Proliferation resistance and physical protection working group: methodology and applications

International Nuclear Information System (INIS)

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

2012-01-01

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

PROLIFERATION RESISTANCE AND PHYSICAL PROTECTION WORKING GROUP: METHODOLOGY AND APPLICATIONS

Energy Technology Data Exchange (ETDEWEB)

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

2012-11-14

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

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

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

International Nuclear Information System (INIS)

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

2007-11-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2007-11-15

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

Teleconference highlights-NE-NA proliferation resistance review

International Nuclear Information System (INIS)

Miller, Michael C.

2009-01-01

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

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

International Nuclear Information System (INIS)

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

2015-01-01

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

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

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

International Nuclear Information System (INIS)

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

2009-07-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2009-10-26

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

Hop/STI1 modulates retinal proliferation and cell death independent of PrPC

International Nuclear Information System (INIS)

Arruda-Carvalho, Maithe; Njaine, Brian; Silveira, Mariana S.; Linden, Rafael; Chiarini, Luciana B.

2007-01-01

Hop/STI1 is a co-chaperone adaptor protein for Hsp70/Hsp90 complexes. Hop/STI1 is found extracellularly and modulates cell death and differentiation through interaction with the prion protein (PrP C ). Here, we investigated the expression of hop/STI1 and its role upon cell proliferation and cell death in the developing retina. Hop/STI1 is more expressed in developing rat retina than in the mature tissue. Hop/STI1 blocks retinal cell death in the neuroblastic layer (NBL) in a PrP C dependent manner, but failed to protect ganglion cells against axotomy-induced cell death. An antibody raised against hop/STI1 (α-STI1) blocked both ganglion cell and NBL cell death independent of PrP C . cAMP/PKA, ERK, PI3K and PKC signaling pathways were not involved in these effects. Hop/STI1 treatment reduced proliferation, while α-STI1 increased proliferation in the developing retina, both independent of PrP C . We conclude that hop/STI1 can modulate both proliferation and cell death in the developing retina independent of PrP C

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

International Nuclear Information System (INIS)

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

2004-01-01

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

Development of Proliferation Resistance Assessment Methodology Based on International Standards

International Nuclear Information System (INIS)

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

2009-03-01

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

Framework of Comprehensive Proliferation Resistance Evaluation Methodology

International Nuclear Information System (INIS)

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

2007-01-01

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

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

International Nuclear Information System (INIS)

Chang, Hong Lae; Ko, Won Il

2008-01-01

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

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

International Nuclear Information System (INIS)

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

2010-01-01

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

Evaluation of proliferation resistance using the INPRO methodology

International Nuclear Information System (INIS)

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

2007-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-10-15

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

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.

Comparative analysis of proliferation resistance assessment methodologies

International Nuclear Information System (INIS)

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

2005-01-01

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

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.

Model for evaluating nuclear strategies with proliferation resistance

International Nuclear Information System (INIS)

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

1979-03-01

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

Application of the GIF PR and PP methodology to a commercial fast reactor system for a preliminary analysis of PR scenarios

International Nuclear Information System (INIS)

Rossi, Fabiana

2015-01-01

The Generation IV International Forum (GIF) Proliferation Resistance and Physical Protection (PR and PP) Working Group has developed a methodology for the PR and PP evaluation of the next generation Nuclear Energy Systems (NESs). Following the methodology proposed by the working group, applicable to assessing the proliferation resistance of an NES and its individual elements, the main objective of this work is to apply the methodology to show an example of how its results could be used by designers to improve the PR of the system. In this study, the reactor site of a hypothetical and commercial sodium‑cooled fast neutron nuclear reactor system (SFR) was used as the target NES for the application of the methodology. The design of this SFR is based on the layout of the Japanese Sodium Fast Reactor (JSFR) with a safeguards design based on the safeguards approach of the Japanese prototype fast breeder reactor Monju. The methodology is applied to all the PR scenarios described in the methodology: diversion, misuse and breakout. The methodology was first applied to the SFR to check if this system meets the target of PR as described in the GIF goal; secondly, a comparison between the SFR and a light water reactor (LWR) with an open fuel cycle was performed to evaluate if and how it would be possible to improve the PR and PP of the SFR. The LWR layout is based on the European Pressurized Water Reactor. The comparison was implemented according to the following example development target: achieving proliferation resistance to material diversion similar or superior to domestic and international advanced LWR. Three main actions were performed: implement the evaluation methodology based on its assumptions; characterize the PR and PP for the nuclear energy system applying the methodology to the SFR; and identify recommendations for system designers through comparing the SFR with the LWR.

Methodologies for evaluating the proliferation resistance of nuclear fuel cycles

International Nuclear Information System (INIS)

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

2001-01-01

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

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.

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

Review of GIF PR and PP Evaluation Case Study for Application to Pyroprocessing

Energy Technology Data Exchange (ETDEWEB)

Kim, H. M.; Ahn, S. K.; Kwon, E. H.; Kim, H. D. [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2014-05-15

This paper has summarized and reviewed the ESFR case study, as it relates to the application of the evaluation methods to pyroprocessing facilities as well as the sodium fast reactor fuel cycle in the future as a self-assessment study. The GIF PR and PP evaluation methodology and the case study both addressed physical protection, but this paper focuses only on proliferation resistance. It does not consider physical protection. The Generation IV International Forum (GIF) emphasizes proliferation resistance and physical protection (PR and PP) as one of the main aspects to be considered regarding future nuclear energy systems (NESs). As such, the PR and PP Working Group developed an evaluation methodology and applied it to the Example Sodium Fast Reactor (ESFR) as a case study. This paper has summarized and reviewed the ESFR case study, as it relates to the application of the evaluation methods to pyroprocessing facilities as well as the sodium fast reactor fuel cycle in the future as a self-assessment study. The GIF PR and PP evaluation methodology and the case study both addressed physical protection, but this paper focuses only on proliferation resistance. It does not consider physical protection.

Review of GIF PR and PP Evaluation Case Study for Application to Pyroprocessing

International Nuclear Information System (INIS)

Kim, H. M.; Ahn, S. K.; Kwon, E. H.; Kim, H. D.

2014-01-01

This paper has summarized and reviewed the ESFR case study, as it relates to the application of the evaluation methods to pyroprocessing facilities as well as the sodium fast reactor fuel cycle in the future as a self-assessment study. The GIF PR and PP evaluation methodology and the case study both addressed physical protection, but this paper focuses only on proliferation resistance. It does not consider physical protection. The Generation IV International Forum (GIF) emphasizes proliferation resistance and physical protection (PR and PP) as one of the main aspects to be considered regarding future nuclear energy systems (NESs). As such, the PR and PP Working Group developed an evaluation methodology and applied it to the Example Sodium Fast Reactor (ESFR) as a case study. This paper has summarized and reviewed the ESFR case study, as it relates to the application of the evaluation methods to pyroprocessing facilities as well as the sodium fast reactor fuel cycle in the future as a self-assessment study. The GIF PR and PP evaluation methodology and the case study both addressed physical protection, but this paper focuses only on proliferation resistance. It does not consider physical protection

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

Energy Technology Data Exchange (ETDEWEB)

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

2000-07-01

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

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

International Nuclear Information System (INIS)

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

2000-07-01

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

Proliferation resistance assessment of thermal recycle systems

International Nuclear Information System (INIS)

1979-02-01

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

INCREASED PROLIFERATION RESISTANCE FOR 21ST CENTURY NUCLEAR POWER

International Nuclear Information System (INIS)

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

2007-01-01

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

Limiting Future Proliferation and Security Risks

International Nuclear Information System (INIS)

Bari, R.

2011-01-01

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

Revised INPRO Methodology in the Area of Proliferation Resistance

International Nuclear Information System (INIS)

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

2008-01-01

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

Neutronic simulation calculations to assess the proliferation resistance of nuclear technologies

International Nuclear Information System (INIS)

Englert, Matthias

2009-01-01

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

Technical features to enhance proliferation resistance of nuclear energy systems

International Nuclear Information System (INIS)

2010-01-01

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

PrP Knockout Cells Expressing Transmembrane PrP Resist Prion Infection.

Science.gov (United States)

Marshall, Karen E; Hughson, Andrew; Vascellari, Sarah; Priola, Suzette A; Sakudo, Akikazu; Onodera, Takashi; Baron, Gerald S

2017-01-15

Glycosylphosphatidylinositol (GPI) anchoring of the prion protein (PrP C ) influences PrP C misfolding into the disease-associated isoform, PrP res , as well as prion propagation and infectivity. GPI proteins are found in cholesterol- and sphingolipid-rich membrane regions called rafts. Exchanging the GPI anchor for a nonraft transmembrane sequence redirects PrP C away from rafts. Previous studies showed that nonraft transmembrane PrP C variants resist conversion to PrP res when transfected into scrapie-infected N2a neuroblastoma cells, likely due to segregation of transmembrane PrP C and GPI-anchored PrP res in distinct membrane environments. Thus, it remained unclear whether transmembrane PrP C might convert to PrP res if seeded by an exogenous source of PrP res not associated with host cell rafts and without the potential influence of endogenous expression of GPI-anchored PrP C To further explore these questions, constructs containing either a C-terminal wild-type GPI anchor signal sequence or a nonraft transmembrane sequence containing a flexible linker were expressed in a cell line derived from PrP knockout hippocampal neurons, NpL2. NpL2 cells have physiological similarities to primary neurons, representing a novel and advantageous model for studying transmissible spongiform encephalopathy (TSE) infection. Cells were infected with inocula from multiple prion strains and in different biochemical states (i.e., membrane bound as in brain microsomes from wild-type mice or purified GPI-anchorless amyloid fibrils). Only GPI-anchored PrP C supported persistent PrP res propagation. Our data provide strong evidence that in cell culture GPI anchor-directed membrane association of PrP C is required for persistent PrP res propagation, implicating raft microdomains as a location for conversion. Mechanisms of prion propagation, and what makes them transmissible, are poorly understood. Glycosylphosphatidylinositol (GPI) membrane anchoring of the prion protein (PrP C

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

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

Establishment of Assessment Methodology Improvement of IAEA INPRO Proliferation Resistance

Energy Technology Data Exchange (ETDEWEB)

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

2008-03-15

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

Establishment of Assessment Methodology Improvement of IAEA INPRO Proliferation Resistance

International Nuclear Information System (INIS)

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

2008-03-01

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

Cell-specific regulation of proliferation by Ano1/TMEM16A in breast cancer with different ER, PR, and HER2 status.

Science.gov (United States)

Wu, Huizhe; Wang, Hui; Guan, Shu; Zhang, Jing; Chen, Qiuchen; Wang, Xiaodong; Ma, Ke; Zhao, Pengfei; Zhao, Haishan; Yao, Weifan; Jin, Feng; Xiao, Qinghuan; Wei, Minjie

2017-10-17

The calcium-activated chloride channel Ano1 (TMEM16A) is overexpressed in many tumors. However, conflicting data exist regarding the role of Ano1 in cell proliferation. Here, we performed immunohistochemistry to investigate the expression of Ano1 and Ki67 in 403 patients with breast cancer, and analyzed the association between the expression of Ano1 and Ki67 in breast cancer subtypes categorized according to estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Ano1 expression was negatively correlated with Ki67 expression. Ano1 overexpression more frequently occurred in ER-positive or HER2-negative patients with the low expression of Ki67. Ano1 overexpression was associated with longer overall survival (OS) in breast cancer with the low expression of Ki67, especially in ER-positive, PR-positive, and HER2-negative breast cancer. Multivariate Cox regression analysis showed that Ano1 overexpression was a prognostic factor for longer overall survival in ER-positive, PR-positive, or HER2-negative patients with the low expression of Ki67. Furthermore, Ano1 promoted cell proliferation in ER-positive, PR-positive, and HER2-negative MCF7 cells, but inhibited cell proliferation in ER-negative, PR-negative, and HER2-negative MDA-MB-435S cells. Our findings suggest that Ano1 may differentially regulate cell proliferation in a subtype of breast cancer defined by ER, PR, and HER2. Combined expression of Ano1 and Ki67 may be used for predicting clinical outcomes of breast cancer patients with different subtypes of ER, PR, and HER2.

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

International Nuclear Information System (INIS)

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

2001-01-01

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

Proliferation resistance assessment of high temperature gas reactors

Energy Technology Data Exchange (ETDEWEB)

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

2014-10-15

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

Proliferation resistance assessment of high temperature gas reactors

International Nuclear Information System (INIS)

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

2014-10-01

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

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

PrPST, a Soluble, Protease Resistant and Truncated PrP Form Features in the Pathogenesis of a Genetic Prion Disease

Science.gov (United States)

Frid, Kati; Binyamin, Orli; Gabizon, Ruth

2013-01-01

While the conversion of PrPC into PrPSc in the transmissible form of prion disease requires a preexisting PrPSc seed, in genetic prion disease accumulation of disease related PrP could be associated with biochemical and metabolic modifications resulting from the designated PrP mutation. To investigate this possibility, we looked into the time related changes of PrP proteins in the brains of TgMHu2ME199K/wt mice, a line modeling for heterozygous genetic prion disease linked to the E200K PrP mutation. We found that while oligomeric entities of mutant E199KPrP exist at all ages, aggregates of wt PrP in the same brains presented only in advanced disease, indicating a late onset conversion process. We also show that most PK resistant PrP in TgMHu2ME199K mice is soluble and truncated (PrPST), a pathogenic form never before associated with prion disease. We next looked into brain samples from E200K patients and found that both PK resistant PrPs, PrPST as in TgMHu2ME199K mice, and “classical” PrPSc as in infectious prion diseases, coincide in the patient's post mortem brains. We hypothesize that aberrant metabolism of mutant PrPs may result in the formation of previously unknown forms of the prion protein and that these may be central for the fatal outcome of the genetic prion condition. PMID:23922744

Lessons Learned from PR and PP Case Study

Energy Technology Data Exchange (ETDEWEB)

Bley, D.C. [Buttonwood Consulting, Inc., 11738 English Mill Court, Oakton, VA 22124 (United States)

2009-06-15

The Generation-IV International Forum (GIF) working group on proliferation resistance and physical protection (PR and PP) has developed a methodology for evaluating the PR and PP effectiveness of Gen-IV nuclear energy systems. A number of applications studies culminating in the 2008-2009 Case Study have been helpful in developing the methodology, and in testing its ease of use and ability to provide useful information to designers and policy/decision makers. This paper examines the lessons learned from these studies. The applications studies evaluated a set of PR and PP measures for an 'Example Sodium Fast Reactor' (ESFR), a hypothetical design incorporating many features of anticipated Gen-IV energy systems. The objectives of the 2008- 2009 Case Study were to exercise the GIF PR and PP Methodology for a complete Gen-IV reactor/fuel cycle system; to demonstrate, via the comparison of different design options, that the methodology can generate meaningful results for designers and decision makers; to provide examples of PR and PP evaluations for future users; to facilitate transition to other studies; and to facilitate other ongoing collaborative efforts (e.g., INPRO) and associated efforts (e.g., GNEP). We will explain how the Case Study met these goals. PR Lessons Learned. We found that completeness in 'diversion' pathways can be ensured and that a set of diversion pathway segments can be developed along with proliferation resistance measures for each pathway. The examination of 'misuse' found that misuse, for achieving weapons-usable fissile material, is a complex process, i.e., it is not a single action on a single piece of equipment, but rather an integrated exploitation of various assets and system elements. We found that 'breakout' is a modifying strategy within the diversion and misuse threats and takes various forms that depend upon intent and aggressiveness, and ultimately the proliferation time assumed by a

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

International Nuclear Information System (INIS)

Kim, Min Su

2007-02-01

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

Proliferation resistance criteria for fissile material disposition

International Nuclear Information System (INIS)

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

1995-04-01

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

MEHODOLOGY FOR PROLIFERATION RESISTANCE FOR ADVANCE NUCLEAR ENERGY SYSTEMS

International Nuclear Information System (INIS)

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

2006-01-01

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

Enhancing VVER annular proliferation resistance fuel with minor actinides

International Nuclear Information System (INIS)

Chang, G. S.

2007-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2016-10-15

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

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

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

International Nuclear Information System (INIS)

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

2004-01-01

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

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

PrP(ST), a soluble, protease resistant and truncated PrP form features in the pathogenesis of a genetic prion disease.

Science.gov (United States)

Friedman-Levi, Yael; Mizrahi, Michal; Frid, Kati; Binyamin, Orli; Gabizon, Ruth

2013-01-01

While the conversion of PrP(C) into PrP(Sc) in the transmissible form of prion disease requires a preexisting PrP(Sc) seed, in genetic prion disease accumulation of disease related PrP could be associated with biochemical and metabolic modifications resulting from the designated PrP mutation. To investigate this possibility, we looked into the time related changes of PrP proteins in the brains of TgMHu2ME199K/wt mice, a line modeling for heterozygous genetic prion disease linked to the E200K PrP mutation. We found that while oligomeric entities of mutant E199KPrP exist at all ages, aggregates of wt PrP in the same brains presented only in advanced disease, indicating a late onset conversion process. We also show that most PK resistant PrP in TgMHu2ME199K mice is soluble and truncated (PrP(ST)), a pathogenic form never before associated with prion disease. We next looked into brain samples from E200K patients and found that both PK resistant PrPs, PrP(ST) as in TgMHu2ME199K mice, and "classical" PrP(Sc) as in infectious prion diseases, coincide in the patient's post mortem brains. We hypothesize that aberrant metabolism of mutant PrPs may result in the formation of previously unknown forms of the prion protein and that these may be central for the fatal outcome of the genetic prion condition.

PrP(ST, a soluble, protease resistant and truncated PrP form features in the pathogenesis of a genetic prion disease.

Directory of Open Access Journals (Sweden)

Yael Friedman-Levi

Full Text Available While the conversion of PrP(C into PrP(Sc in the transmissible form of prion disease requires a preexisting PrP(Sc seed, in genetic prion disease accumulation of disease related PrP could be associated with biochemical and metabolic modifications resulting from the designated PrP mutation. To investigate this possibility, we looked into the time related changes of PrP proteins in the brains of TgMHu2ME199K/wt mice, a line modeling for heterozygous genetic prion disease linked to the E200K PrP mutation. We found that while oligomeric entities of mutant E199KPrP exist at all ages, aggregates of wt PrP in the same brains presented only in advanced disease, indicating a late onset conversion process. We also show that most PK resistant PrP in TgMHu2ME199K mice is soluble and truncated (PrP(ST, a pathogenic form never before associated with prion disease. We next looked into brain samples from E200K patients and found that both PK resistant PrPs, PrP(ST as in TgMHu2ME199K mice, and "classical" PrP(Sc as in infectious prion diseases, coincide in the patient's post mortem brains. We hypothesize that aberrant metabolism of mutant PrPs may result in the formation of previously unknown forms of the prion protein and that these may be central for the fatal outcome of the genetic prion condition.

Stanniocalcin 2 promotes cell proliferation and cisplatin resistance in cervical cancer

International Nuclear Information System (INIS)

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

2015-01-01

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

Nuclear PIM1 confers resistance to rapamycin-impaired endothelial proliferation

Energy Technology Data Exchange (ETDEWEB)

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

2012-12-07

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

Low fraction of the 222K PrP variant in the protease-resistant moiety of PrPres in heterozygous scrapie positive goats.

Science.gov (United States)

Mazza, Maria; Guglielmetti, Chiara; Ingravalle, Francesco; Brusadore, Sonia; Langeveld, Jan P M; Ekateriniadou, Loukia V; Andréoletti, Olivier; Casalone, Cristina; Acutis, Pier Luigi

2017-07-01

The presence of lysine (K) at codon 222 has been associated with resistance to classical scrapie in goats, but few scrapie cases have been identified in 222Q/K animals. To investigate the contribution of the 222K variant to PrPres formation in natural and experimental Q/K scrapie cases, we applied an immunoblotting method based on the use of two different monoclonal antibodies, F99/97.6.1 and SAF84, chosen for their different affinities to 222K and 222Q PrP variants. Our finding that PrPres seems to be formed nearly totally by the 222Q variant provides evidence that the 222K PrP variant confers resistance to conversion to PrPres formation and reinforces the view that this mutation has a protective role against classical scrapie in goats.

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

International Nuclear Information System (INIS)

2012-05-01

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

Proliferation resistance of the lithium reduction process

International Nuclear Information System (INIS)

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

2002-01-01

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

Proliferation resistance criteria for fissile material disposition issues

International Nuclear Information System (INIS)

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

1995-01-01

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

Proliferation resistance assessment of nuclear systems

International Nuclear Information System (INIS)

1978-09-01

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

Complexities in gauging time-dependency of proliferation resistance

International Nuclear Information System (INIS)

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

2004-01-01

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

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

International Nuclear Information System (INIS)

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

2003-10-01

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

Low-decontamination approach to a proliferation-resistant fuel cycle

International Nuclear Information System (INIS)

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

1978-01-01

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

Assessment of proliferation resistance of thermal recycle systems

International Nuclear Information System (INIS)

1979-02-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Englert, Matthias

2009-07-13

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

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

International Nuclear Information System (INIS)

Coles, Garill A.; Zentner, Michael D.

2007-01-01

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

Overexpression of NtPR-Q Up-Regulates Multiple Defense-Related Genes in Nicotiana tabacum and Enhances Plant Resistance to Ralstonia solanacearum

Directory of Open Access Journals (Sweden)

Yuanman Tang

2017-11-01

Full Text Available Various classes of plant pathogenesis-related proteins have been identified in the past several decades. PR-Q, a member of the PR3 family encoding chitinases, has played an important role in regulating plant resistance and preventing pathogen infection. In this paper, we functionally characterized NtPR-Q in tobacco plants and found that the overexpression of NtPR-Q in tobacco Yunyan87 resulted in higher resistance to Ralstonia solanacearum inoculation. Surprisingly, overexpression of NtPR-Q led to the activation of many defense-related genes, such as salicylic acid (SA-responsive genes NtPR1a/c, NtPR2 and NtCHN50, JA-responsive gene NtPR1b and ET production-associated genes NtACC Oxidase and NtEFE26. Consistent with the role of NtPR-Q in multiple stress responses, NtPR-Q transcripts were induced by the exogenous hormones SA, ethylene and methyl jasmonate, which could enhance the resistance of tobacco to R. solanacearum. Collectively, our results suggested that NtPR-Q overexpression led to the up-regulation of defense-related genes and enhanced plant resistance to R. solanacearum infection.

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

International Nuclear Information System (INIS)

Saito, Masaki

2005-01-01

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

How Much Do We Know about Drug Resistance Due to PrEP Use? Analysis of Experts' Opinion and Its Influence on the Projected Public Health Impact.

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Dobromir T Dimitrov

Full Text Available Randomized controlled trials reported that pre-exposure prophylaxis (PrEP with tenofovir and emtricitabine rarely selects for drug resistance. However, drug resistance due to PrEP is not completely understood. In daily practice, PrEP will not be used under the well-controlled conditions available in the trials, suggesting that widespread use of PrEP can result in increased drug resistance.We surveyed expert virologists with questions about biological assumptions regarding drug resistance due to PrEP use. The influence of these assumptions on the prevalence of drug resistance and the fraction of HIV transmitted resistance was studied with a mathematical model. For comparability, 50% PrEP-coverage of and 90% per-act efficacy of PrEP in preventing HIV acquisition are assumed in all simulations.Virologists disagreed on the following: the time until resistance emergence (range: 20-180 days in infected PrEP users with breakthrough HIV infections; the efficacy of PrEP against drug-resistant HIV (25%-90%; and the likelihood of resistance acquisition upon transmission (10%-75%. These differences translate into projections of 0.6%- 1% and 3.5%-6% infected individuals with detectable resistance 10 years after introducing PrEP, assuming 100% and 50% adherence, respectively. The rate of resistance emergence following breakthrough HIV infection and the rate of resistance reversion after PrEP use is discontinued, were the factors identified as most influential on the expected resistance associated with PrEP. Importantly, 17-23% infected individuals could virologically fail treatment as a result of past PrEP use or transmitted resistance to PrEP with moderate adherence.There is no broad consensus on quantification of key biological processes that underpin the emergence of PrEP-associated drug resistance. Despite this, the contribution of PrEP use to the prevalence of the detectable drug resistance is expected to be small. However, individuals who become

Proliferation resistance fuel cycle technology

Energy Technology Data Exchange (ETDEWEB)

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

1999-02-01

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

The Japanese PR and PP program

International Nuclear Information System (INIS)

Senzaki, Masao; Inoue, Naoko; Kuno, Yusuke

2008-01-01

Japan has established the commercial nuclear fuel cycle with LWR as a non-weapon state, and now has been developing RF fuel cycle as the next generation technology. Japanese studies on proliferation resistance have started in 1990's by JNC, predecessor concern of JAEA. The early study was focused on the intrinsic features of Pu and safeguards technologies. Based on TOPS report, JNC has developed a quantitative assessment methodology and modified it by JNC designers. JNC and JAEA intends to play the role as a hub that contributes international collaborative study such as GEN IV PR and PP Experts Group and INPRO based on Japanese experiences of safeguards and nonproliferation efforts, and feedback to domestic experts. These efforts include not only the contribution into those programs, but also introduce these activities to Japanese domestic experts, holding international workshops, symposiums as a 'Hub' of domestic and international experts. This paper will introduce the Japanese Proliferation Resistance studies including, the early studies, international workshops/symposiums, the study in FaCT, international collaboration studies, and the future direction identified for the nuclear fuel cycle systems. (author)

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

International Nuclear Information System (INIS)

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

2015-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2009-06-15

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

Low fraction of the 222K PrP variant in the protease-resistant moiety of PrPres in heterozygous scrapie positive goats

OpenAIRE

Mazza, Maria; Guglielmetti, Chiara; Ingravalle, Francesco; Brusadore, Sonia; Langeveld, Jan P. M.; Ekateriniadou, Loukia V.; Andréoletti, Olivier; Casalone, Cristina; Acutis, Pier Luigi

2017-01-01

The presence of lysine (K) at codon 222 has been associated with resistance to classical scrapie in goats, but few scrapie cases have been identified in 222Q/K animals. To investigate the contribution of the 222K variant to PrPres formation in natural and experimental Q/K scrapie cases, we applied an immunoblotting method based on the use of two different monoclonal antibodies, F99/97.6.1 and SAF84, chosen for their different affinities to 222K and 222Q PrP variants. Our finding that PrPres s...

Proliferation resistance assessment of nuclear systems

International Nuclear Information System (INIS)

1978-09-01

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

The Novel Gene VpPR4-1 from Vitis pseudoreticulata Increases Powdery Mildew Resistance in Transgenic Vitis vinifera L.

Science.gov (United States)

Dai, Lingmin; Wang, Dan; Xie, Xiaoqing; Zhang, Chaohong; Wang, Xiping; Xu, Yan; Wang, Yuejin; Zhang, Jianxia

2016-01-01

Pathogenesis-related proteins (PRs) can lead to increased resistance of the whole plant to pathogen attack. Here, we isolate and characterize a PR-4 protein (VpPR4-1) from a wild Chinese grape Vitis pseudoreticulata which shows greatly elevated transcription following powdery mildew infection. Its expression profiles under a number of abiotic stresses were also investigated. Powdery mildew, salicylic acid, and jasmonic acid methyl ester significantly increased the VpPR4-1 induction while NaCl and heat treatments just slightly induced VpPR4-1 expression. Abscisic acid and cold treatment slightly affected the expression level of VpPR4-1. The VpPR4-1 gene was overexpressed in 30 regenerated V. vinifera cv. Red Globe via Agrobacterium tumefaciens-mediated transformation and verified by the Western blot. The 26 transgenic grapevines exhibited higher expression levels of PR-4 protein content than wild-type vines and six of them were inoculated with powdery mildew which showed that the growth of powdery mildew was repressed. The powdery mildew-resistance of Red Globe transformed with VpPR4-1 was enhanced inoculated with powdery mildew. Moreover, other powdery mildew resistant genes were associated with feedback regulation since VpPR4-1 is in abundance. This study demonstrates that PR-4 protein in grapes plays a vital role in defense against powdery mildew invasion.

A new method for the characterization of strain-specific conformational stability of protease-sensitive and protease-resistant PrPSc.

Directory of Open Access Journals (Sweden)

Laura Pirisinu

Full Text Available Although proteinacious in nature, prions exist as strains with specific self-perpetuating biological properties. Prion strains are thought to be associated with different conformers of PrP(Sc, a disease-associated isoform of the host-encoded cellular protein (PrP(C. Molecular strain typing approaches have been developed which rely on the characterization of protease-resistant PrP(Sc. However, PrP(Sc is composed not only of protease-resistant but also of protease-sensitive isoforms. The aim of this work was to develop a protocol for the molecular characterization of both, protease-resistant and protease-sensitive PrP(Sc aggregates. We first set up experimental conditions which allowed the most advantageous separation of PrP(C and PrP(Sc by means of differential centrifugation. The conformational solubility and stability assay (CSSA was then developed by measuring PrP(Sc solubility as a function of increased exposure to GdnHCl. Brain homogenates from voles infected with human and sheep prion isolates were analysed by CSSA and showed strain-specific conformational stabilities, with mean [GdnHCl](1/2 values ranging from 1.6 M for MM2 sCJD to 2.1 for scrapie and to 2.8 M for MM1/MV1 sCJD and E200K gCJD. Interestingly, the rank order of [GdnHCl](1/2 values observed in the human and sheep isolates used as inocula closely matched those found following transmission in voles, being MM1 sCJD the most resistant (3.3 M, followed by sheep scrapie (2.2 M and by MM2 sCJD (1.6 M. In order to test the ability of CSSA to characterise protease-sensitive PrP(Sc, we analysed sheep isolates of Nor98 and compared them to classical scrapie isolates. In Nor98, insoluble PrP(Sc aggregates were mainly protease-sensitive and showed a conformational stability much lower than in classical scrapie. Our results show that CSSA is able to reveal strain-specified PrP(Sc conformational stabilities of protease-resistant and protease-sensitive PrP(Sc and that it is a valuable tool

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

Directory of Open Access Journals (Sweden)

Francesco Negro

2009-01-01

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

Report and analysis on 'PR and PP evaluation. Example sodium fast reactor full system case study'

International Nuclear Information System (INIS)

Sagara, Hiroshi; Inoue, Naoko; Kawakubo, Yoko; Watahiki, Masaru

2011-01-01

The Generation IV (GEN IV) Nuclear Energy Systems International Forum (GIF) Proliferation Resistance and Physical Protection Working Group (PRPP WG) was established in December 2002 in order to develop the PR and valuation methodology for GEN IV nuclear energy systems. In the final report of 'PR and PP Evaluation: Example Sodium Fast Reactor (ESFR) Full System Case Study,' issued in October 2009, the demonstration study of PR and PP evaluation with the qualitative approach are summarized using ESFR with four scenario threats. The present paper reviews and analyzes some results of the ESFR case study, and identifies the challenges and direction for the PR and PP evaluation methodology with quantitative approach. (author)

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

International Nuclear Information System (INIS)

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

2008-01-01

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

Study on GIF PR/PP evaluation methodology

Energy Technology Data Exchange (ETDEWEB)

Lee, B. H.; Kwon, E. H.; Kim, H. D. [KAERI, Daejeon (Korea, Republic of)

2012-10-15

Proliferation resistance (PR) and physical protection (PP) is one of the four technology goals of generation IV nuclear energy systems (NESs). The PR component of the goal focuses on providing strong assurance that generation IV NESs are the least desirable sources for the diversion or undeclared production of nuclear materials, whereas the PP portion of the goal ensures that generation IV NESs are robust against theft and sabotage. In 2002, the road map of the Generation IV International Forum (GIF) envisioned that the R and D program for PR and PP would have three areas: 1) safeguards and physical protection technology R and D for each GIF system; 2) formulation of PR and PP criteria and metrics; and 3) evaluation of the criteria and metrics. To cover these R and D items, the PR and PP Working Group (PRPPWG) was formed in late 2002 and has since developed a methodology for PR and PP evaluation. In a succession of revisions beginning in 2004, consensus was achieved amongst all participating GIF countries and related organizations (i.e., IAEA and EU), and Revision 6 of the methodology report was approved by GIF for open distribution in 2011. The paper describes in detail the methodology developed by the PRPPWG and discusses its applicability to the sodium-cooled fast reactor (SFR) fuel cycle with pyro processing currently under development in Korea.

