic Cyanobacterial Proliferations in Low Nutrient Rivers

Science.gov (United States)

Wood, Susanna A.; Depree, Craig; Brown, Logan; McAllister, Tara; Hawes, Ian

2015-01-01

Proliferations of the benthic mat-forming cyanobacteria Phormidium have been reported in rivers worldwide. Phormidium commonly produces natural toxins which pose a health risk to animal and humans. Recent field studies in New Zealand identified that sites with Phormidium proliferations consistently have low concentrations of water column dissolved reactive phosphorus (DRP). Unlike other river periphyton, Phormidium mats are thick and cohesive, with water and fine sediment trapped in a mucilaginous matrix. We hypothesized that daytime photosynthetic activity would elevate pH inside the mats, and/or night time respiration would reduce dissolved oxygen. Either condition could be sufficient to facilitate desorption of phosphates from sediment incorporated within mats, thus allowing Phormidium to utilize it for growth. Using microelectrodes, optodes and pulse amplitude modulation fluorometry we demonstrated that photosynthetic activity results in elevated pH (>9) during daytime, and that night-time respiration causes oxygen depletion (river water and this, together with elevated concentrations of elements, including iron, suggest phosphorus release from entrapped sediment. Sequential extraction of phosphorus from trapped sediment was used to investigate the role of sediment at sites on the Mangatainoka River (New Zealand) with and without Phormidium proliferations. Deposition of fine sediment (sediment can provide a source of phosphorus to support Phormidium growth and proliferation. PMID:26479491

Conference day - Dissuasion, proliferation, disarmament: the nuclear debate beyond 2010. Conference proceedings; Journee d'etude - Dissuasion, proliferation, desarmement: le debat nucleaire apres 2010. Actes de la conference

Energy Technology Data Exchange (ETDEWEB)

NONE

2010-09-15

A first set of contributions (round tables) addresses the relationship between NATO, nuclear deterrence and antimissile defence. The second set of contributions addresses nuclear policies of emerging powers (Russia, China, Iran...) and proliferation risks. The third one addresses the perspectives of non proliferation, civil nuclear energy actors, and disarmament

Acid-reducing vagotomy is associated with reduced risk of subsequent ischemic heart disease in complicated peptic ulcer

Science.gov (United States)

Wu, Shih-Chi; Fang, Chu-Wen; Chen, William Tzu-Liang; Muo, Chih-Hsin

2016-01-01

Abstract Persistent exacerbation of a peptic ulcer may lead to a complicated peptic ulcer (perforation or/and bleeding). The management of complicated peptic ulcers has shifted from acid-reducing vagotomy, drainage, and gastrectomy to simple local suture or non-operative (endoscopic/angiographic) hemostasis. We were interested in the long-term effects of this trend change. In this study, complicated peptic ulcer patients who received acid-reducing vagotomy were compared with those who received simple suture/hemostasis to determine the risk of ischemic heart disease (IHD). This retrospective cohort study analyzed 335,680 peptic ulcer patients recorded from 2000 to 2006 versus 335,680 age-, sex-, comorbidity-, and index-year matched comparisons. Patients with Helicobacter pylori (HP) infection were excluded. In order to identify the effect of vagus nerve severance, patients who received gastrectomy or antrectomy were also excluded. The incidence of IHD in both cohorts, and in the complicated peptic ulcer patients who received acid-reducing vagotomy versus those who received simple suture or hemostasis was evaluated. The overall incidence of IHD was higher in patients with peptic ulcer than those without peptic ulcer (17.00 vs 12.06 per 1000 person-years), with an adjusted hazard ratio (aHR) of 1.46 based on multivariable Cox proportional hazards regression analysis controlling for age, sex, Charlson's comorbidity index, and death (competing risk). While comparing peptic ulcer patients with acid-reducing vagotomy to those with simple suture/hemostasis or those without surgical treatment, the aHR (0.58) was the lowest in the acid-reducing vagotomy group. Patients with peptic ulcer have an elevated risk of IHD. However, complicated peptic ulcer patients who received acid-reducing vagotomy were associated with reduced risk of developing IHD. PMID:27977613

Metallic gold treatment reduces proliferation of inflammatory cells, increases expression of VEGF and FGF, and stimulates cell proliferation in the subventricular zone following experimental traumatic brain injury

DEFF Research Database (Denmark)

Pedersen, Mie Østergaard; Larsen, Agnete; Pedersen, Dan Sonne

2009-01-01

Traumatic brain injury represents a leading cause of morbidity in young individuals and there is an imperative need for neuroprotective treatments limiting the neurologic impairment following such injury. It has recently been demonstrated that bio-liberated gold ions liberated from small metallic...... gold implants reduce inflammation and neuronal apoptosis, while generating an increased neuronal stem cell response following focal brain damage. In this study mice were subjected to a unilateral traumatic cryo-lesion with concomitant injection of 25-45 microm gold particles near the lesion. Placebo...... increase in cell proliferation in both the ipsilateral and the contralateral subventricular zone was found in response to gold-treatment. In conclusion: we confirmed the previously demonstrated anti-inflammatory effect of bio-liberated gold ions, and further show that metallic gold increases growth factor...

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.

Overexpression of Mitofusin 2 inhibited oxidized low-density lipoprotein induced vascular smooth muscle cell proliferation and reduced atherosclerotic lesion formation in rabbit

International Nuclear Information System (INIS)

Guo Yanhong; Chen Kuanghueih; Gao Wei; Li Qian; Chen Li; Wang Guisong; Tang Jian

2007-01-01

Our previous studies have implies that Mitofusin 2 (Mfn2), which was progressively reduced in arteries from ApoE -/- mice during the development of atherosclerosis, may take part in pathogenesis of atherosclerosis. In this study, we found that overexpression of Mfn2 inhibited oxidized low-density lipoprotein or serum induced vascular smooth muscle cell proliferation by down-regulation of Akt and ERK phosphorylation. Then we investigated the in vivo role of Mfn2 on the development of atherosclerosis in rabbits using adenovirus expressing Mitofusin 2 gene (AdMfn2). By morphometric analysis we found overexpression of Mfn2 inhibited atherosclerotic lesion formation and intima/media ratio by 66.7% and 74.6%, respectively, compared with control group. These results suggest that local Mfn2 treatment suppresses the development of atherosclerosis in vivo in part by attenuating the smooth muscle cell proliferation induced by lipid deposition and vascular injury

High relative humidity pre-harvest reduces post-harvest proliferation of Salmonella in tomatoes

NARCIS (Netherlands)

Devleesschauwer, Brecht; Marvasi, Massimiliano; Giurcanu, Mihai C.; Hochmuth, George J.; Speybroeck, Niko; Havelaar, Arie H.; Teplitski, Max

2017-01-01

Outbreaks of human illness caused by enteric pathogens such as Salmonella are increasingly linked to the consumption of fruits and vegetables. Knowledge on the factors affecting Salmonella proliferation on fresh produce therefore becomes increasingly important to safeguard public health. Previous

Introduction of Counter-Proliferation Capabilities in Development States

International Nuclear Information System (INIS)

Caulfield, P.; Edwards, T.; Witkin, A.; Elgebaly, A.

2010-01-01

In recent history we have seen a number of States develop their indigenous industrial skills to a point suitable for the manufacture of nuclear components. Private individuals unbeknown to the State have then utilized this capability to supply directly into proliferation networks - potentially reducing international confidence in such a State. To combat this possibility, a developing State must recognize the challenges that are raised by its emerging skills and take action to introduce measures that not only help the State identify proliferation activities but also ensure the national security of the State. One of those measures might be to develop a capability within the State to recognize and counter the activities of would-be-proliferators. In many States this capability is managed and applied through a dedicated counter-proliferation unit that has strong links with border controls and customs organizations. A counter-proliferation unit, once established could show dramatic returns for a modest investment. The activities of such a Unit could save the State political embarrassment by hindering and narrowing the chances of unintentional proliferation activities. The Unit should not be introduced as part of a Safeguards agreement or as part of a non proliferation treaty. It should rather be established as an act by the State to protect and control its emerging technologies from being involved, willingly or unwittingly, in proliferation activities. This is a sovereign act of the State - solely for its benefit and should not be imposed by any external power. Today's would-be-proliferators around the world cooperate and act together; similarly emerging counter-proliferation units should act and work together in order to be a step ahead of the proliferators. Improved world-wide cooperation should increase the detection rate of proliferation incidents which will in turn curtail the spread of nuclear weapons - for the benefit of all. (author)

Monovalent ions control proliferation of Ehrlich Lettre ascites cells

DEFF Research Database (Denmark)

Klausen, Thomas Kjaer; Preisler, Sarah; Pedersen, Stine Helene Falsig

2010-01-01

of Ehrlich Lettre ascites (ELA) cells. We measured the intracellular concentration of each ion in G(0), G(1), and S phases of the cell cycle following synchronization by serum starvation and release. We show that intracellular concentrations and content of Na+ and Cl(-) were reduced in the G(0)-G(1) phase...... effect. Western blots showed reduced chloride intracellular channel CLIC1 and chloride channel ClC-2 expression in the plasma membrane in S compared with G(1). Our results suggest that Na+ regulates ELA cell proliferation by regulating intracellular pH while Cl(-) may regulate proliferation by fine...

Conference day - Dissuasion, proliferation, disarmament: the nuclear debate beyond 2010. Conference proceedings

International Nuclear Information System (INIS)

2010-09-01

A first set of contributions (round tables) addresses the relationship between NATO, nuclear deterrence and antimissile defence. The second set of contributions addresses nuclear policies of emerging powers (Russia, China, Iran...) and proliferation risks. The third one addresses the perspectives of non proliferation, civil nuclear energy actors, and disarmament

Information report on Proliferation geo-strategic stakes

International Nuclear Information System (INIS)

2009-11-01

This large report, notably based on interviews of many representatives of international institutions and politicians, ambassadors and researchers of different countries, all involved or specialized in nuclear and defence issues, starts with a description of the evolution of the international and geo-strategic context from the Cold War to a period of a new nuclear proliferation, with, in between, a period of stabilisation between the USA and the USSR. It also questions the various forms of proliferation which could be ballistic, biological, chemical, and cybernetic. Then, it analyses the role which mass destruction weapons have in international relationships, making a distinction between countries possessing such weapons (USA, Russia, China, France, Great-Britain), Israel which has been a newcomer for thirty years, the new actors (India, Pakistan, Iran, North Korea) with their own and different motivations, and the possible new actors (Libya, Syria). It comments the meaning of the ballistic threat and of the anti-missile defence. The third part of this report deals with the dissemination of proliferating technologies, describing the proliferation networks and the failure of actions against state-based proliferations, questioning the reality of the associated risks (discussion about the impact of September 11 attacks, about a chemical and biological terrorist threat which is realistic as well as difficult to be implemented, and about cybernetic attacks). The fourth part comments the impact of the international community on proliferation, outlining the different efficiencies of the international agreements and institutions (Chemical Weapons Convention, IAEA, Non Proliferation Treaty, Biological Weapons Convention, The Hague Code of Conduct), commenting the opportunities associated with other texts (those about nuclear free areas, or those produced by exporter groups), and discussing the attitude of the international community with respect to proliferation, and the

Seipin knockout in mice impairs stem cell proliferation and progenitor cell differentiation in the adult hippocampal dentate gyrus via reduced levels of PPARγ

Directory of Open Access Journals (Sweden)

Guoxi Li

2015-12-01

Full Text Available The seipin gene (BSCL2 was originally identified in humans as a loss-of-function gene associated with congenital generalized lipodystrophy type 2 (CGL2. Neuronal seipin-knockout (seipin-nKO mice display a depression-like phenotype with a reduced level of hippocampal peroxisome proliferator-activated receptor gamma (PPARγ. The present study investigated the influence of seipin deficiency on adult neurogenesis in the hippocampal dentate gyrus (DG and the underlying mechanisms of the effects. We show that the proliferative capability of stem cells in seipin-nKO mice was substantially reduced compared to in wild-type (WT mice, and that this could be rescued by the PPARγ agonist rosiglitazone (rosi. In seipin-nKO mice, neuronal differentiation of progenitor cells was inhibited, with the enhancement of astrogliogenesis; both of these effects were recovered by rosi treatment during early stages of progenitor cell differentiation. In addition, rosi treatment could correct the decline in hippocampal ERK2 phosphorylation and cyclin A mRNA level in seipin-nKO mice. The MEK inhibitor U0126 abolished the rosi-rescued cell proliferation and cyclin A expression in seipin-nKO mice. In seipin-nKO mice, the hippocampal Wnt3 protein level was less than that in WT mice, and there was a reduction of neurogenin 1 (Neurog1 and neurogenic differentiation 1 (NeuroD1 mRNA, levels of which were corrected by rosi treatment. STAT3 phosphorylation (Tyr705 was enhanced in seipin-nKO mice, and was further elevated by rosi treatment. Finally, rosi treatment for 10 days could alleviate the depression-like phenotype in seipin-nKO mice, and this alleviation was blocked by the MEK inhibitor U0126. The results indicate that, by reducing PPARγ, seipin deficiency impairs proliferation and differentiation of neural stem and progenitor cells, respectively, in the adult DG, which might be responsible for the production of the depression-like phenotype in seipin-nKO mice.

Dendritic cells modulate burn wound healing by enhancing early proliferation.

Science.gov (United States)

Vinish, Monika; Cui, Weihua; Stafford, Eboni; Bae, Leon; Hawkins, Hal; Cox, Robert; Toliver-Kinsky, Tracy

2016-01-01

Adequate wound healing is vital for burn patients to reduce the risk of infections and prolonged hospitalization. Dendritic cells (DCs) are antigen presenting cells that release cytokines and are central for the activation of innate and acquired immune responses. Studies have showed their presence in human burn wounds; however, their role in burn wound healing remains to be determined. This study investigated the role of DCs in modulating healing responses within the burn wound. A murine model of full-thickness contact burns was used to study wound healing in the absence of DCs (CD11c promoter-driven diphtheria toxin receptor transgenic mice) and in a DC-rich environment (using fms-like tyrosine kinase-3 ligand, FL- a DC growth factor). Wound closure was significantly delayed in DC-deficient mice and was associated with significant suppression of early cellular proliferation, granulation tissue formation, wound levels of TGFβ1 and formation of CD31+ vessels in healing wounds. In contrast, DC enhancement significantly accelerated early wound closure, associated with increased and accelerated cellular proliferation, granulation tissue formation, and increased TGFβ1 levels and CD31+ vessels in healing wounds. We conclude that DCs play an important role in the acceleration of early wound healing events, likely by secreting factors that trigger the proliferation of cells that mediate wound healing. Therefore, pharmacological enhancement of DCs may provide a therapeutic intervention to facilitate healing of burn wounds. © 2016 by the Wound Healing Society.

Gallic acid reduces cell viability, proliferation, invasion and angiogenesis in human cervical cancer cells

Science.gov (United States)

ZHAO, BING; HU, MENGCAI

2013-01-01

Gallic acid is a trihydroxybenzoic acid, also known as 3,4,5-trihydroxybenzoic acid, which is present in plants worldwide, including Chinese medicinal herbs. Gallic acid has been shown to have cytotoxic effects in certain cancer cells, without damaging normal cells. The objective of the present study was to determine whether gallic acid is able to inhibit human cervical cancer cell viability, proliferation and invasion and suppress cervical cancer cell-mediated angiogenesis. Treatment of HeLa and HTB-35 human cancer cells with gallic acid decreased cell viability in a dose-dependent manner. BrdU proliferation and tube formation assays indicated that gallic acid significantly decreased human cervical cancer cell proliferation and tube formation in human umbilical vein endothelial cells, respectively. Additionally, gallic acid decreased HeLa and HTB-35 cell invasion in vitro. Western blot analysis demonstrated that the expression of ADAM17, EGFR, p-Akt and p-Erk was suppressed by gallic acid in the HeLa and HTB-35 cell lines. These data indicate that the suppression of ADAM17 and the downregulation of the EGFR, Akt/p-Akt and Erk/p-Erk signaling pathways may contribute to the suppression of cancer progression by Gallic acid. Gallic acid may be a valuable candidate for the treatment of cervical cancer. PMID:24843386

Meta-analysis: Does garlic intake reduce risk of gastric cancer?

Science.gov (United States)

Kodali, R T; Eslick, Guy D

2015-01-01

In the past 2 decades, various epidemiological studies investigated whether garlic can positively modify the risk of gastric cancer. Garlic contains numerous sulfide compounds, including diallyl trisulfide, which have anticarcinogenic properties. We conducted a meta-analysis to determine if garlic intake reduces the risk of gastric cancer. An electronic search of MEDLINE, PubMed, and EMBASE to June 2014 was completed. There were 14 case control studies, 2 randomized controlled studies, and 1 cohort study that fulfilled our inclusion criteria. We used a random effects model to calculate pooled odds ratios (OR) and 95% confidence intervals (CIs) for risk of gastric cancer with garlic consumption. Meta-analysis of a total of 8,621 cases and 14,889 controls was conducted. Significant variability in duration of garlic intake and reference categories for amount of intake was noted. High, low, and any garlic intake were all associated with reduced risk of gastric cancer. High intake had the most significant risk reduction, OR = 0.49 (95% CI: 0.38-0.62). Heterogeneity was low (I² = 30.85, P = 0.17). A more modest risk reduction was associated with low intake, OR = 0.75 (95% CI: 0.58-0.97). Half of the studies did not separate garlic intake into high or low amounts, intake was only noted as consumption vs. non-consumption. Any amount of consumption still showed a risk reduction similar to low intake, OR = 0.77 (95% CI: 0.60-1.00). Low and any amount of consumption showed moderate heterogeneity (58% and 45%, respectively). Garlic intake appears to be associated with reduced risk of gastric cancer. Further high quality studies are required to confirm this finding and to assess the amount of garlic that needs to be consumed for protective effect.

Effect of Interlukin-1β on proliferation of gastric epithelial cells in culture

OpenAIRE

Beales, Ian LP

2002-01-01

Abstract Background Helicobacter pylori is the main risk factor for the development of non-cardia gastric cancer. Increased proliferation of the gastric mucosa is a feature of H. pylori infection. Mucosal interkeukin-1β production is increased in H. pylori infection and IL-1β genotypes associated with increased pro-inflammatory activity are risk factors for the development of gastric cancer. The effect of IL-1β on gastric epithelial cell proliferation has been examined in this study. Methods ...

BCG strain S4-Jena: An early BCG strain is capable to reduce the proliferation of bladder cancer cells by induction of apoptosis

Directory of Open Access Journals (Sweden)

Hermann Inge-Marie

2010-06-01

Full Text Available Abstract Background Intravesical immunotherapy with Mycobacterium bovis bacillus Calmette-Guérin has been established as the most effective adjuvant treatment for high risk non-muscle-invasive bladder cancer (NMIBC. We investigated the differences between the S4-Jena BCG strain and commercially available BCG strains. We tested the genotypic varieties between S4-Jena and other BCG strains and analysed the effect of the BCG strains TICE and S4-Jena on two bladder cancer cell lines. Results In contrast to commercially available BCG strains the S4-Jena strain shows genotypic differences. Spoligotyping verifies the S4-Jena strain as a BCG strain. Infection with viable S4-Jena or TICE decreased proliferation in the T24 cell line. Additionally, hallmarks of apoptosis were detectable. In contrast, Cal29 cells showed only a slightly decreased proliferation with TICE. Cal29 cells infected with S4-Jena, though, showed a significantly decreased proliferation in contrast to TICE. Concordantly with these results, infection with TICE had no effect on the morphology and hallmarks of apoptosis of Cal29 cells. However, S4-Jena strain led to clearly visible morphological changes and caspases 3/7 activation and PS flip. Conclusions S4-Jena strain has a direct influence on bladder cancer cell lines as shown by inhibition of cell proliferation and induction of apoptosis. The data implicate that the T24 cells are responder for S4-Jena and TICE BCG. However, the Cal29 cells are only responder for S4-Jena and they are non-responder for TICE BCG. S4-Jena strain may represent an effective therapeutic agent for NMIBC.

A Non-Proliferating Fuel Cycle: No Enrichment, Reprocessing or Accessible Spent Fuel - 12375

Energy Technology Data Exchange (ETDEWEB)

Parker, Frank L. [Vanderbilt University (United States)

2012-07-01

Current fuel cycles offer a number of opportunities for access to plutonium, opportunities to create highly enriched uranium and access highly radioactive wastes to create nuclear weapons and 'dirty' bombs. The non-proliferating fuel cycle however eliminates or reduces such opportunities and access by eliminating the mining, milling and enrichment of uranium. The non-proliferating fuel cycle also reduces the production of plutonium per unit of energy created, eliminates reprocessing and the separation of plutonium from the spent fuel and the creation of a stream of high-level waste. It further simplifies the search for land based deep geologic repositories and interim storage sites for spent fuel in the USA by disposing of the spent fuel in deep sub-seabed sediments after storing the spent fuel at U.S. Navy Nuclear Shipyards that have the space and all of the necessary equipment and security already in place. The non-proliferating fuel cycle also reduces transportation risks by utilizing barges for the collection of spent fuel and transport to the Navy shipyards and specially designed ships to take the spent fuel to designated disposal sites at sea and to dispose of them there in deep sub-seabed sediments. Disposal in the sub-seabed sediments practically eliminates human intrusion. Potential disposal sites include Great Meteor East and Southern Nares Abyssal Plain. Such sites then could easily become international disposal sites since they occur in the open ocean. It also reduces the level of human exposure in case of failure because of the large physical and chemical dilution and the elimination of a major pathway to man-seawater is not potable. Of course, the recovery of uranium from sea water and the disposal of spent fuel in sub-seabed sediments must be proven on an industrial scale. All other technologies are already operating on an industrial scale. If externalities, such as reduced terrorist threats, environmental damage (including embedded

Reducing sequence risk using trend following and the CAPE ratio

OpenAIRE

Clare, A.; Thomas, S.; Smith, P. N.; Seaton, J.

2017-01-01

The risk of experiencing bad investment outcomes at the wrong time, or sequence risk, is a poorly understood, but crucial aspect of the risk faced by investors, in particular those in the decumulation phase of their savings journey, typically over the period of retirement financed by a defined contributions pension scheme. Using US equity return data from 1872-2014 we show how this risk can be significantly reduced by applying trend-following investment strategies. We also demonstrate that kn...

Model for nuclear proliferation resistance analysis using decision making tools

International Nuclear Information System (INIS)

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

2003-06-01

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

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.

Cities at risk: status of Italian planning system in reducing seismic and hydrogeological risks

Directory of Open Access Journals (Sweden)

Grazia Di Giovanni

2016-03-01

Full Text Available Italy and its urban systems are under high seismic and hydrogeological risks. The awareness about the role of human activities in the genesis of disasters is achieved in the scientific debate, as well as the role of urban and regional planning in reducing risks. The paper reviews the state of Italian major cities referred to hydrogeological and seismic risk by: 1 extrapolating data and maps about seismic hazard and landslide risk concerning cities with more than 50.000 inhabitants and metropolitan contexts, and 2 outlining how risk reduction is framed in Italian planning system (at national and regional levels. The analyses of available data and the review of the normative framework highlight the existing gaps in addressing risk reduction: nevertheless a wide knowledge about natural risks afflicting Italian territory and an articulated regulatory framework, the available data about risks are not exhaustive, and risk reduction policies and multidisciplinary pro-active approaches are only partially fostered and applied.

Peroxisome proliferator-activated receptor-γ (PPARγ) Pro12Ala polymorphism and colorectal cancer (CRC) risk.

Science.gov (United States)

Wang, Wei; Shao, Yan; Tang, Shenhua; Cheng, Xianyong; Lian, Haifeng; Qin, Chengyong

2015-01-01

The association between the peroxisome proliferator-activated receptor-γ (PPARγ) Pro12Ala polymorphism and colorectal cancer (CRC) risk was inconclusive. We conducted a meta-analysis to evaluate the association between PPARγ Pro12Ala polymorphism and CRC risk. We searched Pubmed, EMBASE, and China National Knowledge Infrastructure databases. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. A total of 17 case-control studies with 12635 and 15803 controls were included in this meta-analysis. Overall, PPARγ Pro12Ala polymorphism was associated with CRC risk (OR = 0.84, 95% CI 0.75-0.94, P = 0.003, I(2) = 35%). In the subgroup analysis by ethnicity, a significant association was found among Caucasians (OR = 0.85, 95% CI 0.75-0.96, P = 0.007, I(2) = 38%) but not among Asians (OR = 0.76, 95% CI 0.51-1.12, P = 0.17, I(2) = 28%). In the subgroup analysis by CRC site, a significant association was found among colon cancer (OR = 0.81, 95% CI 0.66-0.98, P = 0.03, I(2) = 16%) but not among rectal cancer (OR = 0.83, 95% CI 0.57-1.21, P = 0.34, I(2) = 63%). The sensitivity analysis did not influence the result by omitting low-quality studies (OR = 0.76, 95% CI 0.63-0.93, P = 0.006, I(2) = 51%). In conclusion, this meta-analysis suggested that PPARγ Pro12Ala polymorphism was significant associated with CRC risk.

Reduced risk of UC in families affected by appendicitis

DEFF Research Database (Denmark)

Nyboe Andersen, Nynne; Gørtz, Sanne; Frisch, Morten

2017-01-01

OBJECTIVE: The possible aetiological link between appendicitis and UC remains unclear. In order to investigate the hereditary component of the association, we studied the risk of UC in family members of individuals with appendicitis. DESIGN: A cohort of 7.1 million individuals was established...... million person-years of follow-up between 1977 and 2011, a total of 190 004 cohort members developed appendicitis and 45 202 developed UC. Individuals having a first-degree relative with appendicitis before age 20 years had significantly reduced risk of UC (RR 0.90; 95% CI 0.86 to 0.95); this association...... was stronger in individuals with a family predisposition to UC (RR 0.66; 95% CI 0.51 to 0.83). CONCLUSIONS: Individuals with a first-degree relative diagnosed with appendicitis before age 20 years are at reduced risk of UC, particularly when there is a family predisposition to UC. Our findings question...

Nuclear proliferation and civilian nuclear power: report of the nonproliferation alternative systems assessment program. Volume V. Economics and systems analysis

International Nuclear Information System (INIS)

1979-12-01

This NASAP assessment considers the economics of alternative nuclear reactor and fuel-cycle systems in the light of possible patterns of uranium supply and energy demand, as well as the economic implications of improving the proliferation resistance of the various systems. The assessment focuses on the costs of alternative nuclear technologies and the possible timing of their implementation, based on their economic attractiveness. The objectives of this assessment are to identify when economic incentives to deploy advanced nuclear power systems might exist, to estimate the costs of using technologies that would reduce the risk of proliferation, to assess the impact of major economic uncertainties on the transition to new technologies, and to compare the investments required for alternative systems

Improvement of endocytoscopic findings after per oral endoscopic myotomy (POEM in esophageal achalasia; does POEM reduce the risk of developing esophageal carcinoma? Per oral endoscopic myotomy, endocytoscopy and carcinogenesis

Directory of Open Access Journals (Sweden)

Minami Hitomi

2013-01-01

Full Text Available Abstract Background Per oral endoscopic myotomy (POEM has been reported to be a new therapeutic option for esophageal achalasia. The possibility that POEM could reduce the risk of developing esophageal squamous cell carcinoma was evaluated. Methods This was a single-centre, retrospective study. Fifteen consecutive patients with esophageal achalasia who underwent POEM in our institution between August 2010 and January 2012 were enrolled. Ultra-high magnification with endocytoscopy was performed, and both histopathological and immunohistochemical evaluations for Ki-67 and p53 were assessed before and 3 months after POEM. Results POEM was successfully performed and effectively released the dysphagia symptom in all patients without severe complications. Subjective symptoms (mean Ekcardt score, before 7.4 vs. after 0.5, p Conclusions POEM appears to be an effective and less invasive treatment of choice against achalasia and may reduce the risk of esophageal carcinogenesis. Endocytoscopy can be useful for the assessment of esophageal cellular proliferation.

Indirect risk effects reduce feeding efficiency of ducks during spring.

Science.gov (United States)

Behney, Adam C; O'Shaughnessy, Ryan; Eichholz, Michael W; Stafford, Joshua D

2018-01-01

Indirect risk effects of predators on prey behavior can have more of an impact on prey populations than direct consumptive effects. Predation risk can elicit more vigilance behavior in prey, reducing the amount of time available for other activities, such as foraging, which could potentially reduce foraging efficiency. Understanding the conditions associated with predation risk and the specific effects predation risk have on prey behavior is important because it has direct influences on the profitability of food items found under various conditions and states of the forager. The goals of this study were to assess how ducks perceived predation risk in various habitat types and how strongly perceived risk versus energetic demand affected foraging behavior. We manipulated food abundance in different wetland types in Illinois, USA to reduce confounding between food abundance and vegetation structure. We conducted focal-animal behavioral samples on five duck species in treatment and control plots and used generalized linear mixed-effects models to compare the effects of vegetation structure versus other factors on the intensity with which ducks fed and the duration of feeding stints. Mallards fed more intensively and, along with blue-winged teal, used longer feeding stints in open habitats, consistent with the hypothesis that limited visibility was perceived to have a greater predation risk than unlimited visibility. The species temporally nearest to nesting, wood ducks, were willing to take more risks for a greater food reward, consistent with an increase in a marginal value of energy as they approached nesting. Our results indicate that some duck species value energy differently based on the surrounding vegetation structure and density. Furthermore, increases in the marginal value of energy can be more influential than perceived risk in shaping foraging behavior patterns. Based on these findings, we conclude that the value of various food items is not solely

Cigarette smoking risk-reducing beliefs: Findings from the United States Health Information National Trends Survey.

Science.gov (United States)

Kaufman, Annette R; Coa, Kisha I; Nguyen, Anh B

2017-09-01

Cigarette smoking risk-reducing beliefs are ideas that certain health promoting behaviors (e.g., exercise) may mitigate the risks associated with smoking. The objective of this study was to describe smoking risk-reducing beliefs and the belief that quitting can reduce the harmful effects of smoking among the U.S. adult population and the associations between these beliefs, current smoking status, and sociodemographics. Data were from the Health Information National Trends Survey 4 (HINTS 4) Cycles 3 and 4 (2013-2014; N=6862). Descriptive analyses were conducted to examine bivariate associations among the quit smoking belief, smoking risk-reducing beliefs, and covariates. Weighted ordinal logistic regression models examined the adjusted associations between smoking status and sociodemographics, with quit smoking belief and risk-reducing beliefs. Eighty-two percent of the population reported that quitting cigarette smoking can help reduce the harmful effects of smoking a lot: former smokers and individuals with higher educational attainment were more likely to endorse this belief than never smokers and those with lower educational attainment. Many people endorsed smoking risk-reducing beliefs about exercise (79.3%), fruits and vegetables (71.8%), vitamins (67.2%), and sleep (68.5%). Former smokers were less likely to subscribe to these beliefs than never smokers. Vulnerable populations who may be most at risk of smoking attributable morbidity and mortality were more likely to endorse risk-reducing beliefs. Future studies are needed to better understand how risk-reducing beliefs are formed and if modifying these beliefs may help to reduce cigarette smoking in the U.S. Published by Elsevier Inc.

Elements of safety and non proliferation

International Nuclear Information System (INIS)

Jalouneix, Jean; Aurelle, Jacques; Funk, Pierre; Ladsous, David; Bon Nguyen, Romuald; Goue, Georges; Lefevre, Odile

2015-01-01

This book on nuclear safety and non proliferation is based on knowledge and expertise of the IRSN. The first chapter addresses the safety of nuclear materials, of their installations and of their transportations. It proposes some contextual elements, presents the general guidelines of the French nuclear safety arrangement, the approach to take risks into account, the involved governmental and public bodies, the legal framework, and the protection and control arrangement (in terms of planning of safety-related activities, in terms of operator obligations, in terms of exercises and management crisis). The second part addresses the safety of radioactive sources: context (peculiarity, losses and thefts), international framework (source categories, Euratom directive), and the French organisation. The third chapter addresses nuclear non proliferation: historical background (creation and role of the IAEA and of the EAEC, definitions), principle of statements, inspection process, and French organisation (legal framework, governmental bodies, the IRSN). The last chapter addresses the issue of chemical non proliferation: historical background, international context (Convention on chemical weapons, organisation for their ban), and the French organisation

How do women at increased breast cancer risk perceive and decide between risks of cancer and risk-reducing treatments? A synthesis of qualitative research.

Science.gov (United States)

Fielden, Hannah G; Brown, Stephen L; Saini, Pooja; Beesley, Helen; Salmon, Peter

2017-09-01

Risk-reducing procedures can be offered to people at increased cancer risk, but many procedures can have iatrogenic effects. People therefore need to weigh risks associated with both cancer and the risk-reduction procedure in their decisions. By reviewing relevant literature on breast cancer (BC) risk reduction, we aimed to understand how women at relatively high risk of BC perceive their risk and how their risk perceptions influence their decisions about risk reduction. Synthesis of 15 qualitative studies obtained from systematic searches of SCOPUS, Web of Knowledge, PsychINFO, and Medline electronic databases (inception-June 2015). Women did not think about risk probabilistically. Instead, they allocated themselves to broad risk categories, typically influenced by their own or familial experiences of BC. In deciding about risk-reduction procedures, some women reported weighing the risks and benefits, but papers did not describe how they did so. For many women, however, an overriding wish to reduce intense worry about BC led them to choose aggressive risk-reducing procedures without such deliberation. Reasoning that categorisation is a fundamental aspect of risk perception, we argue that patients can be encouraged to develop more nuanced and accurate categorisations of their own risk through their interactions with clinicians. Empirically-based ethical reflection is required to determine whether and when it is appropriate to provide risk-reduction procedures to alleviate worry. © 2016 The Authors. Psycho-Oncology Published by John Wiley & Sons Ltd.

Medical interventional procedures--reducing the radiation risks

International Nuclear Information System (INIS)

Cousins, C.; Sharp, C.

2004-01-01

Over the last 40 years, the number of percutaneous interventional procedures using radiation has increased significantly, with many secondary care clinicians using fluoroscopically guided techniques. Many procedures can deliver high radiation doses to patients and staff, with the potential to cause immediate and delayed radiation effects. The challenge for interventionists is to maximize benefit, whilst minimizing radiation risk to patients and staff. Non-radiologist clinicians are often inadequately trained in radiation safety and radiobiology. However, clinical governance and legislation now requires a more rigorous approach to protecting patients and staff. Protection can be ensured, and risks can be controlled, by appropriate design, procurement and commissioning of equipment; quality assurance; and optimal operational technique, backed by audit. Interventionists need knowledge and skills to reduce the risks. Appropriate training should include awareness of the potential for radiation injury, equipment operational parameters, doses measurement and recording methods and dose reduction techniques. Clinical governance requires informed consent, appropriate patient counselling and follow-up

Medical interventional procedures--reducing the radiation risks

Energy Technology Data Exchange (ETDEWEB)

Cousins, C. E-mail: claire.cousins@addenbrookes.nhs.uk; Sharp, C

2004-06-01

Over the last 40 years, the number of percutaneous interventional procedures using radiation has increased significantly, with many secondary care clinicians using fluoroscopically guided techniques. Many procedures can deliver high radiation doses to patients and staff, with the potential to cause immediate and delayed radiation effects. The challenge for interventionists is to maximize benefit, whilst minimizing radiation risk to patients and staff. Non-radiologist clinicians are often inadequately trained in radiation safety and radiobiology. However, clinical governance and legislation now requires a more rigorous approach to protecting patients and staff. Protection can be ensured, and risks can be controlled, by appropriate design, procurement and commissioning of equipment; quality assurance; and optimal operational technique, backed by audit. Interventionists need knowledge and skills to reduce the risks. Appropriate training should include awareness of the potential for radiation injury, equipment operational parameters, doses measurement and recording methods and dose reduction techniques. Clinical governance requires informed consent, appropriate patient counselling and follow-up.

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

Reducing health risk assigned to organic emissions from a chemical weapons incinerator.

Science.gov (United States)

Laman, David M; Weiler, B Douglas; Skeen, Rodney S

2013-03-01

Organic emissions from a chemical weapons incinerator have been characterized with an improved set of analytical methods to reduce the human health risk assigned to operations of the facility. A gas chromatography/mass selective detection method with substantially reduced detection limits has been used in conjunction with scanning electron microscopy/energy dispersive X-ray spectrometry and Fourier transform infrared microscopy to improve the speciation of semi-volatile and non-volatile organics emitted from the incinerator. The reduced detection limits have allowed a significant reduction in the assumed polycyclic aromatic hydrocarbon (PAH) and aminobiphenyl (ABP) emission rates used as inputs to the human health risk assessment for the incinerator. A mean factor of 17 decrease in assigned human health risk is realized for six common local exposure scenarios as a result of the reduced PAH and ABP detection limits.

Simultaneous Treatment with Statins and Aspirin Reduces the Risk of Prostate Cancer Detection and Tumorigenic Properties in Prostate Cancer Cell Lines

Science.gov (United States)

Olivan, M.; Rigau, M.; Colás, E.; Garcia, M.; Montes, M.; Sequeiros, T.; Regis, L.; Celma, A.; Planas, J.; Placer, J.; Reventós, J.; de Torres, I.; Doll, A.; Morote, J.

2015-01-01

Nowadays prostate cancer is the most common solid tumor in men from industrialized countries and the second leading cause of death. At the ages when PCa is usually diagnosed, mortality related to cardiovascular morbidity is high; therefore, men at risk for PCa frequently receive chronic lipid-lowering and antiplatelet treatment. The aim of this study was to analyze how chronic treatment with statins, aspirin, and their combination influenced the risk of PCa detection. The tumorigenic properties of these treatments were evaluated by proliferation, colony formation, invasion, and migration assays using different PCa cell lines, in order to assess how these treatments act at molecular level. The results showed that a combination of statins and aspirin enhances the effect of individual treatments and seems to reduce the risk of PCa detection (OR: 0.616 (95% CI: 0.467–0.812), P < 0.001). However, if treatments are maintained, aspirin (OR: 1.835 (95% CI: 1.068–3.155), P = 0.028) or the combination of both drugs (OR: 3.059 (95% CI: 1.894–4.939), P < 0.001) represents an increased risk of HGPCa. As observed at clinical level, these beneficial effects in vitro are enhanced when both treatments are administered simultaneously, suggesting that chronic, concomitant treatment with statins and aspirin has a protective effect on PCa incidence. PMID:25649906

Reduced cancer risk in vegetarians: an analysis of recent reports.

Science.gov (United States)

Lanou, Amy Joy; Svenson, Barbara

2010-12-20

This report reviews current evidence regarding the relationship between vegetarian eating patterns and cancer risk. Although plant-based diets including vegetarian and vegan diets are generally considered to be cancer protective, very few studies have directly addressed this question. Most large prospective observational studies show that vegetarian diets are at least modestly cancer protective (10%-12% reduction in overall cancer risk) although results for specific cancers are less clear. No long-term randomized clinical trials have been conducted to address this relationship. However, a broad body of evidence links specific plant foods such as fruits and vegetables, plant constituents such as fiber, antioxidants and other phytochemicals, and achieving and maintaining a healthy weight to reduced risk of cancer diagnosis and recurrence. Also, research links the consumption of meat, especially red and processed meats, to increased risk of several types of cancer. Vegetarian and vegan diets increase beneficial plant foods and plant constituents, eliminate the intake of red and processed meat, and aid in achieving and maintaining a healthy weight. The direct and indirect evidence taken together suggests that vegetarian diets are a useful strategy for reducing risk of cancer.

Reducing the risk of Legionnaires' disease associated with cooling towers

Energy Technology Data Exchange (ETDEWEB)

Freije, M.R. [HC Information Resources Inc., Carlsbad, CA (United States)

2008-08-15

To reduce the health and legal risks associated with Legionnaires' disease, facility managers should take steps to minimize Legionella bacteria in plumbing systems, open industrial equipment, water features, cooling towers, and other aerosolizing water systems. The risk of Legionnaires' disease associated with cooling towers can be reduced by controlling Legionella bacteria in cooling water and preventing transmission of the bacteria from towers to people. This paper presents nine reasonable ways to accomplish these goals. (orig.)

Policies for Reducing Coastal Risk on the East and Gulf Coasts

Science.gov (United States)

Glickson, D.; Johnson, S.

2014-12-01

Hurricane- and coastal storm-related economic losses have increased substantially over the past century, largely due to expanding population and development in susceptible coastal areas. Concurrent with this growth, the federal government has assumed an increasing proportion of the financial responsibility associated with U.S. coastal storms, which may discourage state and local governments from taking appropriate actions to reduce risk and enhance resilience. Strategies to manage coastal storm risks fall into two categories: reducing the probability of flooding or wave impact (such as seawalls, storm surge barriers, beach nourishment, dune building, restoration/expansion of oyster reefs, salt marshes, and mangroves) and reducing the number or vulnerability of people or structures (such as relocation, land-use planning, and elevating or floodproofing buildings). Over the past century, most coastal risk management programs have emphasized coastal armoring, while doing little to decrease development in harm's way. This National Research Council report calls for the development of a national vision for managing coastal risks that includes a long-term view, regional solutions, and recognition of all benefits. A national coastal risk assessment is needed to identify high priority areas. Benefit-cost analysis provides a reasonable framework to evaluate national investments in coastal risk reduction, if constrained by other important environmental, social, and life-safety factors. Extensive collaboration and additional policy changes will be necessary to move from a nation that is primarily reactive to coastal disasters to one that invests wisely in coastal risk reduction and builds resilience among coastal communities.

Reducing mortality risk by targeting specific air pollution sources: Suva, Fiji.

Science.gov (United States)

Isley, C F; Nelson, P F; Taylor, M P; Stelcer, E; Atanacio, A J; Cohen, D D; Mani, F S; Maata, M

2018-01-15

Health implications of air pollution vary dependent upon pollutant sources. This work determines the value, in terms of reduced mortality, of reducing ambient particulate matter (PM 2.5 : effective aerodynamic diameter 2.5μm or less) concentration due to different emission sources. Suva, a Pacific Island city with substantial input from combustion sources, is used as a case-study. Elemental concentration was determined, by ion beam analysis, for PM 2.5 samples from Suva, spanning one year. Sources of PM 2.5 have been quantified by positive matrix factorisation. A review of recent literature has been carried out to delineate the mortality risk associated with these sources. Risk factors have then been applied for Suva, to calculate the possible mortality reduction that may be achieved through reduction in pollutant levels. Higher risk ratios for black carbon and sulphur resulted in mortality predictions for PM 2.5 from fossil fuel combustion, road vehicle emissions and waste burning that surpass predictions for these sources based on health risk of PM 2.5 mass alone. Predicted mortality for Suva from fossil fuel smoke exceeds the national toll from road accidents in Fiji. The greatest benefit for Suva, in terms of reduced mortality, is likely to be accomplished by reducing emissions from fossil fuel combustion (diesel), vehicles and waste burning. Copyright © 2017. Published by Elsevier B.V.

Breast-feeding reduces the risk for childhood eczema.

Science.gov (United States)

Kull, Inger; Böhme, Maria; Wahlgren, Carl-Fredrik; Nordvall, Lennart; Pershagen, Göran; Wickman, Magnus

2005-09-01

The evidence for a preventive effect of breast-feeding on the development of eczema in childhood remains controversial. To investigate the effect of breast-feeding in various phenotypes of eczema to 4 years. A birth cohort of 4089 children made up the study base. Data on breast-feeding, allergic symptoms, and potential confounders were obtained from questionnaires when the children were 2 months and 1, 2, and 4 years old. At 4 years, blood specific IgE was analyzed. Children with symptoms of eczema and asthma during the period of breast-feeding were excluded in most analyses on risk assessment of eczema and asthma, respectively, to avoid disease-related modification of exposure. Exclusive breast-feeding for >or=4 months reduced the risk for eczema at the age of 4 years (odds ratio [OR], 0.78; 95% CI, 0.63--0.96) irrespective of combination with asthma, sensitization to common allergens, or parental allergic disease. This decreased risk was most evident for children with onset of eczema during the first 2 years persisting to 4 years (OR, 0.59; 95% CI, 0.45--0.77). Among children with early-onset eczema, irrespective of persistency, followed by late onset of asthma or early-onset asthma irrespective of persistency, followed by late-onset eczema to 4 years, a protective effect of breast-feeding was also seen (OR, 0.48; 95% CI, 0.30--0.76). Breast-feeding 4 months or more reduces the risk for eczema and onset of the allergy march to age 4.

Study Shows Aspirin Reduces Colorectal Cancer in Those at High Risk

Science.gov (United States)

Findings from the first large clinical trial of its kind indicate that taking high doses of aspirin daily for at least 2 years substantially reduces the risk of colorectal cancer among people at increased risk of the disease.

'For good and for bad': the relations between universal obligations and particular efforts in the field of nuclear non-proliferation

International Nuclear Information System (INIS)

Dassen Van, L.

2005-01-01

the NPT system may undermine the system of universal obligations and rights. This will if worst comes to worst backfire on all efforts to reduce proliferation risks as created by states and sub-state actors. It is thus the crucial but complex relationship between cooperative threat reduction and NPT mechanisms that will be scrutinized with respect to their uses of language and concepts, their practices, policies and consequences. (author)

Comparison of human exposure pathways in an urban brownfield: reduced risk from paving roads.

Science.gov (United States)

James, Kyle; Farrell, Richard E; Siciliano, Steven D

2012-10-01

Risk assessments often do not quantify the risk associated with soil inhalation. This pathway generally makes a negligible contribution to the cumulative risk, because soil ingestion is typically the dominant exposure pathway. Conditions in northern or rural centers in Canada characterized by large areas of exposed soil, including unpaved roads, favor the resuspension of soil particles, making soil inhalation a relevant risk pathway. The authors determined and compared human exposure to metals and polycyclic aromatic hydrocarbons (PAHs) from soil ingestion and inhalation and analyzed the carcinogenic and noncarcinogenic risks before and after roads were paved in a northern community. To determine the inhalation exposure, three size fractions of airborne particulate matter were collected (total suspended particulates [TSP], particulate matter with an aerodynamic diameter less than 10 µm [PM10], and particulate matter with an aerodynamic diameter less than 2.5 µm [PM2.5]) before and after roads were paved. Road paving reduced the concentration of many airborne contaminants by 25 to 75%, thus reducing risk. For example, before paving, the carcinogenic risk associated with inhalation of Cr was 3.4 excess cancers per 100,000 people exposed, whereas after paving, this risk was reduced to 1.6 in 100,000. Paving roads reduced the concentrations of total suspended particulates (TSP; p roads is an effective method of reducing risk from the inhalation of soil particles. Copyright © 2012 SETAC.

Natural disturbance reduces disease risk in endangered rainforest frog populations.

Science.gov (United States)

Roznik, Elizabeth A; Sapsford, Sarah J; Pike, David A; Schwarzkopf, Lin; Alford, Ross A

2015-08-21

Natural disturbances can drive disease dynamics in animal populations by altering the microclimates experienced by hosts and their pathogens. Many pathogens are highly sensitive to temperature and moisture, and therefore small changes in habitat structure can alter the microclimate in ways that increase or decrease infection prevalence and intensity in host populations. Here we show that a reduction of rainforest canopy cover caused by a severe tropical cyclone decreased the risk of endangered rainforest frogs (Litoria rheocola) becoming infected by a fungal pathogen (Batrachochytrium dendrobatidis). Reductions in canopy cover increased the temperatures and rates of evaporative water loss in frog microhabitats, which reduced B. dendrobatidis infection risk in frogs by an average of 11-28% in cyclone-damaged areas, relative to unaffected areas. Natural disturbances to the rainforest canopy can therefore provide an immediate benefit to frogs by altering the microclimate in ways that reduce infection risk. This could increase host survival and reduce the probability of epidemic disease outbreaks. For amphibian populations under immediate threat from this pathogen, targeted manipulation of canopy cover could increase the availability of warmer, drier microclimates and therefore tip the balance from host extinction to coexistence.

Cereal fiber intake may reduce risk of gastric adenocarcinomas : The EPIC-EURGAST study

NARCIS (Netherlands)

Mendez, M. A.; Pera, Guillem; Aguclo, Antonio; Bueno-de-Mesquita, H. Bas; Palli, Domenico; Boeing, Heiner; Carneiro, Ftima; Berrino, Franco; Sacerdote, Carlotta; Tumino, Rosario; Panico, Salvatore; Berglund, Goeran; Manjer, Jonas; Johansson, Ingegerd; Stenling, Roger; Martinez, Carmen; Dorronsoro, Miren; Barricarte, Aurelio; Tormo, Maria J.; Quiros, Jose R.; Allen, Naomi; Key, Timothy J.; Bingham, Sheila; Linseisen, Jakob; Kaaks, Rudolf; Overvad, Kim; Jensen, Majken; Olsen, Anja; Tjonneland, Anne; Peeters, Petra H. M.; Numans, Mattijs E.; Ocke, Marga C.; Clavel-Chapelon, Francoise; Boutron-Ruault, Marie-Christine; Trichopoulou, Antonia; Lund, Eiliv; Slimani, Nadia; Jenab, Mazda; Ferrari, Pietro; Riboli, Elio; Gonzalez, Carlos A.

2007-01-01

Numerous case-control studies suggest dietary fiber may reduce risk of gastric cancer, but this has not been confirmed prospectively. A previous case-control study reported reduced risk of gastric cardia adenocarcinomas associated with cereal fiber, but not with fruit or vegetable fiber. To date,

Modulating Estrogen Receptor-related Receptor-α Activity Inhibits Cell Proliferation*

OpenAIRE

Bianco, Stéphanie; Lanvin, Olivia; Tribollet, Violaine; Macari, Claire; North, Sophie; Vanacker, Jean-Marc

2009-01-01

High expression of the estrogen receptor-related receptor (ERR)-α in human tumors is correlated to a poor prognosis, suggesting an involvement of the receptor in cell proliferation. In this study, we show that a synthetic compound (XCT790) that modulates the activity of ERRα reduces the proliferation of various cell lines and blocks the G1/S transition of the cell cycle in an ERR...

Global risks from energy consumption

International Nuclear Information System (INIS)

von Hippel, F.

1983-01-01

A discussion of some of the global risks associated with current and frequently proposed future levels of consumption of energy from oil, coal, fission, fusion, and renewable sources points out the the dangers are serious and relatively near term. These include world war over Persian Gulf oil, climate change due to the buildup of atmospheric carbon dioxide, the accelerated proliferation of nuclear weapons, and competition between food and energy for land and water. The author urges placing a greater emphasis on how we use energy and how to reduce energy waste. At the levels of consumption which economically justified levels of energy efficiency could bring about, enough flexibility could develop in our choice of a future energy-supply mix to dramatically reduce the associated global risks. 47 references, 3 figures

Risk-reducing mastectomy and salpingo-oophorectomy in unaffected BRCA mutation carriers: uptake and timing

DEFF Research Database (Denmark)

Skytte, A-B; Gerdes, Anne-Marie Axø; Andersen, M K

2010-01-01

from 306 healthy BRCA carriers with no personal history of ovarian or breast cancer. We found a 10-year uptake of 75% for risk-reducing salpingo-oophorectomy and 50% for risk-reducing mastectomy by time to event analysis. Age and childbirth influenced this decision. The uptake rate has not changed......Once female carriers of a BRCA mutation are identified they have to make decisions on risk management. The aim of this study is to outline the uptake of risk-reducing surgery in the Danish population of BRCA mutation positive women and to search for factors affecting this decision. We analysed data...

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

Opportunities to reduce risk associated with nuclear logging techniques

International Nuclear Information System (INIS)

Wraight, P.D.; Robinson, E.; de Fleurieu, R.

1991-01-01

Nuclear logging provides petroleum exploration and production companies with data that are critical to their decisions and operations. Because this type data is so important, environmentally conscious well-logging and service companies are constantly reviewing the risks to people and environment associated with nuclear sources with the ALARA (as low as reasonably achievable) principle in mind. Opportunities to additionally reduce risks, which can be accomplished only with the active involvement of oil companies, are proposed in this paper

Motivators and barriers of tamoxifen use as risk-reducing medication amongst women at increased breast cancer risk: a systematic literature review.

Science.gov (United States)

Meiser, B; Wong, W K T; Peate, M; Julian-Reynier, C; Kirk, J; Mitchell, G

2017-01-01

Selective estrogen receptor modulators, such as tamoxifen, reduce breast cancer risk by up to 50% in women at increased risk for breast cancer. Despite tamoxifen's well-established efficacy, many studies show that most women are not taking up tamoxifen. This systematic literature review aimed to identify the motivators and barriers to tamoxifen use 's amongst high-risk women. Using MEDLINE, PsycINFO, and Embase plus reviewing reference lists of relevant articles published between 1995 and 2016, 31 studies (published in 35 articles) were identified, which addressed high-risk women's decisions about risk-reducing medication to prevent breast cancer and were peer-reviewed primary clinical studies. A range of factors were identified as motivators of, and barriers to, tamoxifen uptake including: perceived risk, breast-cancer-related anxiety, health professional recommendation, perceived drug effectiveness, concerns about side-effects, knowledge and access to information about side-effects, beliefs about the role of risk-reducing medication, provision of a biomarker, preference for other forms of breast cancer risk reduction, previous treatment experience, concerns about randomization in clinical trial protocols and finally altruism. Results indicate that the decision for high-risk women regarding tamoxifen use or non-use as a risk-reducing medication is not straightforward. Support of women making this decision is essential and needs to encompass the full range of factors, both informational and psychological.

A novel anti-EMMPRIN function-blocking antibody reduces T cell proliferation and neurotoxicity: relevance to multiple sclerosis.

Science.gov (United States)

Agrawal, Smriti M; Silva, Claudia; Wang, Janet; Tong, Jade Pui-Wai; Yong, V Wee

2012-04-05

Extracellular matrix metalloproteinase inducer (EMMPRIN; CD147, basigin) is an inducer of the expression of several matrix metalloproteinases (MMPs). We reported previously that blocking EMMPRIN activity reduced neuroinflammation and severity of disease in an animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). To improve upon EMMPRIN blockade, and to help unravel the biological functions of EMMPRIN in inflammatory disorders, we have developed several anti-EMMPRIN monoclonal antibodies. Of these monoclonal antibodies, a particular one, clone 10, was efficient in binding mouse and human cells using several methods of detection. The specificity of clone 10 was demonstrated by its lack of staining of EMMPRIN-null embryos compared to heterozygous and wild-type mouse samples. Functionally, human T cells activated with anti-CD3 and anti-CD28 elevated their expression of EMMPRIN and the treatment of these T cells with clone 10 resulted in decreased proliferation and matrix metalloproteinase- 9 (MMP-9) production. Activated human T cells were toxic to human neurons in culture and clone 10 pretreatment reduced T cell cytotoxicity correspondent with decrease of granzyme B levels within T cells. In vivo, EAE mice treated with clone 10 had a markedly reduced disease score compared to mice treated with IgM isotype control. We have produced a novel anti-EMMPRIN monoclonal antibody that blocks several aspects of T cell activity, thus highlighting the multiple roles of EMMPRIN in T cell biology. Moreover, clone 10 reduces EAE scores in mice compared to controls, and has activity on human cells, potentially allowing for the testing of anti-EMMPRIN treatment not only in EAE, but conceivably also in MS.

A novel anti-EMMPRIN function-blocking antibody reduces T cell proliferation and neurotoxicity: relevance to multiple sclerosis

Directory of Open Access Journals (Sweden)

Agrawal Smriti M

2012-04-01

Full Text Available Abstract Background Extracellular matrix metalloproteinase inducer (EMMPRIN; CD147, basigin is an inducer of the expression of several matrix metalloproteinases (MMPs. We reported previously that blocking EMMPRIN activity reduced neuroinflammation and severity of disease in an animal model of multiple sclerosis (MS, experimental autoimmune encephalomyelitis (EAE. Methods To improve upon EMMPRIN blockade, and to help unravel the biological functions of EMMPRIN in inflammatory disorders, we have developed several anti-EMMPRIN monoclonal antibodies. Results Of these monoclonal antibodies, a particular one, clone 10, was efficient in binding mouse and human cells using several methods of detection. The specificity of clone 10 was demonstrated by its lack of staining of EMMPRIN-null embryos compared to heterozygous and wild-type mouse samples. Functionally, human T cells activated with anti-CD3 and anti-CD28 elevated their expression of EMMPRIN and the treatment of these T cells with clone 10 resulted in decreased proliferation and matrix metalloproteinase- 9 (MMP-9 production. Activated human T cells were toxic to human neurons in culture and clone 10 pretreatment reduced T cell cytotoxicity correspondent with decrease of granzyme B levels within T cells. In vivo, EAE mice treated with clone 10 had a markedly reduced disease score compared to mice treated with IgM isotype control. Conclusions We have produced a novel anti-EMMPRIN monoclonal antibody that blocks several aspects of T cell activity, thus highlighting the multiple roles of EMMPRIN in T cell biology. Moreover, clone 10 reduces EAE scores in mice compared to controls, and has activity on human cells, potentially allowing for the testing of anti-EMMPRIN treatment not only in EAE, but conceivably also in MS.

Proliferation resistance assessment of pyro processing

Energy Technology Data Exchange (ETDEWEB)

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

2012-10-15

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

Reducing risk where tectonic plates collide

Science.gov (United States)

Gomberg, Joan S.; Ludwig, Kristin A.

2017-06-19

Most of the world’s earthquakes, tsunamis, landslides, and volcanic eruptions are caused by the continuous motions of the many tectonic plates that make up the Earth’s outer shell. The most powerful of these natural hazards occur in subduction zones, where two plates collide and one is thrust beneath another. The U.S. Geological Survey’s (USGS) “Reducing Risk Where Tectonic Plates Collide—A USGS Plan to Advance Subduction Zone Science” is a blueprint for building the crucial scientific foundation needed to inform the policies and practices that can make our Nation more resilient to subduction zone-related hazards.

What can individuals do to reduce personal health risks from air pollution?

Science.gov (United States)

Laumbach, Robert; Meng, Qingyu; Kipen, Howard

2015-01-01

In many areas of the world, concentrations of ambient air pollutants exceed levels associated with increased risk of acute and chronic health problems. While effective policies to reduce emissions at their sources are clearly preferable, some evidence supports the effectiveness of individual actions to reduce exposure and health risks. Personal exposure to ambient air pollution can be reduced on high air pollution days by staying indoors, reducing outdoor air infiltration to indoors, cleaning indoor air with air filters, and limiting physical exertion, especially outdoors and near air pollution sources. Limited evidence suggests that the use of respirators may be effective in some circumstances. Awareness of air pollution levels is facilitated by a growing number of public air quality alert systems. Avoiding exposure to air pollutants is especially important for susceptible individuals with chronic cardiovascular or pulmonary disease, children, and the elderly. Research on mechanisms underlying the adverse health effects of air pollution have suggested potential pharmaceutical or chemopreventive interventions, such as antioxidant or antithrombotic agents, but in the absence of data on health outcomes, no sound recommendations can be made for primary prevention. Health care providers and their patients should carefully consider individual circumstances related to outdoor and indoor air pollutant exposure levels and susceptibility to those air pollutants when deciding on a course of action to reduce personal exposure and health risks from ambient air pollutants. Careful consideration is especially warranted when interventions may have unintended negative consequences, such as when efforts to avoid exposure to air pollutants lead to reduced physical activity or when there is evidence that dietary supplements, such as antioxidants, have potential adverse health effects. These potential complications of partially effective personal interventions to reduce exposure or

Extreme Geohazards: Reducing the Disaster Risk and Increasing Resilience

Science.gov (United States)

Plag, Hans-Peter; Stein, Seth; Brocklebank, Sean; Jules-Plag, Shelley; Marsh, Stuart; Campus, Paola

2013-04-01

Extreme geohazards have the potential to escalate the global sustainability crisis and put us close to the boundaries of the safe operating space for humanity. Exposure of human assets to geohazards has increased dramatically in recent decades, and the sensitivity of the built environment and the embedded socio-economic fabric have changed. We are putting the urban environment, including megacities, in harm's way. Paradoxically, innovation during recent decades, in particular, urban innovation, has increased the disaster risk and coupled this risk to the sustainability crisis. Only more innovation can reduce disaster risk and lead us out of the sustainability crisis. Extreme geohazards (volcanic eruptions, earthquakes, tsunamis) that occurred regularly throughout the last few millennia mostly did not cause major disasters because population density was low and the built environment was not sprawling into hazardous areas to the same extent as today. Similar extreme events today would cause unparalleled damage on a global scale and could worsen the sustainability crisis. Simulation of these extreme hazards under present conditions can help to assess the disaster risk. The Geohazards Community of Practice of the Group on Earth Observations (GEO) with support from the European Science Foundation is preparing a white paper assessing the contemporary disaster risks associated with extreme geohazards and developing a vision for science and society to engage in deliberations addressing this risk (see http://www.geohazcop.org/projects/extgeowp). Risk awareness and monitoring is highly uneven across the world, and this creates two kinds of problems. Firstly, potential hazards are much more closely monitored in wealthy countries than in the developing world. But the largest hazards are global in nature, and it is critical to get as much forewarning as possible to develop an effective response. The disasters and near-misses of the past show that adherence to scientific

Cftr Modulates Wnt/β-Catenin Signaling and Stem Cell Proliferation in Murine Intestine

Directory of Open Access Journals (Sweden)

Ashlee M. Strubberg

2018-01-01

Conclusions: CF intestine shows increased ISC proliferation and Wnt/β-catenin signaling. Loss of Cftr increases pHi in ISCs, which stabilizes the plasma membrane association of the Wnt transducer Dvl, likely facilitating Wnt/β-catenin signaling. Absence of Cftr-dependent suppression of ISC proliferation in the CF intestine may contribute to increased risk for intestinal tumors.