Progesterone receptors (PR) mediate STAT actions: PR and prolactin receptor signaling crosstalk in breast cancer models.

Science.gov (United States)

Leehy, Katherine A; Truong, Thu H; Mauro, Laura J; Lange, Carol A

2018-02-01

Estrogen is the major mitogenic stimulus of mammary gland development during puberty wherein ER signaling acts to induce abundant PR expression. PR signaling, in contrast, is the primary driver of mammary epithelial cell proliferation in adulthood. The high circulating levels of progesterone during pregnancy signal through PR, inducing expression of the prolactin receptor (PRLR). Cooperation between PR and prolactin (PRL) signaling, via regulation of downstream components in the PRL signaling pathway including JAKs and STATs, facilitates the alveolar morphogenesis observed during pregnancy. Indeed, these pathways are fully integrated via activation of shared signaling pathways (i.e. JAKs, MAPKs) as well as by the convergence of PRs and STATs at target genes relevant to both mammary gland biology and breast cancer progression (i.e. proliferation, stem cell outgrowth, tissue cell type heterogeneity). Thus, rather than a single mediator such as ER, transcription factor cascades (ER>PR>STATs) are responsible for rapid proliferative and developmental programming in the normal mammary gland. It is not surprising that these same mediators typify uncontrolled proliferation in a majority of breast cancers, where ER and PR are most often co-expressed and may cooperate to drive malignant tumor progression. This review will primarily focus on the integration of PR and PRL signaling in breast cancer models and the importance of this cross-talk in cancer progression in the context of mammographic density. Components of these PR/PRL signaling pathways could offer alternative drug targets and logical complements to anti-ER or anti-estrogen-based endocrine therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oxidation of Helix-3 methionines precedes the formation of PK resistant PrP.

Directory of Open Access Journals (Sweden)

Tamar Canello

2010-07-01

Full Text Available While elucidating the peculiar epitope of the alpha-PrP mAb IPC2, we found that PrPSc exhibits the sulfoxidation of residue M213 as a covalent signature. Subsequent computational analysis predicted that the presence of sulfoxide groups at both Met residues 206 and 213 destabilize the alpha-fold, suggesting oxidation may facilitate the conversion of PrPC into PrPSc. To further study the effect of oxidation on prion formation, we generated pAbs to linear PrP peptides encompassing the Helix-3 region, as opposed to the non-linear complexed epitope of IPC2. We now show that pAbs, whose epitopes comprise Met residues, readily detected PrPC, but could not recognize most PrPSc bands unless they were vigorously reduced. Next, we showed that the alpha-Met pAbs did not recognize newly formed PrPSc, as is the case for the PK resistant PrP present in lines of prion infected cells. In addition, these reagents did not detect intermediate forms such as PK sensitive and partially aggregated PrPs present in infected brains. Finally, we show that PrP molecules harboring the pathogenic mutation E200K, which is linked to the most common form of familial CJD, may be spontaneously oxidized. We conclude that the oxidation of methionine residues in Helix-3 represents an early and important event in the conversion of PrPC to PrPSc. We believe that further investigation into the mechanism and role of PrP oxidation will be central in finally elucidating the mechanism by which a normal cell protein converts into a pathogenic entity that causes fatal brain degeneration.

Genome sequencing and annotation of multidrug resistant Mycobacterium tuberculosis (MDR-TB PR10 strain

Directory of Open Access Journals (Sweden)

Mohd Zakihalani A. Halim

2016-03-01

Full Text Available Here, we report the draft genome sequence and annotation of a multidrug resistant Mycobacterium tuberculosis strain PR10 (MDR-TB PR10 isolated from a patient diagnosed with tuberculosis. The size of the draft genome MDR-TB PR10 is 4.34 Mbp with 65.6% of G + C content and consists of 4637 predicted genes. The determinants were categorized by RAST into 400 subsystems with 4286 coding sequences and 50 RNAs. The whole genome shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession number CP010968. Keywords: Mycobacterium tuberculosis, Genome, MDR, Extrapulmonary

[Properties of live antibiotics-resistant anthrax vaccine STI-PR after long-term storage].

Science.gov (United States)

Aksenova, L Iu; Buravtseva, N P; Kogotkova, O I; Eremenko, E I; Tsygankova, O I

2007-01-01

Study showed that cultural, morphologic, genetic, immunologic characteristics, and resistance to antibiotics of STI-PR anthrax vaccine did not change after storage during 20 years in lyophilized condition. It has been shown that medium for lyophilization plays important role in preservation of vitality of anthrax spores. Optimal preservative properties have been observed for thioureal and sucrose-gelatinous media for lyophilization. Obtained results give reasons for prolongation of shelf live of STI-PR vaccine from 2 - 3 to 5 - 8 years.

Proliferation resistance considerations for remote small modular reactors

Energy Technology Data Exchange (ETDEWEB)

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

2013-07-01

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

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

International Nuclear Information System (INIS)

Ebbinghaus, B; Choi, J; Meier, T

2003-01-01

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

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

International Nuclear Information System (INIS)

Chang, Yoon I.

2000-01-01

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

S1P/S1PR3 signaling mediated proliferation of pericytes via Ras/pERK pathway and CAY10444 had beneficial effects on spinal cord injury.

Science.gov (United States)

Tang, Hai-Bin; Jiang, Xiao-Jian; Wang, Chen; Liu, Shi-Chang

2018-04-15

Pericytes have long been regarded merely to maintain structural and functional integrity of blood-brain barrier (BBB). Nevertheless, it has also been identified as a component of scar-forming stromal cells after spinal cord injury (SCI). In process of enlargement of spinal cavity after SCI, the number of pericytes increased and outnumbered astrocytes. However, the mechanism of proliferation of pericytes remains unclear. Sphingosine-1-phosphate (S1P) has been reported to play important roles in the formation of glia scar, but previous studies had paid more attention to the astrocytes. The present study aimed to observe the effects of S1P and S1P receptors (S1PRs) on proliferation of pericytes and investigate the underlying mechanism. By double immunostaining, we found that the number of PDGFRβ-positive pericytes was gradually increased and sealed the cavity, which surrounded by reactive astrocytes. Moreover, the subtype of S1PR3 was found to be induced by SCI and mainly expressed on pericytes. Further, by use of CAY10444, an inhibitor of S1PR3, we showed that S1P/S1PR3 mediated the proliferation of pericytes through Ras/pERK pathway. Moreover, CAY10444 was found to have the effects of enhancing neuronal survival, alleviating glial scar formation, and improving locomotion recovery after SCI. The results suggested that S1P/S1PR3 might be a promising target for clinical therapy for SCI. Copyright © 2018 Elsevier Inc. All rights reserved.

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

International Nuclear Information System (INIS)

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

2000-01-01

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

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

International Nuclear Information System (INIS)

2008-11-01

INPRO methodology in the area of proliferation resistance has been developed further in comparison to TECDOC-1434 resulting in modified wording of the basic principle, user requirements and criteria. The development of the INPRO criteria is not completed at the time this report was written; thus, the INPRO assessment of the existing criteria has to be based mainly on expert judgment. In Annex A the status of the analysis method for PR, developed within INPRO, is documented. The development of this analysis method is also ongoing. The main differences between the analysis method in Annex A and the assessment method in Chapter 3 are: (1) in Chapter 3 the INPRO method of assessment for PR is presented. This method requires the definition of indicators and acceptance limits for each criterion to enable the INPRO assessor to perform his judgement whether the INS assessed has the potential to meet the criterion; (2) the analysis method of PR, presented in Annex A, has defined at the moment almost exclusively indicators and as a sub-level evaluation parameters, and only for specific criteria the corresponding acceptance limits (e.g. first indicator of UR1). However detailed background of each of the evaluation parameters is provided; (3) therefore in Chapter 3 only those indicators and evaluation parameters of Annex A were used that are already developed enough to define corresponding acceptance limits but it is expected that in the future all will be integrated into the INPRO assessment method. Annex B lists some additional terms and definitions in the area of PR. Annex C provides a table with some important properties of nuclides relevant for PR. Annex D lays out a short description of acquisition/diversion analysis. Annex E provides tables defining criteria for termination of safeguards. Annex F provides a table that could be used by the INPRO assessor to summarize the results of his assessment

A Qualitative Assessment of Diversion Scenarios for an Example Sodium Fast Reactor Using the GEN IV PR and PP Methodology

International Nuclear Information System (INIS)

Zentner, Michael D.; Coles, Garill A.; Therios, Ike

2012-01-01

FAST REACTORS;NUCLEAR ENERGY;NUCLEAR MATERIALS MANAGEMENT;PROLIFERATION;SAFEGUARDS;THEFT; A working group was created in 2002 by the Generation IV International Forum (GIF) for the purpose of developing an internationally accepted methodology for assessing the Proliferation Resistance of a nuclear energy system (NES) and its individual elements. A two year case study is being performed by the experts group using this methodology to assess the proliferation resistance of a hypothetical NES called the Example Sodium Fast Reactor (ESFR). This work demonstrates how the PR and PP methodology can be used to provide important information at various levels of details to NES designers, safeguard administrators and decision makers. The study analyzes the response of the complete ESFR nuclear energy system to different proliferation and theft strategies. The challenges considered include concealed diversion, concealed misuse and 'break out' strategies. This paper describes the work done in performing a qualitative assessment of concealed diversion scenarios from the ESFR.

Partitioning and transmutation - Technical feasibility, proliferation resistance and safeguardability

International Nuclear Information System (INIS)

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

2001-01-01

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

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

Framework for Proliferation Resistance and Physical Protection for Nonproliferation Impact Assessments

International Nuclear Information System (INIS)

Bari, R.

2008-01-01

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

Temperature dependence of colossal electro-resistance of Pr0.7Ca0.3MnO3 thin films

International Nuclear Information System (INIS)

Odagawa, A.; Kanno, T.; Adachi, H.; Sato, H.; Inoue, I.H.; Akoh, H.; Kawasaki, M.; Tokura, Y.

2005-01-01

The electronic conduction through a Pr 0.7 Ca 0.3 MnO 3 thin film is investigated by measurements using dc and pulsed bias. Pr 0.7 Ca 0.3 MnO 3 films sandwiched by electrodes exhibit two stable resistance states by means of applying voltage pulses. Both of the states show semiconducting behavior. The ratio of the two resistance states induces a colossal electro-resistance (CER) effect greater than 1000%. The CER behavior is seen in the temperature range of 300 K down to 150 K. The observed conduction characteristics exhibit the space-charge-limited-current effect, and the switching behavior can be ascribed to a carrier trapping/detrapping of the trap sites in the perovskite manganite

Revisiting progesterone receptor (PR) actions in breast cancer: Insights into PR repressive functions.

Science.gov (United States)

Proietti, Cecilia J; Cenciarini, Mauro E; Elizalde, Patricia V

2018-05-01

Progesterone receptor (PR) is a master regulator in female reproductive tissues that controls developmental processes and proliferation and differentiation during the reproductive cycle and pregnancy. PR also plays a role in progression of endocrine-dependent breast cancer. As a member of the nuclear receptor family of ligand-dependent transcription factors, the main action of PR is to regulate networks of target gene expression in response to binding its cognate steroid hormone, progesterone. Liganded-PR transcriptional activation has been thoroughly studied and associated mechanisms have been described while progesterone-mediated repression has remained less explored. The present work summarizes recent advances in the understanding of how PR-mediated repression is accomplished in breast cancer cells and highlights the significance of fully understanding the determinants of context-dependent PR action. Copyright © 2018 Elsevier Inc. All rights reserved.

A Qualitative Assessment Of Diversion Scenarios For A Example Sodium Fast Reactor Using The Gen IV PR And PP Methodology

International Nuclear Information System (INIS)

Zentner, Michael D.

2008-01-01

A working group was created in 2002 by the Generation IV International Forum (GIF) for the purpose of developing an internationally accepted methodology for assessing the Proliferation Resistance of a nuclear energy system (NES) and its individual elements. A two year case study is being performed by the experts group using this methodology to assess the proliferation resistance of a hypothetical NES called the Example Sodium Fast Reactor (ESFR). This work demonstrates how the PR and PP methodology can be used to provide important information at various levels of details to NES designers, safeguard administrators and decision makers. The study analyzes the response of the complete ESFR nuclear energy system to different proliferation and theft strategies. The challenges considered include concealed diversion, concealed misuse and 'break out' strategies. This paper describes the work done in performing a qualitative assessment of concealed diversion scenarios from the ESFR.

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

International Nuclear Information System (INIS)

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

2005-01-01

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

The epiphytic fungus Pseudozyma aphidis induces jasmonic acid- and salicylic acid/nonexpressor of PR1-independent local and systemic resistance.

Science.gov (United States)

Buxdorf, Kobi; Rahat, Ido; Gafni, Aviva; Levy, Maggie

2013-04-01

Pseudozyma spp. are yeast-like fungi, classified in the Ustilaginales, which are mostly epiphytic or saprophytic and are not pathogenic to plants. Several Pseudozyma species have been reported to exhibit biological activity against powdery mildews. However, previous studies have reported that Pseudozyma aphidis, which can colonize plant surfaces, is not associated with the collapse of powdery mildew colonies. In this report, we describe a novel P. aphidis strain and study its interactions with its plant host and the plant pathogen Botrytis cinerea. This isolate was found to secrete extracellular metabolites that inhibit various fungal pathogens in vitro and significantly reduce B. cinerea infection in vivo. Moreover, P. aphidis sensitized Arabidopsis (Arabidopsis thaliana) plants' defense machinery via local and systemic induction of pathogenesis-related1 (PR1) and plant defensin1.2 (PDF1.2) expression. P. aphidis also reduced B. cinerea infection, locally and systemically, in Arabidopsis mutants impaired in jasmonic acid (JA) or salicylic acid (SA) signaling. Thus, in addition to direct inhibition, P. aphidis may inhibit B. cinerea infection via induced resistance in a manner independent of SA, JA, and Nonexpressor of PR1 (NPR1). P. aphidis primed the plant defense machinery and induced stronger activation of PDF1.2 after B. cinerea infection. Finally, P. aphidis fully or partially reconstituted PR1 and PDF1.2 expression in npr1-1 mutant and in plants with the SA hydroxylase NahG transgene, but not in a jasmonate resistant1-1 mutant, after B. cinerea infection, suggesting that P. aphidis can bypass the SA/NPR1, but not JA, pathway to activate PR genes. Thus, either partial gene activation is sufficient to induce resistance, or the resistance is not directed solely through PR1 and PDF1.2 but probably through other pathogen-resistance genes or pathways as well.

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

Directory of Open Access Journals (Sweden)

Sabnis Gauri

2011-06-01

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

Low-temperature resistivity anomaly in underdoped Pr0.8Sr0.2MnO3 manganite nanoparticles

International Nuclear Information System (INIS)

Das, Proloy T.; Giri, S.K.; Panda, J.; Taraphder, A.; Nath, T.K.; Nigam, A.K.

2013-01-01

High resolution electrical resistivity measurements were carried out of under-doped Pr 0.8 Sr 0.2 MnO 3 manganite nanoparticles with grain size modulation down to 40 nm in magnetic fields H, from 0 to 9 T in the low temperature regime down to a temperature of 4.2 K. In the temperature range below 80 K, a distinct resistivity minima is observed for all the samples with different particle sizes for all H. While trying to fit low temperature resistivity data with different models for the observed resistivity minima with negative temperature coefficient of resistance (TCR) for all H, it appears that all the data for different particle sizes, can be best described by electron-electron (e-e) interaction effect in comparison with other models, e.g., Kondo model, coulomb blockades etc. The low temperature data for all H have been fitted with an expression containing three terms, namely, residual resistivity, inelastic scattering, e-e interaction and Kondo effects. We conclude that the e-e interaction is the dominant transport mechanism at low temperatures for the observed negative TCR in this strongly disordered nanometric Pr 0.8 Sr 0.2 MnO 3 phase separated manganite system. (author)

Progesterone receptor (PR) polyproline domain (PPD) mediates inhibition of epidermal growth factor receptor (EGFR) signaling in non-small cell lung cancer cells.

Science.gov (United States)

Kawprasertsri, Sornsawan; Pietras, Richard J; Marquez-Garban, Diana C; Boonyaratanakornkit, Viroj

2016-05-01

Recent evidence has suggested a possible role for progesterone receptor (PR) in the progression of non-small cell lung cancer (NSCLC). However, little is known concerning roles of PR in NSCLC. PR contains a polyproline domain (PPD), which directly binds to the SH3 domain of signaling molecules. Because PPD-SH3 interactions are essential for EGFR signaling, we hypothesized that the presence of PR-PPD interfered with EGFR-mediated signaling and cell proliferation. We examined the role of PR-PPD in cell proliferation and signaling by stably expressing PR-B, or PR-B with disrupting mutations in the PPD (PR-BΔSH3), from a tetracycline-regulated promoter in A549 NSCLC cells. PR-B dose-dependently inhibited cell growth in the absence of ligand, and progestin (R5020) treatment further suppressed the growth. Treatment with RU486 abolished PR-B- and R5020-mediated inhibition of cell proliferation. Expression of PR-BΔSH3 and treatment with R5020 or RU486 had no effect on cell proliferation. Furthermore, PR-B expression but not PR-BΔSH3 expression reduced EGF-induced A549 proliferation and activation of ERK1/2, in the absence of ligand. Taken together, our data demonstrated the significance of PR extranuclear signaling through PPD interactions in EGFR-mediated proliferation and signaling in NSCLC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

PR and PP evaluation. ESFR full system case study final report (Tentative translation)

International Nuclear Information System (INIS)

Sagara, Hiroshi; Kawakubo, Yoko; Inoue, Naoko

2014-01-01

The Generation IV (GEN IV) International Forum (GIF) Proliferation Resistance and Physical Protection Working Group (PRPP WG) was established in December, 2002, as one of the crosscut groups under GIF, in order to develop a methodology for evaluating PR and PP of potential GEN IV options. The group currently consists of the experts from the U.S. national laboratories and universities, from Canada, France, Republic of Korea (ROK), Japan, the International Atomic Energy Agency (IAEA), and European Union(EU). The present report, published in Oct. 2009, was used as a supporting study for development of the evaluation methodology for proliferation resistance and physical protection of GEN IV nuclear energy systems. The present report is summarizing the case study of the PR and PP evaluation of Example Sodium Fast Reactor (ESFR), a hypothetical nuclear energy system consisting of nine main system elements, and it provides for designers the practical experience of applying the PR and PP evaluation methodology to a nuclear energy system. The development of the future nuclear fuel cycle system with sufficient PR and PP features is a crucial task in Japan, and the demonstration and explanation about its effectiveness to the domestic and international society will be required. With the usefulness the present report for such purposes, it was translated and published here as a Japanese-language edition with the concurrence of the OECD-NEA. The original report in English language can be downloaded at the OECD-NEA website. The translation was performed as closely as possible to the original, and special attention was paid to the technical term translation for consistency. Terms difficult to be translated appropriately into Japanese was written with the original English wording. Safeguards terms were translated with reference to “IAEA Safeguards Glossary 2001 Edition” (Japanese), published by the Nuclear Material Control Center Japan (NMCC). The authors are grateful to the GIF

The influence of ingot annealing on the corrosion resistance of a PrFeCoBNbP alloy

International Nuclear Information System (INIS)

Oliveira, M.C.L.; Takiishi, H.; Faria, R.N.; Costa, I.

2008-01-01

The influence of the annealing time on the corrosion resistance of a Pr-Fe-Co-B-Nb alloy with the addition of 0.1 wt% P was investigated here using potentiodynamic polarization and electrochemical impedance spectroscopy (EIS). The cast ingot alloys were annealed at 1100 deg. C for 10, 15 and 20 h. The specimens were immersed for 30 days in naturally aerated 0.02 M Na 2 HPO 4 solution at room temperature, during which period the evolution of the electrochemical behavior was assessed using EIS. The results indicated that the corrosion resistance of the Pr 14 Fe bal Co 16 B 6 Nb 0.1 P 0.25 alloy was related to the annealing time and, hence, to its microstructure. Annealing at 1100 deg. C for 10 h was insufficient to eliminate the Fe-α phase from the alloy microstructure, whereas annealing for 15 and 20 h removed an increasing amount of Fe-α phase, thereby increasing the alloy's corrosion resistance

The novel gene VpPR4-1 from Vitis pseudoreticulata increases powdery mildew resistance in transgenic Vitis vinifera L.

Directory of Open Access Journals (Sweden)

Lingmin eDai

2016-05-01

Full Text Available Pathogenesis-related proteins (PRs can lead to increased resistance of the whole plant to pathogen attack. Here, we isolate and characterize a PR-4 protein from a wild Chinese grape Vitis pseudoreticulata which shows greatly elevated transcription following powdery mildew infection. Its expression profiles under a number of abiotic stresses were also investigated. The PR-4 gene was overexpressed in regenerated V. vinifera cv. Red Globe via Agrobacterium tumefaciens-mediated transformation and verified by the Western blot. The transgenic grapevines exhibited higher expression levels of PR-4 protein content than wild-type vines and also repressed the growth of powdery mildew. The PR gene responds differently to different stresses in the PR-4 transformants. This study demonstrates that PR-4 protein in grapes plays a vital role in defense against powdery mildew invasion.

A Qualitative Assessment of Diversion Scenarios for a GEN IV Example Sodium Fast Reactor Using the GEN IV PR and PP Methodology

Energy Technology Data Exchange (ETDEWEB)

Zentner, M.D.; Coles, G.A. [PNNL, P.O. Box 999, 902 Battelle Boulvard, Richland, WA 99336 (United States); Therios, I.U. [Argonne National Lab. - ANL (United States)

2009-06-15

An experts working group was created in 2002 by The Generation IV International Forum for the purpose of developing an internationally accepted methodology for assessing the proliferation resistance of a nuclear energy system (NES) and its individual elements. A two year case study was performed by the working group using this methodology to assess the proliferation resistance of a hypothetical NES called the Example Sodium Fast Reactor (ESFR). This work demonstrates how the PR and PP methodology can be used to provide important information to designers at various levels of details, including pre-conceptual design stage. The study analyzes the response of the ESFR entire nuclear energy system to different proliferation and theft strategies. The challenges considered comprise concealed diversion, concealed misuse and abrogation strategies. This paper describes the work done in performing a qualitative assessment of potential concealed diversion scenarios from the ESFR, and includes an evaluation of the potential effect of changes in the conversion ratio on diversion strategies. (authors)

Applying the PR and PP Methodology for a qualitative assessment of a misuse scenario in a notional Generation IV Example Sodium Fast Reactor. Assessing design variations

Energy Technology Data Exchange (ETDEWEB)

Cojazzi, G.G.M.; Renda, G. [European Commission, Joint Research Centre, Institute for the Protection and Security of the Citizen, TP 210, Via E. Fermi 2749, I-21027, Ispra - Va (Italy); Hassberger, J. [Lawrence Livermore National Laboratory (United States)

2009-06-15

The Generation IV International Forum (GIF) Proliferation Resistance and Physical Protection (PR and PP) Working Group has developed a methodology for the PR and PP evaluation of advanced nuclear energy systems. The methodology is organised as a progressive approach applying alternative methods at different levels of thoroughness as more design information becomes available and research improves the depth of technical knowledge. The GIF Proliferation Resistance and Physical Protection (PR and PP) Working Group developed a notional sodium cooled fast neutron nuclear reactor, named the Example Sodium Fast Reactor (ESFR), for use in developing and testing the methodology. The ESFR is a hypothetical nuclear energy system consisting of four sodium-cooled fast reactors of medium size, co-located with an on-site dry fuel storage facility and a Fuel Cycle Facility with pyrochemical processing of the spent fuel and re-fabrication of new ESFR fuel elements. The baseline design is an actinide burner, with LWR spent fuel elements as feed material processed on the site. In the years 2007 and 2008 the GIF PR and PP Working Group performed a case study designed to both test the methodology and demonstrate how it can provide useful feedback to designers even during pre-conceptual design. The Study analysed the response of the entire ESFR system to different proliferation and theft strategies. Three proliferation threats were considered: Concealed diversion, Concealed Misuse and Abrogation. An overt theft threat was also studied. One of the objectives of the case study is to confirm the capability of the methodology to capture PR and PP differences among varied design configurations. To this aim Design Variations (DV) have been also defined corresponding respectively to a) a small variation of the baseline design (DV0), b) a deep burner configuration (DV1), c) a self sufficient core (DV2), and c) a breeder configuration (DV3). This paper builds on the approach followed for the

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

Science.gov (United States)

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

2016-05-10

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-06-14

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

Remanent resistance changes in metal- PrCaMnO-metal sandwich structures

Energy Technology Data Exchange (ETDEWEB)

Scherff, Malte; Meyer, Bjoern-Uwe; Scholz, Julius; Hoffmann, Joerg; Jooss, Christian [Institute of Materials Physics, University of Goettingen (Germany)

2012-07-01

The non-volatile electric pulse induced resistance change (EPIR) seems to be a rather common feature of oxides sandwiched by electrodes. However, microscopic mechanisms are discussed controversially. We present electrical transport measurements of sputtered Pr{sub 0.7}Ca{sub 0.3}MnO{sub 3} films sandwiched by metallic electrodes with variation of electrode materials, device geometry and PCMO deposition parameters. Cross-plane transport measurements have been performed as function of temperature and magnetic field. Specifically, the transition from dynamic resistance changes due to non-linear transport to remanent switching is analyzed. By analyzing changes of magneto-resistance at low temperatures in different resistance states we aim for separation between interface and film contributions to switching. Comparing switching behavior in symmetric and asymmetric electrode configuration allows for identification of the active, single interface in the switching process and the origin of an observed switching polarity inversion. The influence of excitation field and power on the switching characteristics of different noble metal electrodes is discussed. Samples from macroscopic devices and in situ stimulated sandwich structures were studied in a transmission electron microscope in order to investigate the induced structural, chemical and electronic changes.

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

Science.gov (United States)

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

2017-01-01

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

Recombinant PrPSc shares structural features with brain-derived PrPSc: Insights from limited proteolysis.

Science.gov (United States)

Sevillano, Alejandro M; Fernández-Borges, Natalia; Younas, Neelam; Wang, Fei; R Elezgarai, Saioa; Bravo, Susana; Vázquez-Fernández, Ester; Rosa, Isaac; Eraña, Hasier; Gil, David; Veiga, Sonia; Vidal, Enric; Erickson-Beltran, Melissa L; Guitián, Esteban; Silva, Christopher J; Nonno, Romolo; Ma, Jiyan; Castilla, Joaquín; R Requena, Jesús

2018-01-01

Very solid evidence suggests that the core of full length PrPSc is a 4-rung β-solenoid, and that individual PrPSc subunits stack to form amyloid fibers. We recently used limited proteolysis to map the β-strands and connecting loops that make up the PrPSc solenoid. Using high resolution SDS-PAGE followed by epitope analysis, and mass spectrometry, we identified positions ~116/118, 133-134, 141, 152-153, 162, 169 and 179 (murine numbering) as Proteinase K (PK) cleavage sites in PrPSc. Such sites likely define loops and/or borders of β-strands, helping us to predict the threading of the β-solenoid. We have now extended this approach to recombinant PrPSc (recPrPSc). The term recPrPSc refers to bona fide recombinant prions prepared by PMCA, exhibiting infectivity with attack rates of ~100%. Limited proteolysis of mouse and bank vole recPrPSc species yielded N-terminally truncated PK-resistant fragments similar to those seen in brain-derived PrPSc, albeit with varying relative yields. Along with these fragments, doubly N- and C-terminally truncated fragments, in particular ~89/97-152, were detected in some recPrPSc preparations; similar fragments are characteristic of atypical strains of brain-derived PrPSc. Our results suggest a shared architecture of recPrPSc and brain PrPSc prions. The observed differences, in particular the distinct yields of specific PK-resistant fragments, are likely due to differences in threading which result in the specific biochemical characteristics of recPrPSc. Furthermore, recombinant PrPSc offers exciting opportunities for structural studies unachievable with brain-derived PrPSc.

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

Energy Technology Data Exchange (ETDEWEB)

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

2016-05-15

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

The Epiphytic Fungus Pseudozyma aphidis Induces Jasmonic Acid- and Salicylic Acid/Nonexpressor of PR1-Independent Local and Systemic Resistance1[C][W

Science.gov (United States)

Buxdorf, Kobi; Rahat, Ido; Gafni, Aviva; Levy, Maggie

2013-01-01

Pseudozyma spp. are yeast-like fungi, classified in the Ustilaginales, which are mostly epiphytic or saprophytic and are not pathogenic to plants. Several Pseudozyma species have been reported to exhibit biological activity against powdery mildews. However, previous studies have reported that Pseudozyma aphidis, which can colonize plant surfaces, is not associated with the ‎‎collapse of powdery ‎mildew colonies. In this report, we describe a novel P. aphidis strain and study its interactions with its plant host and the plant pathogen Botrytis cinerea. This isolate was found to secrete extracellular metabolites that inhibit various fungal pathogens in vitro and significantly reduce B. cinerea infection in vivo. Moreover, P. aphidis sensitized Arabidopsis (Arabidopsis thaliana) plants’ defense machinery via local and systemic induction of PATHOGENESIS-RELATED1 (PR1) and PLANT DEFENSIN1.2 (PDF1.2) expression. P. aphidis also reduced B. cinerea infection, locally and systemically, in Arabidopsis mutants impaired in jasmonic acid (JA) or salicylic acid (SA) signaling. Thus, in addition to direct inhibition, P. aphidis may inhibit B. cinerea infection via induced resistance in a manner independent of SA, JA, and Nonexpressor of PR1 (NPR1). P. aphidis primed the plant defense machinery and induced stronger activation of PDF1.2 after B. cinerea infection. Finally, P. aphidis fully or partially reconstituted PR1 and PDF1.2 expression in npr1-1 mutant and in plants with the SA hydroxylase NahG transgene, but not in a jasmonate resistant1-1 mutant, after B. cinerea infection, suggesting that P. aphidis can bypass the SA/NPR1, but not JA, pathway to activate PR genes. Thus, either partial gene activation is sufficient to induce resistance, or the resistance is not directed solely through PR1 and PDF1.2 but probably through other pathogen-resistance genes or pathways as well. PMID:23388119

Resistive switching properties and low resistance state relaxation in Al/Pr0.7Ca0.3MnO3/Pt junctions

International Nuclear Information System (INIS)

Li Songlin; Liao, Z L; Li, J; Gang, J L; Zheng, D N

2009-01-01

Metal/insulator/metal structures composed of active Al top electrodes (TEs) and oxygen-deficient Pr 0.7 Ca 0.3 MnO 3 (PCMO) insulator layers are prepared on platinized silicon substrates. The junction resistance exhibits an obvious negative differential resistance region in the first bias sweep and an irreversible increase from 2 to 100 MΩ in repeated ±4 V sweeps. The pulse duration needed to fully switch the junctions is found to be on the order of milliseconds. When 100-500 μs negative pulses are used, the junctions show an incomplete switch to the low resistance state (LRS) which exhibits fluctuating resistances. The fluctuation in the LRS is suppressed and the high-to-low resistance ratio increases gradually when the negative pulse duration is increased from 100 to 500 μs. For relaxed junctions, pulse switching experiments reveal that the LRS undergoes a dynamically stable process at the beginning and then reaches a lower and metastable resistance value. Resistance retention tests also indicate that the high resistance state is very stable, while the metastable LRS gradually relaxes to higher resistance values. The experimental results are discussed with the formation and dissociation of an interfacial AlO x layer at the interface between Al TEs and PCMO layers.