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.)

Damage-reducing measures to manage flood risks in a changing climate

Science.gov (United States)

Kreibich, Heidi; Bubeck, Philip; Van Vliet, Mathijs; De Moel, Hans

2014-05-01

Damage due to floods has increased during the last few decades, and further increases are expected in several regions due to climate change and a growing vulnerability. To address the projected increase in flood risk, a combination of structural and non-structural flood risk mitigation measures is considered as a promising adaptation strategy. Such a combination takes into account that flood defence systems may fail, and prepare for unexpected crisis situations via land-use planning, building construction, evacuation and disaster response. Non-structural flood risk mitigation measures like shielding with water shutters or sand bags, building fortification or safeguarding of hazardous substances are often voluntary: they demand self-dependent action by the population at risk (Bubeck et al. 2012; 2013). It is believed that these measures are especially effective in areas with frequent flood events and low flood water levels, but some types of measures showed a significant damage-reducing effect also during extreme flood events, such as the Elbe River flood in August 2002 in Germany (Kreibich et al. 2005; 2011). Despite the growing importance of damage-reducing measures, information is still scarce about factors that motivate people to undertake such measures, the state of implementation of various non-structural measures in different countries and their damage reducing effects. Thus, we collected information and undertook an international review about this topic in the framework of the Dutch KfC project "Climate proof flood risk management". The contribution will present an overview about the available information on damage-reducing measures and draw conclusions for practical flood risk management in a changing climate. References: Bubeck, P., Botzen, W. J. W., Suu, L. T. T., Aerts, J. C. J. H. (2012): Do flood risk perceptions provide useful insights for flood risk management? Findings from central Vietnam. Journal of Flood Risk Management, 5, 4, 295-302 Bubeck, P

Reducing the Risk of Methadone Overdose PSA (:60)

Centers for Disease Control (CDC) Podcasts

2012-07-03

This 60 second PSA is based on the July 2012 CDC Vital Signs report. Approximately 14 people die every day of overdoses related to methadone. Listen to learn how to reduce your risk of an overdose.  Created: 7/3/2012 by Centers for Disease Control and Prevention (CDC).   Date Released: 7/3/2012.

Pharmacist intervention reduces gastropathy risk in patients using NSAIDs.

Science.gov (United States)

Ibañez-Cuevas, Victoria; Lopez-Briz, Eduardo; Guardiola-Chorro, M Teresa

2008-12-01

To establish a detection and intervention strategy in order to reduce the number of non-steroidal anti-inflammatory drug (NSAIDs) users at risk of gastropathy from receiving either inadequate or no gastroprotection. Community Pharmacies in Valencia, Spain. Prospective longitudinal intervention study without control group carried out by 79 Community Pharmacies. Patients over 18 who asked for any systemic NSAID were interviewed according to standard procedure. Pharmacist intervention was carried out when a patient at risk of serious NSAID-induced gastrointestinal complications due to inadequate or no gastric protection was identified. The doctor responsible was informed in order to then be able to assess the need to prescribe gastroprotection or change it if inadequate. In the case of over-the-counter (OTC) drugs, pharmacist intervention mainly involved replacing NSAIDs for safer medications. Firstly, the number of patients who had no prescribed gastroprotection or inadequate gastroprotection was determined. Pharmacist intervention then brought about changes in pharmacotherapy in this situation. Of the 6,965 patients who asked for NSAIDs during the study period, 3,054 (43.9%) presented NSAID gastropathy risk factors. 35.6% of the latter (1,089) were not prescribed gastroprotection or were prescribed inadequate gastroprotection. Pharmacist intervention was carried out in 1,075 of these cases. On 391 occasions such risk situations were reported to doctors, who accepted pharmacist intervention on 309 occasions (79.0%) and then either prescribed gastroprotection (77% of cases); changed it (13.9%); withdrew the NSAID (5.8%) or substituted it (3.2%). 235 Pharmacist interventions took place when dispensing OTC NSAIDs. Our strategy allowed us to identify a large number of patients who asked for NSAIDs in Community Pharmacies and who were at risk of NSAID gastropathy, as they received either inadequate gastroprotection or no gastroprotection whatsoever. Moreover, the

Nuclear proliferation: present, past and future

International Nuclear Information System (INIS)

Alonso, M.; Zaleski, P.

1993-01-01

Since the end of WW II one of the more, if not the most, serious concerns of all people in the world has been to preserve this planet avoiding a nuclear war. On the positive side, in spite of the huge arsenal of strategic and tactical nuclear weapons (NW) accumulated over the years by the US and the former SU and the innumerable military conflicts we have witnessed since WW II, no NW have been used again. But this should not be a great consolation: the fact that countries have refrained from using NW does not necessarily mean that it will always be that way. As long as countries try to solve their differences by the use of force the danger of a nuclear confrontation remains, and nuclear disarmament and proliferation should cotinue to be a serious concern. This concern has profound political, social and ethical components that have been analyzed extensively and profusely. The purpose of this paper is more limited: to provide an overview of the national and international efforts to minimize the risk of a nuclear war by regulating, restricting and containing the development and possession of NW. This is what has become know as the nuclear non-proliferation regime. Any nuclear non-proliferation regime must have two essential goals: achieving nuclear disarmament by the NWS (and thereby eliminating vertical proliferation). To make a regime effective it must rely on international agreements, a system of safeguards coupled with inspection and verification procedures, and above all on the good faith of all nations involved. It should be stated from the very beginning that nuclear non-proliferation efforts, like all disarmament efforts, are essentially of political nature, albeit having an important scientific and technological component. They are effective only to the extent that countries really renounce NW and are prepared to severely sanction those who do not. (Author) 31 refs

Intermittent hypoxia reduces microglia proliferation and induces DNA damage in vitro

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Song Liu

2016-05-01

Full Text Available Objective(s:Intermittent hypoxia (IH, caused by obstructive sleep apnea (OSA, could cause hippocampus or neuron damage through multiple signaling pathways, while the underlying mechanisms are still unclear. Thus, the present study aimed to explore the effect of IH on the biological functions of microglia cells. Materials and Methods:Cell proliferation of BV2 cells after exposure to IH were observed by MTT assay and then DNA damage was detected by comet assay. RNA-sequencing assay was performed in cells under IH condition and normal conditions to find out the differentially expressed genes, which were further confirmed by reverse transcriptase polymerase chain reaction (RT-PCR and Western blot assay. Results:As results, IH inhibited the proliferation of BV2 cells, as well as caused DNA damage. RNA-sequencing assay revealed 4 differentially expressed genes (p21, Cyclin D1, Cyclin E2, and Gadd45α which were associated with the network of P53 signaling pathways in BV2 cells, among which, p21 and Gadd45α were dramatically increased while Cyclin D1 and Cyclin E2 were both decreased significantly. Moreover, inflammatory factors including IL-6, TNF-α and iNOS were significantly up-regulated in microglia cells under IH conditions for 8 hr. Conclusion:Our results indicated that IH could inhibit cyclin D1 and cyclin E2 expression via initiating multiple P53 pathways, which further blocked cell cycle transition and attenuated proliferative capability of BV2 cells. Meanwhile, IH activated inflammation reactions in BV2 cells. Present study elaborate the effects of IH on biological functions of microglia and provide theoretical foundation for further study on new therapy methods for OSA.

Active fans and grizzly bears: Reducing risks for wilderness campers

Science.gov (United States)

Sakals, M. E.; Wilford, D. J.; Wellwood, D. W.; MacDougall, S. A.

2010-03-01

Active geomorphic fans experience debris flows, debris floods and/or floods (hydrogeomorphic processes) that can be hazards to humans. Grizzly bears ( Ursus arctos) can also be a hazard to humans. This paper presents the results of a cross-disciplinary study that analyzed both hydrogeomorphic and grizzly bear hazards to wilderness campers on geomorphic fans along a popular hiking trail in Kluane National Park and Reserve in southwestern Yukon Territory, Canada. Based on the results, a method is proposed to reduce the risks to campers associated with camping on fans. The method includes both landscape and site scales and is based on easily understood and readily available information regarding weather, vegetation, stream bank conditions, and bear ecology and behaviour. Educating wilderness campers and providing a method of decision-making to reduce risk supports Parks Canada's public safety program; a program based on the principle of user self-sufficiency. Reducing grizzly bear-human conflicts complements the efforts of Parks Canada to ensure a healthy grizzly bear population.

Using detection and deterrence to reduce insider risk

International Nuclear Information System (INIS)

Eggers, R.F.; Carlson, R.L.; Udell, C.J.

1988-01-01

This paper addresses a new concept of interaction between adversary detection and deterrence. It provides an initial evaluation of the effects of these variables on the risk of theft of special nuclear material by an insider adversary and can be extended to the sabotage threat. A steady-state risk equation is used. Exercises with this equation show that deterrence, resulting from the prospect of detection, has a greater ability to reduce the risk than the detection exercise itself. This is true for all cases except those in which the probabilty of detection is 1. Cases were developed for three different types of adversaries that can be distinguished from one another by the level of detection they are willing to tolerate before they are deterred from attempting a theft. By considering the effects of detection, deterrence, and adversary type, the ground work is laid for designing cost-effective insider threat-protection systems

Reduced cancer risk in vegetarians: an analysis of recent reports

Directory of Open Access Journals (Sweden)

Amy Joy Lanou

2010-12-01

Full Text Available Amy Joy Lanou1, Barbara Svenson21Department of Health and Wellness, 2Ramsey Library, University of North Carolina Asheville, Asheville, NC, USAAbstract: This report reviews current evidence regarding the relationship between vegetarian eating patterns and cancer risk. Although plant-based diets including vegetarian and vegan diets are generally considered to be cancer protective, very few studies have directly addressed this question. Most large prospective observational studies show that vegetarian diets are at least modestly cancer protective (10%–12% reduction in overall cancer risk although results for specific cancers are less clear. No long-term randomized clinical trials have been conducted to address this relationship. However, a broad body of evidence links specific plant foods such as fruits and vegetables, plant constituents such as fiber, antioxidants and other phytochemicals, and achieving and maintaining a healthy weight to reduced risk of cancer diagnosis and recurrence. Also, research links the consumption of meat, especially red and processed meats, to increased risk of several types of cancer. Vegetarian and vegan diets increase beneficial plant foods and plant constituents, eliminate the intake of red and processed meat, and aid in achieving and maintaining a healthy weight. The direct and indirect evidence taken together suggests that vegetarian diets are a useful strategy for reducing risk of cancer.Keywords: diet, vegan, prevention

Endothelial cell proliferation in swine experimental aneurysm after coil embolization.

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Yumiko Mitome-Mishima

Full Text Available After coil embolization, recanalization in cerebral aneurysms adversely influences long-term prognosis. Proliferation of endothelial cells on the coil surface may reduce the incidence of recanalization and further improve outcomes after coil embolization. We aimed to map the expression of proliferating tissue over the aneurysmal orifice and define the temporal profile of tissue growth in a swine experimental aneurysm model. We compared the outcomes after spontaneous thrombosis with those of coil embolization using histological and morphological techniques. In aneurysms that we not coiled, spontaneous thrombosis was observed, and weak, easily detachable proliferating tissue was evident in the aneurysmal neck. In contrast, in the coil embolization group, histological analysis showed endothelial-like cells lining the aneurysmal opening. Moreover, immunohistochemical and morphological analysis suggested that these cells were immature endothelial cells. Our results indicated the existence of endothelial cell proliferation 1 week after coil embolization and showed immature endothelial cells in septal tissue between the systemic circulation and the aneurysm. These findings suggest that endothelial cells are lead to and proliferate in the former aneurysmal orifice. This is the first examination to evaluate the temporal change of proliferating tissue in a swine experimental aneurysm model.

Nicotine enhances proliferation, migration, and radioresistance of human malignant glioma cells through EGFR activation

International Nuclear Information System (INIS)

Khalil, A.A.; Jameson, M.J.; Broaddus, W.C.; Lin, P.S.; Chung, T.D.

2013-01-01

It has been suggested that continued tobacco use during radiation therapy contributes to maintenance of neoplastic growth despite treatment with radiation. Nicotine is a cigarette component that is an established risk factor for many diseases, neoplastic and otherwise. The hypothesis of this work is that nicotine promotes the proliferation, migration, and radioresistance of human malignant glioma cells. The effect of nicotine on cellular proliferation, migration, signaling, and radiation sensitivity were evaluated for malignant glioma U87 and GBM12 cells by use of the AlamarBlue, scratch healing, and clonogenic survival assays. Signal transduction was assessed by immunoblotting for activated EGFR, extracellular regulated kinase (ERK), and AKT. At concentrations comparable with those found in chronic smokers, nicotine induced malignant glioma cell migration, growth, colony formation, and radioresistance. Nicotine increased phosphorylation of EGFR tyr992 , AKT ser473 , and ERK. These molecular effects were reduced by pharmacological inhibitors of EGFR, PI3K, and MEK. It was therefore concluded that nicotine stimulates the malignant behavior of glioma cells in vitro by activation of the EGFR and downstream AKT and ERK pathways. (author)

Innovative Corporate Initiatives to Reduce Climate Risk: Lessons from East Asia

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Edward B. Barbier

2017-12-01

Full Text Available Businesses, investors, and insurers are requiring better quantitative assessments of their exposure to climate risks and their impact on climate change. They are incorporating these assessments in their day-to-day management and long-term investment decisions. Already, there are efforts to develop international guidelines, common policies and legal frameworks for such assessments, as well as the desire to foster climate financing. We examine recent progress in East Asia and the rest of the world in setting targets, pricing policies, and other mechanisms to reduce climate risks. We develop a model that demonstrates how reduced climate risk management may lower the total cost of capital of firms, thus making them more attractive to investors. We discuss the additional policies needed to support improved climate risk management in investment decisions, private investments in climate science, technology and innovation (STI expansion, and more widespread adoption of climate financing and principles. Central banks, financial authorities, and governments can advance this objective by creating financial incentives to support investment decision-making. This would take into account factors such as improving climate performance, establishing better climate risk management and reporting requirements to foster green STI, and developing international guidelines and common policy and legal frameworks to support better climate risk management, assessments and reporting.

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)

Modulating Estrogen Receptor-related Receptor-α Activity Inhibits Cell Proliferation*

Science.gov (United States)

Bianco, Stéphanie; Lanvin, Olivia; Tribollet, Violaine; Macari, Claire; North, Sophie; Vanacker, Jean-Marc

2009-01-01

High expression of the estrogen receptor-related receptor (ERR)-α in human tumors is correlated to a poor prognosis, suggesting an involvement of the receptor in cell proliferation. In this study, we show that a synthetic compound (XCT790) that modulates the activity of ERRα reduces the proliferation of various cell lines and blocks the G1/S transition of the cell cycle in an ERRα-dependent manner. XCT790 induces, in a p53-independent manner, the expression of the cell cycle inhibitor p21waf/cip1 at the protein, mRNA, and promoter level, leading to an accumulation of hypophosphorylated Rb. Finally, XCT790 reduces cell tumorigenicity in Nude mice. PMID:19546226

Cyclophilin A enhances cell proliferation and tumor growth of liver fluke-associated cholangiocarcinoma

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Sawanyawisuth Kanlayanee

2011-08-01

Full Text Available Abstract Background Cyclophilin A (CypA expression is associated with malignant phenotypes in many cancers. However, the role and mechanisms of CypA in liver fluke-associated cholangiocarcinoma (CCA are not presently known. In this study, we investigated the expression of CypA in CCA tumor tissues and CCA cell lines as well as regulation mechanisms of CypA in tumor growth using CCA cell lines. Methods CypA expression was determined by real time RT-PCR, Western blot or immunohistochemistry. CypA silence or overexpression in CCA cells was achieved using gene delivery techniques. Cell proliferation was assessed using MTS assay or Ki-67 staining. The effect of silencing CypA on CCA tumor growth was determined in nude mice. The effect of CypA knockdown on ERK1/2 activation was assessed by Western blot. Results CypA was upregulated in 68% of CCA tumor tissues. Silencing CypA significantly suppressed cell proliferation in several CCA cell lines. Likewise, inhibition of CypA peptidyl-prolyl cis-trans isomerase (PPIase activity using cyclosporin A (CsA decreased cell proliferation. In contrast, overexpression of CypA resulted in 30% to 35% increases in proliferation of CCA cell lines. Interestingly, neither silence nor overexpression of CypA affected cell proliferation of a non-tumor human cholangiocyte cell line, MMNK1. Suppression of CypA expression attenuated ERK1/2 activity in CCA M139 cells by using both transient and stable knockdown methods. In the in vivo study, there was a 43% reduction in weight of tumors derived from CypA-silenced CCA cell lines compared with control vector CCA tumors in mice; these tumors with stable CypA silencing showed a reduced cell proliferation. Conclusions CypA is upregulated in majority of CCA patients' tissues and confers a significant growth advantage in CCA cells. Suppression of CypA expression decreases proliferation of CCA cell lines in vitro and reduces tumor growth in the nude mouse model. Inhibition of Cyp

Postnatal Treadmill Exercise Alleviates Prenatal Stress-Induced Anxiety in Offspring Rats by Enhancing Cell Proliferation Through 5-Hydroxytryptamine 1A Receptor Activation

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Sam Jun Lee

2016-05-01

Full Text Available Purpose: Stress during pregnancy is a risk factor for the development of anxiety-related disorders in offspring later in life. The effects of treadmill exercise on anxiety-like behaviors and hippocampal cell proliferation were investigated using rats exposed to prenatal stress. Methods: Exposure of pregnant rats to a hunting dog in an enclosed room was used to induce stress. Anxiety-like behaviors of offspring were evaluated using the elevated plus maze test. Immunohistochemistry for the detection of 5-bromo-2ʹ- deoxyuridine and doublecortin (DCX in the hippocampal dentate gyrus and 5-hydroxytryptamine 1A receptors (5-HT1A in the dorsal raphe was conducted. Brain-derived neurotrophic factor (BDNF and tyrosine kinase B (TrkB levels in the hippocampus were evaluated by western blot analysis. Results: Offspring of maternal rats exposed to stress during pregnancy showed anxiety-like behaviors. Offspring also showed reduced expression of BDNF, TrkB, and DCX in the dentate gyrus, decreased cell proliferation in the hippocampus, and reduced 5-HT1A expression in the dorsal raphe. Postnatal treadmill exercise by offspring, but not maternal exercise during pregnancy, enhanced cell proliferation and expression of these proteins. Conclusions: Postnatal treadmill exercise ameliorated anxiety-like behaviors in offspring of stressed pregnant rats, and the alleviating effect of exercise on these behaviors is hypothesized to result from enhancement of cell proliferation through 5-HT1A activation in offspring rats.

Uranium dependence and the proliferation problem

International Nuclear Information System (INIS)

Jacoby, H.D.

1977-01-01

A 20-year ''breathing space'' of adequate uranium supplies is felt to warrant delaying breeder technology until the threat of proliferation can be met with adequate internationally controlled stockpiles and marketing. Although a shift to breeder reactors developed as concern grew over the possibility of depleted uranium reserves, U.S. policy has now reversed this trend in favor of nuclear systems with a lower risk of proliferation. A review of uranium dependence analyzes the fuel cycle, current and projected reserves, reliable enrichment services, and international effects of proliferation and market disruptions. Uranium supply forecasts are more positive now because overstated reactor buildup projections led utilities to order more fuel than they will need until the late 1980s. These surpluses of light-water reactor fuel could be stockpiled at a cost of $20 billion, felt to be a relatively modest figure in terms of the total cost of nuclear power. A stockpile able to meet demand levels could offer the security of domestic supplies with trade opportunities and would retain levels of exploration and extraction. Several strategies for managing stockpiles are possible, but international control is seen as the best way to maintain reliable prices and uniform supply policies for all nations

Nuclear Proliferation Risk Mitigation Approaches and Impacts in the Recycle of Used Nuclear Fuel in the USA

International Nuclear Information System (INIS)

Hesketh, K.; Gregg, R.; Phillips, Ch.

2009-01-01

EnergySolutions and its team partners, which include the UK National Nuclear Laboratory (NNL), are one of four industry teams to have received an award from the US Department of Energy to carry out design studies in support of the US Global Nuclear Energy Partnership (GNEP). This team has developed a detailed scenario model for a future US nuclear fuel cycle based on a closed used nuclear fuel recycle as an alternative to the current once-though-and-store system. This scenario enables the uranium and plutonium in Light Water Reactor (LWR) used fuel from the current reactor fleet, and from a fleet of replacement LWRs, to be recycled as both Uranium Oxide and Mixed Oxide (MOX) fuel using reprocessing plants that conform to the requirements of GNEP. There is also a provision for 'burning' in thermal reactors certain long-lived transuranics (Np, Am, Cm) formed into targets. The residual fission product waste, without these long-term heat emitters, will be vitrified and consigned to the US National Geologic repository. Later in the scenario a fleet of Advanced Recycle Reactors (ARR), based on sodium cooled fast reactor technology, are introduced to enable full transmutation of all transuranics and thus attain the GNEP sustainability goal. The recycle scenario avoids the need for the Yucca Mountain repository to receive unprocessed used nuclear fuel and is effective at prolonging its lifetime and delaying the need for a second repository. This paper explains the process by which EnergySolutions selected the U-Pu and U-Pu-Np MOX products and the technological requirements for the recycle plants and describes materials flow analysis that has been carried for the US nuclear fuel cycle scenario using NNL's ORION scenario modelling program. One of the prime requisites of GNEP is to ensure that the risk of proliferation is minimized and the paper describes NNL's approach to objectively assessing the proliferation risk of the scenario relative to that of a conventional recycle

Using detection and deterrence to reduce insider risk

Energy Technology Data Exchange (ETDEWEB)

Eggers, R F; Carlson, R L; Udell, C J

1988-06-01

This paper addresses a new concept of interaction between adversary detection and deterrence. It provides an initial evaluation of the effects of these variables on the risk of theft of special nuclear material by an insider adversary and can be extended to the sabotage threat. A steady-state risk equation is used. Exercises with this equation show that deterrence, resulting from the prospect of detection, has a greater ability to reduce the risk than the detection exercise itself. This is true for all cases except those in which the probability of detection is 1. Cases were developed for three different types of adversaries that can be distinguished from one another by the level of detection they are willing to tolerate before they are deterred from attempting a theft. By considering the effects of detection, deterrence, and adversary type, the ground work is laid for designing cost-effective insider threat-protection systems. 2 refs., 6 figs.

Nuclear weapons proliferation and the new world order

International Nuclear Information System (INIS)

Krause, J.

1994-01-01

The proliferation of nuclear weapons has become the priority safety problem since the end of the cold war. The danger that new nuclear states may arise from the former Soviet Union, the limited effectiveness of existing control systems, the increased attractiveness of nuclear weapons for countries in which a 'safety vacuum' has developed since the withdrawal of American and Russian forces, as well as the danger that additional nuclear states (China, India, Pakistan) may become unstable or disintegrate, make it necessary to explore and show the ensuing risks. The study contains analyses from well-respected experts from Germany, Russia, Japan and the USA. They show how the changes in regional security situations could lead to nuclear risks under certain circumstances, and the likely international consequences. A second point of emphasis consens the feasibility of new approaches or instruments in international non-proliferatic policy. New possibilities for the improvement of excisting control systems and the extension of international consensus on an intensification of the non-proliferation regime are offered by the changes in world politics. (orig.) [de

Reduced 25-hydroxyvitamin D and risk of Alzheimer's disease and vascular dementia

DEFF Research Database (Denmark)

Afzal, Shoaib; Bojesen, Stig E; Nordestgaard, Børge G

2014-01-01

BACKGROUND: Vitamin D deficiency has been implicated as a risk factor for dementia in several cross-sectional studies. We tested the hypothesis that reduced plasma 25-hydroxyvitamin D (25[OH]D) is associated with increased risk of Alzheimer's disease (AD) and vascular dementia in the general.......28 (95% CI, 1.00-1.64) for 25(OH)D less than 25 nmol/L vs. greater than or equal to 50 nmol/L, and 1.27 (95% CI, 1.01-1.60) for less than the 25th vs. more than the 50th seasonally adjusted 25(OH)D. CONCLUSIONS: We observed an association of reduced plasma 25(OH)D with increased risk of the combined end...

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

The Antidiabetic Drug Metformin Inhibits the Proliferation of Bladder Cancer Cells in Vitro and in Vivo

Directory of Open Access Journals (Sweden)

Tao Zhang

2013-12-01

Full Text Available Recent studies suggest that metformin, a widely used antidiabetic agent, may reduce cancer risk and improve prognosis of certain malignancies. However, the mechanisms for the anti-cancer effects of metformin remain uncertain. In this study, we investigated the effects of metformin on human bladder cancer cells and the underlying mechanisms. Metformin significantly inhibited the proliferation and colony formation of 5637 and T24 cells in vitro; specifically, metformin induced an apparent cell cycle arrest in G0/G1 phases, accompanied by a strong decrease of cyclin D1, cyclin-dependent kinase 4 (CDK4, E2F1 and an increase of p21waf-1. Further experiments revealed that metformin activated AMP-activated protein kinase (AMPK and suppressed mammalian target of rapamycin (mTOR, the central regulator of protein synthesis and cell growth. Moreover, daily treatment of metformin led to a substantial inhibition of tumor growth in a xenograft model with concomitant decrease in the expression of proliferating cell nuclear antigen (PCNA, cyclin D1 and p-mTOR. The in vitro and in vivo results demonstrate that metformin efficiently suppresses the proliferation of bladder cancer cells and suggest that metformin may be a potential therapeutic agent for the treatment of bladder cancer.

Reduced risk HTGR concept for industrial heat application

International Nuclear Information System (INIS)

Boardman, C.E.; Lipps, A.J.

1982-01-01

The industrial process heat market has been identified as major market for the High Temperature Gas-Cooled Reactor (HTGR), however, this market introduces stringent availability requirements on the reactor system relative to electric plants which feed a large existing grid. The characteristics and requirements of the industrial heat markets are summarized; the risks associated with serving this market with a single large HTGR will be discussed; and the modular concept, which has the potential to reduce both safety and investment risks, will be described. The reference modular concept described consists of several small, relatively benign nuclear heat sources linked together to supply heat energy to a balance-of-plant incorporating a process gas train/thermochemical pipe line system and a normal steam-electric plant

A Dictyostelium chalone uses G proteins to regulate proliferation.

Science.gov (United States)

Bakthavatsalam, Deenadayalan; Choe, Jonathan M; Hanson, Nana E; Gomer, Richard H

2009-07-27

Several studies have shown that organ size, and the proliferation of tumor metastases, may be regulated by negative feedback loops in which autocrine secreted factors called chalones inhibit proliferation. However, very little is known about chalones, and how cells sense them. We previously identified two secreted proteins, AprA and CfaD, which act as chalones in Dictyostelium. Cells lacking AprA or CfaD proliferate faster than wild-type cells, and adding recombinant AprA or CfaD to cells slows their proliferation. We show here that cells lacking the G protein components Galpha8, Galpha9, and Gbeta proliferate faster than wild-type cells despite secreting normal or high levels of AprA and CfaD. Compared with wild-type cells, the proliferation of galpha8-, galpha9- and gbeta- cells are only weakly inhibited by recombinant AprA (rAprA). Like AprA and CfaD, Galpha8 and Gbeta inhibit cell proliferation but not cell growth (the rate of increase in mass and protein per nucleus), whereas Galpha9 inhibits both proliferation and growth. galpha8- cells show normal cell-surface binding of rAprA, whereas galpha9- and gbeta- cells have fewer cell-surface rAprA binding sites, suggesting that Galpha9 and Gbeta regulate the synthesis or processing of the AprA receptor. Like other ligands that activate G proteins, rAprA induces the binding of [3H]GTP to membranes, and GTPgammaS inhibits the binding of rAprA to membranes. Both AprA-induced [3H]GTP binding and the GTPgammaS inhibition of rAprA binding require Galpha8 and Gbeta but not Galpha9. Like aprA- cells, galpha8- cells have reduced spore viability. This study shows that Galpha8 and Gbeta are part of the signal transduction pathway used by AprA to inhibit proliferation but not growth in Dictyostelium, whereas Galpha9 is part of a differealnt pathway that regulates both proliferation and growth, and that a chalone signal transduction pathway uses G proteins.

Aging increases microglial proliferation, delays cell migration, and decreases cortical neurogenesis after focal cerebral ischemia.

Science.gov (United States)

Moraga, Ana; Pradillo, Jesús M; García-Culebras, Alicia; Palma-Tortosa, Sara; Ballesteros, Ivan; Hernández-Jiménez, Macarena; Moro, María A; Lizasoain, Ignacio

2015-05-10

Aging is not just a risk factor of stroke, but it has also been associated with poor recovery. It is known that stroke-induced neurogenesis is reduced but maintained in the aged brain. However, there is no consensus on how neurogenesis is affected after stroke in aged animals. Our objective is to determine the role of aging on the process of neurogenesis after stroke. We have studied neurogenesis by analyzing proliferation, migration, and formation of new neurons, as well as inflammatory parameters, in a model of cerebral ischemia induced by permanent occlusion of the middle cerebral artery in young- (2 to 3 months) and middle-aged mice (13 to 14 months). Aging increased both microglial proliferation, as shown by a higher number of BrdU(+) cells and BrdU/Iba1(+) cells in the ischemic boundary and neutrophil infiltration. Interestingly, aging increased the number of M1 monocytes and N1 neutrophils, consistent with pro-inflammatory phenotypes when compared with the alternative M2 and N2 phenotypes. Aging also inhibited (subventricular zone) SVZ cell proliferation by decreasing both the number of astrocyte-like type-B (prominin-1(+)/epidermal growth factor receptor (EGFR)(+)/nestin(+)/glial fibrillary acidic protein (GFAP)(+) cells) and type-C cells (prominin-1(+)/EGFR(+)/nestin(-)/Mash1(+) cells), and not affecting apoptosis, 1 day after stroke. Aging also inhibited migration of neuroblasts (DCX(+) cells), as indicated by an accumulation of neuroblasts at migratory zones 14 days after injury; consistently, aged mice presented a smaller number of differentiated interneurons (NeuN(+)/BrdU(+) and GAD67(+) cells) in the peri-infarct cortical area 14 days after stroke. Our data confirm that stroke-induced neurogenesis is maintained but reduced in aged animals. Importantly, we now demonstrate that aging not only inhibits proliferation of specific SVZ cell subtypes but also blocks migration of neuroblasts to the damaged area and decreases the number of new interneurons in

Reducing e-commerce risks using digital certificates

Directory of Open Access Journals (Sweden)

Piščević Miloš

2009-01-01

Full Text Available E-commerce means buying and selling goods and services across the Internet. Secured communication in e-commerce, across unsecured medium, such as the Internet, represents one of the major components in a domain of providing necessary security- critical demands, so the flow of information could go in a secure way. The Internet, as a global computer network must provide five major security services: confidentiality, data integrity, authentication, availability, and non-repudiation of information. Without guaranteeing aformentioned security goals, risks may be very high in e-commerce systems. A possible way to reduce these risks is to use digital certificates. Digital certificates provide a means of proving identity in electronic transactions, and from the point of view of computer communication they are irreplacable, but nevertheless they provide a good mechanism for implementing the major part of this security goal, and therefore, their usage in e-commerce is the major topic of this paper.

Reducing the health risks from radon in the UK overground workplace

International Nuclear Information System (INIS)

Denman, A.R.

2008-01-01

In response to the potential health risk from radon in workplaces in the United Kingdom (UK), the Ionising Radiations Regulations 1999 include the protection of workers from excessive radon levels. Under the Management of Health and Safety at Work Regulations 1999, employers are required to make risk assessments for potential hazards in the workplace. This is taken to apply to the risk from radon in premises in areas where over 1% of domestic housing properties have average annual radon levels over the Action Level. Whilst the UK Action Level in domestic housing has been set at 200 Bq·m -3 , the workplace limit is 400 Bq·m -3 . The Regulations require that this limit be compared to a 24-hour winter maximum, while in domestic properties the annual average radon level is compared to the Action Level. This paper discusses the application of the Regulations in the UK to ensure compliance and reduce risk from radon in the workplace, include use of short-term measurements, and the consideration of seasonal variation. Reduction of radon levels can be achieved by methods similar to those in domestic properties, but, in large buildings, several sump/pump systems may be required. Case studies have shown that the sump/pump system preferentially reduces radon levels at night, when workers are not usually present. Thus to achieve a significant health benefit the average radon level should be reduced below 325 Bq·m -3 . (author)

Effects of celecoxib on proliferation and tenocytic differentiation of tendon-derived stem cells

Energy Technology Data Exchange (ETDEWEB)

Zhang, Kairui; Zhang, Sheng [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Li, Qianqian [Cancer Research Institute, Southern Medical University, Guangzhou 510515 (China); Yang, Jun [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Department of Orthopaedics, 421 Hospital of PLA, Guangzhou 510318 (China); Dong, Weiqiang [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Department of Orthopaedics, The First Affiliated Hospital to Guangzhou Medical University, Guangzhou 510120 (China); Wang, Shengnan; Cheng, Yirong; Al-Qwbani, Mohammed [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Wang, Qiang, E-mail: 1780468505@qq.com [Department of Orthopaedics, Subei People’s Hospital of Jiangsu Province (Clinical Medical College of Yangzhou University), Yangzhou, Jiangsu Province 225001 (China); Yu, Bin, E-mail: carryzhang1985@live.com [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China)

2014-07-18

Highlights: • Celecoxib has no effects on TDSCs cell proliferation in various concentrations. • Celecoxib reduced mRNAs levels of tendon associated transcription factor. • Celecoxib reduced mRNAs levels of main tendon associated collagen. • Celecoxib reduced mRNAs levels of tendon associated molecules. - Abstract: NSAIDs are often ingested to reduce the pain and improve regeneration of tendon after tendon injury. Although the effects of NSAIDs in tendon healing have been reported, the data and conclusions are not consistent. Recently, tendon-derived stem cells (TDSCs) have been isolated from tendon tissues and has been suggested involved in tendon repair. Our study aims to determine the effects of COX-2 inhibitor (celecoxib) on the proliferation and tenocytic differentiation of TDSCs. TDSCs were isolated from mice Achilles tendon and exposed to celecoxib. Cell proliferation rate was investigated at various concentrations (0.1, 1, 10 and 100 μg/ml) of celecoxib by using hemocytometer. The mRNA expression of tendon associated transcription factors, tendon associated collagens and tendon associated molecules were determined by reverse transcription-polymerase chain reaction. The protein expression of Collagen I, Collagen III, Scleraxis and Tenomodulin were determined by Western blotting. The results showed that celecoxib has no effects on TDSCs cell proliferation in various concentrations (p > 0.05). The levels of most tendon associated transcription factors, tendon associated collagens and tendon associated molecules genes expression were significantly decreased in celecoxib (10 μg/ml) treated group (p < 0.05). Collagen I, Collagen III, Scleraxis and Tenomodulin protein expression were also significantly decreased in celecoxib (10 μg/ml) treated group (p < 0.05). In conclusion, celecoxib inhibits tenocytic differentiation of tendon-derived stem cells but has no effects on cell proliferation.

Effects of celecoxib on proliferation and tenocytic differentiation of tendon-derived stem cells

International Nuclear Information System (INIS)

Zhang, Kairui; Zhang, Sheng; Li, Qianqian; Yang, Jun; Dong, Weiqiang; Wang, Shengnan; Cheng, Yirong; Al-Qwbani, Mohammed; Wang, Qiang; Yu, Bin

2014-01-01

Highlights: • Celecoxib has no effects on TDSCs cell proliferation in various concentrations. • Celecoxib reduced mRNAs levels of tendon associated transcription factor. • Celecoxib reduced mRNAs levels of main tendon associated collagen. • Celecoxib reduced mRNAs levels of tendon associated molecules. - Abstract: NSAIDs are often ingested to reduce the pain and improve regeneration of tendon after tendon injury. Although the effects of NSAIDs in tendon healing have been reported, the data and conclusions are not consistent. Recently, tendon-derived stem cells (TDSCs) have been isolated from tendon tissues and has been suggested involved in tendon repair. Our study aims to determine the effects of COX-2 inhibitor (celecoxib) on the proliferation and tenocytic differentiation of TDSCs. TDSCs were isolated from mice Achilles tendon and exposed to celecoxib. Cell proliferation rate was investigated at various concentrations (0.1, 1, 10 and 100 μg/ml) of celecoxib by using hemocytometer. The mRNA expression of tendon associated transcription factors, tendon associated collagens and tendon associated molecules were determined by reverse transcription-polymerase chain reaction. The protein expression of Collagen I, Collagen III, Scleraxis and Tenomodulin were determined by Western blotting. The results showed that celecoxib has no effects on TDSCs cell proliferation in various concentrations (p > 0.05). The levels of most tendon associated transcription factors, tendon associated collagens and tendon associated molecules genes expression were significantly decreased in celecoxib (10 μg/ml) treated group (p < 0.05). Collagen I, Collagen III, Scleraxis and Tenomodulin protein expression were also significantly decreased in celecoxib (10 μg/ml) treated group (p < 0.05). In conclusion, celecoxib inhibits tenocytic differentiation of tendon-derived stem cells but has no effects on cell proliferation

Acid-reducing vagotomy is associated with reduced risk of subsequent ischemic heart disease in complicated peptic ulcer: An Asian population study.

Science.gov (United States)

Wu, Shih-Chi; Fang, Chu-Wen; Chen, William Tzu-Liang; Muo, Chih-Hsin

2016-12-01

Persistent exacerbation of a peptic ulcer may lead to a complicated peptic ulcer (perforation or/and bleeding). The management of complicated peptic ulcers has shifted from acid-reducing vagotomy, drainage, and gastrectomy to simple local suture or non-operative (endoscopic/angiographic) hemostasis. We were interested in the long-term effects of this trend change. In this study, complicated peptic ulcer patients who received acid-reducing vagotomy were compared with those who received simple suture/hemostasis to determine the risk of ischemic heart disease (IHD).This retrospective cohort study analyzed 335,680 peptic ulcer patients recorded from 2000 to 2006 versus 335,680 age-, sex-, comorbidity-, and index-year matched comparisons. Patients with Helicobacter pylori (HP) infection were excluded. In order to identify the effect of vagus nerve severance, patients who received gastrectomy or antrectomy were also excluded. The incidence of IHD in both cohorts, and in the complicated peptic ulcer patients who received acid-reducing vagotomy versus those who received simple suture or hemostasis was evaluated.The overall incidence of IHD was higher in patients with peptic ulcer than those without peptic ulcer (17.00 vs 12.06 per 1000 person-years), with an adjusted hazard ratio (aHR) of 1.46 based on multivariable Cox proportional hazards regression analysis controlling for age, sex, Charlson's comorbidity index, and death (competing risk). While comparing peptic ulcer patients with acid-reducing vagotomy to those with simple suture/hemostasis or those without surgical treatment, the aHR (0.58) was the lowest in the acid-reducing vagotomy group.Patients with peptic ulcer have an elevated risk of IHD. However, complicated peptic ulcer patients who received acid-reducing vagotomy were associated with reduced risk of developing IHD.

Nuclear proliferation and civilian nuclear power: report of the Nonproliferation Alternative Systems Assessment Program. Volume V. Economics and systems analysis

International Nuclear Information System (INIS)

1979-12-01

This assessment considers the economics of alternative nuclear reactor and fuel-cycle systems in the light of possible patterns of uranium supply and energy demand, as well as the economic implications of improving the proliferation resistance of the various systems. The assessment focuses on the costs of alternative nuclear technologies and the possible timing of their implementation, based on their economic attractiveness. The objectives of this assessment are to identify when economic incentives to deploy advanced nuclear power systems might exist, to estimate the costs of using technologies that would reduce the risk of proliferation, to assess the impact of major economic uncertainties on the transition to new technologies, and to compare the investments required for alternative systems. This information can then be used to assess the potential economic benefits of alternative research, development, and demonstration programs and the timing of those programs

Nuclear proliferation and civilian nuclear power: report of the Nonproliferation Alternative Systems Assessment Program. Volume V. Economics and systems analysis

Energy Technology Data Exchange (ETDEWEB)

None

1979-12-01

This assessment considers the economics of alternative nuclear reactor and fuel-cycle systems in the light of possible patterns of uranium supply and energy demand, as well as the economic implications of improving the proliferation resistance of the various systems. The assessment focuses on the costs of alternative nuclear technologies and the possible timing of their implementation, based on their economic attractiveness. The objectives of this assessment are to identify when economic incentives to deploy advanced nuclear power systems might exist, to estimate the costs of using technologies that would reduce the risk of proliferation, to assess the impact of major economic uncertainties on the transition to new technologies, and to compare the investments required for alternative systems. This information can then be used to assess the potential economic benefits of alternative research, development, and demonstration programs and the timing of those programs.

Increase plant safety and reduce cost by implementing risk-informed in-service inspection programs

International Nuclear Information System (INIS)

Billington, A.; Monette, P.

2001-01-01

The idea behind the program is that it is possible to 'inspect less, but inspect better'. In other words, the risk-informed In-Service Inspection (ISI) process is used to improve the effectiveness of examination of piping components, i.e. concentrate inspection resources and enhance inspection strategies on high safety significant locations, and reduce inspection requirements on others. The Westinghouse Owners Group (WOG) risk-informed ISI process has already been applied for full scope (Millstone 3, Surry 1) and limited scope (Beznau, Ringhals 4, Asco, Turkey Point 3). By examining the high safety significant piping segments for the different fluid piping systems, the total piping core damage frequency is reduced. In addition, more than 80% of the risk associated with potential pressure boundary failures is addressed with the WOG risk-informed ISI process, while typically less that 50% of this same risk is addressed by the current inspection programs. The risk-informed ISI processes are used to improve the effectiveness of inspecting safety-significant piping components, to reduce inspection requirements on other piping components, to evaluate improvements to plant availability and enhanced safety measures, including reduction of personnel radiation exposure, and to reduce overall Operation and Maintenance (O and M) costs while maintaining regulatory compliance. A description of the process as well as benefits from past projects is presented, since the methodology is applicable for WWER plant design. (author)

Increase plant safety and reduce cost by implementing risk-informed In-Service Inspection programs

International Nuclear Information System (INIS)

Billington, A.; Monette, P.; Doumont, C.

2000-01-01

The idea behind the program is that it is possible to 'inspect less, but inspect better'. In other words, the risk-informed In-Service Inspection (ISI) process is used to improve the effectiveness of examination of piping components, i.e. concentrate inspection resources and enhance inspection strategies on high safety significant locations, and reduce inspection requirements on others. The Westinghouse Owners Group (WOG) risk-informed ISI process has already been applied for full scope (Millstone 3, Surry 1) and limited scope (Beznau, Ringhals 4, Asco, Turkey Point 3). By examining the high safety significant piping segments for the different fluid piping systems, the total piping core damage frequency is reduced. In addition, more than 80% of the risk associated with potential pressure boundary failures is addressed with the WOG risk-informed ISI process, while typically less than 50% of this same risk is addressed by the current inspection programs. The risk-informed ISI processes are used: to improve the effectiveness of inspecting safety-significant piping components; to reduce inspection requirements on other piping components; to evaluate improvements to plant availability and enhanced safety measures, including reduction of personnel radiation exposure; and to reduce overall Operation and Maintenance (O and M) costs while maintaining regulatory compliance. A description of the process as well as benefits of past projects is presented, since the methodology is applicable for VVER plant design. (author)

Statin use and reduced cancer-related mortality

DEFF Research Database (Denmark)

Nielsen, Sune F; Nordestgaard, Børge G; Bojesen, Stig E

2012-01-01

A reduction in the availability of cholesterol may limit the cellular proliferation required for cancer growth and metastasis. We tested the hypothesis that statin use begun before a cancer diagnosis is associated with reduced cancer-related mortality.......A reduction in the availability of cholesterol may limit the cellular proliferation required for cancer growth and metastasis. We tested the hypothesis that statin use begun before a cancer diagnosis is associated with reduced cancer-related mortality....

Bryostatin I inhibits growth and proliferation of pancreatic cancer ...

African Journals Online (AJOL)

). ... µM reduced MIApaCa 2 cell proliferation from 87 to 26 %. ... tumors in the treatment and untreated groups was 123.67 ± 22.56 and ... κB expression, and therefore, needs to be further investigated for therapeutic application in pancreatic.

Low oxygen level increases proliferation and metabolic changes in bovine granulosa cells.

Science.gov (United States)

Shiratsuki, Shogo; Hara, Tomotaka; Munakata, Yasuhisa; Shirasuna, Koumei; Kuwayama, Takehito; Iwata, Hisataka

2016-12-05

The present study addresses molecular backgrounds underlying low oxygen induced metabolic changes and 1.2-fold change in bovine granulosa cell (GCs) proliferation. RNA-seq revealed that low oxygen (5%) upregulated genes associated with HIF-1 and glycolysis and downregulated genes associated with mitochondrial respiration than that in high oxygen level (21%). Low oxygen level induced high glycolytic activity and low mitochondrial function and biogenesis. Low oxygen level enhanced GC proliferation with high expression levels of HIF-1, VEGF, AKT, mTOR, and S6RP, whereas addition of anti-VEGF antibody decreased cellular proliferation with low phosphorylated AKT and mTOR expression levels. Low oxygen level reduced SIRT1, whereas activation of SIRT1 by resveratrol increased mitochondrial replication and decreased cellular proliferation with reduction of phosphorylated mTOR. These results suggest that low oxygen level stimulates the HIF1-VEGF-AKT-mTOR pathway and up-regulates glycolysis, which contributes to GC proliferation, and downregulation of SIRT1 contributes to hypoxia-associated reduction of mitochondria and cellular proliferation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.)

The Oligo Fucoidan Inhibits Platelet-Derived Growth Factor-Stimulated Proliferation of Airway Smooth Muscle Cells

Directory of Open Access Journals (Sweden)

Chao-Huei Yang

2016-01-01

Full Text Available In the pathogenesis of asthma, the proliferation of airway smooth muscle cells (ASMCs is a key factor in airway remodeling and causes airway narrowing. In addition, ASMCs are also the effector cells of airway inflammation. Fucoidan extracted from marine brown algae polysaccharides has antiviral, antioxidant, antimicrobial, anticlotting, and anticancer properties; however, its effectiveness for asthma has not been elucidated thus far. Platelet-derived growth factor (PDGF-treated primary ASMCs were cultured with or without oligo-fucoidan (100, 500, or 1000 µg/mL to evaluate its effects on cell proliferation, cell cycle, apoptosis, and Akt, ERK1/2 signaling pathway. We found that PDGF (40 ng/mL increased the proliferation of ASMCs by 2.5-fold after 48 h (p < 0.05. Oligo-fucoidan reduced the proliferation of PDGF-stimulated ASMCs by 75%–99% after 48 h (p < 0.05 and induced G1/G0 cell cycle arrest, but did not induce apoptosis. Further, oligo-fucoidan supplementation reduced PDGF-stimulated extracellular signal-regulated kinase (ERK1/2, Akt, and nuclear factor (NF-κB phosphorylation. Taken together, oligo-fucoidan supplementation might reduce proliferation of PDGF-treated ASMCs through the suppression of ERK1/2 and Akt phosphorylation and NF-κB activation. The results provide basis for future animal experiments and human trials.

Fisetin regulates astrocyte migration and proliferation in vitro

Science.gov (United States)

Wang, Nan; Yao, Fang; Li, Ke; Zhang, Lanlan; Yin, Guo; Du, Mingjun; Wu, Bingyi

2017-01-01

Fisetin (3,3′,4′,7-tetrahydroxyflavone) is a plant flavonol found in fruits and vegetables that has been reported to inhibit migration and proliferation in several types of cancer. Reactive astrogliosis involves astrocyte migration and proliferation, and contributes to the formation of glial scars in central nervous system (CNS) disorders. However, the effect of fisetin on the migration and proliferation of astrocytes remains unclear. In this study, we found that fisetin inhibited astrocyte migration in a scratch-wound assay and diminished the phosphorylation of focal adhesion kinase (FAK; Tyr576/577 and paxillin (Tyr118). It also suppressed cell proliferation, as indicated by the decreased number of 5-ethynyl-2′-deoxyuridine (EdU)-positive cells, induced cell cycle arrest in the G1 phase, reduced the percentage of cells in the G2 and S phase (as measured by flow cytometry), and decreased cyclin D1 expression, but had no effect on apoptosis. Fisetin also decreased the phosphorylation levels of Akt and extracellular signal-regulated kinase (Erk)1/2, but had no effect on the phosphorylation of p38 mitogen-activated protein kinase (MAPK). These results indicate that fisetin inhibits aggressive cell phenotypes by suppressing cell migration and proliferation via the Akt/Erk signaling pathway. Fisetin may thus have potential for use as a therapeutic strategy targeting reactive astrocytes, which may lead to the inhibition of glial scar formation in vitro. PMID:28204814

Preconceptional motivational interviewing interventions to reduce alcohol-exposed pregnancy risk.

Science.gov (United States)

Ingersoll, Karen S; Ceperich, Sherry D; Hettema, Jennifer E; Farrell-Carnahan, Leah; Penberthy, J Kim

2013-04-01

Alcohol exposed pregnancy (AEP) is a leading cause of preventable birth defects. While randomized controlled trials (RCTs) have shown that multi-session motivational interviewing-based interventions reduce AEP risk, a one-session intervention could facilitate broader implementation. The purposes of this study were to: (1) test a one-session motivational AEP prevention intervention for community women and (2) compare outcomes to previous RCTs. Participants at risk for AEP (N=217) were randomized to motivational interviewing+assessment feedback (EARLY), informational video, or informational brochure conditions. Outcomes were drinks per drinking day (DDD), ineffective contraception rate, and AEP risk at 3 and 6 months. All interventions were associated with decreased DDD, ineffective contraception rate, and AEP risk. Participants who received EARLY had larger absolute risk reductions in ineffective contraception and AEP risk, but not DDD. Effect sizes were compared to previous RCTs. The one-session EARLY intervention had less powerful effects than multi-session AEP prevention interventions among community women, but may provide a new option in a continuum of preventive care. Copyright © 2013 Elsevier Inc. All rights reserved.

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

Directory of Open Access Journals (Sweden)

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.

Inhibition of cell proliferation by a selective inhibitor of the Ca{sup 2+}-activated Cl{sup -} channel, Ano1

Energy Technology Data Exchange (ETDEWEB)

Mazzone, Amelia; Eisenman, Seth T.; Strege, Peter R. [Enteric NeuroScience Program, Mayo Clinic, Rochester, MN (United States); Yao, Zhen [Laboratory of Molecular Genetics, UCSF, San Francisco, CA (United States); Ordog, Tamas; Gibbons, Simon J. [Enteric NeuroScience Program, Mayo Clinic, Rochester, MN (United States); Farrugia, Gianrico, E-mail: farrugia.gianrico@mayo.edu [Enteric NeuroScience Program, Mayo Clinic, Rochester, MN (United States)

2012-10-19

Highlights: Black-Right-Pointing-Pointer T16A{sub inh}-A01 blocked Ano1 currents in HEK cells expressing Ano1. Black-Right-Pointing-Pointer T16A{sub inh}-A01 reduced proliferation in ICC primary cultures and CFPAC-1 cell line. Black-Right-Pointing-Pointer T16A{sub inh}-A01 reduced proliferation of ICC in intact smooth muscle strips. -- Abstract: Background: Ion channels play important roles in regulation of cellular proliferation. Ano1 (TMEM16A) is a Ca{sup 2+}-activated Cl{sup -} channel expressed in several tumors and cell types. In the muscle layers of the gastrointestinal tract Ano1 is selectively expressed in interstitial cells of Cajal (ICC) and appears to be required for normal gastrointestinal slow wave electrical activity. However, Ano1 is expressed in all classes of ICC, including those that do not generate slow waves suggesting that Ano1 may have other functions. Indeed, a role for Ano1 in regulating proliferation of tumors and ICC has been recently suggested. Recently, a high-throughput screen identified a small molecule, T16A{sub inh}-A01 as a specific inhibitor of Ano1. Aim: To investigate the effect of the T16A{sub inh}-A01 inhibitor on proliferation in ICC and in the Ano1-expressing human pancreatic cancer cell line CFPAC-1. Methods: Inhibition of Ano1 was demonstrated by whole cell voltage clamp recordings of currents in cells transfected with full-length human Ano1. The effect of T16A{sub inh}-A01 on ICC proliferation was examined in situ in organotypic cultures of intact mouse small intestinal smooth muscle strips and in primary cell cultures prepared from these tissues. ICC were identified by Kit immunoreactivity. Proliferating ICC and CFPAC-1 cells were identified by immunoreactivity for the nuclear antigen Ki67 or EdU incorporation, respectively. Results: T16A{sub inh}-A01 inhibited Ca{sup 2+}-activated Cl{sup -} currents by 60% at 10 {mu}M in a voltage-independent fashion. Proliferation of ICC was significantly reduced in primary cultures

Meta-analyses on behavioral interventions to reduce the risk of transmission of HIV.

Science.gov (United States)

Vergidis, Paschalis I; Falagas, Matthew E

2009-06-01

Different behavioral interventions have found to be efficacious in reducing high-risk sexual activity. Interventions have been evaluated in both original research and meta-analytic reviews. Most of the studies have shown that interventions are efficacious among different study populations. In adolescents, both in- and out-of-the classroom interventions showed a decrease in the risk of unprotected sex. In African Americans, greater efficacy was found for interventions including peer education. For Latinos, effect was larger in interventions with segmentation in the same gender. Geographic and social isolation are barriers in approaching MSM. For IDUs, interventions provided within a treatment program have an impact on risk reduction above that produced by drug treatment alone. Finally, people diagnosed with HIV tend to reduce their sexual risk behavior. However, adherence to safe sex practices for life can be challenging. Relentless efforts for implementation of behavioral interventions to decrease high-risk behavior are necessary to decrease HIV transmission.

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 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

Reducing The Risk Of Fires In Conveyor Transport

Science.gov (United States)

Cheremushkina, M. S.; Poddubniy, D. A.

2017-01-01

The paper deals with the actual problem of increasing the safety of operation of belt conveyors in mines. Was developed the control algorithm that meets the technical requirements of the mine belt conveyors, reduces the risk of fires of conveyors belt, and enables energy and resource savings taking into account random sort of traffic. The most effective method of decision such tasks is the construction of control systems with the use of variable speed drives for asynchronous motors. Was designed the mathematical model of the system "variable speed multiengine drive - conveyor - control system of conveyors", that takes into account the dynamic processes occurring in the elements of the transport system, provides an assessment of the energy efficiency of application the developed algorithms, which allows to reduce the dynamic overload in the belt to (15-20)%.

Reducing the risk from radioactive sources

International Nuclear Information System (INIS)

MacKenzie, C.

2006-01-01

Each year the IAEA receives reports of serious injuries or deaths due to misuse or accidents involving sealed radioactive sources. Sealed radioactive sources are used widely in medicine, industry, and agriculture - by doctors to treat cancer, by radiographers to check welds in pipelines, or by specialists to irradiate food to prevent it from spoiling, for example. If these sources are lost or improperly discarded, a serious accident may result. In addition, the security of sealed sources has become a growing concern, particularly the potential that such a source could be used as a radioactive dispersal device or 'dirty bomb'. Preventing the loss or theft of sealed radioactive sources reduces both the risk of accidents and the risk that such sources could become an instrument of misuse. In most countries, radioactive materials and activities that produce radiation are regulated. Those working with sealed radioactive sources are required not just to have proper credentials, but also the needed training and support to deal with unexpected circumstances that may arise when a source is used. Despite these measures, accidents involving sealed sources continue to be reported to the IAEA. Among its many activities to improve the safety and security of sealed sources, the IAEA has been investigating the root causes of major accidents since the 1980s and publishing the findings so that others can learn from them. This information needs to be in the hands of those whose actions and decisions can reduce accidents by preventing a lost source from making it's way into scrap metal. The IAEA has also developed an international catalogue of sealed radioactive sources, and provides assistance to countries to safely contain sources no longer in use. To raise awareness, a Sealed Radioactive Sources Toolkit was issued that focuses on the long-term issues in safely and securely managing radioactive sealed sources. The target audiences are government agencies, radioactive sealed source

EPA'S strategy to reduce risk of radon

International Nuclear Information System (INIS)

Page, S.

1993-01-01

The Indoor Radon Abatement Act of 1988 (IRAA) directed EPA to undertake a variety of activities to address the growing public concern over dangers posed by exposure to indoor radon. Among other requirements, the law directed the Agency to study radon levels, evaluate mitigation methods, establish proficiency programs, assist states with program development, develop training centers, and provide public information. EPA has developed and implemented programs to address each of the key provisions of this statute. This paper presents EPA's broad national strategy to reduce radon risks. It combines and reinforces EPA's basic foundation, including its guiding policies and cooperative partnerships, with an overall management approach and focus for the future. The paper starts with an overview that introduces the strategy's four key elements: underlying policies and scientific principles, a decentralized system of states and other partners for targeting the public, multiple strategies for achieving radon risk reduction, and a strong focus on five key program priorities. This paper then discusses each of these elements in more detail and describes how they interact to guide future efforts and directions of the Agency

Perceptions of Risk of Developing Skin Cancer for Diverse Audiences: Enhancing Relevance of Sun Protection to Reduce the Risk.

Science.gov (United States)

Robinson, June K; Friedewald, John; Gordon, Elisa J

2016-03-01

Sixty-five percent of kidney transplant recipients (KTRs) develop squamous cell carcinoma (SCC). Perceptions of risk of developing skin cancer, amelioration of this risk with sun protection, and having choices among sun protection strategies may enhance sun protection use by KTRS, who are at greater risk than the general population. Thirty KTRs stratified among non-Hispanic Whites, non-Hispanic Blacks, and Hispanic/Latinos evaluated three versions of the interactive, web-based, electronic sun protection program and suggested refinements. The sequence of content presentation prepared the participant to accept the credibility, accuracy, and relevance of the message. Beginning with informing participants that using sun protection reduces the chance of developing skin cancer made the information credible to KTRs. Showing skin cancer on all skin types and patient testimonials enhanced participants' awareness of their susceptibility to develop skin cancer and primed patients to receive their personal risk of developing skin cancer. Coupling presentation of knowledge about the benefits of sun protection in reducing the risk of developing skin cancer with the personal risk of getting the disease was essential to KTRs believing that they could influence their health outcome.

A Dictyostelium chalone uses G proteins to regulate proliferation

Directory of Open Access Journals (Sweden)

Hanson Nana E

2009-07-01

Full Text Available Abstract Background Several studies have shown that organ size, and the proliferation of tumor metastases, may be regulated by negative feedback loops in which autocrine secreted factors called chalones inhibit proliferation. However, very little is known about chalones, and how cells sense them. We previously identified two secreted proteins, AprA and CfaD, which act as chalones in Dictyostelium. Cells lacking AprA or CfaD proliferate faster than wild-type cells, and adding recombinant AprA or CfaD to cells slows their proliferation. Results We show here that cells lacking the G protein components Galpha8, Galpha9, and Gbeta proliferate faster than wild-type cells despite secreting normal or high levels of AprA and CfaD. Compared with wild-type cells, the proliferation of galpha8-, galpha9- and gbeta- cells are only weakly inhibited by recombinant AprA (rAprA. Like AprA and CfaD, Galpha8 and Gbeta inhibit cell proliferation but not cell growth (the rate of increase in mass and protein per nucleus, whereas Galpha9 inhibits both proliferation and growth. galpha8- cells show normal cell-surface binding of rAprA, whereas galpha9- and gbeta- cells have fewer cell-surface rAprA binding sites, suggesting that Galpha9 and Gbeta regulate the synthesis or processing of the AprA receptor. Like other ligands that activate G proteins, rAprA induces the binding of [3H]GTP to membranes, and GTPgammaS inhibits the binding of rAprA to membranes. Both AprA-induced [3H]GTP binding and the GTPgammaS inhibition of rAprA binding require Galpha8 and Gbeta but not Galpha9. Like aprA- cells, galpha8- cells have reduced spore viability. Conclusion This study shows that Galpha8 and Gbeta are part of the signal transduction pathway used by AprA to inhibit proliferation but not growth in Dictyostelium, whereas Galpha9 is part of a differealnt pathway that regulates both proliferation and growth, and that a chalone signal transduction pathway uses G proteins.

The interplay between gait, falls and cognition: can cognitive therapy reduce fall risk?