Implications for advanced safeguards derived from PR and PP case study results

International Nuclear Information System (INIS)

Boyer, Brian D.

2009-01-01

The proliferation resistance and physical protection (PR and PP) working group produced a case study on the Example Sodium Fast Reactor (ESFR). The ESFR is a hypothetical nuclear energy system consisting of four sodium-cooled fast reactors of medium size collocated with an on-site dry fuel storage facility and a spent fuel reprocessing facility using pyroprocessing technology. This study revealed how safeguards would be applied at such site consisting of integrated multiple fuel cycle facilities and the implications of what safeguards technology and safeguards concepts would need to be adapted and developed to safeguard successfully this Generation IV nuclear energy system concept. The major safeguards concepts driving our safeguards analysis are timeliness goals and material quantity goals. Because the fresh transuranic (TRU) fuel to be produced in the ESFR fuel fabrication facility contains plutonium, the ESFR will be reprocessing, using in the reactor, and storing material on site that will have IAEA defined 'direct-use material' in it with stringent timeliness goals and material quantity goals that drive the safeguards implementation. Specifically, the TRU fresh fuel, pyroprocessing in process material, LWR spent fuel sent to the ESFR, and TRU spent fuel will contain plutonium. This material will need to be verified at interim intervals four times per year because the irradiated direct-use material, as defined previously, has three-month timeliness goals and 8 kg material quantity goals for plutonium. The TRU in-process material is, of course, irradiated direct-use material as defined by the IAEA. Keeping the plutonium and uranium together with TRu products should provide a radiation barrier. this radiation barrier slows down the ability to reprocess the fuel. Furthermore, the reprocessing technique, if it has some intrinsic proliferation resistance, will need major modifications to be able to separate plutonium from the uranium and TRU mixture. The ESFR design

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

Science.gov (United States)

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

2015-11-15

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

Estrogen and progesterone receptors have distinct roles in the establishment of the hyperplastic phenotype in PR-A transgenic mice

Energy Technology Data Exchange (ETDEWEB)

Simian, Marina; Bissell, Mina J.; Barcellos-Hoff, Mary Helen; Shyamala, Gopalan

2009-05-11

Expression of the A and B forms of progesterone receptor (PR) in an appropriate ratio is critical for mammary development. Mammary glands of PR-A transgenic mice, carrying an additional A form of PR as a transgene, exhibit morphological features associated with the development of mammary tumors. Our objective was to determine the roles of estrogen (E) and progesterone (P) in the genesis of mammary hyperplasias/preneoplasias in PR-A transgenics. We subjected PR-A mice to hormonal treatments and analyzed mammary glands for the presence of hyperplasias and used BrdU incorporation to measure proliferation. Quantitative image analysis was carried out to compare levels of latency-associated peptide and transforming growth factor beta 1 (TGF{beta}1) between PR-A and PR-B transgenics. Basement membrane disruption was examined by immunofluorescence and proteolytic activity by zymography. The hyperplastic phenotype of PR-A transgenics is inhibited by ovariectomy, and is reversed by treatment with E + P. Studies using the antiestrogen ICI 182,780 or antiprogestins RU486 or ZK 98,299 show that the increase in proliferation requires signaling through E/estrogen receptor alpha but is not sufficient to give rise to hyperplasias, whereas signaling through P/PR has little impact on proliferation but is essential for the manifestation of hyperplasias. Increased proliferation is correlated with decreased TGF{beta}1 activation in the PR-A transgenics. Analysis of basement membrane integrity showed loss of laminin-5, collagen III and collagen IV in mammary glands of PR-A mice, which is restored by ovariectomy. Examination of matrix metalloproteases (MMPs) showed that total levels of MMP-2 correlate with the steady-state levels of PR, and that areas of laminin-5 loss coincide with those of activation of MMP-2 in PR-A transgenics. Activation of MMP-2 is dependent on treatment with E and P in ovariectomized wild-type mice, but is achieved only by treatment with P in PR-A mice. These data

Reproducible low-voltage resistive switching in a low-initial-resistance Pr0.7Ca0.3MnO3 junction

International Nuclear Information System (INIS)

Li Songlin; Gang Jianlei; Li Jie; Chu Haifeng; Zheng Dongning

2008-01-01

Current-voltage (I-V) characteristics are investigated in a low-initial-resistance Ag/Pr 0.7 Ca 0.3 MnO 3 /Pt sandwich structure. It is found that the junction can show stable low and high resistance states in ±0.3 V voltage sweeping cycles. The set and reset voltage values are, respectively, +0.1 V and -0.2 V, which are very low as compared with those reported previously. Furthermore, the I-V curves in both resistance states exhibit rather linear behaviour, without any signature of metal/insulator interface effects. This implies that the Schottky interface mechanism might not be an indispensable factor for the colossal electroresistance effect. The origin of low switching voltages is attributed to the reduced effective distance for electric field action due to the sufficient oxygen content of the PCMO layer. The underlying physics is discussed in terms of the filament network model together with the field-induced oxygen vacancy motion model

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

International Nuclear Information System (INIS)

Brown, N W; Hassberger, J A.

1999-01-01

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

Overexpression of VpPR10.1 by an efficient transformation method enhances downy mildew resistance in V. vinifera.

Science.gov (United States)

Su, Hang; Jiao, Yun-Tong; Wang, Fang-Fang; Liu, Yue-E; Niu, Wei-Li; Liu, Guo-Tian; Xu, Yan

2018-05-01

Putrescine and spermidine increase the transformation efficiency of Vitis vinifera L. cv. Thompson seedless. Accumulation of VpPR10.1 in transgenic V. vinifera Thompson seedless, likely increases its resistance to downy mildew. A more efficient method is described for facilitating Agrobacterium-mediated transformation of Vitis vinifera L. cv. Thompson Seedless somatic embryogenesis using polyamines (PAs). The efficacies of putrescine, spermidine and spermine are identified at a range of concentrations (10 µM, 100 µM and 1 mM) added to the culture medium during somatic embryo growth. Putrescine (PUT) and spermidine (SPD) promote the recovery of proembryonic masses (PEM) and the development of somatic embryos (SE) after co-cultivation. Judging from the importance of the time-frame in genetic transformation, PAs added at the co-cultivation stage have a stronger effect than delayed selection treatments, which are superior to antibiotic treatments in the selection stage. Best embryogenic responses are with 1 mM PUT and 100 µM SPD added to the co-culture medium. Using the above method, a pathogenesis-related gene (VpPR10.1) from Chinese wild Vitis pseudoreticulata was transferred into Thompson Seedless for functional evaluation. The transgenic line, confirmed by western blot analysis, was inoculated with Plasmopara viticola to test for downy mildew resistance. Based on observed restrictions of hyphal growth and increases in H 2 O 2 accumulation in the transgenic plants, the accumulation of VpPR10.1 likely enhanced the transgenic plants resistance to downy mildew.

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

Science.gov (United States)

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

2013-08-01

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

PrP N-terminal domain triggers PrPSc-like aggregation of Dpl

International Nuclear Information System (INIS)

Erlich, Paul; Cesbron, Jean-Yves; Lemaire-Vieille, Catherine; Curt, Aurelie; Andrieu, Jean-Pierre; Schoehn, Guy; Jamin, Marc; Gagnon, Jean

2008-01-01

Transmissible spongiform encephalopathies are fatal neurodegenerative disorders thought to be transmitted by self-perpetuating conformational conversion of a neuronal membrane glycoprotein (PrP C , for 'cellular prion protein') into an abnormal state (PrP Sc , for 'scrapie prion protein'). Doppel (Dpl) is a protein that shares significant biochemical and structural homology with PrP C . In contrast to its homologue PrP C , Dpl is unable to participate in prion disease progression or to achieve an abnormal PrP Sc -like state. We have constructed a chimeric mouse protein, composed of the N-terminal domain of PrP C (residues 23-125) and the C-terminal part of Dpl (residues 58-157). This chimeric protein displays PrP-like biochemical and structural features; when incubated in presence of NaCl, the α-helical monomer forms soluble β-sheet-rich oligomers which acquire partial resistance to pepsin proteolysis in vitro, as do PrP oligomers. Moreover, the presence of aggregates akin to protofibrils is observed in soluble oligomeric species by electron microscopy

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

International Nuclear Information System (INIS)

1980-06-01

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

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

International Nuclear Information System (INIS)

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

2009-01-01

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

The influence of thermal treatment and irradiation on specific resistance of (SnSe)1-x - (PrSe)x solid solutions

International Nuclear Information System (INIS)

Huseynov, J.I.; Murguzov, M.I.; Ismayilov, Sh.S.; Jafarov, T.A.

2014-01-01

Full text: It was studied some kinetic coefficients in cluding specific resistance of (SnSe) 1 -x - (PrSe) x solid solutions as well. Special interest was caused by composetions of above mentioned system for which the influence of irradiation and thermal treatment following this irradiation was explored. By its electric characteristics praseodymium monoselenide belongs to metals because a metallic link is formed among cation atoms in PrSe, at the expense of cohich praseodymium atoms possess an oxidation degree equalling to 3+

A Fluorescent Oligothiophene-Bis-Triazine ligand interacts with PrP fibrils and detects SDS-resistant oligomers in human prion diseases.

Science.gov (United States)

Imberdis, Thibaut; Ayrolles-Torro, Adeline; Duarte Rodrigues, Alysson; Torrent, Joan; Alvarez-Martinez, Maria Teresa; Kovacs, Gabor G; Verdier, Jean-Michel; Robitzer, Mike; Perrier, Véronique

2016-01-26

Prion diseases are characterized by the accumulation in the central nervous system of an abnormally folded isoform of the prion protein, named PrP(Sc). Aggregation of PrP(Sc) into oligomers and fibrils is critically involved in the pathogenesis of prion diseases. Oligomers are supposed to be the key neurotoxic agents in prion disease, so modulation of prion aggregation pathways with small molecules can be a valuable strategy for studying prion pathogenicity and for developing new diagnostic and therapeutic approaches. We previously identified thienyl pyrimidine compounds that induce SDS-resistant PrP(Sc) (rSDS-PrP(Sc)) oligomers in prion-infected samples. Due to the low effective doses of the thienyl pyrimidine hits, we synthesized a quaterthiophene-bis-triazine compound, called MR100 to better evaluate their diagnostic and therapeutic potentials. This molecule exhibits a powerful activity inducing rSDS-PrP(Sc) oligomers at nanomolar concentrations in prion-infected cells. Fluorescence interaction studies of MR100 with mouse PrP fibrils showed substantial modification of the spectrum, and the interaction was confirmed in vitro by production of rSDS-oligomer species upon incubation of MR100 with fibrils in SDS-PAGE gel. We further explored whether MR100 compound has a potential to be used in the diagnosis of prion diseases. Our results showed that: (i) MR100 can detect rSDS-oligomers in prion-infected brain homogenates of various species, including human samples from CJD patients; (ii) A protocol, called "Rapid Centrifugation Assay" (RCA), was developed based on MR100 property of inducing rSDS-PrP(Sc) oligomers only in prion-infected samples, and avoiding the protease digestion step. RCA allows the detection of both PK-sensitive and PK-resistant PrP(Sc) species in rodents samples but also from patients with different CJD forms (sporadic and new variant); (iii) A correlation could be established between the amount of rSDS-PrP(Sc) oligomers revealed by MR100 and the

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-09-26

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

Homeobox A7 stimulates breast cancer cell proliferation by up-regulating estrogen receptor-alpha

International Nuclear Information System (INIS)

Zhang, Yu; Cheng, Jung-Chien; Huang, He-Feng; Leung, Peter C.K.

2013-01-01

Highlights: •HOXA7 regulates MCF7 cell proliferation. •HOXA7 up-regulates ERα expression. •HOXA7 mediates estrogen-induced MCF7 cell proliferation. -- Abstract: Breast cancer is the most common hormone-dependent malignancy in women. Homeobox (HOX) transcription factors regulate many cellular functions, including cell migration, proliferation and differentiation. The aberrant expression of HOX genes has been reported to be associated with human reproductive cancers. Estradiol (E2) and its nuclear receptors, estrogen receptor (ER)-alpha and ER-beta, are known to play critical roles in the regulation of breast cancer cell growth. However, an understanding of the potential relationship between HOXA7 and ER in breast cancer cells is limited. In this study, our results demonstrate that knockdown of HOXA7 in MCF7 cells significantly decreased cell proliferation and ERα expression. In addition, HOXA7 knockdown attenuated E2-induced cell proliferation as well as progesterone receptor (PR) expression. The stimulatory effects of E2 on cell proliferation and PR expression were abolished by co-treatment with ICI 182780, a selective ERα antagonist. In contrast, overexpression of HOXA7 significantly stimulated cell proliferation and ERα expression. Moreover, E2-induced cell proliferation, as well as PR expression, was enhanced by the overexpression of HOXA7. Neither knockdown nor overexpression of HOXA7 affected the ER-beta levels. Our results demonstrate a novel mechanistic role for HOXA7 in modulating breast cancer cell proliferation via regulation of ERα expression. This finding contributes to our understanding of the role HOXA7 plays in regulating the proliferation of ER-positive cancer cells

Homeobox A7 stimulates breast cancer cell proliferation by up-regulating estrogen receptor-alpha

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yu [Department of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006 (China); Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4 (Canada); Cheng, Jung-Chien [Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4 (Canada); Huang, He-Feng, E-mail: huanghefg@hotmail.com [Department of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006 (China); Leung, Peter C.K., E-mail: peter.leung@ubc.ca [Department of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006 (China); Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4 (Canada)

2013-11-01

Highlights: •HOXA7 regulates MCF7 cell proliferation. •HOXA7 up-regulates ERα expression. •HOXA7 mediates estrogen-induced MCF7 cell proliferation. -- Abstract: Breast cancer is the most common hormone-dependent malignancy in women. Homeobox (HOX) transcription factors regulate many cellular functions, including cell migration, proliferation and differentiation. The aberrant expression of HOX genes has been reported to be associated with human reproductive cancers. Estradiol (E2) and its nuclear receptors, estrogen receptor (ER)-alpha and ER-beta, are known to play critical roles in the regulation of breast cancer cell growth. However, an understanding of the potential relationship between HOXA7 and ER in breast cancer cells is limited. In this study, our results demonstrate that knockdown of HOXA7 in MCF7 cells significantly decreased cell proliferation and ERα expression. In addition, HOXA7 knockdown attenuated E2-induced cell proliferation as well as progesterone receptor (PR) expression. The stimulatory effects of E2 on cell proliferation and PR expression were abolished by co-treatment with ICI 182780, a selective ERα antagonist. In contrast, overexpression of HOXA7 significantly stimulated cell proliferation and ERα expression. Moreover, E2-induced cell proliferation, as well as PR expression, was enhanced by the overexpression of HOXA7. Neither knockdown nor overexpression of HOXA7 affected the ER-beta levels. Our results demonstrate a novel mechanistic role for HOXA7 in modulating breast cancer cell proliferation via regulation of ERα expression. This finding contributes to our understanding of the role HOXA7 plays in regulating the proliferation of ER-positive cancer cells.

Efficacy and mechanism of action of Proellex, an antiprogestin in aromatase overexpressing and Letrozole resistant T47D breast cancer cells.

Science.gov (United States)

Gupta, Akash; Mehta, Rajeshwari; Alimirah, Fatouma; Peng, Xinjian; Murillo, Genoveva; Wiehle, Ronald; Mehta, Rajendra G

2013-01-01

Aromatase inhibitors (AI) are considered as a first line therapy for ER+PR+ breast cancers. However, many patients acquire resistance to AI. In this study, we determined the response of antiprogestin CDB-4124 (Proellex) on the aromatase overexpressing and Letrozole resistant cell lines and also studies its mechanism of action in inhibition of breast cancer cell proliferation. For these studies we generated aromatase overexpressing T47D (T47Darom) and respective control (T47Dcon) breast cancer cell lines by stable transfection with plasmid containing CYP19A1 gene, or empty vector respectively. Letrozole resistant cell line (T47DaromLR) was generated by incubating T47Darom for 75 weeks in the presence of 10 μM Letrozole. Cell proliferation was determined by MTT or crystal violet assays. Gene expressions were quantified by QRT-PCR whereas proteins were identified by western blot analyses, flow cytometry and immunofluorescence staining. Aromatase activity was determined by estradiol ELISA. The effects of Proellex on the anchorage independent growth were measured by soft agar colony formation. Statistical differences between the various groups were determined by Student's 't' test or ANOVA followed by Bonferroni's post hoc test. Results showed that T47Darom and T47DaromLR cell lines had significantly higher aromatase expression (mRNA; 80-90 fold and protein) and as a result exhibited increased aromatization of testosterone to estradiol as compared to T47Dcon. Both these cell lines showed enhanced growth in the presence of Testosterone (50-60%). In T47DaromLR cells increased PR-B and EGFR expression as compared to T47Dcon cells was observed. Proellex and other known aromatase inhibitors (Letrozole, Anastrozole, and Exemestane) inhibited testosterone induced cell proliferation and anchorage independent growth of T47Darom cells. Cell growth inhibition was significantly greater when cells were treated with Proellex alone or in combination with other AIs as compared to AIs

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-08-09

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

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

International Nuclear Information System (INIS)

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

2013-01-01

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

Complete nucleotide sequence of the multidrug resistance IncA/C plasmid pR55 from Klebsiella pneumoniae isolated in 1969.

Science.gov (United States)

Doublet, Benoît; Boyd, David; Douard, Gregory; Praud, Karine; Cloeckaert, Axel; Mulvey, Michael R

2012-10-01

To determine the complete nucleotide sequence of the multidrug resistance IncA/C plasmid pR55 from a clinical Klebsiella pneumoniae strain that was isolated from a urinary tract infection in 1969 in a French hospital and compare it with those of contemporary emerging IncA/C plasmids. The plasmid was purified and sequenced using a 454 sequencing approach. After draft assembly, additional PCRs and walking reads were performed for gap closure. Sequence comparisons and multiple alignments with other IncA/C plasmids were done using the BLAST algorithm and CLUSTAL W, respectively. Plasmid pR55 (170 810 bp) revealed a shared plasmid backbone (>99% nucleotide identity) with current members of the IncA/C(2) multidrug resistance plasmid family that are widely disseminating antibiotic resistance genes. Nevertheless, two specific multidrug resistance gene arrays probably acquired from other genetic elements were identified inserted at conserved hotspot insertion sites in the IncA/C backbone. A novel transposon named Tn6187 showed an atypical mixed transposon configuration composed of two mercury resistance operons and two transposition modules that are related to Tn21 and Tn1696, respectively, and an In0-type integron. IncA/C(2) multidrug resistance plasmids have a broad host range and have been implicated in the dissemination of antibiotic resistance among Enterobacteriaceae from humans and animals. This typical IncA/C(2) genetic scaffold appears to carry various multidrug resistance gene arrays and is now also a successful vehicle for spreading AmpC-like cephalosporinase and metallo-β-lactamase genes, such as bla(CMY) and bla(NDM), respectively.

Biro Konsultan PR dan Kompetensi Praktisi PR di Era Industrialisasi Komunikasi dan Pencitraan

Directory of Open Access Journals (Sweden)

Dina Sekar Vusparatih

2013-04-01

Full Text Available The world of communication starts to experience rapid development in various aspects of life, almost all over the world. In Indonesia, it is marked by the emergence of a lot of tv and radio stations, and started the trend of imaging strategy efforts that is used to win the regional election, nasional election, and even to win marketing competition through company’s products or services image branding. This phenomenon is the opportunity for PR consultants to be successful team in designing appropriate communication strategies and appropriate steps to build the image. This opportunity is used by many people which is characterized by the proliferation of consultancies. Competition between consultants becomes so tight considering the companies or organizations that intend to hire consultants also want the best. Competitive bidding process was conducted, to win this, it needs solid team of consultants required in skills and morally. PR competencies of each member are needed to grow into a successful PR consultant. 

Fissile material proliferation risk

International Nuclear Information System (INIS)

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

1996-01-01

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

PrP-C1 fragment in cattle brains reveals features of the transmissible spongiform encephalopathy associated PrPsc.

Science.gov (United States)

Serra, Fabienne; Müller, Joachim; Gray, John; Lüthi, Ramona; Dudas, Sandor; Czub, Stefanie; Seuberlich, Torsten

2017-03-15

Three different types of bovine spongiform encephalopathy (BSE) are known and supposedly caused by distinct prion strains: the classical (C-) BSE type that was typically found during the BSE epidemic, and two relatively rare atypical BSE types, termed H-BSE and L-BSE. The three BSE types differ in the molecular phenotype of the disease associated prion protein, namely the N-terminally truncated proteinase K (PK) resistant prion protein fragment (PrP res ). In this study, we report and analyze yet another PrP res type (PrP res-2011 ), which was found in severely autolytic brain samples of two cows in the framework of disease surveillance in Switzerland in 2011. Analysis of brain tissues from these animals by PK titration and PK inhibitor assays ruled out the process of autolysis as the cause for the aberrant PrP res profile. Immunochemical characterization of the PrP fragments present in the 2011 cases by epitope mapping indicated that PrP res-2011 corresponds in its primary sequence to the physiologically occurring PrP-C1 fragment. However, high speed centrifugation, sucrose gradient assay and NaPTA precipitation revealed biochemical similarities between PrP res-2011 and the disease-associated prion protein found in BSE affected cattle in terms of detergent insolubility, PK resistance and PrP aggregation. Although it remains to be established whether PrP res-2011 is associated with a transmissible disease, our results point out the need of further research on the role the PrP-C1 aggregation and misfolding in health and disease. Copyright © 2017. Published by Elsevier B.V.

Identification of protein expression alterations in gefitinib-resistant human lung adenocarcinoma: PCNT and mPR play key roles in the development of gefitinib-associated resistance

Energy Technology Data Exchange (ETDEWEB)

Lin, Chi-Chen [Institute of Biomedical Science, National Chung-Hsing University, Taichung, Taiwan (China); Institute of Biomedical Science, and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taiwan (China); Department of Medical Research and Education, Taichung Veterans General Hospital, Taichung, Taiwan (China); Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan (China); Chen, Jing-Ting [Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan (China); Lin, Meng-Wei [Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan (China); Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan (China); Chan, Chia-Hao [Department of Obstetrics and Gynecology, Hsinchu Mackay Memorial Hospital, Hsinchu 30071, Taiwan (China); Wen, Yueh-Feng [Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan (China); Department of Internal Medicine, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan (China); Wu, Shin-Bei [Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan (China); Chung, Ting-Wen [Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan (China); Lyu, Kevin W. [Lutheran Medical Center, Brooklyn, NY (United States); Global Scholars Program, St. George' s University/Northumbria University, Newcastle upon Tyne (United Kingdom); Chou, Hsiu-Chuan, E-mail: chouhc@mail.nhcue.edu.tw [Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan (China); and others

2015-11-01

Gefitinib is the first-line chemotherapeutic drug for treating non-small cell lung cancer (NSCLC), which comprises nearly 85% of all lung cancer cases worldwide. However, most patients eventually develop drug resistance after 12–18 months of treatment. Hence, investigating the drug resistance mechanism and resistance-associated biomarkers is necessary. Two lung adenocarcinoma cell lines, PC9 and gefitinib-resistant PC9/Gef, were established for examining resistance mechanisms and identifying potential therapeutic targets. Two-dimensional differential gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry were used for examining global protein expression changes between PC9 and PC9/Gef. The results revealed that 164 identified proteins were associated with the formation of gefitinib resistance in PC9 cells. Additional studies using RNA interference showed that progesterone receptor membrane component 1 and pericentrin proteins have major roles in gefitinib resistance. In conclusion, the proteomic approach enabled identifying of numerous proteins involved in gefitinib resistance. The results provide useful diagnostic markers and therapeutic candidates for treating gefitinib-resistant NSCLC. - Highlights: • 164 proteins associated with gefitinib resistance were identified through proteomic analysis. • In this study, a lung adenocarcinoma and its gefitinib resistant partner were established. • mPR and PCNT proteins have evidenced to play important roles in gefitinib resistance.

Identification of protein expression alterations in gefitinib-resistant human lung adenocarcinoma: PCNT and mPR play key roles in the development of gefitinib-associated resistance

International Nuclear Information System (INIS)

Lin, Chi-Chen; Chen, Jing-Ting; Lin, Meng-Wei; Chan, Chia-Hao; Wen, Yueh-Feng; Wu, Shin-Bei; Chung, Ting-Wen; Lyu, Kevin W.; Chou, Hsiu-Chuan

2015-01-01

Gefitinib is the first-line chemotherapeutic drug for treating non-small cell lung cancer (NSCLC), which comprises nearly 85% of all lung cancer cases worldwide. However, most patients eventually develop drug resistance after 12–18 months of treatment. Hence, investigating the drug resistance mechanism and resistance-associated biomarkers is necessary. Two lung adenocarcinoma cell lines, PC9 and gefitinib-resistant PC9/Gef, were established for examining resistance mechanisms and identifying potential therapeutic targets. Two-dimensional differential gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry were used for examining global protein expression changes between PC9 and PC9/Gef. The results revealed that 164 identified proteins were associated with the formation of gefitinib resistance in PC9 cells. Additional studies using RNA interference showed that progesterone receptor membrane component 1 and pericentrin proteins have major roles in gefitinib resistance. In conclusion, the proteomic approach enabled identifying of numerous proteins involved in gefitinib resistance. The results provide useful diagnostic markers and therapeutic candidates for treating gefitinib-resistant NSCLC. - Highlights: • 164 proteins associated with gefitinib resistance were identified through proteomic analysis. • In this study, a lung adenocarcinoma and its gefitinib resistant partner were established. • mPR and PCNT proteins have evidenced to play important roles in gefitinib resistance.

Implications for Advanced Safeguards Derived from PR and PP Case Study Results

Energy Technology Data Exchange (ETDEWEB)

Boyer, Brian D. [Los Alamos National Laboratory, Nuclear Nonproliferation Division, N-4, Safeguards and Security Group, P. O. Box 1663, N-4, Mail Stop E541, Los Alamos, New Mexico 87545 (United States)

2009-06-15

The proliferation resistance and physical protection (PR and PP) working group produced a case study on the Example Sodium Fast Reactor (ESFR). The ESFR is a hypothetical nuclear energy system consisting of four sodium-cooled fast reactors of medium size collocated with an on-site dry fuel storage facility and a spent fuel reprocessing facility using pyro-processing technology. This study revealed how safeguards would be applied at such site consisting of integrated multiple fuel cycle facilities and the implications of what safeguards technology and safeguards concepts would need to be adapted and developed to safeguard successfully this Generation IV nuclear energy system concept. The major safeguards concepts driving our safeguards analysis are timeliness goals and material quantity goals. Because the fresh transuranic (TRU) fuel to be produced in the ESFR fuel fabrication facility contains plutonium, the ESFR will be reprocessing, using in the reactor, and storing material on site that will have IAEA defined 'direct use material' in it with stringent timeliness goals and material quantity goals that drive the safeguards implementation. Specifically, the TRU fresh fuel, pyro-processing in process material, LWR spent fuel sent to the ESFR, and TRU spent fuel will contain plutonium. This material will need to be verified at interim intervals four times per year because the irradiated direct use material, as defined previously, has three-month timeliness goals and 8 kg material quantity goals for plutonium. The TRU in-process material is, of course, irradiated direct-use material because of keeping the plutonium and uranium together with TRU products that should provide a radiation barrier that slows down the ability to reprocess the fuel and by the process if it intrinsically will take major modification to be able to separate plutonium from the uranium and TRU mixture. This is an issue that the ESFR design must answer to state it has valuable

PrPC from stem cells to cancer

Directory of Open Access Journals (Sweden)

Séverine eMartin-Lannerée

2014-09-01

Full Text Available The cellular prion protein PrPC was initially discovered as the normal counterpart of the pathological scrapie prion protein PrPSc, the main component of the infectious agent of Transmissible Spongiform Encephalopathies. While clues as to the physiological function of this ubiquitous protein were greatly anticipated from the development of knock-out animals, PrP-null mice turned out to be viable and to develop without major phenotypic abnormalities. Notwithstanding, the discovery that hematopoietic stem cells from PrP-null mice have impaired long-term repopulating potential has set the stage for investigating into the role of PrPC in stem cell biology. A wealth of data have now exemplified that PrPC is expressed in distinct types of stem cells and regulates their self-renewal as well as their differentiation potential. A role for PrPC in the fate restriction of embryonic stem cells has further been proposed. Paralleling these observations, an overexpression of PrPC has been documented in various types of tumours. In line with the contribution of PrPC to stemness and to the proliferation of cancer cells, PrPC was recently found to be enriched in subpopulations of tumour-initiating cells. In the present review, we summarize the current knowledge of the role played by PrPC in stem cell biology and discuss how the subversion of its function may contribute to cancer progression.

PPARγ1 phosphorylation enhances proliferation and drug resistance in human fibrosarcoma cells

Energy Technology Data Exchange (ETDEWEB)

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

2014-03-10

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

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

Directory of Open Access Journals (Sweden)

Shila Gilbert

2015-02-01

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

On the nature of the dhcp to fcc transition under pressure in Pr and Pr-Th alloys

International Nuclear Information System (INIS)

Vijayakumar, V.; Godwal, B.K.; Sikka, S.K.; Chidambaram, R.