Science.gov (United States)

Segev-Jacubovski, Orit; Herman, Talia; Yogev-Seligmann, Galit; Mirelman, Anat; Giladi, Nir; Hausdorff, Jeffrey M

2011-01-01

In this article, we briefly summarize the incidence and significant consequences of falls among older adults, the insufficient effectiveness of commonly used multifactorial interventions and the evidence linking falls and cognitive function. Recent pharmacologic and nonpharmacologic studies that evaluated the effects of cognitive therapy on fall risk are reviewed. The results of this article illustrate the potential utility of multiple, diverse forms of cognitive therapy for reducing fall risk. The article also indicates that large-scale, randomized controlled trials are warranted and that additional research is needed to better understand the pathophysiologic mechanisms underlying the interplay between human mobility, fall risk and cognitive function. Nonetheless, we suggest that multimodality interventions that combine motor and cognitive therapy should, eventually, be incorporated into clinical practice to enable older adults and patients to move safer and with a reduced fall risk. PMID:21721921

Hypotheses and fundamental study design characteristics for evaluating potential reduced-risk tobacco products. Part I: Heuristic.

Science.gov (United States)

Murrelle, Lenn; Coggins, Christopher R E; Gennings, Chris; Carchman, Richard A; Carter, Walter H; Davies, Bruce D; Krauss, Marc R; Lee, Peter N; Schleef, Raymond R; Zedler, Barbara K; Heidbreder, Christian

2010-06-01

The risk-reducing effect of a potential reduced-risk tobacco product (PRRP) can be investigated conceptually in a long-term, prospective study of disease risks among cigarette smokers who switch to a PRRP and in appropriate comparison groups. Our objective was to provide guidance for establishing the fundamental design characteristics of a study intended to (1) determine if switching to a PRRP reduces the risk of lung cancer (LC) compared with continued cigarette smoking, and (2) compare, using a non-inferiority approach, the reduction in LC risk among smokers who switched to a PRRP to the reduction in risk among smokers who quit smoking entirely. Using standard statistical methods applied to published data on LC incidence after smoking cessation, we show that the sample size and duration required for a study designed to evaluate the potential for LC risk reduction for an already marketed PRRP, compared with continued smoking, varies depending on the LC risk-reducing effectiveness of the PRRP, from a 5-year study with 8000-30,000 subjects to a 15-year study with <5000 to 10,000 subjects. To assess non-inferiority to quitting, the required sample size tends to be about 10 times greater, again depending on the effectiveness of the PRRP. (c) 2009 Elsevier Inc. All rights reserved.

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.)

Fuel requirements for isotope production and reasearch reactors: Possible alternative ways of meeting non-proliferation objectives

International Nuclear Information System (INIS)

There is a continuing need for access to medium-to-high flux research reactors of intermediate power level (5-50 MW) for the production of industrial and medical radioisotopes, for the provision of neutron beams and for materials research. The construction of further reactors of this type is likely. To obtain the required flux levels in adequate volumes and at the lowest capital cost, past practice has been to design a small-core reactor around a fuel element concept using fully enriched uranium, that is, uranium enriched to 80% U-235 or greater. In recent years, however, it has been recognised that the use of fully enriched uranium in research reactors could give rise to significant risks of nuclear weapons proliferation. Accordingly, there would be advantage if research reactors could be operated on low enriched fuel, that is, enrichment levels of 20% or less. It is the purpose of this paper to explore the implications for proliferation of the enrichment level of research reactor fuel and to draw attention to possible options for reducing proliferation concerns which warrant further study. It does not, however, consider research reactors using very low enriched or natural uranium fuel. The paper is offered to stimulate discussion of the issues and the views expressed do not necessarily represent any formal Australian position

The characterization of a full-thickness excision open foot wound model in n5-streptozotocin (STZ)-induced type 2 diabetic rats that mimics diabetic foot ulcer in terms of reduced blood circulation, higher C-reactive protein, elevated inflammation, and reduced cell proliferation.

Science.gov (United States)

Yu, Caroline Oi-Ling; Leung, Kwok-Sui; Fung, Kwok-Pui; Lam, Francis Fu-Yuen; Ng, Ethel Sau-Kuen; Lau, Kit-Man; Chow, Simon Kwoon-Ho; Cheung, Wing-Hoi

2017-08-05

Delayed foot wound healing is a major complication attributed to hyperglycemia in type 2 diabetes mellitus (DM) patients, and these wounds may develop into foot ulcers. There are at least two types of DM wound models used in rodents to study delayed wound healing. However, clinically relevant animal models are not common. Most models use type 1 DM rodents or wounds created on the back rather than on the foot. An open full-thickness excision wound on the footpad of type 2 DM rats is more clinically relevant, but such a model has not yet been characterized systematically. The objective of this study was to investigate and characterize how DM affected a full-thickness excision open foot wound in n5-streptozotocin (n5-STZ)-induced type 2 DM rats. We hypothesized that elevated inflammation, reduced blood circulation, and cell proliferation due to hyperglycemia could delay the wound healing of DM rats. The wounds of DM rats were compared with those of non-DM rats (Ctrl) at Days 1 and 8 post wounding. The wound healing process of the DM rats was significantly delayed compared with that of the Ctrl rats. The DM rats also had higher C-reactive protein (CRP) and lower blood circulation and proliferating cell nuclear antigen (PCNA) in DM wounds. This confirmed that elevated inflammation and reduced blood flow and cell proliferation delayed foot wound healing in the n5-STZ rats. Hence, this open foot wound animal model provides a good approach to study the process of delayed wound healing.

The characterization of a full-thickness excision open foot wound model in n5-streptozotocin (STZ)-induced type 2 diabetic rats that mimics diabetic foot ulcer in terms of reduced blood circulation, higher C-reactive protein, elevated inflammation, and reduced cell proliferation

Science.gov (United States)

Yu, Caroline Oi-Ling; Leung, Kwok-Sui; Fung, Kwok-Pui; Lam, Francis Fu-Yuen; Ng, Ethel Sau-Kuen; Lau, Kit-Man; Chow, Simon Kwoon-Ho; Cheung, Wing-Hoi

2017-01-01

Delayed foot wound healing is a major complication attributed to hyperglycemia in type 2 diabetes mellitus (DM) patients, and these wounds may develop into foot ulcers. There are at least two types of DM wound models used in rodents to study delayed wound healing. However, clinically relevant animal models are not common. Most models use type 1 DM rodents or wounds created on the back rather than on the foot. An open full-thickness excision wound on the footpad of type 2 DM rats is more clinically relevant, but such a model has not yet been characterized systematically. The objective of this study was to investigate and characterize how DM affected a full-thickness excision open foot wound in n5-streptozotocin (n5-STZ)-induced type 2 DM rats. We hypothesized that elevated inflammation, reduced blood circulation, and cell proliferation due to hyperglycemia could delay the wound healing of DM rats. The wounds of DM rats were compared with those of non-DM rats (Ctrl) at Days 1 and 8 post wounding. The wound healing process of the DM rats was significantly delayed compared with that of the Ctrl rats. The DM rats also had higher C-reactive protein (CRP) and lower blood circulation and proliferating cell nuclear antigen (PCNA) in DM wounds. This confirmed that elevated inflammation and reduced blood flow and cell proliferation delayed foot wound healing in the n5-STZ rats. Hence, this open foot wound animal model provides a good approach to study the process of delayed wound healing. PMID:28413186

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

Psychosocial factors and uptake of risk-reducing salpingo-oophorectomy in women at high risk for ovarian cancer.

Science.gov (United States)

Meiser, Bettina; Price, Melanie A; Butow, Phyllis N; Karatas, Janan; Wilson, Judy; Heiniger, Louise; Baylock, Brandi; Charles, Margaret; McLachlan, Sue-Anne; Phillips, Kelly-Anne

2013-03-01

Bilateral risk-reducing salpingo-oophorectomy (RRSO) has been shown to significantly reduce the risk of ovarian cancer. This study assessed factors predicting uptake of RRSO. Women participating in a large multiple-case breast cancer family cohort study who were at increased risk for ovarian and fallopian tube cancer (i.e. BRCA1 or BRCA2 mutation carrier or family history including at least one first- or second-degree relative with ovarian or fallopian tube cancer), with no personal history of cancer and with at least one ovary in situ at cohort enrolment, were eligible for this study. Women who knew they did not carry the BRCA1 or BRCA2 mutation segregating in their family (true negatives) were excluded. Sociodemographic, biological and psychosocial factors, including cancer-specific anxiety, perceived ovarian cancer risk, optimism and social support, were assessed using self-administered questionnaires and interviews at cohort enrolment. RRSO uptake was self-reported every three years during systematic follow-up. Of 2,859 women, 571 were eligible. Mean age was 43.3 years; 62 women (10.9 %) had RRSO a median of two years after cohort entry. Factors predicting RRSO were: being parous (OR 3.3, p = 0.015); knowing one's mutation positive status (OR 2.9, p cancer (OR 2.5, p = 0.013). Psychological variables measured at cohort entry were not associated with RRSO. These results suggest that women at high risk for ovarian cancer make decisions about RRSO based on risk and individual socio-demographic characteristics, rather than in response to psychological factors such as anxiety.

Proliferation of Genetically Modified Human Cells on Electrospun Nanofiber Scaffolds

Directory of Open Access Journals (Sweden)

Mandula Borjigin

2012-01-01

Full Text Available Gene editing is a process by which single base mutations can be corrected, in the context of the chromosome, using single-stranded oligodeoxynucleotides (ssODNs. The survival and proliferation of the corrected cells bearing modified genes, however, are impeded by a phenomenon known as reduced proliferation phenotype (RPP; this is a barrier to practical implementation. To overcome the RPP problem, we utilized nanofiber scaffolds as templates on which modified cells were allowed to recover, grow, and expand after gene editing. Here, we present evidence that some HCT116-19, bearing an integrated, mutated enhanced green fluorescent protein (eGFP gene and corrected by gene editing, proliferate on polylysine or fibronectin-coated polycaprolactone (PCL nanofiber scaffolds. In contrast, no cells from the same reaction protocol plated on both regular dish surfaces and polylysine (or fibronectin-coated dish surfaces proliferate. Therefore, growing genetically modified (edited cells on electrospun nanofiber scaffolds promotes the reversal of the RPP and increases the potential of gene editing as an ex vivo gene therapy application.

Inhibition of the proliferation and acceleration of migration of vascular endothelial cells by increased cysteine-rich motor neuron 1

International Nuclear Information System (INIS)

Nakashima, Yukiko; Morimoto, Mayuka; Toda, Ken-ichi; Shinya, Tomohiro; Sato, Keizo; Takahashi, Satoru

2015-01-01

Cysteine-rich motor neuron 1 (CRIM1) is upregulated only in extracellular matrix gels by angiogenic factors such as vascular endothelial growth factor (VEGF). It then plays a critical role in the tube formation of endothelial cells. In the present study, we investigated the effects of increased CRIM1 on other endothelial functions such as proliferation and migration. Knock down of CRIM1 had no effect on VEGF-induced proliferation or migration of human umbilical vein endothelial cells (HUVECs), indicating that basal CRIM1 is not involved in the proliferation or migration of endothelial cells. Stable CRIM1-overexpressing endothelial F-2 cells, termed CR1 and CR2, were constructed, because it was difficult to prepare monolayer HUVECs that expressed high levels of CRIM1. Proliferation was reduced and migration was accelerated in both CR1 and CR2 cells, compared with normal F-2 cells. Furthermore, the transient overexpression of CRIM1 resulted in decreased proliferation and increased migration of bovine aortic endothelial cells. In contrast, neither proliferation nor migration of COS-7 cells were changed by the overexpression of CRIM1. These results demonstrate that increased CRIM1 reduces the proliferation and accelerates the migration of endothelial cells. These CRIM1 effects might contribute to tube formation of endothelial cells. CRIM1 induced by angiogenic factors may serve as a regulator in endothelial cells to switch from proliferating cells to morphological differentiation. - Highlights: • CRIM1 was upregulated only in tubular endothelial cells, but not in monolayers. • Increased CRIM1 reduced the proliferation of endothelial cells. • Increased CRIM1 accelerated the migration of endothelial cells. • Increased CRIM1 had no effect on the proliferation or migration of COS-7 cells

Inhibition of the proliferation and acceleration of migration of vascular endothelial cells by increased cysteine-rich motor neuron 1

Energy Technology Data Exchange (ETDEWEB)

Nakashima, Yukiko; Morimoto, Mayuka [Department of Immunobiology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women' s University, 11-68 Koshien Kyuban-cho, Nishinomiya, Hyogo 663-8179 (Japan); Toda, Ken-ichi [Department of Dermatology, Kitano Hospital, The Tazuke Kofukai Nedical Institute, 2-4-20 Ohgimachi, Kita-ku, Osaka 530-8480 (Japan); Shinya, Tomohiro; Sato, Keizo [Department of Clinical Biochemistry, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Nobeoka, Miyazaki 882-8508 (Japan); Takahashi, Satoru, E-mail: imwalrus@mukogawa-u.ac.jp [Department of Immunobiology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women' s University, 11-68 Koshien Kyuban-cho, Nishinomiya, Hyogo 663-8179 (Japan); Institute for Biosciences, Mukogawa Women' s University, 11-68 Koshien Kyuban-cho, Nishinomiya, Hyogo 663-8179 (Japan)

2015-07-03

Cysteine-rich motor neuron 1 (CRIM1) is upregulated only in extracellular matrix gels by angiogenic factors such as vascular endothelial growth factor (VEGF). It then plays a critical role in the tube formation of endothelial cells. In the present study, we investigated the effects of increased CRIM1 on other endothelial functions such as proliferation and migration. Knock down of CRIM1 had no effect on VEGF-induced proliferation or migration of human umbilical vein endothelial cells (HUVECs), indicating that basal CRIM1 is not involved in the proliferation or migration of endothelial cells. Stable CRIM1-overexpressing endothelial F-2 cells, termed CR1 and CR2, were constructed, because it was difficult to prepare monolayer HUVECs that expressed high levels of CRIM1. Proliferation was reduced and migration was accelerated in both CR1 and CR2 cells, compared with normal F-2 cells. Furthermore, the transient overexpression of CRIM1 resulted in decreased proliferation and increased migration of bovine aortic endothelial cells. In contrast, neither proliferation nor migration of COS-7 cells were changed by the overexpression of CRIM1. These results demonstrate that increased CRIM1 reduces the proliferation and accelerates the migration of endothelial cells. These CRIM1 effects might contribute to tube formation of endothelial cells. CRIM1 induced by angiogenic factors may serve as a regulator in endothelial cells to switch from proliferating cells to morphological differentiation. - Highlights: • CRIM1 was upregulated only in tubular endothelial cells, but not in monolayers. • Increased CRIM1 reduced the proliferation of endothelial cells. • Increased CRIM1 accelerated the migration of endothelial cells. • Increased CRIM1 had no effect on the proliferation or migration of COS-7 cells.

Proliferation of Estrogen Receptor alpha Positive Mammary Epithelial Cells is Restrained by TGFbeta1 in Adult Mice

Energy Technology Data Exchange (ETDEWEB)

Ewan, Kenneth B.R.; Oketch-Rabah, Hellen A.; Ravani, Shraddha A.; Shyamala, G.; Moses, Harold L.; Barcellos-Hoff, Mary Helen

2005-03-03

Transforming growth factor {beta}1 (TGF{beta}1) is a potent inhibitor of mammary epithelial proliferation. In human breast, estrogen receptor {alpha} (ER{alpha}) cells rarely co-localize with markers of proliferation, but their increased frequency correlates with breast cancer risk. To determine whether TGF{beta}1 is necessary for the quiescence of ER{alpha}-positive population, we examined mouse mammary epithelial gland at estrus. Approximately 35% of cells showed TGF{beta}1 activation, which co-localized with nuclear receptor-phosphorylated Smad 2/3, indicating that TGF{beta} signaling is autocrine. Furthermore, nuclear Smad co-localized with nuclear ER{alpha}. To test whether TGF{beta} was functional, we examined genetically engineered mice with different levels of TGF{beta}1. ER{alpha} co-localization with markers of proliferation (i.e. Ki-67 or BrdU) at estrus was significantly increased in the mammary glands of Tgf{beta}1 C57/bl/129SV heterozygote mice. This relationship was maintained following pregnancy, but was absent at puberty. Conversely, mammary epithelial expression of constitutively active TGF{beta}1 via the MMTV promoter suppressed proliferation of ER{alpha} positive cells. Thus, TGF{beta}1 activation functionally restrains ER{alpha} positive cells from proliferating in adult mammary gland. Accordingly, we propose that TGF{beta}1 dysregulation may promote proliferation of ER{alpha} positive cells associated with breast cancer risk in humans.

Dafachronic acid inhibits C. elegans germ cell proliferation in a DAF-12-dependent manner.

Science.gov (United States)

Mukherjee, Madhumati; Chaudhari, Snehal N; Balachandran, Riju S; Vagasi, Alexandra S; Kipreos, Edward T

2017-12-15

Dafachronic acid (DA) is a bile acid-like steroid hormone that regulates dauer formation, heterochrony, and lifespan in C. elegans. Here, we describe that DA is an inhibitor of C. elegans germ stem cell proliferation in adult hermaphrodites. Using a C. elegans germ cell primary culture system, we show that DA inhibits the proliferation of germ cells in vitro. Exogenous DA reduces the frequency of large tumors in adult tumorous germline mutants and decreases the proliferation of wild-type germ stem cells in adult hermaphrodites. In contrast, DA has no appreciable effect on the proliferation of larval-stage germ cells in wild type. The inhibition of adult germ cell proliferation by DA requires its canonical receptor DAF-12. Blocking DA production by inactivating the cytochrome P450 DAF-9 increases germ cell proliferation in wild-type adult hermaphrodites and the frequency of large tumors in germline tumorous mutants, suggesting that DA inhibits the rate of germ cell proliferation under normal growth conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Update on raloxifene: role in reducing the risk of invasive breast cancer in postmenopausal women

Directory of Open Access Journals (Sweden)

Vogel VG

2011-10-01

Full Text Available Victor G Vogel Cancer Institute, Geisinger Health System, Danville, PA, USA Abstract: Risk factors allow us to define women who are at increased lifetime risk for breast cancer, and the most important factor is age. Benign breast disease increases risk, and the most important histologies are atypical lobular or ductal hyperplasia and lobular carcinoma in situ. Family history of breast cancer among first-degree relatives (mother, sisters, daughters also increases risk. Quantitative measures of risk give accurate predictions of breast cancer incidence for groups of women but not for individual subjects. Multiple published, randomized controlled trials, which employed selective estrogen receptor (ER modulators (SERMs, have demonstrated consistent reductions of 35% or greater in the risk of ER-positive invasive and noninvasive breast cancer in postmenopausal women. Professional organizations in the US now recommend the use of SERMs to reduce the risk of breast cancer in high-risk, postmenopausal women. Raloxifene and tamoxifen reduce the risk of ER-positive invasive breast cancer with equal efficacy, but raloxifene is associated with a lower risk of thromboembolic disease, benign uterine conditions, and cataracts than tamoxifen in postmenopausal women. No evidence exists establishing whether a reduction in breast cancer risk from either agent translates into reduced breast cancer mortality. Overall quality of life is similar with raloxifene or tamoxifen, but the incidence of dyspareunia, weight gain, and musculoskeletal complaints is higher with raloxifene use, whereas vasomotor symptoms, bladder incontinence, gynecologic symptoms, and leg cramps were higher with tamoxifen use. Keywords: selective estrogen receptor modulators (SERMs, raloxifene, risk reduction, chemoprevention

The HEART score is useful to predict cardiovascular risks and reduces unnecessary cardiac imaging in low-risk patients with acute chest pain.

Science.gov (United States)

Dai, Siping; Huang, Bo; Zou, Yunliang; Guo, Jianbin; Liu, Ziyong; Pi, Dangyu; Qiu, Yunhong; Xiao, Chun

2018-06-01

The present study was to investigate whether the HEART score can be used to evaluate cardiovascular risks and reduce unnecessary cardiac imaging in China.Acute coronary syndrome patients with the thrombosis in myocardial infarction risk score risk HEART score group and 2 patients (1.5%) in the high risk HEART score group had cardiovascular events. The sensitivity of HEART score to predict cardiovascular events was 100% and the specificity was 46.7%. The potential unnecessary cardiac testing was 46.3%. Cox proportional hazards regression analysis showed that per one category increase of the HEART score was associated with nearly 1.3-fold risk of cardiovascular events.In the low-risk acute chest pain patients, the HEART score is useful to physicians in evaluating the risk of cardiovascular events within the first 30 days. In addition, the HEART score is also useful in reducing the unnecessary cardiac imaging.

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

Analysis of nuclear proliferation resistance reprocessing and recycling technologies

International Nuclear Information System (INIS)

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

2011-01-01

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

Analysis of nuclear proliferation resistance reprocessing and recycling technologies

Energy Technology Data Exchange (ETDEWEB)

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

2011-05-01

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

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

Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection

DEFF Research Database (Denmark)

Borges, Alvaro Humberto Diniz; Neuhaus, Jacqueline; Babiker, Abdel G

2016-01-01

BACKGROUND:  In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 cell counts a...

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

Gallic acid reduces cell viability, proliferation, invasion and angiogenesis in human cervical cancer cells

OpenAIRE

ZHAO, BING; HU, MENGCAI

2013-01-01

Gallic acid is a trihydroxybenzoic acid, also known as 3,4,5-trihydroxybenzoic acid, which is present in plants worldwide, including Chinese medicinal herbs. Gallic acid has been shown to have cytotoxic effects in certain cancer cells, without damaging normal cells. The objective of the present study was to determine whether gallic acid is able to inhibit human cervical cancer cell viability, proliferation and invasion and suppress cervical cancer cell-mediated angiogenesis. Treatment of HeLa...

New trends of activity on supporting of non-proliferation regime

International Nuclear Information System (INIS)

Issaeva, G.M.; Tyupkina, O.G.

2002-01-01

Taking into account the necessity of all possible strengthening of non-proliferation regimes Kazakhstan participates in a number of agreements and associations: Nuclear Non-proliferation Treaty, Comprehensive Test-Ban-Treaty, International Atomic Energy Agency, Nuclear Supplier Group, Missile Technology Control Regime, Conference on Disarmament, etc. The Cooperative Threat Reduction Program (CTR) greatly influenced on the development on non-proliferation regime in Kazakhstan. During initial stage of CTR activity (1993-1995) military projects prevailed. Later (1995-1997) the projects on liquidation of infrastructure for nuclear and bio- weapons were successfully realized. Last years, since 1999, the attention was shifted towards proliferation prevention of hazardous nuclear and biological materials. Recent terrorist acts and world community activity on global safety strengthening underline an urgency of quite new problems that entirely applied to Kazakhstan: monitoring of hazardous materials; enhancement of safety systems of 'risky' facilities and technologies; creation and/or upgrading of safety systems for industry infrastructure. The proposals of these new trends of non-proliferation have been developed. Development of physical protection system for oil and gas industry infrastructure of Kazakhstan based on safety concepts of nuclear facilities; Evaluation of radionuclide contamination and safety of oil and gas facilities of the Caspian region; Counteraction to nuclear materials proliferation; Cooperative approaches in preventing/reducing of illicit trafficking and use of WMD-related explosive materials. Implementation of the project would make of substantial contribution to successful solution of either regional or global safety problem

Ki67 and proliferation in breast cancer.

Science.gov (United States)

Pathmanathan, Nirmala; Balleine, Rosemary L

2013-06-01

New approaches to the prognostic assessment of breast cancer have come from molecular profiling studies. A major feature of this work has been to emphasise the importance of cancer cell proliferation as a key discriminative indicator of recurrence risk for oestrogen receptor positive breast cancer in particular. Mitotic count scoring, as a component of histopathological grade, has long formed part of a routine evaluation of breast cancer biology. However, there is an increasingly compelling case to include a specific proliferation score in breast cancer pathology reports based on expression of the cell cycle regulated protein Ki67. Immunohistochemical staining for Ki67 is a widely available and economical test with good tolerance of pre-analytical variations and staining conditions. However, there is currently no evidence based protocol established to derive a reliable and informative Ki67 score for routine clinical use. In this circumstance, pathologists must establish a standardised framework for scoring Ki67 and communicating results to a multidisciplinary team.

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

Scientific and Regulatory Policy Committee (SRPC) Review: Interpretation and Use of Cell Proliferation Data in Cancer Risk Assessment

Science.gov (United States)

Increased cell proliferation is a defining feature of carcinogenesis and a central key event in the mode of action for many non-genotoxic carcinogens. Quantitative cell proliferation data thus play an important role in the safety assessment of many pharmaceutical and environment...

GPNMB promotes proliferation of developing eosinophils.

Science.gov (United States)

Hwang, Sae Mi; Kang, Jin Hyun; Kim, Bo Kyum; Uhm, Tae Gi; Kim, Hye Jeong; Lee, Hyune-Hwan; Binas, Bert; Chung, Il Yup

2017-08-01

Glycoprotein non-metastatic melanoma protein B (GPNMB) is a type I transmembrane protein that is expressed in a wide variety of cell types, including haematopoietic lineages. We previously demonstrated that GPNMB is one of the most highly expressed genes at an early and intermediate stage of eosinophil development. We herein examined GPNMB expression and its possible functional effect using cord blood (CB) CD34+ haematopoietic stem cells differentiating toward eosinophils during a 24-day culture period. Western blot and confocal microscopy analyses showed that GPNMB reached its highest levels at day 12 with most GPNMB-positive cells also expressing major basic protein 1 (MBP1), an eosinophil granule protein. GPNMB declined thereafter, but was still present at an appreciable level at day 24, the time when CB eosinophils most abundantly expressed MBP1 and were thus considered fully differentiated. When the developing CB cells were cultured in the presence of a blocking anti-GPNMB antibody, cell proliferation was significantly reduced. In agreement, ectopic expression of GPNMB in heterologous cells resulted in a significant increase in cell proliferation, while small interfering RNA of GPNMB inhibited the GPNMB-mediated proliferation. Thus, GPNMB is expressed in a temporal manner during eosinophil development and delivers a proliferative signal upon activation. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Leptin Regulates Proliferation and Apoptosis in Human Prostate

Directory of Open Access Journals (Sweden)

Eduardo Leze

2012-01-01

Full Text Available This paper aimed to evaluate the leptin role on the cellular proliferation and the expression of fibroblast growth factor 2, aromatase enzyme, and apoptotic genes in the human prostate tissue. Methods. Fifteen samples of hyperplasic prostate tissue were divided in four symmetric parts maintained in RPMI medium supplemented with 10% fetal bovine serum, 1 ng/mL of gentamicin, and added with 50 ng/mL leptin (L or not (C. After 3 hours of incubation, gene expression was evaluated by real time RT-PCR. Cellular proliferation was evaluated by immunohistochemistry for PCNA. Results. The leptin treatment led to an increase cellular proliferation (C=21.8±0.5; L=64.8±0.9; P<0.0001 and in the expression of Bax (C=0.4±0.1; L=0.9±0.2; P<0.05 while Bcl-2 (C=19.9±5.6; L=5.6±1.8; P<0.05, Bcl-x (C=0.2±0.06; L=0.07±0.02; P<0.05, and aromatase expressions (C=1.9±0.6; L=0.4±0.1; P<0.04 were significantly reduced. Conclusion. Leptin has an important role in maintaining the physiological growth of the prostate since it stimulates both cellular proliferation and apoptosis, with the decrement in the aromatase gene expression.

Risk-reducing salpingectomy with delayed oophorectomy in BRCA1/2 mutation carriers: Patients' and professionals' perspectives

NARCIS (Netherlands)

Jong, M. de; Harmsen, M.G.; Hoogerbrugge, N.; Massuger, L.F.A.G.; Hermens, R.P.M.G.; Hullu, J.A. de

2015-01-01

OBJECTIVE: To identify influencing factors of BRCA1/2 mutation carriers and their professionals for risk-reducing salpingectomy (RRS) with delayed oophorectomy (RRO) as a substitute for risk-reducing salpingo-oophorectomy (RRSO) and for study participation on this concept. METHODS: A qualitative

The Nuclear Progress And The Non-Proliferation Policies

Energy Technology Data Exchange (ETDEWEB)

Popa-Simil, Liviu [Los Alamos, NM 87544 (United States)

2009-06-15

The 2008 fall crisis showed the limits of globalization under the actual rules and de-regulations promoted by few developed countries. It also showed the weakness of the planetary economy induced by strong economic connections that makes the propagation of crises faster than the spread of welfare. The increase in severe weather and natural disasters showed how fast the civilization can be spoiled while the competition for oil resources made the interstate tensions grow. For almost all states, the development of the nuclear power becomes a prime option, even oil producers started to show interest in nuclear technology and also, policies that in particular are clearly oriented towards national development policies. The fact that anybody mastering nuclear technologies and uses for power production is capable in a reasonable time to produce weapons is a well-known fact. Therefore, in order to reduce the proliferation risk it is necessary to contain the nuclear science development. An alternative is to shift the weight in promoting renewable energies, as potential future energy alternative. Considering rigorously the future climate change effects, it becomes obvious that any delay in nuclear development will turn very costly for any nation ignoring all these facts and, the complexity of the real nonproliferation is growing. This new trend raises serious challenges in front of all states regarding the non-proliferation and, in order to keep control and stimulate a sound nuclear development, some of the actual non-proliferation concepts and policies have to be reformulated and enhanced. This has to be done in parallel with a more intensive implication of the international organisms in the real development of the nuclear power at national level. The large diversity of nuclear applications with huge collateral implication in every national economy makes the role of the international organisms orders of magnitude more important. The new challenges posed in front of the

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

Effect of syngeneic thymocytes on proliferation of the small intestinal epithelium in mice

International Nuclear Information System (INIS)

Shmakov, A.N.; Aparovich, G.G.; Trufakin, V.A.

1986-01-01

This paper describes the study of the action of syngeneic thymocytes on proliferation of the epithelium of the mouse small intestine. The mice were injected with 3 H-thymidine in the experiments. Under the experimental conditions presented here, syngeneic thymocytes can reduce the number of DNA-synthesizing cells in the intestinal epithelium, causing narrowing of the zone of proliferation and enlargement of the zone of differentiation of the enterocytes

Fisetin regulates astrocyte migration and proliferation in vitro.

Science.gov (United States)

Wang, Nan; Yao, Fang; Li, Ke; Zhang, Lanlan; Yin, Guo; Du, Mingjun; Wu, Bingyi

2017-04-01

Fisetin (3,3',4',7-tetrahydroxyflavone) is a plant flavonol found in fruits and vegetables that has been reported to inhibit migration and proliferation in several types of cancer. Reactive astrogliosis involves astrocyte migration and proliferation, and contributes to the formation of glial scars in central nervous system (CNS) disorders. However, the effect of fisetin on the migration and proliferation of astrocytes remains unclear. In this study, we found that fisetin inhibited astrocyte migration in a scratch-wound assay and diminished the phosphorylation of focal adhesion kinase (FAK; Tyr576/577 and paxillin (Tyr118). It also suppressed cell proliferation, as indicated by the decreased number of 5-ethynyl-2'-deoxyuridine (EdU)-positive cells, induced cell cycle arrest in the G1 phase, reduced the percentage of cells in the G2 and S phase (as measured by flow cytometry), and decreased cyclin D1 expression, but had no effect on apoptosis. Fisetin also decreased the phosphorylation levels of Akt and extracellular signal-regulated kinase (Erk)1/2, but had no effect on the phosphorylation of p38 mitogen-activated protein kinase (MAPK). These results indicate that fisetin inhibits aggressive cell phenotypes by suppressing cell migration and proliferation via the Akt/Erk signaling pathway. Fisetin may thus have potential for use as a therapeutic strategy targeting reactive astrocytes, which may lead to the inhibition of glial scar formation in vitro.