1988-01-01

The results of electrical resistance (R), thermoelectric power (TEP) and X-ray diffraction measurements on praseodymium (Pr) and its alloys with thorium under pressure are reported. The maximum in R vs P curve exhibited by Pr persists only in the dhcp phase of Pr-Th alloy. X-ray measurements confirmed that in the alloys also the maximum in R vs P curve is due to the dhcp → fcc transition. Thus the behaviour of Pr and Pr-Th alloys is different from that of La and its alloys with Ce and Th where the maximum in the R vs P curve is electronic in origin and is exhibited by the dhcp, fcc and dist fcc phases. (author). 14 refs

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

International Nuclear Information System (INIS)

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

2013-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-07-12

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

Resistance changes of Pr0.7Ca0.3MnO3 films deposited through rf-magnetron sputtering

International Nuclear Information System (INIS)

Lee, Kwangseok; Han, Seungwoo; Park, Kyoungwan; Sok, Junghyun

2006-01-01

In this paper, the resistance-change behavior of a perovskite material was studied. In particular, Pr 0.7 Ca 0.3 MnO 3 (PCMO) films were deposited on a Pt bottom electrode by using an rf-magnetron sputtering system. The PCMO films showed a resistance-switching behavior at room temperature. They were then deposited at 300 .deg. C with different oxygen flow rates, and the deposited films were post-annealed at various temperatures in an O 2 or N 2 atmosphere. The ratio of the resistance change of the post-annealed PCMO films in the high-resistance state to that in the low-resistance state in an O 2 atmosphere turned out to be much larger than that of the post-annealed films in a N 2 atmosphere. The electrical properties of the PCMO films were also significantly affected by the top electrode. The resistance changes of the Ag/PCMO/Pt device turned out to be larger than those of the Au/PCMO/Pt device. It can, therefore, be concluded that the O 2 content and the top electrode improve the electroresistance.

Progesterone Alleviates Endometriosis via Inhibition of Uterine Cell Proliferation, Inflammation and Angiogenesis in an Immunocompetent Mouse Model

Science.gov (United States)

Kannan, Athilakshmi; Davila, Juanmahel; Zhao, Yuechao; Nowak, Romana A.; Bagchi, Milan K.; Bagchi, Indrani C.; Li, Quanxi

2016-01-01

Endometriosis, defined as growth of the endometrial cells outside the uterus, is an inflammatory disorder that is associated with chronic pelvic pain and infertility in women of childbearing age. Although the estrogen-dependence of endometriosis is well known, the role of progesterone in development of this disease remains poorly understood. In this study, we developed a disease model in which endometriosis was induced in the peritoneal cavities of immunocompetent female mice, and maintained with exogenous estrogen. The endometriosis-like lesions that were identified at a variety of ectopic locations exhibited abundant blood supply and extensive adhesions. Histological examination revealed that these lesions had a well-organized endometrial architecture and fibrotic response, resembling those recovered from clinical patients. In addition, an extensive proliferation, inflammatory response, and loss of estrogen receptor alpha (ERα) and progesterone receptor (PR) expression were also observed in these lesions. Interestingly, administration of progesterone before, but not after, lesion induction suppressed lesion expansion and maintained ERα and PR expressions. These progesterone-pretreated lesions exhibited attenuation in KI67, CD31, and pro-inflammatory cytokine expression as well as macrophage infiltration, indicating that progesterone ameliorates endometriosis progression by inhibiting cell proliferation, inflammation and neovascularization. Our studies further showed that suppression of global DNA methylation by application of DNA methyltransferase inhibitor to female mice bearing ectopic lesions restrained lesion expansion and restored ERα and PR expression in eutopic endometrium and ectopic lesions. These results indicate that epigenetic regulation of target gene expression via DNA methylation contributes, at least in part, to progesterone resistance in endometriosis. PMID:27776183

Progesterone Alleviates Endometriosis via Inhibition of Uterine Cell Proliferation, Inflammation and Angiogenesis in an Immunocompetent Mouse Model.

Directory of Open Access Journals (Sweden)

Yanfen Li

Full Text Available Endometriosis, defined as growth of the endometrial cells outside the uterus, is an inflammatory disorder that is associated with chronic pelvic pain and infertility in women of childbearing age. Although the estrogen-dependence of endometriosis is well known, the role of progesterone in development of this disease remains poorly understood. In this study, we developed a disease model in which endometriosis was induced in the peritoneal cavities of immunocompetent female mice, and maintained with exogenous estrogen. The endometriosis-like lesions that were identified at a variety of ectopic locations exhibited abundant blood supply and extensive adhesions. Histological examination revealed that these lesions had a well-organized endometrial architecture and fibrotic response, resembling those recovered from clinical patients. In addition, an extensive proliferation, inflammatory response, and loss of estrogen receptor alpha (ERα and progesterone receptor (PR expression were also observed in these lesions. Interestingly, administration of progesterone before, but not after, lesion induction suppressed lesion expansion and maintained ERα and PR expressions. These progesterone-pretreated lesions exhibited attenuation in KI67, CD31, and pro-inflammatory cytokine expression as well as macrophage infiltration, indicating that progesterone ameliorates endometriosis progression by inhibiting cell proliferation, inflammation and neovascularization. Our studies further showed that suppression of global DNA methylation by application of DNA methyltransferase inhibitor to female mice bearing ectopic lesions restrained lesion expansion and restored ERα and PR expression in eutopic endometrium and ectopic lesions. These results indicate that epigenetic regulation of target gene expression via DNA methylation contributes, at least in part, to progesterone resistance in endometriosis.

Anatomy of a nonhost disease resistance response of pea to Fusarium solani: PR gene elicitation via DNase, chitosan and chromatin alterations.

Directory of Open Access Journals (Sweden)

Lee A Hadwiger

2015-06-01

Full Text Available Of the multiplicity of plant pathogens in nature, only a few are virulent on a given plant species. Conversely, plants develop a rapid nonhost resistance response to the majority of the pathogens. The anatomy of the nonhost resistance of pea endocarp tissue against a pathogen of bean, Fusarium solani f.sp. phaseoli (Fsph and the susceptibility of pea to F. solani f sp. pisi (Fspi has been described cytologically, biochemically and molecular-biologically. Cytological changes have been followed by electron microscope and stain differentiation under white and UV light. The induction of changes in transcription, protein synthesis, expression of pathogenesis-related (PR genes, and increases in metabolic pathways culminating in low molecular weight, antifungal compounds are described biochemically. Molecular changes initiated by fungal signals to host organelles, primarily to the chromatin within host nuclei, are identified according to source of the signal and the mechanisms utilized in activating defense genes. The functions of some PR genes are defined. A hypothesis based on this data is developed to explain both why fungal growth is suppressed in nonhost resistance and why growth can continue in a susceptible reaction.

Anatomy of a nonhost disease resistance response of pea to Fusarium solani: PR gene elicitation via DNase, chitosan and chromatin alterations

Science.gov (United States)

Hadwiger, Lee A.

2015-01-01

Of the multiplicity of plant pathogens in nature, only a few are virulent on a given plant species. Conversely, plants develop a rapid “nonhost” resistance response to the majority of the pathogens. The anatomy of the nonhost resistance of pea endocarp tissue against a pathogen of bean, Fusarium solani f.sp. phaseoli (Fsph) and the susceptibility of pea to F. solani f sp. pisi (Fspi) has been described cytologically, biochemically and molecular-biologically. Cytological changes have been followed by electron microscope and stain differentiation under white and UV light. The induction of changes in transcription, protein synthesis, expression of pathogenesis-related (PR) genes, and increases in metabolic pathways culminating in low molecular weight, antifungal compounds are described biochemically. Molecular changes initiated by fungal signals to host organelles, primarily to chromatin within host nuclei, are identified according to source of the signal and the mechanisms utilized in activating defense genes. The functions of some PR genes are defined. A hypothesis based on this data is developed to explain both why fungal growth is suppressed in nonhost resistance and why growth can continue in a susceptible reaction. PMID:26124762

Anatomy of a nonhost disease resistance response of pea to Fusarium solani: PR gene elicitation via DNase, chitosan and chromatin alterations.

Science.gov (United States)

Hadwiger, Lee A

2015-01-01

Of the multiplicity of plant pathogens in nature, only a few are virulent on a given plant species. Conversely, plants develop a rapid "nonhost" resistance response to the majority of the pathogens. The anatomy of the nonhost resistance of pea endocarp tissue against a pathogen of bean, Fusarium solani f.sp. phaseoli (Fsph) and the susceptibility of pea to F. solani f sp. pisi (Fspi) has been described cytologically, biochemically and molecular-biologically. Cytological changes have been followed by electron microscope and stain differentiation under white and UV light. The induction of changes in transcription, protein synthesis, expression of pathogenesis-related (PR) genes, and increases in metabolic pathways culminating in low molecular weight, antifungal compounds are described biochemically. Molecular changes initiated by fungal signals to host organelles, primarily to chromatin within host nuclei, are identified according to source of the signal and the mechanisms utilized in activating defense genes. The functions of some PR genes are defined. A hypothesis based on this data is developed to explain both why fungal growth is suppressed in nonhost resistance and why growth can continue in a susceptible reaction.

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

International Nuclear Information System (INIS)

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

2015-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-11-27

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

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

International Nuclear Information System (INIS)

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

2001-01-01

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

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

DEFF Research Database (Denmark)

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

2017-01-01

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

Redox induces diverse effects on recombinant human wild-type PrP and mutated PrP with inserted or deleted octarepeats.

Science.gov (United States)

Shi, Qi; Chen, Cao; Zhang, Bao-Yun; Zhou, Wei; Xiao, Kang; Dong, Xiao-Ping

2018-04-01

Normal prion protein (PrP) contains two cysteines at amino acids 179 and 214, which may form intra‑ and interpeptide disulfide bonds. To determine the possible effects of this disulfide bridge on the biochemical features of PrP, prokaryotic recombinant human wild‑type PrP (PG5), and mutated PrPs with seven extra octarepeats (PG12) or with all five octarepeats removed (PG0), were subjected to redox in vitro. Sedimentation assays revealed a large portion of aggregation in redox‑treated PG5, but not in PG0 and PG12. Circular dichroism analysis detected increased β‑sheet and decreased α‑helix in PG5 subjected to redox, increased random‑coil and decreased β‑sheet in PG0, and increased random‑coil, but limited changes to β‑sheet content, in PG12. Thioflavin T fluorescence tests indicated that fluorescent value was increased in PG5 subjected to redox. In addition, proteinase K (PK) digestions indicated that PK resistance was stronger in PG12 and PG0 compared with in PG5; redox enhanced the PK resistance of all three PrP constructs, particularly PG0 and PG12. These data indicated that formation of a disulfide bond induces marked alterations in the secondary structure and biochemical characteristics of PrP. In addition, the octarepeat region within the PrP peptide markedly influences the effects of redox on the biochemical phenotypes of PrP, thus highlighting the importance of the number of octarepeats in the biological functions of PrP.

Fissile material disposition and proliferation risk

Energy Technology Data Exchange (ETDEWEB)

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

1996-05-01

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

Fissile material disposition and proliferation risk

International Nuclear Information System (INIS)

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

1996-01-01

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

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

NARCIS (Netherlands)

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

2002-01-01

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

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

Science.gov (United States)

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

2013-01-01

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

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

Directory of Open Access Journals (Sweden)

Mototaka Sato

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2016-08-15

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

In vitro T lymphocyte responses to proteinase 3 (PR3) and linear peptides of PR3 in patients with Wegener's granulomatosis (WG)

NARCIS (Netherlands)

Van der Geld, YM; Huitema, MG; Franssen, CFM; Limburg, PC; Kallenberg, CGM; van der Zee, R.

2000-01-01

T cell-mediated immunity is thought to play an important role in the pathogenesis of WG. In previous studies a minority of WG patients as well as some healthy controls showed in vitro proliferation of their peripheral blood mononuclear cells (PBMC) to PR3, the main autoantigen in WG. The relevant

Demographic differences in PrEP–related stereotypes: Implications for implementation

Science.gov (United States)

Golub, Sarit. A.; Gamarel, Kristi E.; Surace, Anthony

2015-01-01

Qualitative interviews about pre-exposure prophylaxis (PrEP) stereotypes were conducted with a subsample of 160 MSM who participated in a PrEP messaging study. Negative stereotypes about PrEP users were identified by 80% of participants. Two types of stereotypes were most common: PrEP users are HIV-infected (and lying about it), and PrEP users are promiscuous and resistant to condom use. Participants’ identification of these stereotype categories differed significantly by demographic factors (i.e. race/ethnicity, education). Expanding access to PrEP requires recognizing potential differences in the experience or anticipation of PrEP-related stereotypes that might impact willingness to discuss PrEP with providers, friends, or partners. PMID:26143247

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

International Nuclear Information System (INIS)

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

2011-01-01

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

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

Science.gov (United States)

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

2017-01-17

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

The PR-1 domain accounts for the anti-angiogenic activity of a cysteine-rich secretory protein member from the buccal glands of Lampetra japonica.

Science.gov (United States)

Duan, Dandan; Wang, Hongyan; Zhou, Rong; Jiang, Qi; Xiao, Rong

2018-02-01

Previous studies have shown that cysteine-rich buccal gland protein (CRBGP) from buccal glands of Lampetra japonica could suppress angiogenesis in chick chorioallantoic membrane models. As CRBGP is composed of a pathogenesis-related group 1 (PR-1) domain and a cysteine-rich domain (CRD), which domain accounts for the effects of CRBGP on anti-angiogenesis? In the present study, recombinant PR-1 and CRD (rL-PR-1 and rL-CRD) were obtained. MTT assays showed rL-PR-1 inhibited the proliferation of HUVECs significantly in a dose-dependent manner with an IC 50 of 2μM, while rL-CRD had no obviously inhibitory effect on the proliferation of HUVECs, suggested that PR-1 is the main function domain on the anti-angiogenic activity of CRBGP. Similar to CRBGP, rL-PR-1 induced apoptosis in HUVECs in a mitochondrial-dependent pathway by affecting the level of BAX, BCL2 and caspase 3. Also, the cytotoxic property of rL-PR-1 might be one of the factors which suppressed the proliferation of HUVECs. Furthermore, rL-PR-1 blocked the adhesion, migration, invasion and tube formation of HUVECs by disturbing the cytoskeleton arrangement and down-regulating the level of matrix metallo-peptidase 2. In summary, rL-PR-1 has the anti-angiogenic activity which would provide the information on the functions and mechanisms of cysteine-rich secretory protein family members. Copyright © 2017 Elsevier B.V. All rights reserved.

Experimental Models of Inherited PrP Prion Diseases.

Science.gov (United States)

Watts, Joel C; Prusiner, Stanley B

2017-11-01

The inherited prion protein (PrP) prion disorders, which include familial Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease, and fatal familial insomnia, constitute ∼10%-15% of all PrP prion disease cases in humans. Attempts to generate animal models of these disorders using transgenic mice expressing mutant PrP have produced variable results. Although many lines of mice develop spontaneous signs of neurological illness with accompanying prion disease-specific neuropathological changes, others do not. Furthermore, demonstrating the presence of protease-resistant PrP species and prion infectivity-two of the hallmarks of the PrP prion disorders-in the brains of spontaneously sick mice has proven particularly challenging. Here, we review the progress that has been made toward developing accurate mouse models of the inherited PrP prion disorders. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Methamphetamine increases Prion Protein and induces dopamine-dependent expression of protease resistant PrPsc.

Science.gov (United States)

Ferrucci, M; Ryskalin, L; Biagioni, F; Gambardella, S; Busceti, C L; Falleni, A; Lazzeri, G; Fornai, F

2017-07-01

The cellular prion protein (PrPc) is physiologically expressed within selective brain areas of mammals. Alterations in the secondary structure of this protein lead to scrapie-like prion protein (PrPsc), which precipitates in the cell. PrPsc has been detected in infectious, inherited or sporadic neurodegenerative disorders. Prion protein metabolism is dependent on autophagy and ubiquitin proteasome. Despite not being fully elucidated, the physiological role of prion protein relates to chaperones which rescue cells under stressful conditions.Methamphetamine (METH) is a widely abused drug which produces oxidative stress in various brain areas causing mitochondrial alterations and protein misfolding. These effects produce a compensatory increase of chaperones while clogging cell clearing pathways. In the present study, we explored whether METH administration modifies the amount of PrPc. Since high levels of PrPc when the clearing systems are clogged may lead to its misfolding into PrPsc, we further tested whether METH exposure triggers the appearance of PrPsc. We analysed the effects of METH and dopamine administration in PC12 and striatal cells by using SDS-PAGE Coomassie blue, immune- histochemistry and immune-gold electron microscopy. To analyze whether METH administration produces PrPsc aggregates we used antibodies directed against PrP following exposure to proteinase K or sarkosyl which digest folded PrPc but misfolded PrPsc. We fond that METH triggers PrPsc aggregates in DA-containing cells while METH is not effective in primary striatal neurons which do not produce DA. In the latter cells exogenous DA is needed to trigger PrPsc accumulation similarly to what happens in DA containing cells under the effects of METH. The present findings, while fostering novel molecular mechanisms involving prion proteins, indicate that, cell pathology similar to prion disorders can be mimicked via a DA-dependent mechanism by a drug of abuse.

Association between ambient air pollution and proliferation of umbilical cord blood cells

Energy Technology Data Exchange (ETDEWEB)

Novack, L., E-mail: novack@bgu.ac.il [Department of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva (Israel); Yitshak-Sade, M. [Clinical Research Center, Soroka University Medical Center, Beer-Sheva (Israel); Landau, D. [Division of Neonatology, University Medical Center, Beer-Sheva (Israel); Kloog, I. [Department of Geography, Ben-Gurion University of the Negev, Beer-Sheva (Israel); Sarov, B. [Department of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva (Israel); Karakis, I. [Environmental Epidemiology Department, Ministry of Health, Jerusalem (Israel); Ashkelon Academic College, Ashkelon (Israel)

2016-11-15

It has been established as a common knowledge that ambient air pollution (AAP) has an adverse effect on human health. The pathophysiological mechanism of this impact is likely to be related to the oxidative stress. In the current study we estimate the association between AAP and cell proliferation (CP) of umbilical cord blood cells, representing maternal organism most proximal to the fetal body. Blood samples were tested for proliferation in 292 enrolled Arab-Bedouin women at delivery (July 2012–March 2013). The estimates of AAP were defined by a hybrid satellite based model predicting both PM{sub 2.5} (particles<2.5 µm in diameter) and PM{sub 10} (particles<10 µm in diameter) as well as monitoring stations for gaseous air pollutants. Risk estimates of pollution exposure were adjusted to medical history, household risk factors and meteorological factors on the day of delivery or one week prior. Ambient ozone (O{sub 3}) levels on 1, 2, 3and 4 days prior to delivery were associated with lower CP (Prevalence ratio (PR)=0.92, 0.92, 0.93, 0.93, respectively). Increase in inter-quartile range (IOR) of PM{sub 2.5} one day before delivery was associated with 9% increase in CP levels (PR=1.09). The positive direction in association was changed to negative association with CP for PM{sub 2.5} levels measured at more distant time periods (PR=0.90 and 0.93 for lags 5 and 6 days, respectively). Investigation of PM{sub 10} levels indicated a similar pattern (PR=1.05 for pollution values recorded one day before delivery and 0.93 and 0.95 for lags of 5 and 6 days, respectively). Carbon monoxide (CO) levels were associated with lower CP on the day of delivery and 1 day prior (PR=0.92 and PR=0.94). To conclude, the levels of cell proliferation of umbilical cord blood cells appear to be associated with the AAP. More studies are needed to support our findings. - Highlights: • Ambient air pollutants were suggested to have an impact on cell proliferation (CP) of umbilical cord

Association between ambient air pollution and proliferation of umbilical cord blood cells

International Nuclear Information System (INIS)

Novack, L.; Yitshak-Sade, M.; Landau, D.; Kloog, I.; Sarov, B.; Karakis, I.

2016-01-01

It has been established as a common knowledge that ambient air pollution (AAP) has an adverse effect on human health. The pathophysiological mechanism of this impact is likely to be related to the oxidative stress. In the current study we estimate the association between AAP and cell proliferation (CP) of umbilical cord blood cells, representing maternal organism most proximal to the fetal body. Blood samples were tested for proliferation in 292 enrolled Arab-Bedouin women at delivery (July 2012–March 2013). The estimates of AAP were defined by a hybrid satellite based model predicting both PM 2.5 (particles<2.5 µm in diameter) and PM 10 (particles<10 µm in diameter) as well as monitoring stations for gaseous air pollutants. Risk estimates of pollution exposure were adjusted to medical history, household risk factors and meteorological factors on the day of delivery or one week prior. Ambient ozone (O 3 ) levels on 1, 2, 3and 4 days prior to delivery were associated with lower CP (Prevalence ratio (PR)=0.92, 0.92, 0.93, 0.93, respectively). Increase in inter-quartile range (IOR) of PM 2.5 one day before delivery was associated with 9% increase in CP levels (PR=1.09). The positive direction in association was changed to negative association with CP for PM 2.5 levels measured at more distant time periods (PR=0.90 and 0.93 for lags 5 and 6 days, respectively). Investigation of PM 10 levels indicated a similar pattern (PR=1.05 for pollution values recorded one day before delivery and 0.93 and 0.95 for lags of 5 and 6 days, respectively). Carbon monoxide (CO) levels were associated with lower CP on the day of delivery and 1 day prior (PR=0.92 and PR=0.94). To conclude, the levels of cell proliferation of umbilical cord blood cells appear to be associated with the AAP. More studies are needed to support our findings. - Highlights: • Ambient air pollutants were suggested to have an impact on cell proliferation (CP) of umbilical cord blood. • Ozone (O 3 ) and

Quantitating PrP Polymorphisms Present in Prions from Heterozygous Scrapie-Infected Sheep.

Science.gov (United States)

Silva, Christopher J; Erickson-Beltran, Melissa L; Hui, Colleen; Badiola, Juan José; Nicholson, Eric M; Requena, Jesús R; Bolea, Rosa

2017-01-03

Scrapie is a prion (PrP Sc ) disease of sheep. The incubation period of sheep scrapie is strongly influenced by polymorphisms at positions 136, 154, and 171 of a sheep's normal cellular prion protein (PrP C ). Chymotrypsin was used to digest sheep recombinant PrP to identify a set of characteristic peptides [M 132 LGSXMSRPL 141 (X = A or V), Y 153 XENMY 158 (X,= H or R), and Y 166 RPVDXY 172 (X = H, K, Q, or R)] that could be used to detect and quantitate polymorphisms at positions 136, 154, and 171 of sheep PrP C or PrP Sc . These peptides were used to develop a multiple reaction monitoring method (MRM) to detect the amounts of a particular polymorphism in a sample of PrP Sc isolated from sheep heterozygous for their PrP C proteins. The limit of detection for these peptides was less than 50 attomole. Spinal cord tissue from heterozygous (ARQ/VRQ or ARH/ARQ) scrapie-infected Rasa Aragonesa sheep was analyzed using this MRM method. Both sets of heterozygotes show the presence of both polymorphisms in PrP Sc . This was true for samples containing both proteinase K (PK)-sensitive and PK-resistant PrP Sc and samples containing only the PK-resistant PrP Sc . These results show that heterozygous animals contain PrP Sc that is composed of significant amounts of both PrP polymorphisms.

Silencing of acidic pathogenesis-related PR-1 genes increases extracellular beta-(1 -> 3)-glucanase activity at the onset of tobacco defence reactions

DEFF Research Database (Denmark)

Riviere, M.P.; Marais, A.; Ponchet, M.

2008-01-01

silenced. Plants lacking extracellular PR-1s were more susceptible than wild-type plants to the oomycete Phytophthora parasitica but displayed unaffected systemic acquired resistance and developmental resistance to this pathogen. Treatment with salicylic acid up-regulates the PR-1g gene, encoding a basic...... protein of the PR-1 family, in PR-1-deficient tobacco, indicating that PR-1 expression may repress that of PR-1g. This shows that acidic PR-1s are dispensable for expression of salicylic acid-dependent acquired resistances against P. parasitica and may reveal a functional overlap in tobacco defence......The class 1 pathogenesis-related (PR) proteins are thought to be involved in plant defence responses, but their molecular functions are unknown. The function of PR-1 was investigated in tobacco by generating stable PR-1a-silenced lines in which other acidic PR-1 genes (PR-1b and PR-1c) were...

Thermoelectric power of PrMg3

Science.gov (United States)

Isikawa, Yosikazu; Somiya, Kazuya; Koyanagi, Huruto; Mizushima, Toshio; Kuwai, Tomohiko; Tayama, Takashi

2010-01-01

PrMg3 is supposed to be one of the strongly correlated electron systems originated from the hybridization between the Pr 4f and conduction electrons, because the gigantic electronic specific heat coefficient C/T was observed at low temperatures. However, a typical behaviour of - ln T dependence was not observed in the temperature dependence of the electrical resistivity. The thermoelectric power S is a powerful tool to investigate the density of states at the Fermi energy. We measured carefully the thermoelectric power of PrMg3 in the temperature range between 2 and 300 K. S is extremely small, ranged within ±1 μV/K over the whole temperature. The value of S/T at low temperature limit was also significantly smaller than expected from the specific heat results. We therefore conclude that the density of state at the Fermi level is not enhanced in PrMg3.

Thermoelectric power of PrMg3

International Nuclear Information System (INIS)

Isikawa, Yosikazu; Somiya, Kazuya; Koyanagi, Huruto; Mizushima, Toshio; Kuwai, Tomohiko; Tayama, Takashi

2010-01-01

PrMg 3 is supposed to be one of the strongly correlated electron systems originated from the hybridization between the Pr 4f and conduction electrons, because the gigantic electronic specific heat coefficient C/T was observed at low temperatures. However, a typical behaviour of - ln T dependence was not observed in the temperature dependence of the electrical resistivity. The thermoelectric power S is a powerful tool to investigate the density of states at the Fermi energy. We measured carefully the thermoelectric power of PrMg 3 in the temperature range between 2 and 300 K. S is extremely small, ranged within ±1 μV/K over the whole temperature. The value of S/T at low temperature limit was also significantly smaller than expected from the specific heat results. We therefore conclude that the density of state at the Fermi level is not enhanced in PrMg 3 .

Development Proliferation Resistance Assessment Methodology for Regulation Purposes

International Nuclear Information System (INIS)

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

2015-01-01

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

Structural, magnetic, and electronic transport properties of pyrochlore iridate Pr2Ir2O7

Science.gov (United States)

Kumar, Harish; Chaurasia, Rachna; Kumari, Pratibha; Paramanik, A. K.

2018-04-01

We have studied the structural, magnetic, and electronic transport properties of pyrochlore iridate Pr2Ir2O7. Structural investigation has been done using x-ray powder diffraction and Rietveld analysis. Pr2Ir2O7 crystallize in cubic crystallographic phase with Fd-3m space group. Temperature dependent magnetization data does not show magnetic bifurcation down to 2 K. Electrical resistivity data of Pr2Ir2O7 exhibits metallic behavior throughout temperature range. Below 50 K, a small rise in resistivity data of Pr2Ir2O7 is observed down to 12 K.

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

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

International Nuclear Information System (INIS)

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

2015-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-09-01

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

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

International Nuclear Information System (INIS)

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

1999-01-01

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

Strengthening the nuclear non-proliferation regime

International Nuclear Information System (INIS)

Carlson, J.

2003-01-01

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

Lessons learned from the experiences of informal PrEP users in France: results from the ANRS-PrEPage study.

Science.gov (United States)

Rivierez, I; Quatremere, G; Spire, B; Ghosn, J; Rojas Castro, D

2018-05-30

Before January 2016, Pre-Exposure Prophylaxis (PrEP), a new biomedical HIV-prevention tool, was only available in France via ANRS-Ipergay clinical study but informal use was reported outside this setting. PrEPage qualitative study reports profiles and experiences of participants who used PrEP outside of a biomedical trial before this prevention method was authorized. Between March 2015 and February 2016, a cross-section of twenty-four informal PrEP users, mostly MSM, was recruited to complete in-depth semi-structured interviews. While ANRS-Ipergay was still ongoing (2012-2016), participants described their initiation to PrEP, the way they used it and the difficulties they faced to acquire antiretroviral drugs in an environment where PrEP was still not widely known and often criticized . Through the testimonies, different user profiles and motivation toward informal PrEP use emerged: (a) participants who have increasing difficulties using condoms, (b) "opportunists" who tried PrEP without the intention of using it regularly and (c) participants with a risk aversion who sought additional protection against HIV. Participants chose to use PrEP and/or their usual prevention strategies depending on available supplies, type of partners and individual attitudes toward risk. The feeling of living a safer sex life helped participants to outweigh the fear of possible toxicity and drug resistance. Participants' needs and expectations about PrEP implementation in France were also presented.

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

Science.gov (United States)

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

2017-12-01

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

Strengthening the non proliferation regime: French views

International Nuclear Information System (INIS)

Delaune, P.

2013-01-01

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

Interferon-Stimulated Genes Are Transcriptionally Repressed by PR in Breast Cancer.

Science.gov (United States)

Walter, Katherine R; Goodman, Merit L; Singhal, Hari; Hall, Jade A; Li, Tianbao; Holloran, Sean M; Trinca, Gloria M; Gibson, Katelin A; Jin, Victor X; Greene, Geoffrey L; Hagan, Christy R

2017-10-01

The progesterone receptor (PR) regulates transcriptional programs that drive proliferation, survival, and stem cell phenotypes. Although the role of native progesterone in the development of breast cancer remains controversial, PR clearly alters the transcriptome in breast tumors. This study identifies a class of genes, Interferon (IFN)-stimulated genes (ISGs), potently downregulated by ligand-activated PR which have not been previously shown to be regulated by PR. Progestin-dependent transcriptional repression of ISGs was observed in breast cancer cell line models and human breast tumors. Ligand-independent regulation of ISGs was also observed, as basal transcript levels were markedly higher in cells with PR knockdown. PR repressed ISG transcription in response to IFN treatment, the canonical mechanism through which these genes are activated. Liganded PR is robustly recruited to enhancer regions of ISGs, and ISG transcriptional repression is dependent upon PR's ability to bind DNA. In response to PR activation, key regulatory transcription factors that are required for IFN-activated ISG transcription, STAT2 and IRF9, exhibit impaired recruitment to ISG promoter regions, correlating with PR/ligand-dependent ISG transcriptional repression. IFN activation is a critical early step in nascent tumor recognition and destruction through immunosurveillance. As the large majority of breast tumors are PR positive at the time of diagnosis, PR-dependent downregulation of IFN signaling may be a mechanism through which early PR-positive breast tumors evade the immune system and develop into clinically relevant tumors. Implications: This study highlights a novel transcriptional mechanism through which PR drives breast cancer development and potentially evades the immune system. Mol Cancer Res; 15(10); 1331-40. ©2017 AACR . ©2017 American Association for Cancer Research.

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-07-15

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

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

International Nuclear Information System (INIS)

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

2015-01-01

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

PR-PR: cross-platform laboratory automation system.

Science.gov (United States)

Linshiz, Gregory; Stawski, Nina; Goyal, Garima; Bi, Changhao; Poust, Sean; Sharma, Monica; Mutalik, Vivek; Keasling, Jay D; Hillson, Nathan J

2014-08-15

To enable protocol standardization, sharing, and efficient implementation across laboratory automation platforms, we have further developed the PR-PR open-source high-level biology-friendly robot programming language as a cross-platform laboratory automation system. Beyond liquid-handling robotics, PR-PR now supports microfluidic and microscopy platforms, as well as protocol translation into human languages, such as English. While the same set of basic PR-PR commands and features are available for each supported platform, the underlying optimization and translation modules vary from platform to platform. Here, we describe these further developments to PR-PR, and demonstrate the experimental implementation and validation of PR-PR protocols for combinatorial modified Golden Gate DNA assembly across liquid-handling robotic, microfluidic, and manual platforms. To further test PR-PR cross-platform performance, we then implement and assess PR-PR protocols for Kunkel DNA mutagenesis and hierarchical Gibson DNA assembly for microfluidic and manual platforms.

Comparing the physical properties of Pr/Gd and Pr/Ce substitutions in Ru(Gd1.5Ce0.5)Sr2Cu2O10- δ

Science.gov (United States)

Khajehnezhad, A.; Nikseresht, N.; Hadipour, H.; Akhavan, M.

2008-06-01

We have compared the electrical and magnetic properties of Ru(Gd1.5- x Pr x )Ce0.5Sr2Cu2O10- δ (Pr/Gd samples) with x = 0.0, 0.01, 0.03, 0.033, 0.035, 0.04, 0.05, 0.06, 0.1 and RuGd1.5(Ce0.5- x Pr x ) Sr2 Cu2O10- δ (Pr/Ce samples) with x = 0.0, 0.01, 0.03, 0.05, 0.08, 0.1, 0.15, 0.2 prepared by the standard solid-state reaction technique. We obtained the XRD patterns for different samples with various x. The lattice parameters versus x for different substitutions have been obtained from Rietveld analysis. To determine how the magnetic and superconducting properties of these layered cuprate systems can be affected by Pr substitution, the resistivity, and magnetoresistivity, with H ext varying from 0.0 to 15 kOe, have been measured at various temperatures. Superconducting transition temperature T c and magnetic transition T irr , have been obtained through resistivity and ac susceptibility measurements. The T c suppression due to Pr/Gd and Pr/Ce substitutions show competition between pair breaking by magnetic impurities, hole doping due to different valances of ions, difference in ionic radii, and oxygen stoichiometry. Pr/Gd substitution suppresses superconductivity more rapidly than for Pr/Ce, showing that the effect of hole doping and magnetic impurity pair breaking is stronger than the difference in ionic radii. In Pr/Gd substitution, the small difference between the ionic radii of Pr3+,4+ and Gd3+, and absorption of more oxygen due to the higher valence of Pr with respect to Gd, decreases the mean Ru-Ru distance, and as a result, the magnetic exchange interaction becomes stronger with the increase of x. However, Pr/Ce substitution has the opposite effect. The magnetic parameters such as H c , obtained through magnetization measurements versus applied magnetic field isotherm at 77 K and room temperatures, become stronger with x in Pr/Gd and weaker with x in Pr/Ce substitution.

Reduced response of splenocytes after mitogen-stimulation in the prion protein (PrP) gene-deficient mouse: PrPLP/Doppel production and cerebral degeneration

International Nuclear Information System (INIS)

Kim, Chi-Kyeong; Hirose, Yuko; Sakudo, Akikazu; Takeyama, Natsumi; Kang, Chung-Boo; Taniuchi, Yojiro; Matsumoto, Yoshitsugu; Itohara, Shigeyoshi; Sakaguchi, Suehiro; Onodera, Takashi

2007-01-01

Splenocytes of wild-type (Prnp +/+ ) and prion protein gene-deficient (Prnp -/- ) mice were treated with various activation stimuli such as T cell mitogen concanavalin A (ConA), phorbol 12-myristate 13-acetate (PMA) + ionomycin (Io), or B cell mitogen lipopolysaccharide (LPS). Cellular prion protein (PrP C ) expression was enhanced following ConA stimulation, but not PMA + Io or LPS in Prnp +/+ splenocytes. Rikn Prnp -/- splenocytes elicited lower cell proliferations than Prnp +/+ or Zrch I Prnp -/- splenocytes after LPS stimulation and showed sporadic nerve cells in the cerebral cortex and deeper structure. Around the degenerated nerve cells, mild vacuolation in the neuropil was observed. This neural alteration correlated well to the suppressed response of B cells in the spleen. The finding that discrete lesions within the central nervous systems induced marked modulation of immune function probably indicates the existence of a delicately balanced neural-endocrine network by PrP C and PrPLP/Doppel

Influence of the valence states of atoms on conducting properties of PrBa2Cu3O6+x

International Nuclear Information System (INIS)

Romanenko, A.I.; Zakharchuk, N.F.; Naumov, N.G.; Fedorov, V.E.; Paek, U.H.

1997-01-01

Pr 3+ valent state only was discovered in PrBa 2 Cu 3 O 6+x within the oxygen content range 0.4 ≤ x ≤ 0.6. Out of this range, Pr 4+ state appears also. All the samples obtained showed insulating behavior of resistivity r(T). In PrBa 2 Cu 3 O 6+x (0.4 ≤ x ≤ 0.6), the resistivity is Mott variable-range hopping conduction type and is connected with oxygen disorder only. Out of this range, the localization is much stronger; this increase is due to Pr 4+ /Pr 3+ position disorder. Also, the localization decreases after annealing at room temperature is the result of ordering. Thus, the absence of metallic (and therefore superconducting) state in PrBa 2 Cu 3 O 6+x is due to the presence of both Pr 4+ and Pr 4+ /Pr 3+ disorder

Pre-exposure prophylaxis and antiretroviral resistance: HIV prevention at a cost?

Science.gov (United States)

Hurt, Christopher B; Eron, Joseph J; Cohen, Myron S

2011-12-01

Pre-exposure prophylaxis (PrEP), the use of antiretrovirals (ARVs) by human immunodeficiency virus (HIV)-uninfected individuals to prevent acquisition of the virus during high-risk sexual encounters, enjoyed its first 2 major successes with the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 and the Pre-Exposure Prophylaxis Initiative (iPrEx). These successes were buoyed by additional positive results from the TDF2 and Partners PrEP trials. Although no seroconverters in either arm of CAPRISA developed resistance to tenofovir, 2 participants in iPrEx with undetected, seronegative acute HIV infection were randomized to receive daily oral tenofovir-emtricitabine and resistance to emtricitabine was later discovered in both men. A similar case in the TDF2 study resulted in resistance to both ARVs. These cases prompted us to examine existing literature on the nature of resistance mutations elicited by ARVs used for PrEP. Here, we discuss the impact of signature mutations selected by PrEP, how rapidly these emerge with daily ARV exposure, and the individual-level and public health consequences of ARV resistance.

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

International Nuclear Information System (INIS)

Kuznetsov, Vladimir

2008-01-01

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

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

International Nuclear Information System (INIS)

Kuznetsov, V.

2007-01-01

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

Resistance Status and Resistance Mechanisms in a Strain of Aedes aegypti (Diptera: Culicidae) From Puerto Rico.

Science.gov (United States)

Estep, Alden S; Sanscrainte, Neil D; Waits, Christy M; Louton, Jessica E; Becnel, James J

2017-11-07

Puerto Rico (PR) has a long history of vector-borne disease and insecticide-resistant Aedes aegypti (L.). Defining contributing mechanisms behind phenotypic resistance is critical for effective vector control intervention. However, previous studies from PR have each focused on only one mechanism of pyrethroid resistance. This study examines the contribution of P450-mediated enzymatic detoxification and sodium channel target site changes to the overall resistance phenotype of Ae. aegypti collected from San Juan, PR, in 2012. Screening of a panel of toxicants found broad resistance relative to the lab susceptible Orlando (ORL1952) strain. We identified significant resistance to representative Type I, Type II, and nonester pyrethroids, a sodium channel blocker, and a sodium channel blocking inhibitor, all of which interact with the sodium channel. Testing of fipronil, a chloride channel agonist, also showed low but significant levels of resistance. In contrast, the PR and ORL1952 strains were equally susceptible to chlorfenapyr, which has been suggested as an alternative public health insecticide. Molecular characterization of the strain indicated that two common sodium channel mutations were fixed in the population. Topical bioassay with piperonyl butoxide (PBO) indicated cytochrome P450-mediated detoxification accounts for approximately half of the resistance profile. Transcript expression screening of cytochrome P450s and glutathione-S-transferases identified the presence of overexpressed transcripts. This study of Puerto Rican Ae. aegypti with significant contributions from both genetic changes and enzymatic detoxification highlights the necessity of monitoring for resistance but also defining the multiple resistance mechanisms to inform effective mosquito control. Published by Oxford University Press on behalf of Entomological Society of America 2017. This work is written by US Government employees and is in the public domain in the US.

A importância da prática da psicologia baseada em evidências: aspectos conceituais, níveis de evidência, mitos e resistências

Directory of Open Access Journals (Sweden)

Tamara Melnik

2015-04-01

Full Text Available Na atualidade existe uma demanda mundial por práticas na saúde baseadas em evidências em diversas especialidades envolvidas nos cuidados da saúde e sua promoção. A prática da psicologia baseada em evidências (PPBE integra a melhor evidência de pesquisa disponível, a expertise clínica, as preferências e características do cliente na tomada de decisão ao nível clinico e também na orientação de políticas públicas na saúde mental. Esse artigo discute os aspectos conceituais da PPBE, os níveis de evidência para a tomada de decisão, mitos e resistência a PPBE. Atualmente ainda existem muitas fontes de incompreensões e mitos acerca da PPBE, as quais constituem fontes de resistência para sua incorporação à prática clínica. Parte-se do princípio que entender os entraves à aceitação da PPBE é crucial não apenas para a construção de contra-argumentos, mas para auxiliar no processo de construção do conhecimento e da difusão de informações cientificas que possam orientar o cuidado oferecido aos indivíduos de forma efetiva e ética.

Animation of Antimicrobial Resistance

Medline Plus

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

Animation of Antimicrobial Resistance

Medline Plus

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

Utility of Social Modeling for Proliferation Assessment - Preliminary Findings

International Nuclear Information System (INIS)

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

2009-01-01

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

Nuclear data for innovative reactors having persistent resistance to nuclear proliferation

International Nuclear Information System (INIS)

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

2005-01-01

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

Recovery of oscillatory magneto-resistance in phase separated La0.3Pr0.4Ca0.3MnO3 epitaxial thin films

International Nuclear Information System (INIS)

Alagoz, H. S.; Jeon, J.; Mahmud, S. T.; Saber, M. M.; Chow, K. H.; Jung, J.; Prasad, B.; Egilmez, M.

2013-01-01

In-plane angular dependent magneto-resistance has been studied in La 0.3 Pr 0.4 Ca 0.3 MnO 3 (LPCMO) manganite thin films deposited on the (100) oriented NdGaO 3 , and (001) oriented SrTiO 3 and LaAlO 3 substrates. At temperatures where the electronic phase separation is the strongest, a metastable irreversible state exists in the films whose resistivity ρ attains a large time dependent value. The ρ decreases sharply with an increasing angle θ between the magnetic field and the current, and does not display an expected oscillatory cos 2 θ/sin 2 θ dependence for all films. The regular oscillations are recovered during repetitive sweeping of θ between 0° and 180°. We discuss possible factors that could produce these unusual changes in the resistivity

Effects of Pr-deficiency on thermal expansion and electrochemical properties in Pr_1_−_xBaCo_2O_5_+_δ cathodes for IT-SOFCs

International Nuclear Information System (INIS)

Zhang, Leilei; Yao, Guibin; Song, Zhaoyuan; Niu, Bingbing; Long, Wen; Zhang, Lei; Shen, Yu; He, Tianmin

2016-01-01

Highlights: • Single phase oxides P_1_−_xBCO with x = 0.00–0.10 were successfully prepared. • TECs and electrical conductivities of P_1_−_xBCO cathodes decrease with Pr-deficiency. • Among P_1_−_xBCO cathodes, P_0_._9_2BCO exhibits the lowest polarization resistance. • Electron charge transfer plays a dominant role in cathode oxygen reduction. • P_m_a_x of 987 mW cm"−"2 at 800 °C for P_0_._9_2BCO cathode is obtained on SDC electrolyte. - Abstract: Pr-deficient Pr_1_−_xBaCo_2O_5_+_δ (P_1_−_xBCO) oxides are evaluated as cathode materials for intermediate temperature solid oxide fuel cells (IT-SOFCs). Effects of Pr-deficiency on electrical conductivity, thermal expansion and electrochemical properties are investigated. Both the conductivity and thermal expansion coefficient (TEC) decrease with increasing Pr-deficiency. All of the conductivity, thermal expansion and TGA measurements demonstrate the existence of high temperature order-disorder transition. The oxygen reduction mechanism for P_1_−_xBCO cathodes are characterized by electrochemical impedance spectroscopy. Over the temperature range of 600−800 °C, the cathode polarization resistance is mainly contributed from electronic charge transfer over the cathode surface. Proper Pr-deficiency reduces cathode polarization resistance (R_p), and the lowest R_p (0.081 Ω cm"2 at 700 °C) is obtained for the P_0_._9_2BCO cathode. In addition, the effects of order-disorder transition on the properties of P_1_−_xBCO cathodes have also been discussed. Maximum power densities of a single-cell with P_0_._9_2BCO cathode on 300-μm thick Sm_0_._2Ce_0_._8O_1_._9 (SDC) electrolyte achieve 446–987 mW cm"−"2 at 650–800 °C. These results suggest that, among various P_1_−_xBCO oxides, P_0_._9_2BCO is the most promising candidate cathode material for IT-SOFCs.

Animation of Antimicrobial Resistance

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

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

International Nuclear Information System (INIS)

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

2000-01-01

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

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

International Nuclear Information System (INIS)

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

2001-01-01

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

Proliferation Vulnerability Red Team report

Energy Technology Data Exchange (ETDEWEB)

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

1996-10-01

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

Nuclear dilemma: power, proliferation, and development

International Nuclear Information System (INIS)

Miller, M.

1979-01-01

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

Corrosion resistance and microstructure characterization of rare-earth-transition metal-aluminum-magnesium alloys

International Nuclear Information System (INIS)

Banczek, E.P.; Zarpelon, L.M.C.; Faria, R.N.; Costa, I.

2009-01-01

This paper reports the results of investigation carried out to evaluate the corrosion resistance and microstructure of some cast alloys represented by the general formula: La 0.7-x Pr x Mg 0.3 Al 0.3 Mn 0.4 Co 0.5 Ni 3.8 (x = 0, 0.1, 0.3, 0.5, and 0.7). Scanning electron microscopy (SEM) and electrochemical methods, specifically, polarization curves and electrochemical impedance spectroscopy (EIS), have been employed in this study. The effects of Pr substitution on the composition of the various phases in the alloys and their corrosion resistance have been studied. The electrochemical results showed that the alloy without Pr and the one with total La substitution showed the highest corrosion resistance among the studied alloys. The corrosion resistance of the alloys decreased when Pr was present in the lowest concentrations (0.1 and 0.3), but for higher Pr concentrations (0.5 and 0.7), the corrosion resistance increased. Corrosion occurred preferentially in a Mg-rich phase.

Kosmotropic anions promote conversion of recombinant prion protein into a PrPSc-like misfolded form.

Directory of Open Access Journals (Sweden)

Rodrigo Diaz-Espinoza

Full Text Available Prions are self-propagating proteins involved in transmissible spongiform encephalopaties in mammals. An aberrant conformation with amyloid-like features of a cell surface protein, termed prion protein (PrP, is thought to be the essential component of the infectious particle, though accessory co-factor molecules such as lipids and nucleotides may be involved. The cellular co-factors and environmental conditions implicated in PrP misfolding are not completely understood. To address this issue, several studies have been done inducing misfolding of recombinant PrP (recPrP into classical amyloid structures using partially denaturing conditions. In this work, we report that misfolding of recPrP into PrP(Sc-like aggregates can be induced by simply incubating the protein in the presence of kosmotropic salts at concentrations that are known to retain or increase the stability of the protein. We used a simple experimental reaction (protein, buffer and salts submitted to agitation/incubation cycles at physiological temperature and pH. The formation of protease resistant-recPrP was time and salt-concentration dependent and required the presence of kosmotropic anions such as F(- or SO(4(-2. The molecular weights of the protease resistant recPrP fragments are reminiscent of those found in degradation assays of bona fide PrP(Sc. The aggregates also exhibited PrP(Sc-like ultrastructural features including rod-shape morphology under electron microscope, high beta-sheet content and thioflavin-T positive signal. The formation of recPrP aggregates with PrP(Sc biochemical features under conditions closer to physiological in the absence of organic co-factor molecules provides a simple setup that may prove helpful to understand the molecular mechanism of PrP misfolding.

PrP mRNA and protein expression in brain and PrP(c) in CSF in Creutzfeldt-Jakob disease MM1 and VV2.

Science.gov (United States)

Llorens, Franc; Ansoleaga, Belén; Garcia-Esparcia, Paula; Zafar, Saima; Grau-Rivera, Oriol; López-González, Irene; Blanco, Rosi; Carmona, Margarita; Yagüe, Jordi; Nos, Carlos; Del Río, José Antonio; Gelpí, Ellen; Zerr, Inga; Ferrer, Isidre

2013-01-01

Creutzfeldt-Jakob disease (CJD) is a heterogenic neurodegenerative disorder associated with abnormal post-translational processing of cellular prion protein (PrP(c)). CJD displays distinctive clinical and pathological features which correlate with the genotype at the codon 129 (methionine or valine: M or V respectively) in the prion protein gene and with size of the protease-resistant core of the abnormal prion protein PrP(sc) (type 1: 20/21 kDa and type 2: 19 kDa). MM1 and VV2 are the most common sporadic CJD (sCJD) subtypes. PrP mRNA expression levels in the frontal cortex and cerebellum are reduced in sCJD in a form subtype-dependent. Total PrP protein levels and PrP(sc) levels in the frontal cortex and cerebellum accumulate differentially in sCJD MM1 and sCJD VV2 with no relation between PrP(sc) deposition and spongiform degeneration and neuron loss, but with microgliosis, and IL6 and TNF-α response. In the CSF, reduced PrP(c), the only form present in this compartment, occurs in sCJD MM1 and VV2. PrP mRNA expression is also reduced in the frontal cortex in advanced stages of Alzheimer disease, Lewy body disease, progressive supranuclear palsy, and frontotemporal lobe degeneration, but PrP(c) levels in brain varies from one disease to another. Reduced PrP(c) levels in CSF correlate with PrP mRNA expression in brain, which in turn reflects severity of degeneration in sCJD.

Early Delivery of Misfolded PrP from ER to Lysosomes by Autophagy

Science.gov (United States)

Cortes, Constanza J.; Qin, Kefeng; Norstrom, Eric M.; Green, William N.; Bindokas, Vytautas P.; Mastrianni, James A.

2013-01-01

Prion diseases are linked to the accumulation of a misfolded isoform (PrPSc) of prion protein (PrP). Evidence suggests that lysosomes are degradation endpoints and sites of the accumulation of PrPSc. We questioned whether lysosomes participate in the early quality control of newly generated misfolded PrP. We found PrP carrying the disease-associated T182A mutation (Mut-PrP) was delivered to lysosomes in a Golgi-independent manner. Time-lapse live cell imaging revealed early formation and uptake of GFP-tagged Mut-PrP aggregates into LysoTracker labeled vesicles. Compared with Wt-PrP, Mut-PrP expression was associated with an elevation in several markers of the autophagy-lysosomal pathway, and it extensively colocalized with the autophagosome-specific marker, LC3B. In autophagy deficient (ATG5−/−) mouse embryonic fibroblasts, or in normal cells treated with the autophagy-inhibitor 3-MA, Mut-PrP colocalization with lysosomes was reduced to a similar extent. Additionally, 3-MA selectively impaired the degradation of insoluble Mut-PrP, resulting in an increase in protease-resistant PrP, whereas the induction of autophagy by rapamycin reduced it. These findings suggest that autophagy might function as a quality control mechanism to limit the accumulation of misfolded PrP that normally leads to the generation of PrPSc. PMID:24454378

Animation of Antimicrobial Resistance

Medline Plus

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

Generic amyloidogenicity of mammalian prion proteins from species susceptible and resistant to prions.

Science.gov (United States)

Nyström, Sofie; Hammarström, Per

2015-05-11

Prion diseases are lethal, infectious diseases associated with prion protein (PrP) misfolding. A large number of mammals are susceptible to both sporadic and acquired prion diseases. Although PrP is highly conserved and ubiquitously expressed in all mammals, not all species exhibit prion disease. By employing full length recombinant PrP from five known prion susceptible species (human, cattle, cat, mouse and hamster) and two species considered to be prion resistant (pig and dog) the amyloidogenicity of these PrPs has been delineated. All the mammalian PrPs, even from resistant species, were swiftly converted from the native state to amyloid-like structure when subjected to a native condition conversion assay. The PrPs displayed amyloidotypic tinctorial and ultrastructural hallmarks. Self-seeded conversion of the PrPs displayed significantly decreased lag phases demonstrating that nucleation dependent polymerization is a dominating mechanism in the fibrillation process. Fibrils from Aβ1-40, Aβ1-42, Lysozyme, Insulin and Transthyretin did not accelerate conversion of HuPrP whereas fibrils from HuPrP90-231 and HuPrP121-231 as well as full length PrPs of all PrPs efficiently seeded conversion showing specificity of the assay requiring the C-terminal PrP sequence. Our findings have implications for PrP misfolding and could have ramifications in the context of prion resistant species and silent carriers.

Magnetic properties, microstructure and corrosion behavior of (Pr,nd)12.6Fe81.3B6.1-type sintered magnets doped with (Pr,nd)30Fe62Ga8

Science.gov (United States)

Ni, Junjie; Zhang, Zhenyu; Liu, Ying; Jia, Zhengfeng; Huang, Baoxu; Yin, Yibin

2016-10-01

NdFeB sintered magnets with (Pr,Nd)30Fe62Ga8 were prepared by a binary powder blending method and their magnetic properties, microstructure and corrosion behavior were investigated. Addition of 3 wt% (Pr,Nd)30Fe62Ga8 was found to be the most effective for improving (BH)max and iHc of the magnets. The increase in both magnetic parameters was related to the alteration in microstructure. However, in other samples the occurrence of micropore and the aggregation of intergranular phases harmed the magnetic properties. Such disadvantageous microstructure features also caused higher corrosion current density, thus decreasing the corrosion resistance of the sample with higher additive content. In addition, the Ga-containing intergranular phases that are more stable than the (Pr,Nd)-rich phase formed in the additive doped magnets, leading to better corrosion resistance of the 3 wt% additives doped sample in comparison with the contrastive sample.

Evolution of structural, magnetic and transport behavior by Pr doping in SrRuO3

Science.gov (United States)

Gupta, Renu; Pramanik, A. K.

2018-05-01

Here we report the evolution of structural, magnetic and transport behavior in perovskite based ruthenates Sr1-xPrxRuO3 (x=0.0 and 0.1). The substitution of Pr on Sr site retains orthorhombic structure while we find the slight change in structural parameters. The SrRuO3 has itinerant ferromagnet (FM) type nature of ordering temperature ˜160 K and below the transition temperature showing large bifurcation between ZFC and FC magnetization. By Pr doping, the magnetic moment decreases with decreasing bifurcation of ZFC and FC. The ZFC data show three distinct peaks (three transition temperature; TM1,TM2 and TM3). The magnetization study of both the samples, at high temperature fitted with modified CWL showing the decreasing value of ordering temperature by Pr doping matches close to TM2. The low-temperature isothermal magnetization M (H) data show that the high field saturation moment has decreased by Pr doping. The Arrott plot gives spontaneous magnetization (Ms) which is also decreased by Pr substitution. Evolution of Rhodes-Wohlfarth ratio value increases, which suggests that FM in this system evolves toward the more itinerant type by Pr doping. The electrical resistivity ρ(T) of both the samples show metallic behavior, in the all temperature range and ρ(T) increases by Pr doping while around below 45 K, the resistivity decreases by Pr doping and this crossing temperature also matches with ZFC data.

Modulation of RIZ gene expression is associated to estradiol control of MCF-7 breast cancer cell proliferation

International Nuclear Information System (INIS)

Gazzerro, Patrizia; Abbondanza, Ciro; D'Arcangelo, Andrea; Rossi, Mariangela; Medici, Nicola; Moncharmont, Bruno; Puca, Giovanni Alfredo

2006-01-01

The retinoblastoma protein-interacting zinc-finger (RIZ) gene, a member of the nuclear protein methyltransferase superfamily, is characterized by the presence of the N-terminal PR domain. The RIZ gene encodes for two proteins, RIZ1 and RIZ2. While RIZ1 contains the PR (PRDI-BF1 and RIZ homologous) domain, RIZ2 lacks it. RIZ gene expression is altered in a variety of human cancers and RIZ1 is now considered to be a candidate tumor suppressor. Estradiol treatment of MCF-7 cells produced a selective decrease of RIZ1 transcript and an increase of total RIZ mRNA. Experiments of chromatin immunoprecipitation indicated that RIZ2 protein expression was controlled by estrogen receptor and RIZ1 had a direct repressor function on c-myc gene expression. To investigate the role of RIZ gene products as regulators of the proliferation/differentiation transition, we analyzed the effects of forced suppression of RIZ1 induced in MCF-7 cells by siRNA of the PR domain-containing form. Silencing of RIZ1 expression stimulated cell proliferation, similar to the effect of estradiol on these cells, associated with a transient increase of c-myc expression

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

Protease-resistant prions selectively decrease Shadoo protein.

Directory of Open Access Journals (Sweden)

Joel C Watts

2011-11-01

Full Text Available The central event in prion diseases is the conformational conversion of the cellular prion protein (PrP(C into PrP(Sc, a partially protease-resistant and infectious conformer. However, the mechanism by which PrP(Sc causes neuronal dysfunction remains poorly understood. Levels of Shadoo (Sho, a protein that resembles the flexibly disordered N-terminal domain of PrP(C, were found to be reduced in the brains of mice infected with the RML strain of prions [1], implying that Sho levels may reflect the presence of PrP(Sc in the brain. To test this hypothesis, we examined levels of Sho during prion infection using a variety of experimental systems. Sho protein levels were decreased in the brains of mice, hamsters, voles, and sheep infected with different natural and experimental prion strains. Furthermore, Sho levels were decreased in the brains of prion-infected, transgenic mice overexpressing Sho and in infected neuroblastoma cells. Time-course experiments revealed that Sho levels were inversely proportional to levels of protease-resistant PrP(Sc. Membrane anchoring and the N-terminal domain of PrP both influenced the inverse relationship between Sho and PrP(Sc. Although increased Sho levels had no discernible effect on prion replication in mice, we conclude that Sho is the first non-PrP marker specific for prion disease. Additional studies using this paradigm may provide insight into the cellular pathways and systems subverted by PrP(Sc during prion disease.

HTGR strategy for reduced proliferation potential

International Nuclear Information System (INIS)

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

1978-01-01

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

Protease resistance of infectious prions is suppressed by removal of a single atom in the cellular prion protein.

Science.gov (United States)

Leske, Henning; Hornemann, Simone; Herrmann, Uli Simon; Zhu, Caihong; Dametto, Paolo; Li, Bei; Laferriere, Florent; Polymenidou, Magdalini; Pelczar, Pawel; Reimann, Regina Rose; Schwarz, Petra; Rushing, Elisabeth Jane; Wüthrich, Kurt; Aguzzi, Adriano

2017-01-01

Resistance to proteolytic digestion has long been considered a defining trait of prions in tissues of organisms suffering from transmissible spongiform encephalopathies. Detection of proteinase K-resistant prion protein (PrPSc) still represents the diagnostic gold standard for prion diseases in humans, sheep and cattle. However, it has become increasingly apparent that the accumulation of PrPSc does not always accompany prion infections: high titers of prion infectivity can be reached also in the absence of protease resistant PrPSc. Here, we describe a structural basis for the phenomenon of protease-sensitive prion infectivity. We studied the effect on proteinase K (PK) resistance of the amino acid substitution Y169F, which removes a single oxygen atom from the β2-α2 loop of the cellular prion protein (PrPC). When infected with RML or the 263K strain of prions, transgenic mice lacking wild-type (wt) PrPC but expressing MoPrP169F generated prion infectivity at levels comparable to wt mice. The newly generated MoPrP169F prions were biologically indistinguishable from those recovered from prion-infected wt mice, and elicited similar pathologies in vivo. Surprisingly, MoPrP169F prions showed greatly reduced PK resistance and density gradient analyses showed a significant reduction in high-density aggregates. Passage of MoPrP169F prions into mice expressing wt MoPrP led to full recovery of protease resistance, indicating that no strain shift had taken place. We conclude that a subtle structural variation in the β2-α2 loop of PrPC affects the sensitivity of PrPSc to protease but does not impact prion replication and infectivity. With these findings a specific structural feature of PrPC can be linked to a physicochemical property of the corresponding PrPSc.

Proteasome inhibitors promote the sequestration of PrPSc into aggresomes within the cytosol of prion-infected CAD neuronal cells.

Science.gov (United States)

Dron, Michel; Dandoy-Dron, Françoise; Farooq Salamat, Muhammad Khalid; Laude, Hubert

2009-08-01

Dysfunction of the endoplasmic reticulum associated protein degradation/proteasome system is believed to contribute to the initiation or aggravation of neurodegenerative disorders associated with protein misfolding, and there is some evidence to suggest that proteasome dysfunctions might be implicated in prion disease. This study investigated the effect of proteasome inhibitors on the biogenesis of both the cellular (PrP(C)) and abnormal (PrP(Sc)) forms of prion protein in CAD neuronal cells, a newly introduced prion cell system. In uninfected cells, proteasome impairment altered the intracellular distribution of PrP(C), leading to a strong accumulation in the Golgi apparatus. Moreover, a detergent-insoluble and weakly protease-resistant PrP species of 26 kDa, termed PrP(26K), accumulated in the cells, whether they were prion-infected or not. However, no evidence was found that, in infected cells, this PrP(26K) species converts into the highly proteinase K-resistant PrP(Sc). In the infected cultures, proteasome inhibition caused an increased intracellular aggregation of PrP(Sc) that was deposited into large aggresomes. These findings strengthen the view that, in neuronal cells expressing wild-type PrP(C) from the natural promoter, proteasomal impairment may affect both the process of PrP(C) biosynthesis and the subcellular sites of PrP(Sc) accumulation, despite the fact that these two effects could essentially be disconnected.

Supporting non proliferation and global security efforts

International Nuclear Information System (INIS)

Pochon, E.

2013-01-01

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

Partial aphid resistance in lettuce negatively affects parasitoids.

Science.gov (United States)

Lanteigne, Marie-Eve; Brodeur, Jacques; Jenni, Sylvie; Boivin, Guy

2014-10-01

This study investigated the effects of partial plant resistance on the lettuce aphid Nasonovia ribisnigri (Mosley) (Hemiptera: Aphididae), a major pest of cultivated lettuce (Lactuca sativa L.), and one of its parasitoids, Aphidius ervi Haliday (Hymenoptera: Braconidae). Aphids were reared on susceptible (L. sativa variety Estival; S) or partially resistant (Lactuca serriola L. PI 491093; PR) lettuce, and next parasitized by A. ervi females. Fitness proxies were measured for both aphids and parasitoids. Developmental time to adult stage took longer for alate and apterous aphids (an average of 3.5 and 1.5 additional days, respectively) on PR than on S lettuce, and fecundity of alate aphids reared on PR lettuce was reduced by 37.8% relative to those reared on S lettuce. Size (tibia length) and weight of aphids reared on PR lettuce were lower than for aphids reared on S lettuce from the third and second instar onward, respectively. Parasitism of aphids reared on PR plants resulted in lower parasitoid offspring emergence (-49.9%), lower adult female (-30.3%) and male (-27.5%) weight, smaller adult female (-17.5%) and male (-11.9%) size, and lower female fecundity (37.8% fewer eggs) than when parasitoids developed from aphids reared on S plants. Our results demonstrate that partial aphid resistance in lettuce negatively affects both the second and third trophic levels. Host plant resistance in cultivated lettuce may therefore create an ecological sink for aphid parasitoids.