Breastfeeding reduces the risk of obesity in childhood and adolescence

Directory of Open Access Journals (Sweden)

Eleni-Maria Papatesta

2013-06-01

Full Text Available Childhood obesity has increased dramatically over the last decades, representing one of the most serious public health hazards of the 21st century. Efforts must be made by healthcare professionals to prevent it, as it is associated with short- and long-term risks for physical and mental health and because of the increased possibility to persist during adulthood. From antiquity human breast milk was considered the ideal nourishment for the newborn. Breastfeeding is beneficial for the mother-child dyad. Among others, existing data suggest that it reduces the risk for childhood and adolescence obesity. The mechanisms for this are numerous and include the feeding behavior breastfeeding infants acquire, their growth rate, the ‘early protein hypothesis’, the role of leptin that is found in increased levels in human milk, the dietary choices the breastfed infants make during childhood and adolescence and finally the differences in their bowel flora. Meta-analyses provide sufficient evidence for this protective effect, with a dose-response effect as to the duration of breastfeeding. Healthcare professionals involved in the care of the mother-infant dyad must encourage and support mothers to breastfeed their infants for a long period of time, if obesity were to be prevented. Aim of this review is to provide an account of existing data on the association of breastfeeding and the reduced risk of obesity in childhood and adulthood.

Context dependency and consumer acceptance of risk reducing strategies - a choice experiment study on salmonella risks in pork

DEFF Research Database (Denmark)

Mørkbak, Morten Raun; Christensen, Tove; Gyrd-Hansen, Dorte

2012-01-01

The paper investigates to what extent context dependency is present, when consumers are introduced to different risk reducing technologies and how this will affect their preferences for reductions in food risks. In particular, choice experiments are used to elicit consumer preferences for reducin...... findings of bad news having greater effect than good news – now applied to context dependency of preferences for food safety technologies....

Reducing Youth Risk Behaviors Through Interactive Theater Intervention

Directory of Open Access Journals (Sweden)

Ryan J. Watson

2016-02-01

Full Text Available The reduction of risk behaviors in secondary schools is a key concern for parents, teachers, and school administrators. School is one of the primary contexts of socialization for young people; thus, the investment in school-based programs to reduce risk behaviors is essential. In this study, we report on youth who participated in an intervention designed to improve decision-making skills based on positive youth development approaches. We examine changes in decision-making skills before and after involvement in the Teen Interactive Theater Education (TITE program and retrospective self-assessment of change in knowledge, abilities, and beliefs as a result of participating in TITE (n = 127. Youth that reported increases in knowledge, abilities, and beliefs due to the intervention (n = 89 were more likely to think about the consequences of their decisions and list options before making a decision compared to their counterparts that reported less overall learning (n = 38. Implications for intervention research and stakeholders are discussed.

Workplace Interventions to Reduce Obesity and Cardiometabolic Risk.

Science.gov (United States)

Thorndike, Anne N

2011-02-01

The worksite is ideal for implementing interventions to reduce obesity and cardiometabolic risk factors. Although worksite health promotion is not new, employer-sponsored wellness programs have become more widespread due to the rising prevalence and high cost of obesity. Over the past two decades, employers and researchers focused efforts on individual-based programs to change employees' nutrition and exercise behaviors, but more recently, the worksite environment has been targeted. Overall, there is good evidence that individual-based worksite programs can produce modest weight loss, but the evidence for effects on other risk factors and on long-term health outcomes and costs is inconsistent. There is less evidence for the benefit of environmental-based interventions, and more data will be needed to establish conclusions about the benefits of these types of interventions. A major challenge for employers and researchers in the future will be to find the balance between effectiveness and economic viability of worksite wellness programs.

Reduced reward anticipation in youth at high-risk for unipolar depression: A preliminary study

Directory of Open Access Journals (Sweden)

Thomas M. Olino

2014-04-01

Full Text Available Offspring of depressed parents are at risk for depression and recent evidence suggests that reduced positive affect (PA may be a marker of risk. We investigated whether self-reports of PA and fMRI-measured striatal response to reward, a neural correlate of PA, are reduced in adolescent youth at high familial risk for depression (HR relative to youth at low familial risk for depression (LR. Functional magnetic resonance imaging assessments were conducted with 14 HR and 12 LR youth. All youth completed an ecological momentary assessment protocol to measure PA in natural settings and a self-report measure of depression symptomatology. Analyses found that HR youth demonstrated lower striatal response than LR youth during both reward anticipation and outcome. However, after controlling for youth self-reports of depression, HR youth demonstrated lower striatal response than LR youth only during reward anticipation. No significant differences were found between HR and LR youth on subjective ratings of PA or depressive symptoms. Results are consistent with previous findings that reduced reward response is a marker of risk for depression, particularly during reward anticipation, even in the absence of (or accounting for disrupted subjective mood. Further examinations of prospective associations between reward response and depression onset are needed.

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

MicroRNA let-7b regulates neural stem cell proliferation and differentiation by targeting nuclear receptor TLX signaling.

Science.gov (United States)

Zhao, Chunnian; Sun, GuoQiang; Li, Shengxiu; Lang, Ming-Fei; Yang, Su; Li, Wendong; Shi, Yanhong

2010-02-02

Neural stem cell self-renewal and differentiation is orchestrated by precise control of gene expression involving nuclear receptor TLX. Let-7b, a member of the let-7 microRNA family, is expressed in mammalian brains and exhibits increased expression during neural differentiation. However, the role of let-7b in neural stem cell proliferation and differentiation remains unknown. Here we show that let-7b regulates neural stem cell proliferation and differentiation by targeting the stem cell regulator TLX and the cell cycle regulator cyclin D1. Overexpression of let-7b led to reduced neural stem cell proliferation and increased neural differentiation, whereas antisense knockdown of let-7b resulted in enhanced proliferation of neural stem cells. Moreover, in utero electroporation of let-7b to embryonic mouse brains led to reduced cell cycle progression in neural stem cells. Introducing an expression vector of Tlx or cyclin D1 that lacks the let-7b recognition site rescued let-7b-induced proliferation deficiency, suggesting that both TLX and cyclin D1 are important targets for let-7b-mediated regulation of neural stem cell proliferation. Let-7b, by targeting TLX and cyclin D1, establishes an efficient strategy to control neural stem cell proliferation and differentiation.

Design of Work Facilities for Reducing Musculoskeletal Disorders Risk in Paper Pallet Assembly Station

Science.gov (United States)

Mardi Safitri, Dian; Arfi Nabila, Zahra; Azmi, Nora

2018-03-01

Musculoskeletal Disorders (MSD) is one of the ergonomic risks due to manual activity, non-neutral posture and repetitive motion. The purpose of this study is to measure risk and implement ergonomic interventions to reduce the risk of MSD on the paper pallet assembly work station. Measurements to work posture are done by Ovako Working Posture Analysis (OWAS) methods and Rapid Entire Body Assessment (REBA) method, while the measurement of work repetitiveness was using Strain Index (SI) method. Assembly processes operators are identified has the highest risk level. OWAS score, Strain Index, and REBA values are 4, 20.25, and 11. Ergonomic improvements are needed to reduce that level of risk. Proposed improvements will be developed using the Quality Function Deployment (QFD) method applied with Axiomatic House of Quality (AHOQ) and Morphological Chart. As the result, risk level based on OWAS score & REBA score turn out from 4 & 11 to be 1 & 2. Biomechanics analysis of the operator also shows the decreasing values for L4-L5 moment, compression, joint shear, and joint moment strength.

NSAIDs and Cell Proliferation in Colorectal Cancer

Directory of Open Access Journals (Sweden)

Raj Ettarh

2010-06-01

Full Text Available Colon cancer is common worldwide and accounts for significant morbidity and mortality in patients. Fortunately, epidemiological studies have demonstrated that continuous therapy with NSAIDs offers real promise of chemoprevention and adjunct therapy for colon cancer patients. Tumour growth is the result of complex regulation that determines the balance between cell proliferation and cell death. How NSAIDs affect this balance is important for understanding and improving treatment strategies and drug effectiveness. NSAIDs inhibit proliferation and impair the growth of colon cancer cell lines when tested in culture in vitro and many NSAIDs also prevent tumorigenesis and reduce tumour growth in animal models and in patients, but the relationship to inhibition of tumour cell proliferation is less convincing, principally due to gaps in the available data. High concentrations of NSAIDs are required in vitro to achieve cancer cell inhibition and growth retardation at varying time-points following treatment. However, the results from studies with colon cancer cell xenografts are promising and, together with better comparative data on anti-proliferative NSAID concentrations and doses (for in vitro and in vivo administration, could provide more information to improve our understanding of the relationships between these agents, dose and dosing regimen, and cellular environment.

Risk-reducing surgery on the uterine adnexa: timing and type of surgical treatment, and pathology report.

Science.gov (United States)

Signorelli, Mauro; Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Chiappa, Valentina; Lopez, Carlos; Scaffa, Cono; Lorusso, Domenica; Raspagliesi, Francesco

2016-10-01

Inherited mutations in BRCA1 and BRCA2 increase significantly the risk of developing breast and ovarian cancers, and they have been associated with increased risks of developing other types of cancer. Although screening programs have been implemented in order to detect cancers at the early stage, they resulted ineffective. To date, risk-reducing bilateral salpingo-oophorectomy represents the only procedure allowing reducing the incidence of ovarian cancer and increasing survival among BRCA1 and -2 mutation carriers. In the present review we will discuss the advantages and disadvantages related to the execution of prophylactic surgery, thus underlying possible beneficial and detrimental effects of this kind of surgery in premenopausal women. Additionally, we will investigate further therapeutic strategies aimed to reduce the risk of developing ovarian cancer, without affected patients' hormonal status.

Gas Centrifuges and Nuclear Proliferation

Energy Technology Data Exchange (ETDEWEB)

Albright, David

2004-09-15

Gas centrifuges have been an ideal enrichment method for a wide variety of countries. Many countries have built gas centrifuges to make enriched uranium for peaceful nuclear purposes. Other countries have secretly sought centrifuges to make highly enriched uranium for nuclear weapons. In more recent times, several countries have secretly sought or built gas centrifuges in regions of tension. The main countries that have been of interest in the last two decades have been Pakistan, Iraq, Iran, and North Korea. Currently, most attention is focused on Iran, Pakistan, and North Korea. These states did not have the indigenous abilities to make gas centrifuges, focusing instead on illicit and questionable foreign procurement. The presentation covered the following main sections: Spread of centrifuges through illicit procurement; Role of export controls in stopping proliferation; Increasing the transparency of gas centrifuge programs in non-nuclear weapon states; and, Verified dismantlement of gas centrifuge programs. Gas centrifuges are important providers of low enriched uranium for civil nuclear power reactors. They also pose special nuclear proliferation risks. We all have special responsibilities to prevent the spread of gas centrifuges into regions of tension and to mitigate the consequences of their spread into the Middle East, South Asia, and North Asia.

Review article Homebound instruction for students with chronic illness: reducing risk outside of the box

Directory of Open Access Journals (Sweden)

Steven R. Shaw

2014-05-01

Full Text Available Students with chronic illness are at risk for a host of academic and social problems. The risk is exacerbated when students are unable to attend school short term or long term due to medical problems. Educators may be able to reduce academic and social risk for students with chronic illness through effective homebound instruction. However, there remain many barriers to effective homebowund instruction. Effective interdisciplinary and community coordination, development of policies, teacher support, inclusion of families, and use of technology can be combined to overcome these barriers and create effective homebound programs and policies. The result is reduced risk for the large and vulnerable population of students with chronic illness.

Energy in debate. Civil nuclear and proliferation. Energy scenarios and freedom latitudes

International Nuclear Information System (INIS)

1994-01-01

This publication first gives a presentation of a European colloquium on energy strategies between the nuclear risk and the greenhouse effect. Then dealing with the relationship between nuclear energy and nuclear proliferation, a contribution comments the relationship between the civil use of nuclear energy (notably for electricity production) and the use of nuclear materials for nuclear weapons (posture of the five nuclear States, development of the counter-proliferation policy, proliferating countries and actors, evolution of the political context after the fall of the USSR). The next article discusses the rooms to manoeuvre when defining energy strategies, notably with respect to nuclear energy. It also outlines the challenge of energy efficiency improvement in France, particularly for electricity uses, and by limiting the road traffic dramatic increase. A last article is an answer to critics by the author of a book on the greenhouse effect

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.)

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

POTENTIAL HEALTH RISK REDUCTION ARISING FROM REDUCED MERCURY EMISSIONS FROM COAL FIRED POWER PLANTS.

Energy Technology Data Exchange (ETDEWEB)

Sullivan, T. M.; Lipfert, F. W.; Morris, S. C.; Moskowitz, P. D.

2001-09-01

The U.S. Environmental Protection Agency (EPA) has announced plans to regulate mercury (Hg) emissions from coal-fired power plants. EPA has not prepared a quantitative assessment of the reduction in risk that could be achieved through reduction in coal plant emissions of Hg. To address this issue, Brookhaven National Laboratory (BNL) with support from the U.S. Department of Energy Office of Fossil Energy (DOE FE) prepared a quantitative assessment of the reduction in human health risk that could be achieved through reduction in coal plant emissions of Hg. The primary pathway for Hg exposure is through consumption of fish. The most susceptible population to Hg exposure is the fetus. Therefore the risk assessment focused on consumption of fish by women of child-bearing age. Dose response factors were generated from studies on loss of cognitive abilities (language skills, motor skills, etc.) by young children whose mothers consumed large amounts of fish with high Hg levels. Population risks were estimated for the general population in three regions of the country, (the Midwest, Northeast, and Southeast) that were identified by EPA as being heavily impacted by coal emissions. Three scenarios for reducing Hg emissions from coal plants were considered: (1) A base case using current conditions; (2) A 50% reduction; and, (3) A 90% reduction. These reductions in emissions were assumed to translate linearly into a reduction in fish Hg levels of 8.6% and 15.5%, respectively. Population risk estimates were also calculated for two subsistence fisher populations. These groups of people consume substantially more fish than the general public and, depending on location, the fish may contain higher Hg levels than average. Risk estimates for these groups were calculated for the three Hg levels used for the general population analyses. Analysis shows that the general population risks for exposure of the fetus to Hg are small. Estimated risks under current conditions (i.e., no

Assessments and applications to enhance human reliability and reduce risk during less-than-full-power operations

International Nuclear Information System (INIS)

Hannaman, G.W.; Singh, A.

1992-01-01

Study of events, interviews with plant personnel, and applications of risk studies indicate that the risk of a potential accident during less-than-full-power (LTFP) operation is becoming a greater fraction of the risk as improvements are made to the full-power operations. Industry efforts have been increased to reduce risk and the cost of shutdown operations. These efforts consider the development and application of advanced tools to help utilities proactively identify issues and develop contingencies and interventions to enhance reliability and reduce risk of low-power operations at nuclear power plants. The role for human reliability assessments is to help improve utility outage planning to better achieve schedule and risk control objectives. Improvements are expected to include intervention tools to identify and reduce human error, definition of new instructional modules, and prioritization of risk reduction issues for operators. The Electric Power Research Institute is sponsoring a project to address the identification and quantification of factors that affect human reliability during LTFP operation of nuclear power plants. The results of this project are expected to promote the development of proactively applied interventions and contingencies for enhanced human reliability during shutdown operations

Reduced risk avoidance and altered neural correlates of feedback processing in patients with borderline personality disorder.

Science.gov (United States)

Endrass, Tanja; Schuermann, Beate; Roepke, Stefan; Kessler-Scheil, Sonia; Kathmann, Norbert

2016-09-30

Patients with borderline personality disorder (BPD) show deficits in reward-guided decision making and learning. The present study examined risk-taking behavior in combination with feedback processing. Eighteen BPD patients and 18 healthy controls performed a probabilistic two-choice gambling task, while an electroencephalogram was recorded. Options differed in risk, but were identical in expected value and outcome probability. The feedback-related negativity (FRN) and the feedback-related P300 were analyzed. Healthy controls preferred low-risk over high-risk options, whereas BPD patients chose both option with equal probability. FRN amplitudes were reduced in BPD, but effects of feedback valence and risk did not differ between groups. This suggests attenuated outcome processing in the anterior cingulate cortex, but intact reward prediction error signaling. Furthermore, the modulation of the feedback-related P300 with feedback valence and risk was smaller in BPD patients, and decreased P300 amplitudes were associated with increased behavioral risk-taking behavior. These findings could relate to the reduced ability of BPD patients to learn and adequately adjust their behavior based on feedback information, possibly due to reduced significance of negative feedback. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

Assessing the Risk of Occult Cancer and 30-day Morbidity in Women Undergoing Risk-reducing Surgery: A Prospective Experience.

Science.gov (United States)

Bogani, Giorgio; Tagliabue, Elena; Signorelli, Mauro; Chiappa, Valentina; Carcangiu, Maria Luisa; Paolini, Biagio; Casarin, Jvan; Scaffa, Cono; Gennaro, Massimiliano; Martinelli, Fabio; Borghi, Chiara; Ditto, Antonino; Lorusso, Domenica; Raspagliesi, Francesco

To investigate the incidence and predictive factors of 30-day surgery-related morbidity and occult precancerous and cancerous conditions for women undergoing risk-reducing surgery. A prospective study (Canadian Task Force classification II-1). A gynecologic oncology referral center. Breast-related cancer antigen (BRCA) mutation carriers and BRCAX patients (those with a significant family history of breast and ovarian cancer). Minimally invasive risk-reduction surgery. Overall, 85 women underwent risk-reducing surgery: 30 (35%) and 55 (65%) had hysterectomy plus bilateral salpingo-oophorectomy (BSO) and BSO alone, respectively. Overall, in 6 (7%) patients, the final pathology revealed unexpected cancer: 3 early-stage ovarian/fallopian tube cancers, 2 advanced-stage ovarian cancers (stage IIIA and IIIB), and 1 serous endometrial carcinoma. Additionally, 3 (3.6%) patients had incidental finding of serous tubal intraepithelial carcinoma. Four (4.7%) postoperative complications within 30 days from surgery were registered, including fever (n = 3) and postoperative ileus (n = 1); no severe (grade 3 or more) complications were observed. All complications were managed conservatively. The presence of occult cancer was the only factor predicting the development of postoperative complications (p = .02). Minimally invasive risk-reducing surgery is a safe and effective strategy to manage BRCA mutation carriers. Patients should benefit from an appropriate counseling about the high prevalence of undiagnosed cancers observed at the time of surgery. Copyright © 2017 AAGL. Published by Elsevier Inc. All rights reserved.

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

Reducing drinking water supply chemical contamination: risks from underground storage tanks.

Science.gov (United States)

Enander, Richard T; Hanumara, R Choudary; Kobayashi, Hisanori; Gagnon, Ronald N; Park, Eugene; Vallot, Christopher; Genovesi, Richard

2012-12-01

Drinking water supplies are at risk of contamination from a variety of physical, chemical, and biological sources. Ranked among these threats are hazardous material releases from leaking or improperly managed underground storage tanks located at municipal, commercial, and industrial facilities. To reduce human health and environmental risks associated with the subsurface storage of hazardous materials, government agencies have taken a variety of legislative and regulatory actions--which date back more than 25 years and include the establishment of rigorous equipment/technology/operational requirements and facility-by-facility inspection and enforcement programs. Given a history of more than 470,000 underground storage tank releases nationwide, the U.S. Environmental Protection Agency continues to report that 7,300 new leaks were found in federal fiscal year 2008, while nearly 103,000 old leaks remain to be cleaned up. In this article, we report on an alternate evidence-based intervention approach for reducing potential releases from the storage of petroleum products (gasoline, diesel, kerosene, heating/fuel oil, and waste oil) in underground tanks at commercial facilities located in Rhode Island. The objective of this study was to evaluate whether a new regulatory model can be used as a cost-effective alternative to traditional facility-by-facility inspection and enforcement programs for underground storage tanks. We conclude that the alternative model, using an emphasis on technical assistance tools, can produce measurable improvements in compliance performance, is a cost-effective adjunct to traditional facility-by-facility inspection and enforcement programs, and has the potential to allow regulatory agencies to decrease their frequency of inspections among low risk facilities without sacrificing compliance performance or increasing public health risks. © 2012 Society for Risk Analysis.

Reduced reward anticipation in youth at high-risk for unipolar depression: a preliminary study.

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Olino, Thomas M; McMakin, Dana L; Morgan, Judith K; Silk, Jennifer S; Birmaher, Boris; Axelson, David A; Williamson, Douglas E; Dahl, Ronald E; Ryan, Neal D; Forbes, Erika E

2014-04-01

Offspring of depressed parents are at risk for depression and recent evidence suggests that reduced positive affect (PA) may be a marker of risk. We investigated whether self-reports of PA and fMRI-measured striatal response to reward, a neural correlate of PA, are reduced in adolescent youth at high familial risk for depression (HR) relative to youth at low familial risk for depression (LR). Functional magnetic resonance imaging assessments were conducted with 14 HR and 12 LR youth. All youth completed an ecological momentary assessment protocol to measure PA in natural settings and a self-report measure of depression symptomatology. Analyses found that HR youth demonstrated lower striatal response than LR youth during both reward anticipation and outcome. However, after controlling for youth self-reports of depression, HR youth demonstrated lower striatal response than LR youth only during reward anticipation. No significant differences were found between HR and LR youth on subjective ratings of PA or depressive symptoms. Results are consistent with previous findings that reduced reward response is a marker of risk for depression, particularly during reward anticipation, even in the absence of (or accounting for) disrupted subjective mood. Further examinations of prospective associations between reward response and depression onset are needed. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.)

The separation of nuclear power from nuclear proliferation

International Nuclear Information System (INIS)

Starr, C.

1979-01-01

There exists world wide a strong common desire to limit nuclear weapons proliferation so as to inhibit or remove the threat of nuclear warfare. While this is a primary international political objective, there has also developed a secondary objective to limit any potential contribution to such nuclear weapons proliferation which might arise by the diversion of weapons material from the civilian nuclear power fuel cycle. This secondary objective is the basis of the present US government policy to defer the reprocessing of nuclear fuels anywhere. This policy has been generally recognized as a temporary expedient to provide time for international reexamination of the problems of weapons proliferation associated with nuclear power. A successful development of the proposed combination of the Fast Breeder Reactor and the Civex fuel reprocessing facility would provide an economical nuclear power source for many centuries which inherently separates nuclear power from the issue of weapons material diversion and proliferation. Further, by so doing, it permits great flexibility in international and national planning for nuclear power, as the issues of fuel dependence and terrorist and subnational diversions disappear. In addition, the expansion of the FBR/Civex system would eat into the LWR spent fuel stockpile, diminishing steadily this relatively accessible plutonium source. And finally, a rapid development of the FBR/Civex for the above reasons would substantially reduce the worldwide concern as to the adequacy of uranium ore supply. (Auth.)

Clinical effectiveness of telmisartan alone or in combination therapy for controlling blood pressure and vascular risk in the elderly

Directory of Open Access Journals (Sweden)

Bodh I Jugdutt

2010-12-01

Full Text Available Bodh I JugduttDivision of Cardiology, Department of Medicine, University of Alberta and Hospital, Edmonton, CanadaAbstract: Elderly patients (age≥65 years with hypertension are at high risk for vascular complications, especially when diabetes is present. Antihypertensive drugs that inhibit the renin-angiotensin system have been shown to be effective for controlling blood pressure in adult and elderly patients. Importantly, renin-angiotensin system inhibitors were shown to have benefits beyond their classic cardioprotective and vasculoprotective effects, including reducing the risk of new-onset diabetes and associated cardiovascular effects. The discovery that the renin-angiotensin system inhibitor and angiotensin II type 1 (AT1 receptor blocker (ARB, telmisartan, can selectively activate the peroxisome proliferator-activated receptor-γ (PPARγ, an established antidiabetic drug target provides the unique opportunity to prevent and treat cardiovascular complications in high-risk elderly patients with hypertension and new-onset diabetes. Two large clinical trials, ONTARGET (Ongoing Telmisartan Alone in combination with Ramipril Global Endpoint Trial and TRANSCEND (Telmisartan Randomized AssessmeNt Study in ACE-I iNtolerant subjects with cardiovascular disease have assessed the cardioprotective and antidiabetic effects of telmisartan. The collective data suggest that telmisartan is a promising drug for controlling hypertension and reducing vascular risk in high-risk elderly patients with new-onset diabetes.Keywords: elderly, hypertension, telmisartan, angiotensin II type 1 receptor blocker, peroxisome proliferator-activated receptor-γ, diabetes, vascular risk

Does Chocolate Intake During Pregnancy Reduce the Risks of Preeclampsia and Gestational Hypertension?

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Saftlas, Audrey F.; Triche, Elizabeth W.; Beydoun, Hind; Bracken, Michael B.

2010-01-01

Purpose Chocolate consumption is associated with favorable levels of blood pressure and other cardiovascular disease risk markers. We analyzed a prospective cohort study to determine if regular chocolate intake during pregnancy is associated with reduced risks of preeclampsia and gestational hypertension (GH). Methods Subjects were recruited from 13 prenatal care practices in Connecticut (1988-1991). In-person interviews were administered at Chocolate consumption (servings/week) during the 1st and 3rd trimesters was ascertained at initial interview and immediately postpartum, respectively. Consumers of Chocolate intake was more frequent among normotensives (80.7%) than preeclamptics (62.5%) or GH women (75.8%), and associated with reduced odds of preeclampsia (1st trimester: aOR=0.55, 95% CI: 0.32-0.95; 3rd trimester: aOR=0.56, 95% CI: 0.32-0.97). Only 1st trimester intake was associated with reduced odds of GH (aOR=0.65, 95% CI: 0.45-0.87). Conclusions These findings provide additional evidence of the benefits of chocolate. Prospective studies are needed to confirm and delineate protective effects of chocolate intake on risk of preeclampsia. PMID:20609337

Replicating Reducing the Risk: 12-Month Impacts of a Cluster Randomized Controlled Trial

Science.gov (United States)

Blocklin, Michelle; Layzer, Jean; Price, Cristofer; Juras, Randall; Freiman, Lesley

2016-01-01

Objectives. To test the effectiveness of Reducing the Risk, an evidence-based sexual health curriculum designed to help prevent adolescent pregnancy and sexually transmitted infections, on youth sexual behavior and intermediate outcomes thought to lead to these behaviors. Methods. Classes within schools in St. Louis, Missouri; Austin, Texas; and San Diego, California; were randomly assigned to receive Reducing the Risk or “business as usual.” Youths completed Web-based surveys at baseline (preintervention, August 2012–January 2014) and 12 months later (August 2013–January 2015). Intent-to-treat analyses were conducted across sites; we tested for differences in impacts between sites and other subgroups. Results. The program had no overall impact on sexual behaviors. However, at 1 site, program participants were significantly less likely to have engaged in recent sexual intercourse than were control group members. There were positive overall impacts on intermediate outcomes (e.g., knowledge, attitudes). Conclusions. After 12 months, Reducing the Risk was unsuccessful at changing sexual behaviors. Other results were mixed, but promising evidence (e.g., behavioral impacts at 1 site, impacts on intermediate outcomes) suggests potential for more widespread behavioral impacts over a longer term. PMID:27689492

TWEAK induces liver progenitor cell proliferation

Science.gov (United States)

Jakubowski, Aniela; Ambrose, Christine; Parr, Michael; Lincecum, John M.; Wang, Monica Z.; Zheng, Timothy S.; Browning, Beth; Michaelson, Jennifer S.; Baestcher, Manfred; Wang, Bruce; Bissell, D. Montgomery; Burkly, Linda C.

2005-01-01

Progenitor (“oval”) cell expansion accompanies many forms of liver injury, including alcohol toxicity and submassive parenchymal necrosis as well as experimental injury models featuring blocked hepatocyte replication. Oval cells can potentially become either hepatocytes or biliary epithelial cells and may be critical to liver regeneration, particularly when hepatocyte replication is impaired. The regulation of oval cell proliferation is incompletely understood. Herein we present evidence that a TNF family member called TWEAK (TNF-like weak inducer of apoptosis) stimulates oval cell proliferation in mouse liver through its receptor Fn14. TWEAK has no effect on mature hepatocytes and thus appears to be selective for oval cells. Transgenic mice overexpressing TWEAK in hepatocytes exhibit periportal oval cell hyperplasia. A similar phenotype was obtained in adult wild-type mice, but not Fn14-null mice, by administering TWEAK-expressing adenovirus. Oval cell expansion induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) was significantly reduced in Fn14-null mice as well as in adult wild-type mice with a blocking anti-TWEAK mAb. Importantly, TWEAK stimulated the proliferation of an oval cell culture model. Finally, we show increased Fn14 expression in chronic hepatitis C and other human liver diseases relative to its expression in normal liver, which suggests a role for the TWEAK/Fn14 pathway in human liver injury. We conclude that TWEAK has a selective mitogenic effect for liver oval cells that distinguishes it from other previously described growth factors. PMID:16110324

Stimulation of Cellular Proliferation by Hepatitis B Virus X Protein

Directory of Open Access Journals (Sweden)

Charles R. Madden

2001-01-01

Full Text Available Chronic infection with the hepatitis B virus (HBV is a known risk factor in the development of human hepatocellular carcinoma (HCC. The HBV-encoded X protein, HBx, has been investigated for properties that may explain its cancer cofactor role in transgenic mouse lines. We discuss here recent data showing that HBx is able to induce hepatocellular proliferation in vitro and in vivo. This property of HBx is predicted to sensitize hepatocytes to other HCC cofactors, including exposure to carcinogens and to other hepatitis viruses. Cellular proliferation is intimately linked to the mechanism(s by which most tumor-associated viruses transform virus-infected cells. The HBx alteration of the cell cycle provides an additional mechanism by which chronic HBV infection may contribute to HCC.

Principles of resource-effectiveness and regulatory-effectiveness for risk-informed applications: Reducing burdens by improving effectiveness

International Nuclear Information System (INIS)

Vesely, W.E.

1999-01-01

Principles of resource-effectiveness and regulatory-effectiveness are presented which systematically compare the resources expended on a requirement or activity versus its risk importance. To evaluate resource-effectiveness and regulatory-effectiveness, cost-benefit analysis principles are generalized to resource versus risk importance principles. It is shown that by applying resource-importance analyses, current requirements and activities can be systematically evaluated for their resource-effectiveness and their risk-consistency. Strategies can then be developed to maximize both resource-effectiveness and risk-consistency which reduces unnecessary burdens while maintaining risk or reducing risk. The principles, approaches, and implementation schemes which are presented provide a systematic process for evaluating and optimizing resource-effectiveness and regulatory-effectiveness. The illustrations that are presented show that current NRC and industry actions are not resource-effective. By improving their resource-effectiveness and risk-consistency, significant burden reductions are achievable while risk, e.g. core damage frequency, is maintained or is reduced. The illustrations show that by optimizing industry resources and NRC resources with regard to their risk-effectiveness, significant burden reductions are achievable for both the industry and NRC. Algorithms and software exist for broad-scale implementations. Because of the burden reductions which are identified and the improvements in risk-consistency which result, resource-importance analysis should be the first step in risk-informed applications. Resource-importance analysis is so important and can provide such large benefits that it needs to be carried out on all current requirements that are addressed by risk-informed applications

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

Activation of a Neospora caninum EGFR-Like Kinase Facilitates Intracellular Parasite Proliferation

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Xiaoxia Jin

2017-10-01

Full Text Available The Apicomplexan parasite Neospora caninum, an obligate intracellular protozoan, causes serious diseases in a number of mammalian species, especially in cattle. Infection with N. caninum is associated with abortions in both dairy and beef cattle worldwide which have a major economic impact on the cattle industry. However, the mechanism by which N. caninum proliferates within host cells is poorly understood. Epidermal growth factor receptor (EGFR is a protein kinase ubiquitously expressed, present on cell surfaces in numerous species, which has been confirmed to be essential in signal transduction involved in cell growth, proliferation, survival, and many other intracellular processes. However, the presence of EGFR in N. caninum and its role in N. caninum proliferation remain unclear. In the present study, we identified a putative EGFR-like kinase in N. caninum, which could be activated in tachyzoites by infection or treatment with rNcMIC3 [containing four epidermal growth factor (EGF domains] or human EGF. Blockade of EGFR-like in tachyzoites by AG1478 significantly reduced parasite proliferation in host cells. Our data suggested that the activation of tachyzoite EGFR-like might facilitate the intracellular proliferation of N. caninum.

Specifying the ovarian cancer risk threshold of 'premenopausal risk-reducing salpingo-oophorectomy' for ovarian cancer prevention: a cost-effectiveness analysis.

Science.gov (United States)

Manchanda, Ranjit; Legood, Rosa; Antoniou, Antonis C; Gordeev, Vladimir S; Menon, Usha

2016-09-01

Risk-reducing salpingo-oophorectomy (RRSO) is the most effective intervention to prevent ovarian cancer (OC). It is only available to high-risk women with >10% lifetime OC risk. This threshold has not been formally tested for cost-effectiveness. To specify the OC risk thresholds for RRSO being cost-effective for preventing OC in premenopausal women. The costs as well as effects of surgical prevention ('RRSO') were compared over a lifetime with 'no RRSO' using a decision analysis model. RRSO was undertaken in premenopausal women >40 years. The model was evaluated at lifetime OC risk levels: 2%, 4%, 5%, 6%, 8% and 10%. Costs and outcomes are discounted at 3.5%. Uncertainty in the model was assessed using both deterministic sensitivity analysis and probabilistic sensitivity analysis (PSA). Outcomes included in the analyses were OC, breast cancer (BC) and additional deaths from coronary heart disease. Total costs and effects were estimated in terms of quality-adjusted life-years (QALYs); incidence of OC and BC; as well as incremental cost-effectiveness ratio (ICER). Published literature, Nurses Health Study, British National Formulary, Cancer Research UK, National Institute for Health and Care Excellence guidelines and National Health Service reference costs. The time horizon is lifetime and perspective: payer. Premenopausal RRSO is cost-effective at 4% OC risk (life expectancy gained=42.7 days, ICER=£19 536/QALY) with benefits largely driven by reduction in BC risk. RRSO remains cost-effective at >8.2% OC risk without hormone replacement therapy (ICER=£29 071/QALY, life expectancy gained=21.8 days) or 6%if BC risk reduction=0 (ICER=£27 212/QALY, life expectancy gained=35.3 days). Sensitivity analysis indicated results are not impacted much by costs of surgical prevention or treatment of OC/ BC or cardiovascular disease. However, results were sensitive to RRSO utility scores. Additionally, 37%, 61%, 74%, 84%, 96% and 99.5% simulations on PSA are cost

Reducing risks and increasing safety in everyday life: the role of the public

International Nuclear Information System (INIS)

Enander, A.

1998-01-01

Full text of publication follows: in social science risk research more attention has been paid to examining how people in general perceive risks than to how they perceive possible measures to reduce risks and to increase their own safety. The latter area is, however, becoming increasingly important to understand, particularly in the light of current emphasis on individual responsibility in risk prevention and emergency preparedness. For example, in Sweden a major effort to increase safety awareness among the general public and to increase knowledge and skills in a number of safety-related areas is at present being planned. This effort is being undertaken as a cooperative effort between different authorities and institutions and is coordinated by the Swedish Rescue Services Agency. The intentions behind this and similar programmes raise a number of questions concerning how people view risks and safety measures in their own immediate environment. Knowledge of the factors affecting willingness to take precautions is important in the design of communication and information. The factors which are of significance may be risk-related and concern perceptions of personal risk, but may also be related to attitudes an beliefs concerning different precautionary measures, to perception of social norms and conventions as well as to personal experiences and values. This paper presents some data concerning views and actions among lay groups in relation to reducing risks and increasing safety. Factors affecting these views are discussed in the light of previous research and of empirical data from some recent studies. (author)

Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation

Science.gov (United States)

Wang, Jing; Luo, Cheng; Shan, Changliang; You, Qiancheng; Lu, Junyan; Elf, Shannon; Zhou, Yu; Wen, Yi; Vinkenborg, Jan L.; Fan, Jun; Kang, Heebum; Lin, Ruiting; Han, Dali; Xie, Yuxin; Karpus, Jason; Chen, Shijie; Ouyang, Shisheng; Luan, Chihao; Zhang, Naixia; Ding, Hong; Merkx, Maarten; Liu, Hong; Chen, Jing; Jiang, Hualiang; He, Chuan

2015-12-01

Copper is a transition metal that plays critical roles in many life processes. Controlling the cellular concentration and trafficking of copper offers a route to disrupt these processes. Here we report small molecules that inhibit the human copper-trafficking proteins Atox1 and CCS, and so provide a selective approach to disrupt cellular copper transport. The knockdown of Atox1 and CCS or their inhibition leads to a significantly reduced proliferation of cancer cells, but not of normal cells, as well as to attenuated tumour growth in mouse models. We show that blocking copper trafficking induces cellular oxidative stress and reduces levels of cellular ATP. The reduced level of ATP results in activation of the AMP-activated protein kinase that leads to reduced lipogenesis. Both effects contribute to the inhibition of cancer cell proliferation. Our results establish copper chaperones as new targets for future developments in anticancer therapies.

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)

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

Comments on fuel cycle concepts and impacts on nonproliferation and safeguards concerns

International Nuclear Information System (INIS)

Persiani, P.J.

1997-01-01

Fuel cycle technologies have inherently differing levels of proliferation risk profiles. Institutional and/or multi-national arrangements have been effective in reducing the proliferation risk concerns. The implementation of international safeguards further reduces the proliferation risk concerns by the timely detection of a possible physical diversion of SNM from fuel cycle facilities. Fuel cycles are safeguardable, but the proliferation risk characteristics of fuel cycles concepts differ significantly with consequent impacts on the international level of technical safeguards measures. The paper comments on proliferation characteristics of some of the fuel cycle concepts for the purpose of exploring development of advanced nonproliferation and safeguards measures

Reducing drug–herb interaction risk with a computerized reminder system

Science.gov (United States)

Lin, Sheng-Shing; Tsai, Chiu-Lin; Tu, Ching-Yeh; Hsieh, Ching-Liang

2015-01-01

Background Traditional Chinese medicine (TCM) and Western medicine are both popular in Taiwan. Approximately 14.1% of Taiwanese residents use Western drugs and Chinese herbs concurrently; therefore, drug–herb interaction is critical to patient safety. This paper presents a new procedure for reducing the risk of drug interactions. Methods Hospital computer systems are modified to ensure that drug–herb interactions are automatically detected when a TCM practitioner is writing a prescription. A pop-up reminder appears, warning of interactions, and the practitioner may adjust doses, delete herbs, or leave the prescription unchanged. A pharmacist will receive interaction information through the system and provide health education to the patient. Results During the 2011–2013 study period, 256 patients received 891 herbal prescriptions with potential drug–herb interactions. Three of the 50 patients who concurrently used ginseng and antidiabetic drugs manifested hypoglycemia (fasting blood sugar level ≤70 mg/dL). Conclusion Drug–herb interactions can cause adverse reactions. A computerized reminder system can enable TCM practitioners to reduce the risk of drug–herb interactions. In addition, health education for patients is crucial in avoiding adverse reaction by the interactions. PMID:25733840

Apoptosis and reduced cell proliferation of HL-60 cell line caused by human telomerase reverse transcriptase inhibition by siRNA.

Science.gov (United States)

Miri-Moghaddam, Ebrahim; Deezagi, Abdolkhaleg; Soheili, Zahra Sohaila; Shariati, Parvin

2010-01-01

The close correlation between telomerase activity and human telomerase reverse transcriptase (hTERT) expression has made hTERT to be considered as a selective molecular target for human cancer therapy. In this study, the ability of short-interfering RNA (siRNA) to downregulate hTERT expression and its correlation with cell growth and apoptosis in the promyelocytic cell line HL-60 was evaluated. hTERT siRNA was designed and transfected to HL-60. hTERT mRNA expression, cell proliferation and apoptotic cells were measured. The results indicated that hTERT siRNA resulted in 97.2 ± 0.6% downregulation of the hTERT mRNA content; inhibition of the cell proliferation rate was about 52.8 ± 2.3% and the apoptotic index of cells was 30.5 ± 1.5%. hTERT plays an essential role in cell proliferation and control of the viability of leukemic cells, thus promising the development of drugs for leukemia. Copyright © 2010 S. Karger AG, Basel.

Laser enrichment: a new path to proliferation

International Nuclear Information System (INIS)

Casper, B.M.

1977-01-01

The use of lasers to obtain enriched uranium is an easier and cheaper method than methods currently in use. The immediate concern is that it could promote easy access to nuclear weapons by countries that do not presently have them. Mr. Casper feels that the U.S. government is working against itself; while the State Department is seeking to block one path to proliferation, ERDA laboratories are developing new technology that could open another. The proliferation implications have not been factored in a serious way into the decisions to proceed with this research. It is also clear that the United States does not now have a comprehensive policy that deals with all potentially important paths to proliferation, including laser enrichment. Mr. Casper states that there is still time to stop and consider whether laser enrichment should be developed, in light of its broader consequences. But this will not happen if the decisions are left exclusively in the hands of those promoting the technology, the author says. It is just this sort of situation that prompted the creation of several government institutions to provide independent assessments of new technologies. The Office of Technology Assessment, the Nuclear Regulatory Commission, and the Arms Control and Disarmament Agency all have the authority to intervene. Laser enrichment provides a good test of these institutions and of the viability of the concept of technology assessment. The status, benefits and risks, and the policy needed on laser research are discussed

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

The effects of exposure route on DNA adduct formation and cellular proliferation by 1,2,3-trichloropropane.

Science.gov (United States)

La, D K; Schoonhoven, R; Ito, N; Swenberg, J A

1996-09-01

1,2,3-Trichloropropane (TCP) induces high incidences of tumors at multiple sites in mice and rats when administered chronically by gavage. The animal tumor data are being used to predict human risk from potential exposure to TCP in drinking water. Risk assessment may be affected by differences in the route of exposure. Gavage administration, which results in high bolus concentrations compared to drinking water exposure, may quantitatively affect toxicokinetics, cytotoxicity, and genotoxicity. We have examined the effects of TCP exposure by the two routes on the formation of DNA adducts and the induction of cellular proliferation. Male B6C3F1 mice were administered [14C]TCP for 1 week by gavage or in drinking water at the low dose (6 mg/kg) used in the NTP carcinogenesis bioassay. Two target organs (forestomach and liver) and two nontarget organs (glandular stomach and kidney) were examined for DNA adduct formation. Adducts were hydrolyzed from DNA, isolated by HPLC, and quantitated by measuring HPLC fractions for radioactivity. In the forestomach, liver, and kidney, gavage administration of TCP resulted in 1.4-to 2.4-fold greater yields of the major DNA adduct, previously identified as S-[1-(hydroxymethyl)-2-(N7-guanyl)ethyl]glutathione. Significant differences in cell proliferation, as determined by incorporation of bromodeoxyuridine into DNA, were also observed for the two routes. Gavage administration of TCP for 2 weeks resulted in up to a threefold greater cell proliferation rate relative to administration in drinking water. Our findings of exposure-related differences in TCP-induced DNA adduct formation and cell proliferation suggest that a risk assessment based on the existing gavage study may overestimate human risk.

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

Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration.

Science.gov (United States)

Mahmoud, Ahmed I; O'Meara, Caitlin C; Gemberling, Matthew; Zhao, Long; Bryant, Donald M; Zheng, Ruimao; Gannon, Joseph B; Cai, Lei; Choi, Wen-Yee; Egnaczyk, Gregory F; Burns, Caroline E; Burns, C Geoffrey; MacRae, Calum A; Poss, Kenneth D; Lee, Richard T

2015-08-24

Some organisms, such as adult zebrafish and newborn mice, have the capacity to regenerate heart tissue following injury. Unraveling the mechanisms of heart regeneration is fundamental to understanding why regeneration fails in adult humans. Numerous studies have revealed that nerves are crucial for organ regeneration, thus we aimed to determine whether nerves guide heart regeneration. Here, we show using transgenic zebrafish that inhibition of cardiac innervation leads to reduction of myocyte proliferation following injury. Specifically, pharmacological inhibition of cholinergic nerve function reduces cardiomyocyte proliferation in the injured hearts of both zebrafish and neonatal mice. Direct mechanical denervation impairs heart regeneration in neonatal mice, which was rescued by the administration of neuregulin 1 (NRG1) and nerve growth factor (NGF) recombinant proteins. Transcriptional analysis of mechanically denervated hearts revealed a blunted inflammatory and immune response following injury. These findings demonstrate that nerve function is required for both zebrafish and mouse heart regeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

Artistic occupations are associated with a reduced risk of Parkinson's disease.

Science.gov (United States)

Haaxma, Charlotte A; Borm, George F; van der Linden, Dimitri; Kappelle, Arnoud C; Bloem, Bastiaan R

2015-09-01

Parkinson's disease (PD) is preceded by a premotor phase of unknown duration. Dopaminergic degeneration during this phase may lead to subtle cognitive and behavioural changes, such as decreased novelty seeking. Consequently, premotor subjects might be most comfortable in jobs that do not require optimal dopamine levels, leading to an overrepresentation in structured and predictable occupations, or an underrepresentation in artistic occupations. In a case-control study, 750 men with PD (onset ≥40 years) and 1300 healthy men completed a validated questionnaire about their lifetime occupational status. Occupations were classified using the RIASEC model. Odds ratios (ORs) were calculated for the conventional and artistic categories, both for the most recent occupation before symptom onset, and for the very first occupation. Because farming has been associated with a PD risk, ORs were calculated separately for farming. A reduced risk of PD was found for men with an artistic occupation late in life (OR 0.14, 95% CI 0.04-0.53), while an artistic first occupation did not prevent PD (OR 0.72, CI 0.32-1.59). Conventional occupations showed no increased risk (recent: OR 1.07, CI 0.70-1.64; first: OR 1.14, CI 0.77-1.71). In support of previous reports, farming was associated with an increased risk of PD (recent: OR 2.6, CI 1.4-4.6; first: OR 2.7, CI 1.6-4.5). PD patients were older than controls, but various statistical corrections for age all lead to similar results. Artistic occupations late in life are associated with a reduced risk of subsequent PD, perhaps because this reflects a better preserved dopaminergic state. No initial occupation predicted PD, suggesting that the premotor phase starts later in life.

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

Reducing the Risk: Unemployed Migrant Youth and Labour Market Programs. Overview.

Science.gov (United States)

Australian Inst. of Multicultural Affairs, Melbourne (Australia).

This booklet is an overview and summary of the publication "Reducing the Risk: Unemployed Migrant Youth and Labour Market Programs" which reviews programs and services for migrant and refugee youth in Australia. The unemployment rate for this group is higher than for their Australian-born peers, and their participation in governmental…

Proliferation resistance modeling

International Nuclear Information System (INIS)

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

2004-01-01

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

Benign endometrial proliferations mimicking malignancies: a review of problematic entities in small biopsy specimens.

Science.gov (United States)

Ip, Philip Pun-Ching

2018-02-14

Benign proliferations that mimic malignancies are commonly encountered during the course of assessment of small and fragmented endometrial samples. Although benign, endometrial epithelial metaplasias often coexist with premalignant or malignant lesions causing diagnostic confusion. The difficulty with mucinous metaplasia lies in its distinction from atypical mucinous glandular proliferations and mucinous carcinomas, which are associated with significant interobserver variability. Papillary proliferation of the endometrium is commonly associated with hormonal drugs and endometrial polyps and is characterised by papillae with fibrovascular cores covered by epithelial cells without cytologic atypia. They are classified into simple or complex papillary proliferations depending on the architectural complexity and extent of proliferation. Complex papillary proliferations are associated with a high risk of concurrent or subsequent hyperplasia with atypia/carcinoma. Papillary proliferations may have coexisting epithelial metaplasias and, most commonly, mucinous metaplasia and syncytial papillary change. Those with striking mucinous metaplasia overlap morphologically with papillary mucinous metaplasia. The latter has been proposed as a precursor of endometrial mucinous carcinoma. Misinterpreting the Arias-Stella reaction as a malignant or premalignant lesion is more likely to occur if the pathologist is unaware that the patient is pregnant or on hormonal drugs. Endometrial hyperplasia with secretory changes may occasionally be difficult to distinguish from the torturous and crowded glands of a late secretory endometrium. Endometrial polyps may have abnormal features that can be misinterpreted as endometrial hyperplasia or Mullerian adenosarcoma. Awareness of these benign endometrial proliferations and their common association with hormonal medication or altered endogenous hormonal levels will help prevent the over-diagnosis of premalignant and malignant lesions.

Reducing risk of spinal haematoma from spinal and epidural pain procedures.

Science.gov (United States)

Breivik, Harald; Norum, Hilde; Fenger-Eriksen, Christian; Alahuhta, Seppo; Vigfússon, Gísli; Thomas, Owain; Lagerkranser, Michael

2018-04-25

Central neuraxial blocks (CNB: epidural, spinal and their combinations) and other spinal pain procedures can cause serious harm to the spinal cord in patients on antihaemostatic drugs or who have other risk-factors for bleeding in the spinal canal. The purpose of this narrative review is to provide a practise advisory on how to reduce risk of spinal cord injury from spinal haematoma (SH) during CNBs and other spinal pain procedures. Scandinavian guidelines from 2010 are part of the background for this practise advisory. We searched recent guidelines, PubMed (MEDLINE), SCOPUS and EMBASE for new and relevant randomised controlled trials (RCT), case-reports and original articles concerning benefits of neuraxial blocks, risks of SH due to anti-haemostatic drugs, patient-related risk factors, especially renal impairment with delayed excretion of antihaemostatic drugs, and specific risk factors related to the neuraxial pain procedures. Epidural and spinal analgesic techniques, as well as their combination provide superior analgesia and reduce the risk of postoperative and obstetric morbidity and mortality. Spinal pain procedure can be highly effective for cancer patients, less so for chronic non-cancer patients. We did not identify any RCT with SH as outcome. We evaluated risks and recommend precautions for SH when patients are treated with antiplatelet, anticoagulant, or fibrinolytic drugs, when patients' comorbidities may increase risks, and when procedure-specific risk factors are present. Inserting and withdrawing epidural catheters appear to have similar risks for initiating a SH. Invasive neuraxial pain procedures, e.g. spinal cord stimulation, have higher risks of bleeding than traditional neuraxial blocks. We recommend robust monitoring routines and treatment protocol to ensure early diagnosis and effective treatment of SH should this rare but potentially serious complication occur. When neuraxial analgesia is considered for a patient on anti

Orbital fluid shear stress promotes osteoblast metabolism, proliferation and alkaline phosphates activity in vitro

Energy Technology Data Exchange (ETDEWEB)

Aisha, M.D. [Institute of Medical Molecular Biotechnology and Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh 47000, Selangor (Malaysia); Nor-Ashikin, M.N.K. [Institute of Medical Molecular Biotechnology and Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh 47000, Selangor (Malaysia); DDH, Universiti Teknologi MARA, ShahAlam 40450, Selangor (Malaysia); Sharaniza, A.B.R. [DDH, Universiti Teknologi MARA, ShahAlam 40450, Selangor (Malaysia); Nawawi, H. [Center for Pathology Diagnostic and Research Laboratories, Clinical Training Center, Universiti Teknologi MARA, Sungai Buloh 47000, Selangor (Malaysia); I-PPerForM, Universiti Teknologi MARA, Selayang 47000 Selangor (Malaysia); Froemming, G.R.A., E-mail: gabriele@salam.uitm.edu.my [Institute of Medical Molecular Biotechnology and Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh 47000, Selangor (Malaysia); I-PPerForM, Universiti Teknologi MARA, Selayang 47000 Selangor (Malaysia)

2015-09-10

Prolonged disuse of the musculoskeletal system is associated with reduced mechanical loading and lack of anabolic stimulus. As a form of mechanical signal, the multidirectional orbital fluid shear stress transmits anabolic signal to bone forming cells in promoting cell differentiation, metabolism and proliferation. Signals are channeled through the cytoskeleton framework, directly modifying gene and protein expression. For that reason, we aimed to study the organization of Normal Human Osteoblast (NHOst) cytoskeleton with regards to orbital fluid shear (OFS) stress. Of special interest were the consequences of cytoskeletal reorganization on NHOst metabolism, proliferation, and osteogenic functional markers. Cells stimulated at 250 RPM in a shaking incubator resulted in the rearrangement of actin and tubulin fibers after 72 h. Orbital shear stress increased NHOst mitochondrial metabolism and proliferation, simultaneously preventing apoptosis. The ratio of RANKL/OPG was reduced, suggesting that orbital shear stress has the potential to inhibit osteoclastogenesis and osteoclast activity. Increase in ALP activity and OCN protein production suggests that stimulation retained osteoblast function. Shear stress possibly generated through actin seemed to hold an anabolic response as osteoblast metabolism and functional markers were enhanced. We hypothesize that by applying orbital shear stress with suitable magnitude and duration as a non-drug anabolic treatment can help improve bone regeneration in prolonged disuse cases. - Highlights: • OFS stress transmits anabolic signals to osteoblasts. • Actin and tubulin fibers are rearranged under OFS stress. • OFS stress increases mitochondrial metabolism and proliferation. • Reduced RANKL/OPG ratio in response to OFS inhibits osteoclastogenesis. • OFS stress prevents apoptosis and stimulates ALP and OCN.

Inhibition of human lung cancer cell proliferation and survival by wine

Science.gov (United States)

2014-01-01

Background Compounds of plant origin and food components have attracted scientific attention for use as agents for cancer prevention and treatment. Wine contains polyphenols that were shown to have anti-cancer and other health benefits. The survival pathways of Akt and extracellular signal-regulated kinase (Erk), and the tumor suppressor p53 are key modulators of cancer cell growth and survival. In this study, we examined the effects of wine on proliferation and survival of human Non-small cell lung cancer (NSCLC) cells and its effects on signaling events. Methods Human NSCLC adenocarcinoma A549 and H1299 cells were used. Cell proliferation was assessed by thymidine incorporation. Clonogenic assays were used to assess cell survival. Immunoblotting was used to examine total and phosphorylated levels of Akt, Erk and p53. Results In A549 cells red wine inhibited cell proliferation and reduced clonogenic survival at doses as low as 0.02%. Red wine significantly reduced basal and EGF-stimulated Akt and Erk phosphorylation while it increased the levels of total and phosphorylated p53 (Ser15). Control experiments indicated that the anti-proliferative effects of wine were not mediated by the associated contents of ethanol or the polyphenol resveratrol and were independent of glucose transport into cancer cells. White wine also inhibited clonogenic survival, albeit at a higher doses (0.5-2%), and reduced Akt phosphorylation. The effects of both red and white wine on Akt phosphorylation were also verified in H1299 cells. Conclusions Red wine inhibits proliferation of lung cancer cells and blocks clonogenic survival at low concentrations. This is associated with inhibition of basal and EGF-stimulated Akt and Erk signals and enhancement of total and phosphorylated levels of p53. White wine mediates similar effects albeit at higher concentrations. Our data suggest that wine may have considerable anti-tumour and chemoprevention properties in lung cancer and deserves further

Non-proliferation and international safeguards

International Nuclear Information System (INIS)

Blix, H.

1992-01-01

Full text: In my view, drastic nuclear disarmament by nuclear weapon States could be coupled with universal commitment to non-proliferation by non-nuclear weapon States by 1995 when the extension of the NPT Will be discussed. The incentives and disincentives for making and stockpiling nuclear weapons are first of all in the political and security fields, (Global and regional detente reduce the incentive, With the cold war gone, the US and Russia are now agreeing on far-reaching cuts in their nuclear arsenals and at some point the other declared nuclear weapon States Will follow.In the regional fields, we have seen how Argentina and Brazil are about to commit themselves to exclusively peaceful uses of the atom through the Latin American Tlatelolco Treaty. And we have seen how South Africa has joined the NPT. A new wave of States adhering to the NPT may be expected from countries in the former Soviet Union. Some have already come, others are on the way. Detente in the Middle East and on the Indian subcontinent would improve the outlook for non-proliferation in these areas. A second barrier to nuclear proliferation lies in export restrictions on sensitive nuclear material and equipment, Following the discoveries in Iraq, these restrictions are being strengthened in a large number of States. A third barrier to nuclear proliferation lies in the economic and political consequences that would follow for a State if IAEA safeguards inspection revealed activities aimed at the production of nuclear weapons. These must have a high degree of reliability. The case of Iraq showed that it was possible for a closed, highly militarized State to hide nuclear activities from the IAEA and the world We are now drawing the lessons from this case. It is not physically possible for inspectors to look into every building and basement in vast countries, They must have information about where to look, and the IAEA is significantly strengthening its information basis. The IAEA has also re

Does chocolate intake during pregnancy reduce the risks of preeclampsia and gestational hypertension?

Science.gov (United States)

Saftlas, Audrey F; Triche, Elizabeth W; Beydoun, Hind; Bracken, Michael B

2010-08-01

Chocolate consumption is associated with favorable levels of blood pressure and other cardiovascular disease risk markers. We analyzed a prospective cohort study to determine whether regular chocolate intake during pregnancy is associated with reduced risks of preeclampsia and gestational hypertension (GH). Subjects were recruited from 13 prenatal care practices in Connecticut (1988-1991). In-person interviews were administered at Chocolate consumption (servings/week) during the first and third trimesters was ascertained at initial interview and immediately postpartum, respectively. Consumers of less than 1 serving/week comprised the referent group. Adjusted odds ratios (aORs) were estimated by the use of logistic regression. Chocolate intake was more frequent among normotensive (80.7%) than preeclamptic (62.5%) or GH women (75.8%), and associated with reduced odds of preeclampsia (first trimester: aOR, 0.55; 95% confidence interval [95% CI], 0.32-0.95; third trimester: aOR, 0.56; 95% CI, 0.32-0.97). Only first trimester intake was associated with reduced odds of GH (aOR,0.65; 95% CI, 0.45-0.87). These findings provide additional evidence of the benefits of chocolate. Prospective studies are needed to confirm and delineate protective effects of chocolate intake on risk of preeclampsia. 2010 Elsevier Inc. All rights reserved.

Reducing the Risk of Type 2 Diabetes in Nonselected Outpatients With Schizophrenia

DEFF Research Database (Denmark)

Hjorth, Peter; Espensen, Caroline H; Madsen, Nikolaj J

2018-01-01

maintaining such a lifestyle because of factors related to their illness, such as cognitive disturbances, negative and positive symptoms, and side effects of psychotropic medications. OBJECTIVE: To measure and reduce risk factors for type 2 diabetes in patients with schizophrenia and examine characteristics...... and reduction in their risk factors for type 2 diabetes. The clinical intervention incorporated individual guidance, group sessions, and treatment as usual. RESULTS: Patients newly diagnosed with schizophrenia were found to have high consumption of soft drinks and low physical activity at their index evaluation......: The study found that positive outcomes were associated with female sex and a longer duration of illness. Negative outcomes with worsening of risk factors were associated with being newly diagnosed with schizophrenia and male sex. It was possible to produce improvements in some risk factors through...

CD44 plays a functional role in Helicobacter pylori-induced epithelial cell proliferation.

Directory of Open Access Journals (Sweden)

Nina Bertaux-Skeirik

2015-02-01

Full Text Available The cytotoxin-associated gene (Cag pathogenicity island is a strain-specific constituent of Helicobacter pylori (H. pylori that augments cancer risk. CagA translocates into the cytoplasm where it stimulates cell signaling through the interaction with tyrosine kinase c-Met receptor, leading cellular proliferation. Identified as a potential gastric stem cell marker, cluster-of-differentiation (CD CD44 also acts as a co-receptor for c-Met, but whether it plays a functional role in H. pylori-induced epithelial proliferation is unknown. We tested the hypothesis that CD44 plays a functional role in H. pylori-induced epithelial cell proliferation. To assay changes in gastric epithelial cell proliferation in relation to the direct interaction with H. pylori, human- and mouse-derived gastric organoids were infected with the G27 H. pylori strain or a mutant G27 strain bearing cagA deletion (∆CagA::cat. Epithelial proliferation was quantified by EdU immunostaining. Phosphorylation of c-Met was analyzed by immunoprecipitation followed by Western blot analysis for expression of CD44 and CagA. H. pylori infection of both mouse- and human-derived gastric organoids induced epithelial proliferation that correlated with c-Met phosphorylation. CagA and CD44 co-immunoprecipitated with phosphorylated c-Met. The formation of this complex did not occur in organoids infected with ∆CagA::cat. Epithelial proliferation in response to H. pylori infection was lost in infected organoids derived from CD44-deficient mouse stomachs. Human-derived fundic gastric organoids exhibited an induction in proliferation when infected with H. pylori that was not seen in organoids pre-treated with a peptide inhibitor specific to CD44. In the well-established Mongolian gerbil model of gastric cancer, animals treated with CD44 peptide inhibitor Pep1, resulted in the inhibition of H. pylori-induced proliferation and associated atrophic gastritis. The current study reports a unique

Homocysteine inhibits hepatocyte proliferation via endoplasmic reticulum stress.