P-glycoprotein confers acquired resistance to 17-DMAG in lung cancers with an ALK rearrangement

International Nuclear Information System (INIS)

Kim, Hee Joung; Lee, Kye Young; Kim, Young Whan; Choi, Yun Jung; Lee, Jung-Eun; Choi, Chang Min; Baek, In-Jeoung; Rho, Jin Kyung; Lee, Jae Cheol

2015-01-01

Because anaplastic lymphoma kinase (ALK) is dependent on Hsp90 for protein stability, Hsp90 inhibitors are effective in controlling growth of lung cancer cells with ALK rearrangement. We investigated the mechanism of acquired resistance to 17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), a geldanamycin analogue Hsp90 inhibitor, in H3122 and H2228 non-small cell lung cancer cell lines with ALK rearrangement. Resistant cell lines (H3122/DR-1, H3122/DR-2 and H2228/DR) were established by repeated exposure to increasing concentrations of 17-DMAG. Mechanisms for resistance by either NAD(P)H/quinone oxidoreductase 1 (NQO1), previously known as a factor related to 17-DMAG resistance, or P-glycoprotein (P-gp; ABCB1/MDR1) were queried using RT-PCR, western blot analysis, chemical inhibitors, the MTT cell proliferation/survival assay, and cellular efflux of rhodamine 123. The resistant cells showed no cross-resistance to AUY922 or ALK inhibitors, suggesting that ALK dependency persists in cells with acquired resistance to 17-DMAG. Although expression of NQO1 was decreased in H3122/DR-1 and H3122/DR-2, NQO1 inhibition by dicumarol did not affect the response of parental cells (H2228 and H3122) to 17-DMAG. Interestingly, all resistant cells showed the induction of P-gp at the protein and RNA levels, which was associated with an increased efflux of the P-gp substrate rhodamine 123 (Rho123). Transfection with siRNA directed against P-gp or treatment with verapamil, an inhibitor of P-gp, restored the sensitivity to the drug in all cells with acquired resistance to 17-DMAG. Furthermore, we also observed that the growth-inhibitory effect of 17-DMAG was decreased in A549/PR and H460/PR cells generated to over-express P-gp by long-term exposure to paclitaxel, and these cells recovered their sensitivity to 17-DMAG through the inhibition of P-gp. P-gp over-expression is a possible mechanism of acquired resistance to 17-DMAG in cells with ALK rearrangement. The online

Acibenzolar-S-methyl induces lettuce resistance against ...

African Journals Online (AJOL)

... contributing to the enhancement of plant resistance. The effect was comparable with copper treatment. As a marker of resistance, PR protein activity chitinase showed remarkable increase, depending on decreasing bacterial growth in planta. Key words: Acibenzolar-S-methyl, induced resistance, Xanthomonas campestris ...

Age hardening and creep resistance of cast Al–Cu alloy modified by praseodymium

International Nuclear Information System (INIS)

Bai, Zhihao; Qiu, Feng; Wu, Xiaoxue; Liu, Yingying; Jiang, Qichuan

2013-01-01

The effects of praseodymium on age hardening behavior and creep resistance of cast Al–Cu alloy were investigated. The results indicated that praseodymium facilitated the formation of the θ′ precipitates during the age process and improved the hardness of the Al–Cu alloy. Besides, praseodymium resulted in the formation of the Al 11 Pr 3 phase in the grain boundaries and among the dendrites of the modified alloy. Because of the good thermal stability of Al 11 Pr 3 phase, it inhibits grain boundary migration and dislocation movement during the creep process, which contributes to the improvement in the creep resistance of the modified alloy at elevated temperatures. - Highlights: • Pr addition enhances the hardness and creep resistance of the Al–Cu alloy. • Pr addition facilitates the formation of the θ′ precipitates. • Pr addition results in the formation of the Al11Pr3 phase in the Al–Cu alloy

Interplay of cross-plane polaronic transport and resistive switching in Pt–Pr0.67Ca0.33MnO3–Pt heterostructures

International Nuclear Information System (INIS)

Scherff, M; Hoffmann, J; Meyer, B; Danz, Th; Jooss, Ch

2013-01-01

The identification of the cross-plane electric transport mechanisms in different resistance states of metal–oxide sandwich structures is essential for gaining insights into the mechanisms of resistive switching (RS). Here, we present a systematic study of cross-plane electric transport properties of Pr 0.67 Ca 0.33 MnO 3 (PCMO) thin films sandwiched by precious Pt metal electrodes. We observe three different transport regimes: ohmic, nonlinear and RS. The nonlinear regime is associated with colossal magneto-resistance (CMR) and colossal electro-resistance (CER) effects. In contrast to RS, the CMR and CER are volatile resistance effects which persist only during application of strong magnetic or electric fields and they are restricted to low temperatures. At low current densities, the device resistance is dominated by small polaron hopping transport of the PCMO film. At higher electric current densities near the switching threshold, the interface resistance starts to dominate and remarkably also exhibits thermally activated transport properties. Our studies also shed light onto the interplay of colossal resistance effects and RS: at low temperatures, RS can be only induced by reduction of the PCMO resistivity through CMR and CER. This clearly demonstrates the key role of the current density for controlling the amplitude of non-volatile resistive changes. Conversely, the CMR can be used as a probe for the switching induced changes in disorder and correlations. At small switching amplitudes, we observe slight changes in polaron activation energy which can be attributed to changes at the interface. If the switching amplitude exceeds 1000% and more, the CMR effect in the device can be reversibly changed. This indicates persistent changes in electronic or lattice structure of large regions within the PCMO film. (paper)

Arabidopsis genes, AtNPR1, AtTGA2 and AtPR-5, confer partial resistance to soybean cyst nematode (Heterodera glycines) when overexpressed in transgenic soybean roots

Science.gov (United States)

2014-01-01

Background Extensive studies using the model system Arabidopsis thaliana to elucidate plant defense signaling and pathway networks indicate that salicylic acid (SA) is the key hormone triggering the plant defense response against biotrophic and hemi-biotrophic pathogens, while jasmonic acid (JA) and derivatives are critical to the defense response against necrotrophic pathogens. Several reports demonstrate that SA limits nematode reproduction. Results Here we translate knowledge gained from studies using Arabidopsis to soybean. The ability of thirty-one Arabidopsis genes encoding important components of SA and JA synthesis and signaling in conferring resistance to soybean cyst nematode (SCN: Heterodera glycines) are investigated. We demonstrate that overexpression of three of thirty-one Arabidoposis genes in transgenic soybean roots of composite plants decreased the number of cysts formed by SCN to less than 50% of those found on control roots, namely AtNPR1(33%), AtTGA2 (38%), and AtPR-5 (38%). Three additional Arabidopsis genes decreased the number of SCN cysts by 40% or more: AtACBP3 (53% of the control value), AtACD2 (55%), and AtCM-3 (57%). Other genes having less or no effect included AtEDS5 (77%), AtNDR1 (82%), AtEDS1 (107%), and AtPR-1 (80%), as compared to control. Overexpression of AtDND1 greatly increased susceptibility as indicated by a large increase in the number of SCN cysts (175% of control). Conclusions Knowledge of the pathogen defense system gained from studies of the model system, Arabidopsis, can be directly translated to soybean through direct overexpression of Arabidopsis genes. When the genes, AtNPR1, AtGA2, and AtPR-5, encoding specific components involved in SA regulation, synthesis, and signaling, are overexpressed in soybean roots, resistance to SCN is enhanced. This demonstrates functional compatibility of some Arabidopsis genes with soybean and identifies genes that may be used to engineer resistance to nematodes. PMID:24739302

Arabidopsis genes, AtNPR1, AtTGA2 and AtPR-5, confer partial resistance to soybean cyst nematode (Heterodera glycines) when overexpressed in transgenic soybean roots.

Science.gov (United States)

Matthews, Benjamin F; Beard, Hunter; Brewer, Eric; Kabir, Sara; MacDonald, Margaret H; Youssef, Reham M

2014-04-16

Extensive studies using the model system Arabidopsis thaliana to elucidate plant defense signaling and pathway networks indicate that salicylic acid (SA) is the key hormone triggering the plant defense response against biotrophic and hemi-biotrophic pathogens, while jasmonic acid (JA) and derivatives are critical to the defense response against necrotrophic pathogens. Several reports demonstrate that SA limits nematode reproduction. Here we translate knowledge gained from studies using Arabidopsis to soybean. The ability of thirty-one Arabidopsis genes encoding important components of SA and JA synthesis and signaling in conferring resistance to soybean cyst nematode (SCN: Heterodera glycines) are investigated. We demonstrate that overexpression of three of thirty-one Arabidoposis genes in transgenic soybean roots of composite plants decreased the number of cysts formed by SCN to less than 50% of those found on control roots, namely AtNPR1(33%), AtTGA2 (38%), and AtPR-5 (38%). Three additional Arabidopsis genes decreased the number of SCN cysts by 40% or more: AtACBP3 (53% of the control value), AtACD2 (55%), and AtCM-3 (57%). Other genes having less or no effect included AtEDS5 (77%), AtNDR1 (82%), AtEDS1 (107%), and AtPR-1 (80%), as compared to control. Overexpression of AtDND1 greatly increased susceptibility as indicated by a large increase in the number of SCN cysts (175% of control). Knowledge of the pathogen defense system gained from studies of the model system, Arabidopsis, can be directly translated to soybean through direct overexpression of Arabidopsis genes. When the genes, AtNPR1, AtGA2, and AtPR-5, encoding specific components involved in SA regulation, synthesis, and signaling, are overexpressed in soybean roots, resistance to SCN is enhanced. This demonstrates functional compatibility of some Arabidopsis genes with soybean and identifies genes that may be used to engineer resistance to nematodes.

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

Science.gov (United States)

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

2006-04-15

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

Cytosolic PrP Can Participate in Prion-Mediated Toxicity

Science.gov (United States)

Thackray, Alana M.; Zhang, Chang; Arndt, Tina

2014-01-01

ABSTRACT Prion diseases are characterized by a conformational change in the normal host protein PrPC. While the majority of mature PrPC is tethered to the plasma membrane by a glycosylphosphatidylinositol anchor, topological variants of this protein can arise during its biosynthesis. Here we have generated Drosophila transgenic for cytosolic ovine PrP in order to investigate its toxic potential in flies in the absence or presence of exogenous ovine prions. While cytosolic ovine PrP expressed in Drosophila was predominantly detergent insoluble and showed resistance to low concentrations of proteinase K, it was not overtly detrimental to the flies. However, Drosophila transgenic for cytosolic PrP expression exposed to classical or atypical scrapie prion inocula showed a faster decrease in locomotor activity than similar flies exposed to scrapie-free material. The susceptibility to classical scrapie inocula could be assessed in Drosophila transgenic for panneuronal expression of cytosolic PrP, whereas susceptibility to atypical scrapie required ubiquitous PrP expression. Significantly, the toxic phenotype induced by ovine scrapie in cytosolic PrP transgenic Drosophila was transmissible to recipient PrP transgenic flies. These data show that while cytosolic PrP expression does not adversely affect Drosophila, this topological PrP variant can participate in the generation of transmissible scrapie-induced toxicity. These observations also show that PrP transgenic Drosophila are susceptible to classical and atypical scrapie prion strains and highlight the utility of this invertebrate host as a model of mammalian prion disease. IMPORTANCE During prion diseases, the host protein PrPC converts into an abnormal conformer, PrPSc, a process coupled to the generation of transmissible prions and neurotoxicity. While PrPC is principally a glycosylphosphatidylinositol-anchored membrane protein, the role of topological variants, such as cytosolic PrP, in prion-mediated toxicity and

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.)

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-05-01

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

Activation of Pathogenesis-related Genes by the Rhizobacterium, Bacillus sp. JS, Which Induces Systemic Resistance in Tobacco Plants.

Science.gov (United States)

Kim, Ji-Seong; Lee, Jeongeun; Lee, Chan-Hui; Woo, Su Young; Kang, Hoduck; Seo, Sang-Gyu; Kim, Sun-Hyung

2015-06-01

Plant growth promoting rhizobacteria (PGPR) are known to confer disease resistance to plants. Bacillus sp. JS demonstrated antifungal activities against five fungal pathogens in in vitro assays. To verify whether the volatiles of Bacillus sp. JS confer disease resistance, tobacco leaves pre-treated with the volatiles were damaged by the fungal pathogen, Rhizoctonia solani and oomycete Phytophthora nicotianae. Pre-treated tobacco leaves had smaller lesion than the control plant leaves. In pathogenesis-related (PR) gene expression analysis, volatiles of Bacillus sp. JS caused the up-regulation of PR-2 encoding β-1,3-glucanase and acidic PR-3 encoding chitinase. Expression of acidic PR-4 encoding chitinase and acidic PR-9 encoding peroxidase increased gradually after exposure of the volatiles to Bacillus sp. JS. Basic PR-14 encoding lipid transfer protein was also increased. However, PR-1 genes, as markers of salicylic acid (SA) induced resistance, were not expressed. These results suggested that the volatiles of Bacillus sp. JS confer disease resistance against fungal and oomycete pathogens through PR genes expression.

Fluorometric assay for phenotypic differentiation of drug-resistant HIV mutants

Science.gov (United States)

Zhu, Qinchang; Yu, Zhiqiang; Kabashima, Tsutomu; Yin, Sheng; Dragusha, Shpend; El-Mahdy, Ahmed F. M.; Ejupi, Valon; Shibata, Takayuki; Kai, Masaaki

2015-01-01

Convenient drug-resistance testing of viral mutants is indispensable to effective treatment of viral infection. We developed a novel fluorometric assay for phenotypic differentiation of drug-resistant mutants of human immunodeficiency virus-I protease (HIV-PR) which uses enzymatic and peptide-specific fluorescence (FL) reactions and high-performance liquid chromatography (HPLC) of three HIV-PR substrates. This assay protocol enables use of non-purified enzyme sources and multiple substrates for the enzymatic reaction. In this study, susceptibility of HIV mutations to drugs was evaluated by selective formation of three FL products after the enzymatic HIV-PR reaction. This proof-of-concept study indicates that the present HPLC-FL method could be an alternative to current phenotypic assays for the evaluation of HIV drug resistance. PMID:25988960

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

International Nuclear Information System (INIS)

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

2012-01-01

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

Práticas de segregação e resistência nas organizações: uma análise discursiva sobre os “rolezinhos” na cidade de Belo Horizonte (MG

Directory of Open Access Journals (Sweden)

Marco César Ribeiro Nascimento

2016-02-01

Full Text Available Objetivo: O objetivo do artigo é compreender como os discursos da mídia eletrônica apresentam reflexos e refrações das práticas de resistência dos jovens nos espaços organizacionais dos shopping centers. Essas práticas são denominadas atualmente “rolezinhos”. Originalidade/lacuna/relevância/implicações: Considerando os espaços urbanos produzidos socialmente e as cidades como palcos práticos e discursivos de dinâmicas simbólicas segregatórias, analisamos os processos de ocupação dos shopping centers – intitulados pela mídia eletrônica de “rolezinhos” – na cidade de Belo Horizonte, em Minas Gerais, por jovens da periferia. Principais aspectos metodológicos: Adotamos a análise de discurso francesa como base metodológica da pesquisa. O corpus de análise é constituído por discursos presentes em 15 portais eletrônicos de notícias sobre a cidade de Belo Horizonte, em Minas Gerais, que produziram, durante o ano de 2013, 18 reportagens sobre a ocupação coletiva de shopping centers por jovens da periferia. Síntese dos principais resultados: As práticas de resistência ampliam as fronteiras dos espaços organizacionais, na medida em que deslocam pontos de controle das ações dos sujeitos e questionam a construção do shopping center como espaço organizacional de segregação avesso a grupos sociais desfavorecidos, enfatizando o potencial de resistência e de ressignificação de grupos marginalizados nessas organizações. Principais considerações/conclusões: Entendemos os “rolezinhos” como questionamento dos limites do espaço organizacional que produziram deslocamentos das fronteiras das organizações. Eles são efeitos de alterações de relações de forças socioeconômicas que estavam na rua e, quando expandidas para espaços organizacionais, provocaram tensões que continuam latentes, pois a rua continua sua dinâmica e novamente questionará essas fronteiras.

HIV-1 protease-substrate coevolution in nelfinavir resistance.

Science.gov (United States)

Kolli, Madhavi; Ozen, Ayşegül; Kurt-Yilmaz, Nese; Schiffer, Celia A

2014-07-01

Resistance to various human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) challenges the effectiveness of therapies in treating HIV-1-infected individuals and AIDS patients. The virus accumulates mutations within the protease (PR) that render the PIs less potent. Occasionally, Gag sequences also coevolve with mutations at PR cleavage sites contributing to drug resistance. In this study, we investigated the structural basis of coevolution of the p1-p6 cleavage site with the nelfinavir (NFV) resistance D30N/N88D protease mutations by determining crystal structures of wild-type and NFV-resistant HIV-1 protease in complex with p1-p6 substrate peptide variants with L449F and/or S451N. Alterations of residue 30's interaction with the substrate are compensated by the coevolving L449F and S451N cleavage site mutations. This interdependency in the PR-p1-p6 interactions enhances intermolecular contacts and reinforces the overall fit of the substrate within the substrate envelope, likely enabling coevolution to sustain substrate recognition and cleavage in the presence of PR resistance mutations. Resistance to human immunodeficiency virus type 1 (HIV-1) protease inhibitors challenges the effectiveness of therapies in treating HIV-1-infected individuals and AIDS patients. Mutations in HIV-1 protease selected under the pressure of protease inhibitors render the inhibitors less potent. Occasionally, Gag sequences also mutate and coevolve with protease, contributing to maintenance of viral fitness and to drug resistance. In this study, we investigated the structural basis of coevolution at the Gag p1-p6 cleavage site with the nelfinavir (NFV) resistance D30N/N88D protease mutations. Our structural analysis reveals the interdependency of protease-substrate interactions and how coevolution may restore substrate recognition and cleavage in the presence of protease drug resistance mutations. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-03-15

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

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

International Nuclear Information System (INIS)

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

2012-01-01

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

Proliferation resistance of advanced sustainable nuclear fuel cycles

Energy Technology Data Exchange (ETDEWEB)

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

2001-07-01

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

Proliferation resistance of advanced sustainable nuclear fuel cycles

International Nuclear Information System (INIS)

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

2001-01-01

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

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

Science.gov (United States)

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

2016-06-01

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

Recovery of oscillatory magneto-resistance in phase separated La{sub 0.3}Pr{sub 0.4}Ca{sub 0.3}MnO{sub 3} epitaxial thin films

Energy Technology Data Exchange (ETDEWEB)

Alagoz, H. S., E-mail: alagoz@ualberta.ca; Jeon, J.; Mahmud, S. T.; Saber, M. M.; Chow, K. H., E-mail: khchow@ualberta.ca; Jung, J., E-mail: jjung@ualberta.ca [Department of Physics, University of Alberta, Edmonton, Alberta T6G 2E1 (Canada); Prasad, B. [Department of Materials Science and Metallurgy, University of Cambridge, Cambridge CB2 3QZ (United Kingdom); Egilmez, M. [Department of Physics, American University of Sharjah, Sharjah (United Arab Emirates)

2013-12-02

In-plane angular dependent magneto-resistance has been studied in La{sub 0.3}Pr{sub 0.4}Ca{sub 0.3}MnO{sub 3} (LPCMO) manganite thin films deposited on the (100) oriented NdGaO{sub 3}, and (001) oriented SrTiO{sub 3} and LaAlO{sub 3} substrates. At temperatures where the electronic phase separation is the strongest, a metastable irreversible state exists in the films whose resistivity ρ attains a large time dependent value. The ρ decreases sharply with an increasing angle θ between the magnetic field and the current, and does not display an expected oscillatory cos{sup 2}θ/sin{sup 2}θ dependence for all films. The regular oscillations are recovered during repetitive sweeping of θ between 0° and 180°. We discuss possible factors that could produce these unusual changes in the resistivity.

Familial CJD Associated PrP Mutants within Transmembrane Region Induced Ctm-PrP Retention in ER and Triggered Apoptosis by ER Stress in SH-SY5Y Cells

Science.gov (United States)

Wang, Xin; Shi, Qi; Xu, Kun; Gao, Chen; Chen, Cao; Li, Xiao-Li; Wang, Gui-Rong; Tian, Chan; Han, Jun; Dong, Xiao-Ping

2011-01-01

Background Genetic prion diseases are linked to point and inserted mutations in the prion protein (PrP) gene that are presumed to favor conversion of the cellular isoform of PrP (PrPC) to the pathogenic one (PrPSc). The pathogenic mechanisms and the subcellular sites of the conversion are not completely understood. Here we introduce several PRNP gene mutations (such as, PrP-KDEL, PrP-3AV, PrP-A117V, PrP-G114V, PrP-P102L and PrP-E200K) into the cultured cells in order to explore the pathogenic mechanism of familial prion disease. Methodology/Principal Findings To address the roles of aberrant retention of PrP in endoplasmic reticulum (ER), the recombinant plasmids expressing full-length human PrP tailed with an ER signal peptide at the COOH-terminal (PrP-KDEL) and PrP with three amino acids exchange in transmembrane region (PrP-3AV) were constructed. In the preparations of transient transfections, 18-kD COOH-terminal proteolytic resistant fragments (Ctm-PrP) were detected in the cells expressing PrP-KDEL and PrP-3AV. Analyses of the cell viabilities in the presences of tunicamycin and brefeldin A revealed that expressions of PrP-KDEL and PrP-3AV sensitized the transfected cells to ER stress stimuli. Western blots and RT-PCR identified the clear alternations of ER stress associated events in the cells expressing PrP-KDEL and PrP-3AV that induced ER mediated apoptosis by CHOP and capase-12 apoptosis pathway. Moreover, several familial CJD related PrP mutants were transiently introduced into the cultured cells. Only the mutants within the transmembrane region (G114V and A117V) induced the formation of Ctm-PrP and caused the ER stress, while the mutants outside the transmembrane region (P102L and E200K) failed. Conclusions/Significance The data indicate that the retention of PrP in ER through formation of Ctm-PrP results in ER stress and cell apoptosis. The cytopathic activities caused by different familial CJD associated PrP mutants may vary, among them the mutants

Familial CJD associated PrP mutants within transmembrane region induced Ctm-PrP retention in ER and triggered apoptosis by ER stress in SH-SY5Y cells.

Directory of Open Access Journals (Sweden)

Xin Wang

Full Text Available BACKGROUND: Genetic prion diseases are linked to point and inserted mutations in the prion protein (PrP gene that are presumed to favor conversion of the cellular isoform of PrP (PrP(C to the pathogenic one (PrP(Sc. The pathogenic mechanisms and the subcellular sites of the conversion are not completely understood. Here we introduce several PRNP gene mutations (such as, PrP-KDEL, PrP-3AV, PrP-A117V, PrP-G114V, PrP-P102L and PrP-E200K into the cultured cells in order to explore the pathogenic mechanism of familial prion disease. METHODOLOGY/PRINCIPAL FINDINGS: To address the roles of aberrant retention of PrP in endoplasmic reticulum (ER, the recombinant plasmids expressing full-length human PrP tailed with an ER signal peptide at the COOH-terminal (PrP-KDEL and PrP with three amino acids exchange in transmembrane region (PrP-3AV were constructed. In the preparations of transient transfections, 18-kD COOH-terminal proteolytic resistant fragments (Ctm-PrP were detected in the cells expressing PrP-KDEL and PrP-3AV. Analyses of the cell viabilities in the presences of tunicamycin and brefeldin A revealed that expressions of PrP-KDEL and PrP-3AV sensitized the transfected cells to ER stress stimuli. Western blots and RT-PCR identified the clear alternations of ER stress associated events in the cells expressing PrP-KDEL and PrP-3AV that induced ER mediated apoptosis by CHOP and caspase-12 apoptosis pathway. Moreover, several familial CJD related PrP mutants were transiently introduced into the cultured cells. Only the mutants within the transmembrane region (G114V and A117V induced the formation of Ctm-PrP and caused the ER stress, while the mutants outside the transmembrane region (P102L and E200K failed. CONCLUSIONS/SIGNIFICANCE: The data indicate that the retention of PrP in ER through formation of Ctm-PrP results in ER stress and cell apoptosis. The cytopathic activities caused by different familial CJD associated PrP mutants may vary, among them

Fluorometric assay for phenotypic differentiation of drug-resistant HIV mutants

OpenAIRE

Zhu, Qinchang; Yu, Zhiqiang; Kabashima, Tsutomu; Yin, Sheng; Dragusha, Shpend; El-Mahdy, Ahmed F. M.; Ejupi, Valon; Shibata, Takayuki; Kai, Masaaki

2015-01-01

Convenient drug-resistance testing of viral mutants is indispensable to effective treatment of viral infection. We developed a novel fluorometric assay for phenotypic differentiation of drug-resistant mutants of human immunodeficiency virus-I protease (HIV-PR) which uses enzymatic and peptide-specific fluorescence (FL) reactions and high-performance liquid chromatography (HPLC) of three HIV-PR substrates. This assay protocol enables use of non-purified enzyme sources and multiple substrates f...

Ballistic Electron Emission Microscopy (BEEM) of Au/Pr{sub 2}O{sub 3}/Si structures; Ballistische Elektronen Emissions Mikroskopie (BEEM) an Au/Si und Au/Pr{sub 2}O{sub 3}/Si-Strukturen

Energy Technology Data Exchange (ETDEWEB)

Mauch, I.

2007-05-15

This thesis describes Ballistic Electron Emission Microscopy (BEEM) measurements of Au/Si(111) and Au/Pr{sub 2}O{sub 3}/Si(111) structures. This technique is based on Scanning Tunnelling Microscopy (STM). It measures the ballistic transport of hot electrons through parts of the sample and across an interface, which provides a potential barrier. One part of this work was to modify the BEEM apparatus and to implement a lock in method, which modulates the tunnel current with a small frequency. In this way it is possible to study samples with very low resistance (as low as 30 k{omega}), which widely enlarges the number of samples which are appropriate for BEEM measurement at room temperature. Both types of samples studied in this thesis had low resistance and were therefore studied using the lock in method. For the classical BEEM system Au/Si(111), we observed a pronounced dependence of the sample resistance of Au/Si(111)-7 x 7 on the preparation temperature. We developed a model for the resistance of thermal prepared Au/Si(111)-7 x 7 samples. The model identifies that the low resistance is due to the surface conductivity of the reconstructed silicon surface. If the surface is prepared at a lower temperature (but still high enough that the surface is cleaned and the silicon dioxide desorbed) rough areas remain on the surface, which reduce the surface conductivity. For BEEM measurements flat areas of the sample surface are selected. The low temperature prepared samples we were able to obtain BEEM spectra as well as images at room temperature using the lock in method. The sesquioxide of praseodymium (Pr{sub 2}O{sub 3}) is currently discussed as a possible candidate for a gate oxide in semiconductor devices, since it has some of the required material properties such as a high dielectric constant, low leakage current and epitaxial growth on Si(100). We have for the first time performed BEEM measurement of praseodymium oxide. Despite a low resistance of the structures we

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-11-16

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

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

International Nuclear Information System (INIS)

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

1979-03-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1979-03-01

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

WRKY transcription factors involved in PR-1 gene expression in Arabidopsis

NARCIS (Netherlands)

Hussain, Rana Muhammad Fraz

2012-01-01

Salicylic acid (SA) is involved in mediating defense against biotrophic pathogens. The current knowledge of the SA-mediated signaling pathway and its effect on the transcriptional regulation of defense responses are reviewed in this thesis. PR-1 is a marker gene for systemic acquired resistance

SerpinB1 Promotes Pancreatic β Cell Proliferation

Energy Technology Data Exchange (ETDEWEB)

El Ouaamari, Abdelfattah; Dirice, Ercument; Gedeon, Nicholas; Hu, Jiang; Zhou, Jian-Ying; Shirakawa, Jun; Hou, Lifei; Goodman, Jessica; Karampelias, Christos; Qiang, Guifeng; Boucher, Jeremie; Martinez, Rachael; Gritsenko, Marina A.; De Jesus, Dario F.; Kahraman, Sevim; Bhatt, Shweta; Smith, Richard D.; Beer, Hans-Dietmar; Jungtrakoon, Prapaporn; Gong, Yanping; Goldfine, Allison B.; Liew, Chong Wee; Doria, Alessandro; Andersson, Olov; Qian, Wei-Jun; Remold-O’Donnell, Eileen; Kulkarni, Rohit N.

2016-01-01

Compensatory β-cell growth in response to insulin resistance is a common feature in diabetes. We recently reported that liver-derived factors participate in this compensatory response in the liver insulin receptor knockout (LIRKO) mouse, a model of significant islet hyperplasia. Here we show that serpinB1 is a liver-derived secretory protein that controls β-cell proliferation. SerpinB1 is abundant in the hepatocyte secretome and sera derived from LIRKO mice. SerpinB1 and small molecule compounds that partially mimic serpinB1 activity enhanced proliferation of zebrafish, mouse and human β-cells. We report that serpinB1-induced β-cell replication requires protease inhibition activity and mice lacking serpinB1 exhibit attenuated β-cell replication in response to insulin resistance. Finally, SerpinB1-treatment of islets modulated signaling proteins in growth and survival pathways such as MAPK, PKA and GSK3. Together, these data implicate SerpinB1 as a protein that can potentially be harnessed to enhance functional β-cell mass in patients with diabetes.

Suggested non-proliferation criteria for commercial nuclear fuel cycles

International Nuclear Information System (INIS)

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

1978-01-01

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

Animation of Antimicrobial Resistance

Medline Plus

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

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

International Nuclear Information System (INIS)

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

2017-01-01

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

Genetic human prion disease modelled in PrP transgenic Drosophila.

Science.gov (United States)

Thackray, Alana M; Cardova, Alzbeta; Wolf, Hanna; Pradl, Lydia; Vorberg, Ina; Jackson, Walker S; Bujdoso, Raymond

2017-09-20

Inherited human prion diseases, such as fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD), are associated with autosomal dominant mutations in the human prion protein gene PRNP and accumulation of PrP Sc , an abnormal isomer of the normal host protein PrP C , in the brain of affected individuals. PrP Sc is the principal component of the transmissible neurotoxic prion agent. It is important to identify molecular pathways and cellular processes that regulate prion formation and prion-induced neurotoxicity. This will allow identification of possible therapeutic interventions for individuals with, or at risk from, genetic human prion disease. Increasingly, Drosophila has been used to model human neurodegenerative disease. An important unanswered question is whether genetic prion disease with concomitant spontaneous prion formation can be modelled in Drosophila We have used pUAST/PhiC31-mediated site-directed mutagenesis to generate Drosophila transgenic for murine or hamster PrP (prion protein) that carry single-codon mutations associated with genetic human prion disease. Mouse or hamster PrP harbouring an FFI (D178N) or fCJD (E200K) mutation showed mild Proteinase K resistance when expressed in Drosophila Adult Drosophila transgenic for FFI or fCJD variants of mouse or hamster PrP displayed a spontaneous decline in locomotor ability that increased in severity as the flies aged. Significantly, this mutant PrP-mediated neurotoxic fly phenotype was transferable to recipient Drosophila that expressed the wild-type form of the transgene. Collectively, our novel data are indicative of the spontaneous formation of a PrP-dependent neurotoxic phenotype in FFI- or CJD-PrP transgenic Drosophila and show that inherited human prion disease can be modelled in this invertebrate host. © 2017 The Author(s).

Spectroscopic and radiation-resistant properties of Er,Pr:GYSGG laser crystal operated at 2.79 μm

International Nuclear Information System (INIS)

Zhao Xu-Yao; Sun Dun-Lu; Luo Jian-Qiao; Zhang Hui-Li; Fang Zhong-Qing; Quan Cong; Li Xiu-Li; Cheng Mao-Jie; Zhang Qing-Li; Yin Shao-Tang

2017-01-01

We demonstrate the spectroscopic and laser performance before and after 100 Mrad gamma-ray irradiation on an Er,Pr:GYSGG crystal grown by the Czochralski method. The additional absorption of Er,Pr:GYSGG crystal is close to zero in the 968 nm pumping and 2.7–3 μm laser wavelength regions. The lifetimes of the upper and lower levels show faint decreases after gamma-ray irradiation. The maximum output powers of 542 and 526 mW with the slope efficiencies of 17.7% and 17.0% are obtained, respectively, on the GYSGG/Er,Pr:GYSGG composite crystal before and after the gamma-ray irradiation. These results suggest that Er,Pr:GYSGG crystal as a laser gain medium possesses a distinguished anti-radiation ability for application in space and radiant environments. (paper)

The Effects of Rare Earth Pr and Heat Treatment on the Wear Properties of AZ91 Alloy

Directory of Open Access Journals (Sweden)

Ning Li

2018-06-01

Full Text Available This paper investigated the influences of Pr addition and heat treatment (T6 on the dry sliding wear behavior of AZ91 alloy. The wear rates and friction coefficients were measured by using a pin-on-disc tribometer under loads of 30, 60 and 90 N at dry sliding speeds of 100 rpm, over a sliding time of 15 min. The worn surfaces were examined using a scanning electron microscope and was analyzed with an energy dispersive spectrometer. The experimental results revealed that AZ91-1.0%Pr magnesium alloy exhibited lower wear rate and friction coefficient than the other investigated alloys. As the applied load increased, the wear rate and friction coefficient increased. Compared with the as-cast AZ91-1.0%Pr magnesium alloy, the hardness and wear resistance of the alloy after solution treatment were reduced, and through the subsequent aging, the hardness and wear resistance of the alloy were improved and the hardness was 101.1 HB (compared to as-cast AZ91 magnesium alloy, it increased by 45%. The AZ91-1.0%Pr with T6 magnesium alloy exhibited best wear resistance. Abrasion was dominant at load of 30 N, delamination was dominant at load of 60 N and plastic deformation was dominant at load of 90 N. Oxidation was observed at all loads.

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

Directory of Open Access Journals (Sweden)

Pu Li

2017-01-01

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

The pathogenesis-related protein PR-4b from Theobroma cacao presents RNase activity, Ca(2+) and Mg(2+) dependent-DNase activity and antifungal action on Moniliophthora perniciosa.

Science.gov (United States)

Pereira Menezes, Sara; de Andrade Silva, Edson Mario; Matos Lima, Eline; Oliveira de Sousa, Aurizângela; Silva Andrade, Bruno; Santos Lima Lemos, Livia; Peres Gramacho, Karina; da Silva Gesteira, Abelmon; Pirovani, Carlos Priminho; Micheli, Fabienne

2014-06-11

The production and accumulation of pathogenesis-related proteins (PR proteins) in plants in response to biotic or abiotic stresses is well known and is considered as a crucial mechanism for plant defense. A pathogenesis-related protein 4 cDNA was identified from a cacao-Moniliophthora perniciosa interaction cDNA library and named TcPR-4b. TcPR-4b presents a Barwin domain with six conserved cysteine residues, but lacks the chitin-binding site. Molecular modeling of TcPR-4b confirmed the importance of the cysteine residues to maintain the protein structure, and of several conserved amino acids for the catalytic activity. In the cacao genome, TcPR-4b belonged to a small multigene family organized mainly on chromosome 5. TcPR-4b RT-qPCR analysis in resistant and susceptible cacao plants infected by M. perniciosa showed an increase of expression at 48 hours after infection (hai) in both cacao genotypes. After the initial stage (24-72 hai), the TcPR-4b expression was observed at all times in the resistant genotypes, while in the susceptible one the expression was concentrated at the final stages of infection (45-90 days after infection). The recombinant TcPR-4b protein showed RNase, and bivalent ions dependent-DNase activity, but no chitinase activity. Moreover, TcPR-4b presented antifungal action against M. perniciosa, and the reduction of M. perniciosa survival was related to ROS production in fungal hyphae. To our knowledge, this is the first report of a PR-4 showing simultaneously RNase, DNase and antifungal properties, but no chitinase activity. Moreover, we showed that the antifungal activity of TcPR-4b is directly related to RNase function. In cacao, TcPR-4b nuclease activities may be related to the establishment and maintenance of resistance, and to the PCD mechanism, in resistant and susceptible cacao genotypes, respectively.

The pathogenesis-related protein PR-4b from Theobroma cacao presents RNase activity, Ca2+ and Mg2+ dependent-DNase activity and antifungal action on Moniliophthora perniciosa

Science.gov (United States)

2014-01-01

Background The production and accumulation of pathogenesis-related proteins (PR proteins) in plants in response to biotic or abiotic stresses is well known and is considered as a crucial mechanism for plant defense. A pathogenesis-related protein 4 cDNA was identified from a cacao-Moniliophthora perniciosa interaction cDNA library and named TcPR-4b. Results TcPR-4b presents a Barwin domain with six conserved cysteine residues, but lacks the chitin-binding site. Molecular modeling of TcPR-4b confirmed the importance of the cysteine residues to maintain the protein structure, and of several conserved amino acids for the catalytic activity. In the cacao genome, TcPR-4b belonged to a small multigene family organized mainly on chromosome 5. TcPR-4b RT-qPCR analysis in resistant and susceptible cacao plants infected by M. perniciosa showed an increase of expression at 48 hours after infection (hai) in both cacao genotypes. After the initial stage (24-72 hai), the TcPR-4b expression was observed at all times in the resistant genotypes, while in the susceptible one the expression was concentrated at the final stages of infection (45-90 days after infection). The recombinant TcPR-4b protein showed RNase, and bivalent ions dependent-DNase activity, but no chitinase activity. Moreover, TcPR-4b presented antifungal action against M. perniciosa, and the reduction of M. perniciosa survival was related to ROS production in fungal hyphae. Conclusion To our knowledge, this is the first report of a PR-4 showing simultaneously RNase, DNase and antifungal properties, but no chitinase activity. Moreover, we showed that the antifungal activity of TcPR-4b is directly related to RNase function. In cacao, TcPR-4b nuclease activities may be related to the establishment and maintenance of resistance, and to the PCD mechanism, in resistant and susceptible cacao genotypes, respectively. PMID:24920373

An insight to the molecular interactions of the FDA approved HIV PR drugs against L38L↑N↑L PR mutant.

Science.gov (United States)

Sanusi, Zainab K; Govender, Thavendran; Maguire, Glenn E M; Maseko, Sibusiso B; Lin, Johnson; Kruger, Hendrik G; Honarparvar, Bahareh

2018-03-01

The aspartate protease of the human immune deficiency type-1 virus (HIV-1) has become a crucial antiviral target in which many useful antiretroviral inhibitors have been developed. However, it seems the emergence of new HIV-1 PR mutations enhances drug resistance, hence, the available FDA approved drugs show less activity towards the protease. A mutation and insertion designated L38L↑N↑L PR was recently reported from subtype of C-SA HIV-1. An integrated two-layered ONIOM (QM:MM) method was employed in this study to examine the binding affinities of the nine HIV PR inhibitors against this mutant. The computed binding free energies as well as experimental data revealed a reduced inhibitory activity towards the L38L↑N↑L PR in comparison with subtype C-SA HIV-1 PR. This observation suggests that the insertion and mutations significantly affect the binding affinities or characteristics of the HIV PIs and/or parent PR. The same trend for the computational binding free energies was observed for eight of the nine inhibitors with respect to the experimental binding free energies. The outcome of this study shows that ONIOM method can be used as a reliable computational approach to rationalize lead compounds against specific targets. The nature of the intermolecular interactions in terms of the host-guest hydrogen bond interactions is discussed using the atoms in molecules (AIM) analysis. Natural bond orbital analysis was also used to determine the extent of charge transfer between the QM region of the L38L↑N↑L PR enzyme and FDA approved drugs. AIM analysis showed that the interaction between the QM region of the L38L↑N↑L PR and FDA approved drugs are electrostatic dominant, the bond stability computed from the NBO analysis supports the results from the AIM application. Future studies will focus on the improvement of the computational model by considering explicit water molecules in the active pocket. We believe that this approach has the potential to

An insight to the molecular interactions of the FDA approved HIV PR drugs against L38L↑N↑L PR mutant

Science.gov (United States)

Sanusi, Zainab K.; Govender, Thavendran; Maguire, Glenn E. M.; Maseko, Sibusiso B.; Lin, Johnson; Kruger, Hendrik G.; Honarparvar, Bahareh

2018-03-01

The aspartate protease of the human immune deficiency type-1 virus (HIV-1) has become a crucial antiviral target in which many useful antiretroviral inhibitors have been developed. However, it seems the emergence of new HIV-1 PR mutations enhances drug resistance, hence, the available FDA approved drugs show less activity towards the protease. A mutation and insertion designated L38L↑N↑L PR was recently reported from subtype of C-SA HIV-1. An integrated two-layered ONIOM (QM:MM) method was employed in this study to examine the binding affinities of the nine HIV PR inhibitors against this mutant. The computed binding free energies as well as experimental data revealed a reduced inhibitory activity towards the L38L↑N↑L PR in comparison with subtype C-SA HIV-1 PR. This observation suggests that the insertion and mutations significantly affect the binding affinities or characteristics of the HIV PIs and/or parent PR. The same trend for the computational binding free energies was observed for eight of the nine inhibitors with respect to the experimental binding free energies. The outcome of this study shows that ONIOM method can be used as a reliable computational approach to rationalize lead compounds against specific targets. The nature of the intermolecular interactions in terms of the host-guest hydrogen bond interactions is discussed using the atoms in molecules (AIM) analysis. Natural bond orbital analysis was also used to determine the extent of charge transfer between the QM region of the L38L↑N↑L PR enzyme and FDA approved drugs. AIM analysis showed that the interaction between the QM region of the L38L↑N↑L PR and FDA approved drugs are electrostatic dominant, the bond stability computed from the NBO analysis supports the results from the AIM application. Future studies will focus on the improvement of the computational model by considering explicit water molecules in the active pocket. We believe that this approach has the potential to provide

Cellular prion protein and γ-synuclein overexpression in LS 174T colorectal cancer cell drives endothelial proliferation-to-differentiation switch

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Sing-Hui Ong

2018-03-01

Full Text Available Background Tumor-induced angiogenesis is an imperative event in pledging new vasculature for tumor metastasis. Since overexpression of neuronal proteins gamma-synuclein (γ-Syn and cellular prion protein (PrPC is always detected in advanced stages of cancer diseases which involve metastasis, this study aimed to investigate whether γ-Syn or PrPC overexpression in colorectal adenocarcinoma, LS 174T cells affects angiogenesis of endothelial cells, EA.hy 926 (EA. Methods EA cells were treated with conditioned media (CM of LS 174T-γ-Syn or LS 174T-PrP, and their proliferation, invasion, migration, adhesion and ability to form angiogenic tubes were assessed using a range of biological assays. To investigate plausible background mechanisms in conferring the properties of EA cells above, nitrite oxide (NO levels were measured and the expression of angiogenesis-related factors was assessed using a human angiogenesis antibody array. Results EA proliferation was significantly inhibited by LS 174T-PrP CM whereas its telomerase activity was reduced by CM of LS 174T-γ-Syn or LS 174T-PrP, as compared to EA incubated with LS 174T CM. Besides, LS 174T-γ-Syn CM or LS 174T-PrP CM inhibited EA invasion and migration in Boyden chamber assay. Furthermore, LS 174T-γ-Syn CM significantly inhibited EA migration in scratch wound assay. Gelatin zymography revealed reduced secretion of MMP-2 and MMP-9 by EA treated with LS 174T-γ-Syn CM or LS 174T-PrP CM. In addition, cell adhesion assay showed lesser LS 174T-γ-Syn or LS 174T-PrP cells adhered onto EA, as compared to LS 174T. In tube formation assay, LS 174T-γ-Syn CM or LS 174T-PrP CM induced EA tube formation. Increased NO secretion by EA treated with LS 174T-γ-Syn CM or LS 174T-PrP CM was also detected. Lastly, decreased expression of pro-angiogenic factors like CXCL16, IGFBP-2 and amphiregulin in LS 174T-γ-Syn CM or LS 174T-PrP CM was detected using the angiogenesis antibody array. Discussion These results

On PR group classes and PR algebra membership

International Nuclear Information System (INIS)

Lebedenko, V.M.

1978-01-01

The necessary and sufficient conditions are found for the membership of Lee algebras to PR algebra class, to algebras with commutation relations of [Hsub(i), Hsub(j)]=rsub(ij)Hsub(i) (i< j) type. Due to this, a criterion is obtained for the membership of the Lee froups to PR group classes, connected and simply connected Lee groups, which Lee algebras are PR algebras

Future non-proliferation challenges

International Nuclear Information System (INIS)

Yelchenko, Volodymyr

2008-01-01

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

Ferromagnetism in a hexagonal PrRh3 with 4f2 configuration

Science.gov (United States)

Park, G. B.; Yamane, Y.; Onimaru, T.; Umeo, K.; Takabatake, T.

2018-05-01

Electrical resistivity ρ , magnetization M and specific heat C are reported for polycrystalline samples of the hexagonal system PrRh3. The magnetic susceptibility M/B obeys the Curie-Weiss law with the effective magnetic moment μeff = 3.88 μB/Pr and the paramagnetic Curie temperature θp = +2.9 K, which indicates ferro-type magnetic interaction between the trivalent Pr ions. A cusp in C(T) at 3.0 K coincides with a bend in ρ (T). Applying magnetic fields, the peak broadens and shifts to higher temperatures. The field dependence indicates a ferro-type magnetic order. The magnetic entropy Sm is (1/3)Rln2 at TC = 3.0 K, suggesting that part of the Pr ions take part in the magnetic order. A broad tail of the magnetic specific heat Cm observed above TC may result from short-range correlations and/or fluctuations of the active magnetic dipole and quadrupoles in the ground state doublet.

Structure-property correlation in PrFe0.5Mn0.5O2.95

International Nuclear Information System (INIS)

Ganeshraj, C.; Santhosh, P.N.; Sharma, Neetika; Das, A.; Mahendiran, R.

2014-01-01

PrFe 0.5 Mn 0.5 O 2.95 (PFMO) prepared by the conventional ceramic route is analyzed using a variety of techniques to understand the structural, magnetic and electrical properties. From the Neutron diffraction data it is concluded that PFMO crystallizes in an orthorhombic structure (Pnma). The magnetic structure can be represented as Γ 2 : C x G y F z , in Bertaut's notation, which has a net ferromagnetic moment along z-direction, and the spin component along x-direction (C x ) is found to be negligibly small. The canted G-type antiferromagnet PrFe 0.5 Mn 0.5 O 2.95 shows an enhanced Jahn-Teller (JT) distortion below 150 K (T*). The resistivity of the grains can be described by variable range hopping (VRH) between the localized states and there is a dominant grain boundary contribution to dc resistivity, below T*. Above T*, the total dc resistivity follows small polaron hopping (SPH) conduction. By means of complex impedance analysis, it is found that the observed giant dielectric response can be ascribed to Maxwell-Wagner polarization at the grain/grain boundary interfaces. Despite the low concentration of JT active Mn 3+ ions, our result indicates an important role of JT effect on physical properties of PrFe 0.5 Mn 0.5 O 2.95 . (author)

Neutron Scattering from fcc Pr and Pr3Tl

DEFF Research Database (Denmark)

Birgeneau, R. J.; Als-Nielsen, Jens Aage; Bucher, E.

1972-01-01

Elastic-neutron-scattering measurements on the singlet-ground-state ferromagnets fcc Pr and Pr3 Tl are reported. Both exhibit magnetic phase transitions, possibly to a simple ferromagnetic state at 20 and 11.6 °K, respectively. The transitions appear to be of second order although that in fcc Pr...

Relationship between grain colour and preharvest sprouting-resistance in wheat Relação entre cor de grão e resistência à germinação pré-colheita em trigo

Directory of Open Access Journals (Sweden)

Manoel Carlos Bassoi

2005-10-01

Full Text Available Since red alleles (R of the genes that control grain colour are important for the improvement of preharvest sprouting resistance in wheat and there are three independently inherited loci, on chromosomes 3A, 3B and 3D of hexaploid wheat, it is possible to vary the dosage of dominant alleles in a breeding program. The objective of this work was to evaluate the dosage effect of R genes on preharvest sprouting, in a single seed descent population, named TRL, derived from the cross between Timgalen, white-grained wheat, and RL 4137, red-grained wheat. The study was carried out using sprouting data in ripe ears obtained under artificial conditions in a rainfall simulator over three years. According to the results there is a significant effect on preharvest sprouting provided by colour and a weaker effect of increasing R dosage. However, the significant residual genotypic variation between red lines and all lines (reds and whites at 0.1% level showed that preharvest sprouting was also controlled by other genes. There are no significant correlations between sprouting and date of ripeness or between ripeness, R dosage and colour intensity.Uma vez que os alelos dominantes para cor vermelha (R, dos genes que controlam a cor do grão, têm importância no incremento da resistência à germinação pré-colheita, em trigo, e há três locos herdados independentemente, nos cromossomos 3A, 3B e 3D do trigo hexaplóide, é possível variar sua dosagem em um programa de melhoramento. O objetivo deste trabalho foi avaliar o efeito de dosagem dos genes R na germinação pré-colheita, em uma população de descendência por semente única, batizada de TRL, derivada do cruzamento entre Timgalen, trigo de grão branco, e RL 4137, trigo de grão vermelho. O estudo utilizou dados de germinação em espigas maduras, obtidos sob condições artificiais em um simulador de chuva, em três anos. De acordo com os resultados, o efeito da cor de grão e, menos acentuadamente

Modification of a Phenolic Resin with Epoxy- and Methacrylate-Functionalized Silica Sols to Improve the Ablation Resistance of Their Glass Fiber-Reinforced Composites

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Yu Hu

2014-01-01

Full Text Available Functionalized silica sols were obtained by the hydrolytic condensation of (γ-methacryloxypropyltrimethoxysilane (MPMS, (γ-glycidyloxypropyltrimethoxysilane (GPMS and tetraethoxysilane (TEOS. Three different sols were obtained: MPS (derived from MPMS and TEOS, GPS-MPS (derived from GPMS, MPMS and TEOS, and GPSD (derived from GPMS, TEOS and diglycidyl ether of bisphenol A, DGEBA. These silica sols were mixed with a phenolic resin (PR. Ethylenediamine was used as a hardener for epoxy-functionalized sols and benzoyl peroxide was used as an initiator of the free-radical polymerization of methacrylate-functionalized silica sols. Glass fiber-reinforced composites were obtained from the neat PR and MPS-PR, GPS-MPS-PR and GPSD-PR. The resulting composites were evaluated as ablation resistant materials in an acetylene-oxygen flame. A large increase in the ablation resistance was observed when the PR was modified by the functionalized silica sols. The ablation resistance of the composites decreased as follows: GPSD-PR > MPS-PR > GPS-MPS-PR > PR.

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

International Nuclear Information System (INIS)

O'Brien, J.N.

1982-08-01

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

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

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Sanchita Das

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

Utility of Social Modeling for Proliferation Assessment - Preliminary Assessment

Energy Technology Data Exchange (ETDEWEB)

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

2009-06-01

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

Drug-DNA adducts as biomarkers for metabolic activation of the nitro-aromatic nitrogen mustard prodrug PR-104A.

Science.gov (United States)

Stornetta, Alessia; Deng, Kai-Cheng Kieren; Danielli, Sara; Liyanage, H D Sarath; Sturla, Shana J; Wilson, William R; Gu, Yongchuan

2018-04-07

PR-104A is a clinical-stage nitrogen mustard prodrug that is activated for DNA alkylation by reduction of a nitro group to the corresponding hydroxylamine (PR-104H) or amine (PR-104M). Metabolic reduction is catalysed by flavoreductases such as cytochrome P450 oxidoreductase (POR) under hypoxia, or by aldo-ketoreductase 1C3 (AKR1C3) independently of hypoxia. The unstable reduced metabolites are challenging to measure in biological samples, and biomarkers of the metabolic activation of PR-104A have not been used in the clinical evaluation of PR-104 to date. Here, we employ a selected reaction monitoring mass spectrometry assay for DNA crosslinks to assess the capacity of human cancer cells to bioactivate PR-104A. We also test whether the more abundant DNA monoadducts could be used for the same purpose. DNA monoadducts and crosslinks from PR-104A itself, and from its reduced metabolites, accumulated over 4 h in AKR1C3-expressing TF1 erythroleukaemia cells under hypoxia, whereas intracellular concentrations of unstable PR-104H and PR-104M reached steady state within 1 h. We then varied rates of PR-104A reduction by manipulating hypoxia or reductase expression in a panel of cell lines, in which AKR1C3 and POR were quantified by targeted proteomics. Hypoxia or reductase overexpression induced large increases in PR-104A sensitivity (inhibition of proliferation), DNA damage response (γH2AX formation), steady-state concentrations of PR-104H/M and formation of reduced drug-DNA adducts but not DNA adducts retaining the dinitro groups of PR-104A. The fold-change in the sum of PR-104H and PR-104M correlated with the fold-change in reduced crosslinks or monoadducts (R 2  = 0.87 for both), demonstrating their potential for assessing the capacity of cancer cells to bioactivate PR-104A. Copyright © 2018 Elsevier Inc. All rights reserved.

L-Arginine ethylester enhances in vitro amplification of PrP(Sc) in macaques with atypical L-type bovine spongiform encephalopathy and enables presymptomatic detection of PrP(Sc) in the bodily fluids.

Science.gov (United States)

Murayama, Y; Ono, F; Shimozaki, N; Shibata, H

2016-02-12

Protease-resistant, misfolded isoforms (PrP(Sc)) of a normal cellular prion protein (PrP(C)) in the bodily fluids, including blood, urine, and saliva, are expected to be useful diagnostic markers of prion diseases, and nonhuman primate models are suited for performing valid diagnostic tests for human Creutzfeldt-Jakob disease (CJD). We developed an effective amplification method for PrP(Sc) derived from macaques infected with the atypical L-type bovine spongiform encephalopathy (L-BSE) prion by using mouse brain homogenate as a substrate in the presence of polyanions and L-arginine ethylester. This method was highly sensitive and detected PrP(Sc) in infected brain homogenate diluted up to 10(10) by sequential amplification. This method in combination with PrP(Sc) precipitation by sodium phosphotungstic acid is capable of amplifying very small amounts of PrP(Sc) contained in the cerebrospinal fluid (CSF), saliva, urine, and plasma of macaques that have been intracerebrally inoculated with the L-BSE prion. Furthermore, PrP(Sc) was detectable in the saliva or urine samples as well as CSF samples obtained at the preclinical phases of the disease. Thus, our novel method may be useful for furthering the understanding of bodily fluid leakage of PrP(Sc) in nonhuman primate models. Copyright © 2016 Elsevier Inc. All rights reserved.

Electrical resistivity and thermopower of Y1-xPrxCo2 Compounds

International Nuclear Information System (INIS)

Uchima, K; Takaesu, Y; Teruya, A; Akamine, H; Kakihana, M; Tomori, K; Uejo, T; Nakamura, A; Hedo, M; Nakama, T; Yagasaki, K; Burkov, A T

2015-01-01

Electrical resistivity ρ and thermopower S of the pseudo-binary compounds of Y 1-x Pr x Co 2 have been measured in the temperature range between 2 and 300 K under magnetic fields up to 10 T, together with the pressure measurements of ρ and S in Y 0.4 Pr 0.6 Co 2 . The Curie temperature decreases with decreasing x, and vanishes at the critical composition x c ≈ 0.4, where the residual resistivity attains a maximum value. The Curie temperature and the residual resistivity of Y 0.4 Pr 0.6 Co 2 show the same pressure dependence as those of the heavy-rare-earth based compounds. These behaviors of ρ and S indicate the inhomogeneous distribution of the Co 3d magnetization. The magnetoresistance of the light-rare earth Y 1-x Pr x Co 2 system is negative in the whole range of x, except for x = 0 and 1, which is a characteristic behavior related with magnetic state and magnitude of the effective field acting on the Co 3d subsystem

Isothermal sections of the state diagram for the Pr-Ni-Ge system at 870 (0-0,5Pr) and 670 K (0,5-1Pr)

International Nuclear Information System (INIS)

Fedyna, M.F.; Pecharskij, V.K.; Bodak, O.I.

1987-01-01

Method of X-ray phase and microstructural analyses were used to study Pr-Ni-Ge ternary system at 870K (0-0.50 at.fractions of Pr) and 670K (0.50-1.00 at.fractions of Pr). 11 ternary compounds exist in the system: Pr 1-x (NiGe) 13 (x=0.24), PrNi 2 Ge 2 , Pr 2 Ni 3 Ge 5 , PrNiGe 3 , Pr 2 NiGe 6 , Pr 3 Ni 4 Ge 4 , PrNi (1-x) Ge 2 (x=0.33), PrNiGe, Pr(NiGe) 2-x (x=0.14), Pr 3 NiGe 2 , ∼Pr 5 NiGe 4 . Crystal structure was determined for seven ternary compounds

A resistência olha a resistência

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Jorge Ponciano Ribeiro

Full Text Available Resistência é um processo humano que acontece quando a pessoa se encontra sob algum tipo de ameaça. Não é essencialmente um acontecimento psicoterapêutico. Ocorre na terapia não como uma oposição a si mesmo ou ao terapeuta, mas como uma forma de se ajustar a uma nova situação. A resistência, é por natureza, a atualização do instinto de auto-preservação. E o organismo inteligentemente segue a lei da preferência. Resistência é uma forma de contato que não pode ser destruída, mas administrada, porque ela surge como uma defesa da totalidade vivenciada pela pessoa. A Resistência é, às vezes, resistência e awareness mais que ao contato. Ela revela mais o caminho seguido do que oculta a caminhada feita. A resistência é um processo natural, porque o corpo que não resiste, morre, mas falamos em processos de auto-regulação organísmica. Valorizamos mais o que mantêm a resistência funcionando do que à própria resistência. O terapeuta também resiste, ou seja, ele se auto-regula na sua relação com o cliente. Não questionamos a resistência, mas o processo que a mantêm. Trabalhamos com nove mecanismos de defesa, também tradicionalmente, chamados de resistência.

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-05-01

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

Climate Change, Nuclear Power and Nuclear Proliferation: Magnitude Matters

International Nuclear Information System (INIS)

Goldston, Robert J.

2011-01-01

Integrated energy, environment and economics modeling suggests that worldwide electrical energy use will increase from 2.4 TWe today to ∼12 TWe in 2100. It will be challenging to provide 40% of this electrical power from combustion with carbon sequestration, as it will be challenging to provide 30% from renewable energy sources derived from natural energy flows. Thus nuclear power may be needed to provide ∼30%, 3600 GWe, by 2100. Calculations of the associated stocks and flows of uranium, plutonium and minor actinides indicate that the proliferation risks at mid-century, using current light-water reactor technology, are daunting. There are institutional arrangements that may be able to provide an acceptable level of risk mitigation, but they will be difficult to implement. If a transition is begun to fast-spectrum reactors at mid-century, without a dramatic change in the proliferation risks of such systems, at the end of the century global nuclear proliferation risks are much greater, and more resistant to mitigation. Fusion energy, if successfully demonstrated to be economically competitive, would provide a source of nuclear power with much lower proliferation risks than fission.

Climate Change, Nuclear Power and Nuclear Proliferation: Magnitude Matters

Energy Technology Data Exchange (ETDEWEB)

Robert J. Goldston

2011-04-28

Integrated energy, environment and economics modeling suggests that worldwide electrical energy use will increase from 2.4 TWe today to ~12 TWe in 2100. It will be challenging to provide 40% of this electrical power from combustion with carbon sequestration, as it will be challenging to provide 30% from renewable energy sources derived from natural energy flows. Thus nuclear power may be needed to provide ~30%, 3600 GWe, by 2100. Calculations of the associated stocks and flows of uranium, plutonium and minor actinides indicate that the proliferation risks at mid-century, using current light-water reactor technology, are daunting. There are institutional arrangements that may be able to provide an acceptable level of risk mitigation, but they will be difficult to implement. If a transition is begun to fast-spectrum reactors at mid-century, without a dramatic change in the proliferation risks of such systems, at the end of the century global nuclear proliferation risks are much greater, and more resistant to mitigation. Fusion energy, if successfully demonstrated to be economically competitive, would provide a source of nuclear power with much lower proliferation risks than fission.

Melatonin Promotes Apoptosis of Oxaliplatin-resistant Colorectal Cancer Cells Through Inhibition of Cellular Prion Protein.

Science.gov (United States)

Lee, Jun Hee; Yoon, Yeo Min; Han, Yong-Seok; Yun, Chul Won; Lee, Sang Hun

2018-04-01

Drug resistance restricts the efficacy of chemotherapy in colorectal cancer. However, the detailed molecular mechanism of drug resistance in colorectal cancer cells remains unclear. The level of cellular prion protein (PrP C ) in oxaliplatin-resistant colorectal cancer (SNU-C5/Oxal-R) cells was assessed. PrP C level in SNU-C5/Oxal-R cells was significantly increased compared to that in wild-type (SNU-C5) cells. Superoxide dismutase and catalase activities were higher in SNU-C5/Oxal-R cells than in SNU-C5 cells. Treatment of SNU-C5/Oxal-R cells with oxaliplatin and melatonin reduced PrP C expression, while suppressing antioxidant enzyme activity and increasing superoxide anion generation. In SNU-C5/Oxal-R cells, endoplasmic reticulum stress and apoptosis were significantly increased following co-treatment with oxaliplatin and melatonin compared to treatment with oxaliplatin alone. Co-treatment with oxaliplatin and melatonin increased endoplasmic reticulum stress in and apoptosis of SNU-C5/Oxal-R cells through inhibition of PrP C , suggesting that PrP C could be a key molecule in oxaliplatin resistance of colorectal cancer cells. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Photoemission of heavy fermion superconductor PrOs4Sb12 and other Pr compounds

International Nuclear Information System (INIS)

Imada, S.; Yamasaki, A.; Sekiyama, A.; Settai, R.; Onuki, Y.; Suga, S.; Sugawara, H.; Sato, H.; Ochiai, A.