Directory of Open Access Journals (Sweden)

Xue Yu

Full Text Available Homocysteine is an independent risk factor for coronary, cerebral, and peripheral vascular diseases. Recent studies have shown that levels of homocysteine are elevated in patients with impaired hepatic function, but the precise role of homocysteine in the development of hepatic dysfunction is unclear. In this study, we examined the effect of homocysteine on hepatocyte proliferation in vitro. Our results demonstrated that homocysteine inhibited hepatocyte proliferation by up-regulating protein levels of p53 as well as mRNA and protein levels of p21(Cip1 in primary cultured hepatocytes. Homocysteine induced cell growth arrest in p53-positive hepatocarcinoma cell line HepG2, but not in p53-null hepatocarcinoma cell line Hep3B. A p53 inhibitor pifithrin-α inhibited the expression of p21(Cip1 and attenuated homocysteine-induced cell growth arrest. Homocysteine induced TRB3 expression via endoplasmic reticulum stress pathway, resulting in Akt dephosphorylation. Knock-down of endogenous TRB3 significantly suppressed the inhibitory effect of homocysteine on cell proliferation and the phosphorylation of Akt. LiCl reversed homocysteine-mediated cell growth arrest by inhibiting TRB3-mediated Akt dephosphorylation. These results demonstrate that both TRB3 and p21(Cip1 are critical molecules in the homocysteine signaling cascade and provide a mechanistic explanation for impairment of liver regeneration in hyperhomocysteinemia.

EPO-independent functional EPO receptor in breast cancer enhances estrogen receptor activity and promotes cell proliferation

International Nuclear Information System (INIS)

Reinbothe, Susann; Larsson, Anna-Maria; Vaapil, Marica; Wigerup, Caroline; Sun, Jianmin; Jögi, Annika; Neumann, Drorit; Rönnstrand, Lars; Påhlman, Sven

2014-01-01

Highlights: • New anti-human EPOR antibody confirms full-length EPOR expression in breast cancer cells. • Proliferation of breast cancer cells is not affected by rhEPO treatment in vitro. • EPOR knockdown impairs proliferation of ERa positive breast cancer cells. • EPOR knockdown reduces AKT phosphorylation and ERa activity. - Abstract: The main function of Erythropoietin (EPO) and its receptor (EPOR) is the stimulation of erythropoiesis. Recombinant human EPO (rhEPO) is therefore used to treat anemia in cancer patients. However, clinical trials have indicated that rhEPO treatment might promote tumor progression and has a negative effect on patient survival. In addition, EPOR expression has been detected in several cancer forms. Using a newly produced anti-EPOR antibody that reliably detects the full-length isoform of the EPOR we show that breast cancer tissue and cells express the EPOR protein. rhEPO stimulation of cultured EPOR expressing breast cancer cells did not result in increased proliferation, overt activation of EPOR (receptor phosphorylation) or a consistent activation of canonical EPOR signaling pathway mediators such as JAK2, STAT3, STAT5, or AKT. However, EPOR knockdown experiments suggested functional EPO receptors in estrogen receptor positive (ERα + ) breast cancer cells, as reduced EPOR expression resulted in decreased proliferation. This effect on proliferation was not seen in ERα negative cells. EPOR knockdown decreased ERα activity further supports a mechanism by which EPOR affects proliferation via ERα-mediated mechanisms. We show that EPOR protein is expressed in breast cancer cells, where it appears to promote proliferation by an EPO-independent mechanism in ERα expressing breast cancer cells

EPO-independent functional EPO receptor in breast cancer enhances estrogen receptor activity and promotes cell proliferation

Energy Technology Data Exchange (ETDEWEB)

Reinbothe, Susann; Larsson, Anna-Maria; Vaapil, Marica; Wigerup, Caroline [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); CREATE Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Sun, Jianmin [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); Jögi, Annika [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); CREATE Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Neumann, Drorit [Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel); Rönnstrand, Lars [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); Påhlman, Sven, E-mail: sven.pahlman@med.lu.se [Department of Laboratory Medicine, Translational Cancer Research, Medicon Village, Lund University, SE-223 81 Lund (Sweden); CREATE Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv (Israel)

2014-02-28

Highlights: • New anti-human EPOR antibody confirms full-length EPOR expression in breast cancer cells. • Proliferation of breast cancer cells is not affected by rhEPO treatment in vitro. • EPOR knockdown impairs proliferation of ERa positive breast cancer cells. • EPOR knockdown reduces AKT phosphorylation and ERa activity. - Abstract: The main function of Erythropoietin (EPO) and its receptor (EPOR) is the stimulation of erythropoiesis. Recombinant human EPO (rhEPO) is therefore used to treat anemia in cancer patients. However, clinical trials have indicated that rhEPO treatment might promote tumor progression and has a negative effect on patient survival. In addition, EPOR expression has been detected in several cancer forms. Using a newly produced anti-EPOR antibody that reliably detects the full-length isoform of the EPOR we show that breast cancer tissue and cells express the EPOR protein. rhEPO stimulation of cultured EPOR expressing breast cancer cells did not result in increased proliferation, overt activation of EPOR (receptor phosphorylation) or a consistent activation of canonical EPOR signaling pathway mediators such as JAK2, STAT3, STAT5, or AKT. However, EPOR knockdown experiments suggested functional EPO receptors in estrogen receptor positive (ERα{sup +}) breast cancer cells, as reduced EPOR expression resulted in decreased proliferation. This effect on proliferation was not seen in ERα negative cells. EPOR knockdown decreased ERα activity further supports a mechanism by which EPOR affects proliferation via ERα-mediated mechanisms. We show that EPOR protein is expressed in breast cancer cells, where it appears to promote proliferation by an EPO-independent mechanism in ERα expressing breast cancer cells.

Acceptability of mobile health interventions to reduce inactivity-related health risk in central Pennsylvania adults

Directory of Open Access Journals (Sweden)

Chih-Hsiang Yang

2015-01-01

Full Text Available Insufficient physical activity and excessive sedentary behavior elevate health risk. Mobile applications (apps provide one mode for delivering interventions to modify these behaviors and reduce health risk. The purpose of this study was to characterize the need for and acceptability of health behavior interventions among rural adults and evaluate the interest in and the value of app-based interventions in this population. Central Pennsylvania adults with smartphones (N = 258 completed a brief web survey in October–November 2012. Most adults report one or both inactivity-related behavioral risk factors, would use a free app to modify those risk behaviors, and would pay a small amount for that app. Low-cost, efficacious apps to increase physical activity or reduce sedentary behavior should be promoted in public health practice. User experience should be at the forefront of this process to increase value and minimize burden in the service of long-term engagement, behavior change, and health risk reduction.

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

Energy Technology Data Exchange (ETDEWEB)

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

1979-01-19

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

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

International Nuclear Information System (INIS)

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

1979-01-01

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

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...

Electrospun Gelatin–Chondroitin Sulfate Scaffolds Loaded with Platelet Lysate Promote Immature Cardiomyocyte Proliferation

Directory of Open Access Journals (Sweden)

Francesca Saporito

2018-02-01

Full Text Available The aim of the present work was the development of heart patches based on gelatin (G and chondroitin sulfate (CS to be used as implants to improve heart recovery after corrective surgery for critical congenital heart defects (CHD. Patches were prepared by means of electrospinning to obtain nanofibrous scaffolds and they were loaded with platelet lysate (PL as a source of growth factors to further enhance the repair process. Scaffolds were characterized for morphology and mechanical properties and for the capability to support in vitro adhesion and proliferation of dermal fibroblasts in order to assess the system’s general biocompatibility. Adhesion and proliferation of endothelial cells and cardiac cells (cardiomyocytes and cardiac fibroblasts from rat fetuses onto PL-loaded patches was evaluated. Patches presented good elasticity and high stiffness suitable for in vivo adaptation to heart contraction. CS improved adhesion and proliferation of dermal fibroblasts, as proof of their biocompatibility. Moreover, they enhanced the adhesion and proliferation of endothelial cells, a crucial mediator of cardiac repair. Cell adhesion and proliferation could be related to elastic properties, which could favor cell motility. The presence of platelet lysate and CS was crucial for the adhesion and proliferation of cardiac cells and, in particular, of cardiomyocytes: G/CS scaffold embedded with PL appeared to selectively promote proliferation in cardiomyocytes but not cardiac fibroblasts. In conclusion, G/CS scaffold seems to be a promising system to assist myocardial-repair processes in young patient, preserving cardiomyocyte viability and preventing cardiac fibroblast proliferation, likely reducing subsequent uncontrolled collagen deposition by fibroblasts following repair.

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

Oesophageal epithelial cell proliferation and food consumption patterns following irradiation

International Nuclear Information System (INIS)

Burholt, D.R.

1986-01-01

The murine data presented illustrate the influence of food consumption on the proliferative rate of the oesophageal epithelium during recovery from radiation damage. Refeeding at a time before the initiation of the normal hyperplastic response results in a decreased time interval between treatment and increased rates of cell proliferation, while reduced food consumption during the normal period of hyperproliferation results in reduced proliferative activity. The finding that recovery kinetics may be altered by changing food consumption patterns should be an important consideration in the analysis of antineoplastic agent-induced proliferative perturbations, as many treatments themselves produce reduced levels of food consumption. (UK)

Ligand activation of peroxisome proliferator-activated receptor-β/δ suppresses liver tumorigenesis in hepatitis B transgenic mice

International Nuclear Information System (INIS)

Balandaram, Gayathri; Kramer, Lance R.; Kang, Boo-Hyon; Murray, Iain A.; Perdew, Gary H.; Gonzalez, Frank J.; Peters, Jeffrey M.

2016-01-01

Highlights: • The role of PPARβ/δ in HBV-induced liver cancer was examined. • PPARβ/δ inhibits steatosis, inflammation, tumor multiplicity and promotes apoptosis. • Kupffer cell PPARβ/δ mediates these effects independent of DNA binding. - Abstract: Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) inhibits steatosis and inflammation, known risk factors for liver cancer. In this study, the effect of ligand activation of PPARβ/δ in modulating liver tumorigenesis in transgenic hepatitis B virus (HBV) mice was examined. Activation of PPARβ/δ in HBV mice reduced steatosis, the average number of liver foci, and tumor multiplicity. Reduced expression of hepatic CYCLIN D1 and c-MYC, tumor necrosis factor alpha (Tnfa) mRNA, serum levels of alanine aminotransaminase, and an increase in apoptotic signaling was also observed following ligand activation of PPARβ/δ in HBV mice compared to controls. Inhibition of Tnfa mRNA expression was not observed in wild-type hepatocytes. Ligand activation of PPARβ/δ inhibited lipopolysaccharide (LPS)-induced mRNA expression of Tnfa in wild-type, but not in Pparβ/δ-null Kupffer cells. Interestingly, LPS-induced expression of Tnfa mRNA was also inhibited in Kupffer cells from a transgenic mouse line that expressed a DNA binding mutant form of PPARβ/δ compared to controls. Combined, these results suggest that ligand activation of PPARβ/δ attenuates hepatic tumorigenesis in HBV transgenic mice by inhibiting steatosis and cell proliferation, enhancing hepatocyte apoptosis, and modulating anti-inflammatory activity in Kupffer cells.

Elafibranor, an Agonist of the Peroxisome Proliferator-Activated Receptor-alpha and -delta, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening

NARCIS (Netherlands)

Ratziu, V.; Harrison, S.A.; Francque, S.; Bedossa, P.; Lehert, P.; Serfaty, L.; Romero-Gomez, M.; Boursier, J.; Abdelmalek, M.; Caldwell, S.; Drenth, J.P.; Anstee, Q.M.; Hum, D.; Hanf, R.; Roudot, A.; Megnien, S.; Staels, B.; Sanyal, A.

2016-01-01

BACKGROUND & AIMS: Elafibranor is an agonist of the peroxisome proliferator-activated receptor-alpha and peroxisome proliferator-activated receptor-delta. Elafibranor improves insulin sensitivity, glucose homeostasis, and lipid metabolism and reduces inflammation. We assessed the safety and efficacy

MicroRNA-195 inhibits the proliferation of human glioma cells by directly targeting cyclin D1 and cyclin E1.

Directory of Open Access Journals (Sweden)

Wang Hui

Full Text Available Glioma proliferation is a multistep process during which a sequence of genetic and epigenetic alterations randomly occur to affect the genes controlling cell proliferation, cell death and genetic stability. microRNAs are emerging as important epigenetic modulators of multiple target genes, leading to abnormal cellular signaling involving cellular proliferation in cancers.In the present study, we found that expression of miR-195 was markedly downregulated in glioma cell lines and human primary glioma tissues, compared to normal human astrocytes and matched non-tumor associated tissues. Upregulation of miR-195 dramatically reduced the proliferation of glioma cells. Flow cytometry analysis showed that ectopic expression of miR-195 significantly decreased the percentage of S phase cells and increased the percentage of G1/G0 phase cells. Overexpression of miR-195 dramatically reduced the anchorage-independent growth ability of glioma cells. Furthermore, overexpression of miR-195 downregulated the levels of phosphorylated retinoblastoma (pRb and proliferating cell nuclear antigen (PCNA in glioma cells. Conversely, inhibition of miR-195 promoted cell proliferation, increased the percentage of S phase cells, reduced the percentage of G1/G0 phase cells, enhanced anchorage-independent growth ability, upregulated the phosphorylation of pRb and PCNA in glioma cells. Moreover, we show that miR-195 inhibited glioma cell proliferation by downregulating expression of cyclin D1 and cyclin E1, via directly targeting the 3'-untranslated regions (3'-UTR of cyclin D1 and cyclin E1 mRNA. Taken together, our results suggest that miR-195 plays an important role to inhibit the proliferation of glioma cells, and present a novel mechanism for direct miRNA-mediated suppression of cyclin D1 and cyclin E1 in glioma.

Status of the RERTR [Reduced Enrichment Research and Test Reactor] program in Argentina

International Nuclear Information System (INIS)

Giorsetti, D.R.

1987-01-01

The Argentine Atomic Energy Commission started in 1978 the Reduced Enrichment Research and Test Reactors in the field of reactor engineering; engineering, development and manufacturing of fuel elements and research reactors operators. This program was initiated with the conviction that it would contribute to the international efforts to reduce risks of nuclear weapons proliferation owing to an uncontrolled use of highly enriched uranium. It was intended to convert RA-3 reactor to make possible its operation with low enriched fuel (LEU), instead of high enriched fuel (HEU) and to develop manufacturing techniques for said LEU. Afterwards, this program was adapted to assist other countries in reactors conversion, development of the corresponding fuel elements and supply of fuel elements to other countries. (Author)

Is more better or worse? New empirics on nuclear proliferation and interstate conflict by Random Forests1

Directory of Open Access Journals (Sweden)

Akisato Suzuki

2015-06-01

Full Text Available In the literature on nuclear proliferation, some argue that further proliferation decreases interstate conflict, some say that it increases interstate conflict, and others indicate a non-linear relationship between these two factors. However, there has been no systematic empirical investigation on the relationship between nuclear proliferation and a propensity for conflict at the interstate–systemic level. To fill this gap, the current paper uses the machine learning method Random Forests, which can investigate complex non-linear relationships between dependent and independent variables, and which can identify important regressors from a group of all potential regressors in explaining the relationship between nuclear proliferation and the propensity for conflict. The results indicate that, on average, a larger number of nuclear states decrease the systemic propensity for interstate conflict, while the emergence of new nuclear states does not have an important effect. This paper also notes, however, that scholars should investigate other risks of proliferation to assess whether nuclear proliferation is better or worse for international peace and security in general.

Reducing the risk of cyber threats in utilities through log management

Energy Technology Data Exchange (ETDEWEB)

Patnaik, A. [ArcSight, Cupertino, CA (United States)

2010-01-15

Electrical blackouts caused by terrorists hacking into targeted control systems have already occurred in Brazil. A patchwork of security tools is needed to reduce potential threats. The continuous collection and analysis of data is also needed to detect cyber threats. The real time correlation of logs across all systems, applications and users is needed to ensure the reliability and security of the power grid. Solutions must also integrate well with identity management sources in order to prevent remote access account hijacking. Effective log management can be used to detect threats and reduce the risk of power outages. 1 fig.

Balance training reduces falls risk in older individuals with type 2 diabetes.

Science.gov (United States)

Morrison, Steven; Colberg, Sheri R; Mariano, Mira; Parson, Henri K; Vinik, Arthur I

2010-04-01

This study assessed the effects of balance/strength training on falls risk and posture in older individuals with type 2 diabetes. Sixteen individuals with type 2 diabetes and 21 age-matched control subjects (aged 50-75 years) participated. Postural stability and falls risk was assessed before and after a 6-week exercise program. Diabetic individuals had significantly higher falls risk score compared with control subjects. The diabetic group also exhibited evidence of mild-to-moderate neuropathy, slower reaction times, and increased postural sway. Following exercise, the diabetic group showed significant improvements in leg strength, faster reaction times, decreased sway, and, consequently, reduced falls risk. Older individuals with diabetes had impaired balance, slower reactions, and consequently a higher falls risk than age-matched control subjects. However, all these variables improved after resistance/balance training. Together these results demonstrate that structured exercise has wide-spread positive effects on physiological function for older individuals with type 2 diabetes.

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.

Podoplanin as Key Player of Tumor Progression and Lymph Vessel Proliferation in Ovarian Cancer.

Science.gov (United States)

Cobec, Ionut Marcel; Sas, Ioan; Pirtea, Laurențiu; Cimpean, Anca Maria; Moatar, Aurica Elisabeta; Ceaușu, Raluca Amalia; Raica, Marius

2016-10-01

Podoplanin plays a key role in tumor progression and metastasis. We evaluated lymphatics proliferation rate and podoplanin expression in tumor cells of ovarian carcinoma. Seventy-five paraffin-embedded specimens of ovarian cancer were immunohistochemically assessed in order to quantify peritumoral (LMVDP) and intratumoral (LMVDT) lymphatic microvessel density of proliferating lymphatics and for podoplanin variability in tumor cells. LMVDT correlated with proliferating tumor vessels located in the peritumoral area (p=0.024) and with the number of mature vessels located in the intratumoral area (p<0.0001), while LMVDP correlated with peritumoral mature vessels (p<0.000l). Proliferating tumor cells at the invasive front were highly positive for podoplanin. To the best of our knowledge, this study represents the first assessment of lymphatic endothelial cell proliferation correlated with podoplanin expression in tumor cells from ovarian cancer. Our data support podoplanin as a potential target that may help reduce ovarian cancer dissemination and lymphatic metastasis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

A computer-assisted motivational social network intervention to reduce alcohol, drug and HIV risk behaviors among Housing First residents.

Science.gov (United States)

Kennedy, David P; Hunter, Sarah B; Chan Osilla, Karen; Maksabedian, Ervant; Golinelli, Daniela; Tucker, Joan S

2016-03-15

Individuals transitioning from homelessness to housing face challenges to reducing alcohol, drug and HIV risk behaviors. To aid in this transition, this study developed and will test a computer-assisted intervention that delivers personalized social network feedback by an intervention facilitator trained in motivational interviewing (MI). The intervention goal is to enhance motivation to reduce high risk alcohol and other drug (AOD) use and reduce HIV risk behaviors. In this Stage 1b pilot trial, 60 individuals that are transitioning from homelessness to housing will be randomly assigned to the intervention or control condition. The intervention condition consists of four biweekly social network sessions conducted using MI. AOD use and HIV risk behaviors will be monitored prior to and immediately following the intervention and compared to control participants' behaviors to explore whether the intervention was associated with any systematic changes in AOD use or HIV risk behaviors. Social network health interventions are an innovative approach for reducing future AOD use and HIV risk problems, but little is known about their feasibility, acceptability, and efficacy. The current study develops and pilot-tests a computer-assisted intervention that incorporates social network visualizations and MI techniques to reduce high risk AOD use and HIV behaviors among the formerly homeless. CLINICALTRIALS. NCT02140359.

Novel T lymphocyte proliferation assessment using whole mouse cryo-imaging

Science.gov (United States)

Wuttisarnwattana, Patiwet; Raza, Syed A.; Eid, Saada; Cooke, Kenneth R.; Wilson, David L.

2014-03-01

New imaging technologies enable one to assess T-cell proliferation, an important feature of the immunological response. However, none of the traditional imaging modalities allow one to examine quantiatively T-cell function with microscopic resolution and single cell sensitivity over an entire mouse. To address this need, we established T-cells proliferation assays using 3D microscopic cryo-imaging. Assays include: (1) biodistribution of T-cells, (2) secondary lymphoid organ (SLO) volume measurement, (3) carboxyfluorescein succinimidyl ester (CFSE) dilution per cell as cells divide. To demonstrate the application, a graft-versus-host-disease (GVHD) model was used. 3D visualization show that T-cells specifically homed to the SLOs (spleen and lymph nodes) as well as GVHD target organs (such as GI-tract, liver, skin and thymus).The spleen was chosen as representative of the SLOs. For spleen size analysis, volumes of red and white pulp were measured. Spleen volumes of the allogeneic mice (with GVHD) were significantly larger than those of the syngeneic mice (without GVHD) at 72 to 120 hours post-transplant. For CFSE dilution approach, we employed color-coded volume rendering and probability density function (PDF) of single cell intensity to assess T-cell proliferation in the spleen. As compared to syngeneic T-cells, the allogeneic T-cells quickly aggregated in the spleen as indicated by increasing of CFSE signal over the first 48 hours. Then they rapidly proliferated as evidenced by reduced CFSE intensity (at 48-96 hours). Results suggest that assays can be used to study GVHD treatments using T-cell proliferation and biodistibution as assays. In summary, this is the first time that we are able to track and visualize T-cells in whole mouse with single cell sensitivity. We believe that our technique can be an alternative choice to traditional in vitro immunological proliferation assays by providing assessment of proliferation in an in vivo model.

Physical protection and its role in nuclear non-proliferation

International Nuclear Information System (INIS)

Nilsson, A.

1999-01-01

Non-proliferation of nuclear weapons has been one of the main concerns of the international community since the first nuclear weapons were developed. To prevent the proliferation of nuclear weapons has been on the agenda for individual States, groups of States and the international organizations. A number of treaties, conventions and agreements, the most important being the Non-Proliferation Treaty, have been negotiated to prevent the horizontal proliferation of nuclear weapons. States have concluded safeguards agreements with the IAEA to fulfill their obligations according to Article III.1 of the NPT. Other agreements relate to the prevention of vertical proliferation and also to the disarmament of nuclear weapons. It has also been recognized that sub-national, terrorist, or criminal activities may pose a proliferation risk. Illicit trafficking of nuclear material, particularly highly enriched uranium or plutonium, is a non-proliferation concern. States have recognized the need to prevent, as far as possible, the use of nuclear material in unlawful activities. The Convention of Physical Protection of Nuclear Materials, obligates the State Parties to protect nuclear material from theft during international transport, and to make unlawful possession, use, etc., of nuclear material a criminal offense, subject to punishment under national law. Although the physical protection convention recognizes the importance of the physical protection of nuclear material in domestic use, storage and transport, it does not obligate the State party to establish the necessary systems for this purpose. It is this limitation which led many States to believe that the international physical protection regime needs to be strengthened. Although not legally binding per se, the recommendations documented in INFCIRC/225/Rev. 4, The Physical Protection of Nuclear Material and Nuclear Facilities, has obtained wide recognition. There is recognition among States that protecting nuclear material

Proliferation equivalent of 'accelerated repopulation' in mouse oral mucosa

International Nuclear Information System (INIS)

Doerr, W.; Emmendoerfer, H.; Haide, E.; Kummermehr, J.

1994-01-01

The proliferation response and changes in cellularity of mouse tongue epithelium were studied after single doses of X-rays and during 3 weeks of daily irradiation. A single dose of 13 Gy resulted in minimum cellularity (70% of control values) on days 3-5 and complete restoration on day 7. Mitotic activity ceased for 1 day followed by normal-to-supranormal values until day 15. A wave of abnormal mitoses was observed with a peak at days 4-7. Daily irradiation with 3 or 4 Gy induced neither major structural nor visible cellular damage. Cellularity decreased to ∼ 60% during week 1 and subsequently remained at 60-70%. The proliferation activity was reduced to ∼ 8% by day 2. Mitotic activity during weeks 2 and 3 was subnormal-to-normal, with dose-dependent increase to normal counts during the first weekend and a distinct overshoot over the second weekend respectively. A proliferation model is presented to explain the present findings and previous functional measurements of changes in tissue tolerance. Its major features are accelerated symmetrical stem cell divisions and abortive divisions of sterilized cells. (author)

Oxidative DNA damage and mammary cell proliferation by alcohol-derived salsolinol.

Science.gov (United States)

Murata, Mariko; Midorikawa, Kaoru; Kawanishi, Shosuke

2013-10-21

Drinking alcohol is a risk factor for breast cancer. Salsolinol (SAL) is endogenously formed by a condensation reaction of dopamine with acetaldehyde, a major ethanol metabolite, and SAL is detected in blood and urine after alcohol intake. We investigated the possibility that SAL can participate in tumor initiation and promotion by causing DNA damage and cell proliferation, leading to alcohol-associated mammary carcinogenesis. SAL caused oxidative DNA damage including 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), in the presence of transition metal ions, such as Cu(II) and Fe(III)EDTA. Inhibitory effects of scavengers on SAL-induced DNA damage and the electron spin resonance study indicated the involvement of H₂O₂, which is generated via the SAL radical. Experiments on scavengers and site specificity of DNA damage suggested ·OH generation via a Fenton reaction and copper-peroxide complexes in the presence of Fe(III)EDTA and Cu(II), respectively. SAL significantly increased 8-oxodG formation in normal mammary epithelial MCF-10A cells. In addition, SAL induced cell proliferation in estrogen receptor (ER)-negative MCF-10A cells, and the proliferation was inhibited by an antioxidant N-acetylcysteine and an epidermal growth factor receptor (EGFR) inhibitor AG1478, suggesting that reactive oxygen species may participate in the proliferation of MCF-10A cells via EGFR activation. Furthermore, SAL induced proliferation in estrogen-sensitive breast cancer MCF-7 cells, and a surface plasmon resonance sensor revealed that SAL significantly increased the binding activity of ERα to the estrogen response element but not ERβ. In conclusion, SAL-induced DNA damage and cell proliferation may play a role in tumor initiation and promotion of multistage mammary carcinogenesis in relation to drinking alcohol.

Distance factor on reducing scattered radiation risk during interventional fluoroscopy

International Nuclear Information System (INIS)

Husaini Salleh; Mohd Khalid Matori; Muhammad Jamal Mat Isa; Zainal Jamaluddin; Mohd Firdaus Abdul Rahman; Mohd Khairusalih Mohd Zin

2012-01-01

Interventional Radiology (IR) is subspecialty of diagnostic radiology where minimally invasive procedures are performed using an x-ray as a guidance. This procedure can deliver high radiation doses to patient and medical staff compared with other radiological method due to long screening time. The use of proper shielding, shorten the exposure time and keep the distance are the practices to reduce scattered radiation risks to staff involve in this procedure. This project is to study the distance factor on reducing the scattered radiation effect to the medical staff. It also may provide the useful information which can be use to establish the scattered radiation profile during the IR for the sake of radiation protection and safety to the medical staff involved. (author)

Cost-effectiveness of newborn circumcision in reducing lifetime HIV risk among U.S. males.

Directory of Open Access Journals (Sweden)

Stephanie L Sansom

Full Text Available BACKGROUND: HIV incidence was substantially lower among circumcised versus uncircumcised heterosexual African men in three clinical trials. Based on those findings, we modeled the potential effect of newborn male circumcision on a U.S. male's lifetime risk of HIV, including associated costs and quality-adjusted life-years saved. METHODOLOGY/PRINCIPAL FINDINGS: Given published estimates of U.S. males' lifetime HIV risk, we calculated the fraction of lifetime risk attributable to heterosexual behavior from 2005-2006 HIV surveillance data. We assumed 60% efficacy of circumcision in reducing heterosexually-acquired HIV over a lifetime, and varied efficacy in sensitivity analyses. We calculated differences in lifetime HIV risk, expected HIV treatment costs and quality-adjusted life years (QALYs among circumcised versus uncircumcised males. The main outcome measure was cost per HIV-related QALY saved. Circumcision reduced the lifetime HIV risk among all males by 15.7% in the base case analysis, ranging from 7.9% for white males to 20.9% for black males. Newborn circumcision was a cost-saving HIV prevention intervention for all, black and Hispanic males. The net cost of newborn circumcision per QALY saved was $87,792 for white males. Results were most sensitive to the discount rate, and circumcision efficacy and cost. CONCLUSIONS/SIGNIFICANCE: Newborn circumcision resulted in lower expected HIV-related treatment costs and a slight increase in QALYs. It reduced the 1.87% lifetime risk of HIV among all males by about 16%. The effect varied substantially by race and ethnicity. Racial and ethnic groups who could benefit the most from circumcision may have least access to it due to insurance coverage and state Medicaid policies, and these financial barriers should be addressed. More data on the long-term protective effect of circumcision on heterosexual males as well as on its efficacy in preventing HIV among MSM would be useful.

Polybrene inhibits human mesenchymal stem cell proliferation during lentiviral transduction.

Directory of Open Access Journals (Sweden)

Paul Lin

Full Text Available Human mesenchymal stem cells (hMSCs can be engineered to express specific genes, either for their use in cell-based therapies or to track them in vivo over long periods of time. To obtain long-term expression of these genes, a lentivirus- or retrovirus-mediated cell transduction is often used. However, given that the efficiency with these viruses is typically low in primary cells, additives such as polybrene are always used for efficient viral transduction. Unfortunately, as presented here, exposure to polybrene alone at commonly used concentratons (1-8 µg/mL negatively impacts hMSC proliferation in a dose-dependent manner as measured by CyQUANT, EdU incorporation, and cell cycle analysis. This inhibition of proliferation was observable in culture even 3 weeks after exposure. Culturing the cells in the presence of FGF-2, a potent mitogen, did not abrogate this negative effect of polybrene. In fact, the normally sharp increase in hMSC proliferation that occurs during the first days of exposure to FGF-2 was absent at 4 µg/mL or higher concentrations of polybrene. Similarly, the effect of stimulating cell proliferation under simulated hypoxic conditions was also decreased when cells were exposed to polybrene, though overall proliferation rates were higher. The negative influence of polybrene was, however, reduced when the cells were exposed to polybrene for a shorter period of time (6 hr vs 24 hr. Thus, careful evaluation should be done when using polybrene to aid in lentiviral transduction of human MSCs or other primary cells, especially when cell number is critical.