2004-01-01

Full text: Strongly correlated electronic states due to Pr 4f electrons found in several Pr compounds have recently been attracting much attention. The Pr 4f electrons are much more localized than in Ce due to the lanthanoid contraction. Therefore, the number of the Pr systems that show strong electron correlation is much smaller than Ce systems. We will present a comparative study of Pr 4f electronic states in such systems as the heavy fermion superconductor PrOs 4 Sb 12 , the Kondo system PrSn 3 and the localized 4f systems Pr 4 X 3 (X = Sb and Bi). The Pr 4f electronic state was probed by means of the Pr 3d → 4f resonant photoemission (RPES). Because the kinetic energy (E K ) of the photoelectrons is as high as ∼ 900 eV, this method is much more bulk sensitive than the 4d → 4f RPES with E K ∼ 100 eV. The energy resolution could be set to about 100 meV by utilizing the soft X-rays from BL25SU in SPring-8 and the SCIENTA SES-200 analyzer. The Pr 4f excitation spectrum of PrSn 3 was found to show a very strong intensity at the Fermi level (E F ). This can be interpreted as the Kondo resonance which has been observed in the Kondo Ce and Yb compounds. In the Pr 4f spectrum of the heavy fermion superconductor PrOs 4 Sb 12 , the intensity at E F was smaller than in PrSn 3 . This clearly shows that the Kondo temperature (T K ) is much lower in PrOs 4 Sb 12 than in PrSn 3 . We have further found a strong excitation energy dependence in the RPES line shape. In the case of Pr 4 X 3 (X = Sb and Bi), the intensity at E B was much smaller than PrSn 3 and PrOs 4 Sb 12 , which is consistent with the localized character of Pr 4f electrons in Pr 4 X 3 . The Pr 4f spectra of these localized systems are qualitatively well reproduced by a cluster model calculation that takes into account the hybridization between the Pr 4f orbital and the conduction and valence bands made up by the X p and Pr 5d states

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

International Nuclear Information System (INIS)

Haeckel, E.

1990-01-01

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

Colossal anisotropic resistivity and oriented magnetic domains in strained La{sub 0.325}Pr{sub 0.3}Ca{sub 0.375}MnO{sub 3} films

Energy Technology Data Exchange (ETDEWEB)

Jiang, Tao; Yang, Shengwei; Liu, Yukuai; Zhao, Wenbo; Feng, Lei; Li, Xiaoguang, E-mail: lixg@ustc.edu.cn [Hefei National Laboratory for Physical Sciences at Microscale, Department of Physics, University of Science and Technology of China, Hefei 230026 (China); Zhou, Haibiao; Lu, Qingyou [Hefei National Laboratory for Physical Sciences at Microscale, Department of Physics, University of Science and Technology of China, Hefei 230026 (China); High Magnetic Field Laboratory, Chinese Academy of Sciences and University of Science and Technology of China, Hefei 230031 (China); Hou, Yubin [High Magnetic Field Laboratory, Chinese Academy of Sciences and University of Science and Technology of China, Hefei 230031 (China)

2014-05-19

Magnetic and resistive anisotropies have been studied for the La{sub 0.325}Pr{sub 0.3}Ca{sub 0.375}MnO{sub 3} films with different thicknesses grown on low symmetric (011)-oriented (LaAlO{sub 3}){sub 0.3}(SrAl{sub 0.5}Ta{sub 0.5}O{sub 3}){sub 0.7} substrates. In the magnetic and electronic phase separation region, a colossal anisotropic resistivity (AR) of ∼10{sup 5}% and an anomalous large anisotropic magnetoresistance can be observed for 30 nm film. However, for 120 nm film, the maximum AR decreases significantly (∼2 × 10{sup 3}%) due to strain relaxation. The colossal AR is strongly associated with the oriented formation of magnetic domains, and the features of the strain effects are believed to be useful for the design of artificial materials and devices.

Effect of Pr addition on microstructure and mechanical properties of AZ61 magnesium alloy

Directory of Open Access Journals (Sweden)

You Zhiyong

2014-03-01

Full Text Available To improve the strength, hardness and heat resistance of Mg-6Al-1Zn (AZ61 alloy, the effects of Pr addition on the as-cast microstructure and mechanical properties of AZ61 alloy were investigated at room and elevated temperatures by means of Brinell hardness measurement, optical microscope (OM, scanning electron microscope (SEM, energy dispersive spectroscopy (EDS, X-ray diffractometer (XRD and DNS100 electronic universal testing machine. The results show that the microstructures of Pr-containing AZ61 alloys were refined, with primary β-Mg17Al12 phase distributed homogeneously. When the addition of Pr is up to 1.2wt.%, the β phase becomes finer, and new needle-like or short-rod shaped Al11Pr3 phase and blocky AlPr phase appear. As a result, optimal tensile properties are obtained. However, greater than 1.2wt.% Pr addition leads to poorer mechanical properties due to the aggregation of the needle-like phase and large size of grains. The present research findings provide a new way for strengthening of magnesium alloys at room and elevated temperatures, and a method of producing thermally-stable AZ61 magnesium alloy.

Moss Pathogenesis-Related-10 protein enhances resistance to Pythium irregulare in Physcomitrella patens and Arabidopsis thaliana

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Alexandra eCastro

2016-04-01

Full Text Available Plants respond to pathogen infection by activating signaling pathways leading to the accumulation of proteins with diverse roles in defense. Here, we addressed the functional role of PpPR-10, a pathogenesis-related (PR-10 gene, of the moss Physcomitrella patens, in response to biotic stress. PpPR-10 belongs to a multigene family and encodes a protein twice the usual size of PR-10 proteins due to the presence of two Bet v1 domains. Moss PR-10 genes are differentially regulated during development and inoculation with the fungal pathogen Botrytis cinerea. Specifically, PpPR-10 transcript levels increase significantly by treatments with elicitors of Pectobacterium carotovorum subsp. carotovorum, spores of B. cinerea, and the defense hormone salicylic acid. To characterize the role of PpPR-10 in plant defense against pathogens, we conducted overexpression analysis in P. patens and in Arabidopsis thaliana. We demonstrate that constitutive expression of PpPR-10 in moss tissues increased resistance against the oomycete Pythium irregulare. PpPR-10 overexpressing moss plants developed less symptoms and decreased mycelium growth than wild type plants. In addition, PpPR-10 overexpressing plants constitutively produced cell wall depositions in protonemal tissue. Ectopic expression of PpPR-10 in Arabidopsis resulted in increased resistance against P. irregulare as well, evidenced by smaller lesions and less cellular damage compared to wild type plants. These results indicate that PpPR-10 is functionally active in the defense against the pathogen P. irregulare, in both P. patens and Arabidopsis, two evolutionary distant plants. Thus, P. patens can serve as an interesting source of genes to improve resistance against pathogen infection in flowering plants.

Interrelation of androgen receptor and miR-30a and miR-30a function in ER-, PR-, AR+ MDA-MB-453 breast cancer cells.

Science.gov (United States)

Lyu, Shuhua; Liu, Han; Liu, Xia; Liu, Shan; Wang, Yahong; Yu, Qi; Niu, Yun

2017-10-01

The association between androgen-induced androgen receptor (AR) activating signal and microRNA (miR)-30a was investigated, as well as the function of miR-30a in estrogen receptor-negative (ER - ), progesterone receptor-negative (PR - ), and AR-positive (AR + ) MDA-MB-453 breast cancer cells. Androgen-induced AR activating signal upregulated the expression of AR, and downregulated the expression of miR-30a, b and c. Bioinformatics analysis indicated a putative miR-30a, b and c binding site in the 3'-untranslated region of AR mRNA. It was confirmed that the AR gene is a direct target of miR-30a, whereas AR does not target the miR-30a promoter, and AR activating signal may indirectly downregulate miR-30a through other cell signaling pathways. In this positive feedback mechanism AR is then upregulated through miR-30a. Overexpression of miR-30a inhibited cell proliferation, whereas inhibition of miR-30a expression by specific antisense oligonucleotides, increased cell growth. Previously, androgen-induced AR activating signal was demonstrated to inhibit cell proliferation in ER - , PR - and AR + MDA-MB-453 breast cancer cells, but AR activating signal downregulated the expression of miR-30a, relieving the inhibition of MDA-MB-453 cell growth. Therefore, in MDA-MB-453 breast cancer cells, miR-30a has two different functions regarding cell growth: Inhibition of cell proliferation through a positive feedback signaling pathway; and the relative promotion of cell proliferation through downregulation of miR-30a. Thus, the association between AR activating signal and microRNAs is complex, and microRNAs may possess different functions due to different signaling pathways. Although the results of the present study were obtained in one cell line, they contribute to subsequent studies on ER - , PR - and AR + breast cancer.

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

Directory of Open Access Journals (Sweden)

Florence Gizard

2008-01-01

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

Suured prügifirmad valmistuvad prügipuuduseks / Mirko Ojakivi

Index Scriptorium Estoniae

Ojakivi, Mirko

2010-01-01

Ragn-Sells ja Adelan Prügiveod soovivad luba jäätmete pikaajaliseks vaheladestamiseks Tallinna piiril. Ragn-Sells saaks jäätmekütusetehase planeerimise ja ehitamise ajal endale koguda ligi 35 000 t segaolmejäätmeid aastas, Adelan Prügiveod sooviks ladestada ligi 50 000 t prügi aastas

Polymorphisms in the HIV-1 gp41 env gene, natural resistance to enfuvirtide (T-20) and pol resistance among pregnant Brazilian women.

Science.gov (United States)

Reis, Mônica Nogueira da Guarda; de Alcântara, Keila Correa; Cardoso, Ludimila Paula Vaz; Stefani, Mariane Martins Araújo

2014-01-01

The selective pressure of antiretroviral drugs (ARVs) targeting HIV-1 pol can promote drug resistance mutations in other genomic regions, such as env. Drug resistance among women should be monitored to avoid horizontal and mother-to-child transmission. To describe natural resistance to T-20 (enfuvirtide), gp41 env polymorphisms, mutations in pol and HIV-1 subtypes, 124 pregnant women were recruited. For 98 patients, the gp41 env, protease (PR) and reverse transcriptase (RT) fragments were sequenced. The patients were ARV naïve (n = 30), taking mother-to-child transmission prophylaxis (n = 50), or being treated with highly active ARV therapy/HAART (n = 18). The Stanford and IAS/USA databases and other sources were used to analyze PR/RT, gp41 env resistance mutations. The HIV-1 genetic diversity was analyzed by REGA/phylogenetic analyses. The patients' median age was 25 years (range, 16-42), 18.4% had AIDS. The frequency of natural resistance to T-20 (N42D, L44M, and R46M-low-impact mutations) was 6.1% (6/98); 20.4% (20/98) had compensatory mutations in HR2. The prevalence of transmitted drug resistance in the pol was 13.3% (4/30), and the prevalence of secondary drug resistance was 33.3% (6/18). Two patients were infected with multidrug resistant/MDR viruses. The analysis of HIV-1 subtypes (PR/RT/gp41) revealed that 61.2% (60/98) were subtype B, 12.2% (12/98) were subtype C, 4.1% (4/98) were subtype F1, and 22.4% (22/98) were possible recombinants (BF1 = 20.4%; BC = 2%). Natural resistance to T-20 was not associated with pol resistance or previous ARV use. The high rate of secondary resistance, including MDR, indicates that the number of women that may need T-20 salvage therapy may be higher than anticipated. © 2013 Wiley Periodicals, Inc.

Anisotropic Transport and Magnetic Properties of Charge-Density-Wave Materials RSeTe_2 (R = La, Ce, Pr, Nd)

International Nuclear Information System (INIS)

Wang Pei-Pei; Long Yu-Jia; Zhao Ling-Xiao; Chen Dong; Xue Mian-Qi; Chen Gen-Fu

2015-01-01

Single crystals of RSeTe_2 (R = La, Ce, Pr, Nd) are synthesized using LiCl/RbCl flux. Transport and magnetic properties in the directions parallel and perpendicular to the a–c plane are investigated. We find that the resistivity anisotropy ρ_⊥/ρ_‖ lies in the range 486–615 for different compounds at 2 K, indicating the highly two-dimensional character. In both the orientations, the charge-density-wave transitions start near T_C_D_W = 284(3) K, 316(3) K, 359(3) K for NdSeTe_2, PrSeTe_2, CeSeTe_2, respectively, with a considerable increase in dc resistivity. While for LaSeTe_2, no obvious resistivity anomaly is observed up to 380 K. The value of T_C_D_W increases monotonically with the increasing lattice parameters. Below T_C_D_W, slight anomalies can be observed in NdSeTe_2, PrSeTe_2 and CeSeTe_2 with onset temperature at 193(3) K, 161(3) K, 108(3) K, respectively, decreasing as lattice parameters increase. Magnetic susceptibility measurements show that the valence state of rare earth ions are trivalence in these compounds. Antiferromagnetic-type magnetic order is formed in CeSeTe_2 at 2.1 K, while no magnetic transition is observed in PrSeTe_2 and NdSeTe_2 down to 1.8 K. (paper)

Preparation of Pr-Fe-Co-B-Nb-M (M= Al, P, Cu, Ga and/or Gd) HDDR magnets and alloys and characterization of their magnetic properties and corrosion resistance

International Nuclear Information System (INIS)

Oliveira, Mara Cristina Lopes de

2009-01-01

HDDR process has attracted great interest for producing polymer- bonded rare earth based magnets. It presents commercial advantages when compared with conventional sintered magnets owing to easy and low cost manufacturing. With the development of anisotropic powders using praseodymium, the expectations about this process grow e also the need for studying new compositions and alloy additions. In this work the magnetic properties of polymer-bonded magnets prepared with PrFeB magnetic alloys using HDDR process have been studied. Pr 14 Fe bal Co 16 B 6 Nb 0,1 was used as the reference alloy Phosphorus, copper, aluminium, gallium and gadolinium additions have been performed to increase the magnetic properties of the reference alloy. The microstructural characterization of the magnets has been carried out through optical microscopy and SEM. The complex microstructure influences the electrochemical behavior of the magnetic alloys. The literature about this subject is scarce. Thus, the corrosion resistance of the different alloys prepared during this work was evaluated using electrochemical impedance spectroscopy and potentiodynamic polarization curves. A correlation between the microstructural features and the electrochemical behavior of the alloys has been established. The results showed that phosphorus and aluminium additions up to 1.0wt% had a beneficial effect on the magnetic properties and corrosion resistance of the alloys. Copper additions, on the other hand, strongly diminished the magnetic properties of the reference alloy. (author)

Crystallographic and electrical properties of Pr substituted Gd-123 nanometre sized high temperature superconductors

International Nuclear Information System (INIS)

Huse, V.R.; Mote, V.D.; Shah, S.S.; Dole, B.N.; Purushotham, Y.; Dhar, S.K.

2011-01-01

The samples of Gd 1-x Pr x Ba 2 Cu 3 O 7-δ with compositions x = 0.0, 0.1 and 0.3 were prepared by ceramic route. The XRD study of all samples is carried out. The XRD studies of the samples prepared by ceramic route show GdPr-123 system have an orthorhombic perovskite structure. The lattice parameters, oxygen content, volume of unit cell, orthorhombic perovskite structure. The lattice parameters, oxygen content, volume of unit cell, orthorhombic distortion, hole concentration in CuO 2 plane and charge on Cu-O plane were evaluated using XRD data. It is found that the lattice parameters, volume of unit cell increase while oxygen content orthorhombic distortion, hole concentration (Psh) and average charge (p) decrease as doping percentage of Pr increases. The resistivity measurement shows the transition temperature decreases while transition width increases with increasing Pr concentration. The suppression of superconductivity may be due to reduction in hole concentration or magnetic pair breaking. We report such qualitative results of Pr substituted Gd-123 in this paper quantitatively. (author)

Evidence of multiple/cross resistance to Bt and organophosphate insecticides in Puerto Rico population of the fall armyworm, Spodoptera frugiperda.

Science.gov (United States)

Zhu, Yu Cheng; Blanco, Carlos A; Portilla, Maribel; Adamczyk, John; Luttrell, Randall; Huang, Fangneng

2015-07-01

Fall armyworm (FAW) is a damaging pest of many economic crops. Long-term use of chemical control prompted resistance development to many insecticide classes. Many populations were found to be significantly less susceptible to major Bt toxins expressed in transgenic crops. In this study, a FAW strain collected from Puerto Rico (PR) with 7717-fold Cry1F-resistance was examined to determine if it had also developed multiple/cross resistance to non-Bt insecticides. Dose response assays showed that the PR strain developed 19-fold resistance to acephate. Besides having a slightly smaller larval body weight and length, PR also evolved a deep (2.8%) molecular divergence in mitochondrial oxidase subunit II. Further examination of enzyme activities in the midgut of PR larvae exhibited substantial decreases of alkaline phosphatase (ALP), aminopeptidase (APN), 1-NA- and 2-NA-specific esterase, trypsin, and chymotrypsin activities, and significant increases of PNPA-specific esterase and glutathione S-transferase (GST) activities. When enzyme preparations from the whole larval body were examined, all three esterase, GST, trypsin, and chymotrypsin activities were significantly elevated in the PR strain, while ALP and APN activities were not significantly different from those of susceptible strain. Data indicated that multiple/cross resistances may have developed in the PR strain to both Bt toxins and conventional insecticides. Consistently reduced ALP provided evidence to support an ALP-mediated Bt resistance mechanism. Esterases and GSTs may be associated with acephate resistance through elevated metabolic detoxification. Further studies are needed to clarify whether and how esterases, GSTs, and other enzymes (such as P450s) are involved in cross resistance development to Bt and other insecticide classes. Published by Elsevier Inc.

Salicylic acid confers enhanced resistance to Glomerella leaf spot in apple.

Science.gov (United States)

Zhang, Ying; Shi, Xiangpeng; Li, Baohua; Zhang, Qingming; Liang, Wenxing; Wang, Caixia

2016-09-01

Glomerella leaf spot (GLS) caused by Glomerella cingulata is a newly emergent disease that results in severe defoliation and fruit spots in apple. Currently, there are no effective means to control this disease except for the traditional fungicide sprays. Induced resistance by elicitors against pathogens infection is a widely accepted eco-friendly strategy. In the present study, we investigated whether exogenous application of salicylic acid (SA) could improve resistance to GLS in a highly susceptible apple cultivar (Malus domestica Borkh. cv. 'Gala') and the underlying mechanisms. The results showed that pretreatment with SA, at 0.1-1.0 mM, induced strong resistance against GLS in 'Gala' apple leaves, with SA treated leaves showing significant reduction in lesion numbers and disease index. Concurrent with the enhanced disease resistance, SA treatment markedly increased the total antioxidant capacity (T-AOC) and defence-related enzyme activities, including catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), phenylalanine ammonia-lyase (PAL) and polyphenol oxidase (PPO). As expected, SA treatment also induced the expression levels of five pathogenesis-related (PR) genes including PR1, PR5, PR8, Chitinase and β-1,3-glucanase. Furthermore, the most pronounced and/or rapid increase was observed in leaves treated with SA and subsequently inoculated with G. cingulata compared to the treatment with SA or inoculation with the pathogen. Together, these results suggest that exogenous SA triggered increase in reactive oxygen species levels and the antioxidant system might be responsible for enhanced resistance against G. cingulata in 'Gala' apple leaves. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

Science.gov (United States)

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

2015-01-01

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

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

Directory of Open Access Journals (Sweden)

Tao Yu

2015-01-01

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

Crystal Field Levels of Pr3+ in PrFeO3 and PrGaO3 Determined by Inelastic Neutron Scattering

DEFF Research Database (Denmark)

Feldmann, K.; Henning, K.; Kaun, L.

1975-01-01

The crystal field splitting of the 3H4 ground state of the Pr ion in PrFeO3 and PrGaO3 has been investigated by inelastic scattering of thermal neutrons. At several temperatures the transitions have been measured by TAS and TOF methods for polycrystalline PrFeO3 and by the TOF method...... for polycrystalline PrGaO3. Energy level schemes which are different for these materials are given....

Bi3+–Pr3+ energy transfer processes and luminescent properties of LuAG:Bi,Pr and YAG:Bi,Pr single crystalline films

International Nuclear Information System (INIS)

Zorenko, Y.; Gorbenko, V.; Savchyn, V.; Zorenko, T.; Nikl, M.; Mares, J.A.; Beitlerova, A.; Jary, V.

2013-01-01

Absorption, cathodoluminescence, excitation spectra of photoluminescence (PL) and PL decay kinetics were studied at 300 K for the double doped with Bi 3+ –Pr 3+ and separately doped with Bi 3+ and Pr 3+ Lu 3 Al 5 O 12 (LuAG) and Y 3 Al 5 O 12 (YAG) single crystalline film (SCF) phosphors grown by the liquid phase epitaxy method. The emission bands in the UV range arising from the intrinsic radiative transitions of Bi 3+ based centers, and emission bands in the visible range, related to the luminescence of excitons localized around Bi 3+ based centers, were identified both in Bi–Pr and Bi-doped LuAG and YAG SCFs. The energy transfer processes from the host lattice simultaneously to Bi 3+ and Pr 3+ ions and from Bi 3+ to Pr 3+ ions were investigated. Competition between Pr 3+ and Bi 3+ ions in the energy transfer processes from the LuAG and YAG hosts was evidenced. The strong decrease of the intensity of Pr 3+ luminescence both in LuAG:Pr and YAG:Pr SCFs phosphors, grown from Bi 2 O 3 flux, is observed due to the quenching influence of Bi 3+ flux related impurity. Due to overlap of the UV emission band of Bi 3+ centers with the f–d absorption bands of Pr 3+ ions in the UV range and the luminescence of excitons localized around Bi ions with the f–f absorption bands of Pr 3+ ions in the visible range, an effective energy transfer from Bi 3+ ions to Pr 3+ ions takes place in LuAG:Bi,Pr and YAG:Bi,Pr SCFs, resulting in the appearance of slower component in the decay kinetics of the Pr 3+ d–f luminescence. -- Highlights: • Bi and Pr doped film phosphor grown by liquid phase epitaxy method. • Energy transfer from Bi 3+ to Pr 3+ ions. • Strong quenching of the Pr 3+ luminescence by Bi 3+ co-dopant

Animation of Antimicrobial Resistance

Medline Plus

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

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

International Nuclear Information System (INIS)

Slessarev, Igor

2008-01-01

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

Constitutive expression of a fungus-inducible carboxylesterase improves disease resistance in transgenic pepper plants.

Science.gov (United States)

Ko, Moonkyung; Cho, Jung Hyun; Seo, Hyo-Hyoun; Lee, Hyun-Hwa; Kang, Ha-Young; Nguyen, Thai Son; Soh, Hyun Cheol; Kim, Young Soon; Kim, Jeong-Il

2016-08-01

Resistance against anthracnose fungi was enhanced in transgenic pepper plants that accumulated high levels of a carboxylesterase, PepEST in anthracnose-susceptible fruits, with a concurrent induction of antioxidant enzymes and SA-dependent PR proteins. A pepper esterase gene (PepEST) is highly expressed during the incompatible interaction between ripe fruits of pepper (Capsicum annuum L.) and a hemibiotrophic anthracnose fungus (Colletotrichum gloeosporioides). In this study, we found that exogenous application of recombinant PepEST protein on the surface of the unripe pepper fruits led to a potentiated state for disease resistance in the fruits, including generation of hydrogen peroxide and expression of pathogenesis-related (PR) genes that encode mostly small proteins with antimicrobial activity. To elucidate the role of PepEST in plant defense, we further developed transgenic pepper plants overexpressing PepEST under the control of CaMV 35S promoter. Molecular analysis confirmed the establishment of three independent transgenic lines carrying single copy of transgenes. The level of PepEST protein was estimated to be approximately 0.002 % of total soluble protein in transgenic fruits. In response to the anthracnose fungus, the transgenic fruits displayed higher expression of PR genes, PR3, PR5, PR10, and PepThi, than non-transgenic control fruits did. Moreover, immunolocalization results showed concurrent localization of ascorbate peroxidase (APX) and PR3 proteins, along with the PepEST protein, in the infected region of transgenic fruits. Disease rate analysis revealed significantly low occurrence of anthracnose disease in the transgenic fruits, approximately 30 % of that in non-transgenic fruits. Furthermore, the transgenic plants also exhibited resistance against C. acutatum and C. coccodes. Collectively, our results suggest that overexpression of PepEST in pepper confers enhanced resistance against the anthracnose fungi by activating the defense signaling

Future technology challenges in non-proliferation

International Nuclear Information System (INIS)

Richardson, J.H.

2004-01-01

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

Animation of Antimicrobial Resistance

Medline Plus

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

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

Directory of Open Access Journals (Sweden)

T. M. Sokolova

2007-01-01

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

Pathophysiological mechanisms of death resistance in colorectal carcinoma.

Science.gov (United States)

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

2015-11-07

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

Climate Change, Nuclear Power and Nuclear Proliferation: Magnitude Matters

International Nuclear Information System (INIS)

Goldston, Robert J.

2010-01-01

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

Climate Change, Nuclear Power and Nuclear Proliferation: Magnitude Matters

Energy Technology Data Exchange (ETDEWEB)

Robert J. Goldston

2010-03-03

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

Localization of disease-related PrP in Danish patients with different subtypes of prion disease

DEFF Research Database (Denmark)

Bergström, A. L.; Heegaard, Peter M. H.; Dyrbye, H.

2009-01-01

Objective: The transmissible spongiform encephalopaties are characterized by vacuolization, neuronal loss, gliosis and deposition of a misfilded and Proteinase K resistant isoform of the prion protein (PrPSc) in the central nervous system. Methods, materials and patients: Paraffin-embedded tissue...

Electronic and magnetic properties of quasi-skutterudite PrCo2Ga8 compound

Science.gov (United States)

Ogunbunmi, Michael O.; Sondezi, Buyisiwe M.; Nair, Harikrishnan S.; Strydom, André M.

2018-05-01

PrCo2Ga8 is an orthorhombic quasi-skutterudite type compound which crystallizes in the CaCo2Al8 structure type, with space group Pbam (No. 55). The Pr3+ ion has a site symmetry of Cs which predicts a crystal electric field (CEF) level splitting into 9 singlets for J = 4. However, a phase transition at Tm = 1.28 K is observed in electrical resistivity and specific heat results and is reported in this paper. The electrical resistivity shows an upturn below Tm due to the superzone-gap formation. This transition is tuneable in fields and is suppressed to lower temperatures with applied magnetic fields. The electronic specific heat Cp(T) / T increases below Tm and reaches a value of 7.37 J/(mol K2) at 0.4 K. The Sommerfeld coefficient, γ extracted from the low temperature analysis of C4f(T) / T is 637 mJ/(mol K2) indicating a possible mass enhancement of the quasiparticles. The calculated entropy value of 3.05 J/(mol K) is recovered around Tm exhibiting almost 53% of Rln2, where R is the universal gas constant. Magnetic susceptibility results obeys the Curie-Weiss law for data above 100 K with an estimated effective magnetic moment, μeff = 3.37 μB/Pr and Weiss temperature, θp = -124 K.

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-07-01

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

Interaction between Shadoo and PrP Affects the PrP-Folding Pathway.

Science.gov (United States)

Ciric, Danica; Richard, Charles-Adrien; Moudjou, Mohammed; Chapuis, Jérôme; Sibille, Pierre; Daude, Nathalie; Westaway, David; Adrover, Miguel; Béringue, Vincent; Martin, Davy; Rezaei, Human

2015-06-01

Prion diseases are characterized by conformational changes of a cellular prion protein (PrP(C)) into a β-sheet-enriched and aggregated conformer (PrP(Sc)). Shadoo (Sho), a member of the prion protein family, is expressed in the central nervous system (CNS) and is highly conserved among vertebrates. On the basis of histoanatomical colocalization and sequence similarities, it is suspected that Sho and PrP may be functionally related. The downregulation of Sho expression during prion pathology and the direct interaction between Sho and PrP, as revealed by two-hybrid analysis, suggest a relationship between Sho and prion replication. Using biochemical and biophysical approaches, we demonstrate that Sho forms a 1:1 complex with full-length PrP with a dissociation constant in the micromolar range, and this interaction consequently modifies the PrP-folding pathway. Using a truncated PrP that mimics the C-terminal C1 fragment, an allosteric binding behavior with a Hill number of 4 was observed, suggesting that at least a tetramerization state occurs. A cell-based prion titration assay performed with different concentrations of Sho revealed an increase in the PrP(Sc) conversion rate in the presence of Sho. Collectively, our observations suggest that Sho can affect the prion replication process by (i) acting as a holdase and (ii) interfering with the dominant-negative inhibitor effect of the C1 fragment. Since the inception of the prion theory, the search for a cofactor involved in the conversion process has been an active field of research. Although the PrP interactome presents a broad landscape, candidates corresponding to specific criteria for cofactors are currently missing. Here, we describe for the first time that Sho can affect PrP structural dynamics and therefore increase the prion conversion rate. A biochemical characterization of Sho-PrP indicates that Sho acts as an ATP-independent holdase. Copyright © 2015, American Society for Microbiology. All Rights

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

International Nuclear Information System (INIS)

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

2007-03-01

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

Pr-magnetism in the quasi-skutterudite compound PrFe2Al8.

Science.gov (United States)

Nair, Harikrishnan S; Ogunbunmi, Michael O; Kumar, C M N; Adroja, D T; Manuel, P; Fortes, D; Taylor, J; Strydom, A M

2017-08-31

The intermetallic compound PrFe 2 Al 8 that possesses a three-dimensional network structure of Al polyhedra centered at the transition metal element Fe and the rare earth Pr is investigated through neutron powder diffraction and inelastic neutron scattering in order to elucidate the magnetic ground state of Pr and Fe and the crystal field effects of Pr. Our neutron diffraction study confirms long-range magnetic order of Pr below [Formula: see text] K in this compound. Subsequent magnetic structure estimation reveals a magnetic propagation vector [Formula: see text] with a magnetic moment value of [Formula: see text]/Pr along the orthorhombic c-axis and evidence the lack of ordering in the Fe sublattice. The inelastic neutron scattering study reveals one crystalline electric field excitation near 19 meV at 5 K in PrFe 2 Al 8 . The energy-integrated intensity of the 19 meV excitation as a function of [Formula: see text] follows the square of the magnetic form factor of [Formula: see text] thereby confirming that the inelastic excitation belongs to the Pr sublattice. The second sum rule applied to the dynamic structure factor indicates only 1.6(2) [Formula: see text] evolving at the 19 meV peak compared to the 3.58 [Formula: see text] for free [Formula: see text], indicating that the crystal field ground state is magnetic and the missing moment is associated with the resolution limited quasi-elastic line. The magnetic order occurring in Pr in PrFe 2 Al 8 is counter-intuitive to the symmetry-allowed crystal field level scheme, hence, is suggestive of exchange-mediated mechanisms of ordering stemming from the magnetic ground state of the crystal field levels.

A cerato-platanin protein SsCP1 targets plant PR1 and contributes to virulence of Sclerotinia sclerotiorum

DEFF Research Database (Denmark)

Yang, Guogen; Tang, Liguang; Gong, Yingdi

2018-01-01

in the apoplast to facilitate infection by S. sclerotiorum. Overexpressing PR1 enhanced resistance to the wild-type strain, but not to the Sscp1 knockout strain of S. sclerotiorum. Sscp1-expressing transgenic plants showed increased concentrations of salicylic acid (SA) and higher levels of resistance to several...

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

Directory of Open Access Journals (Sweden)

Mariko Abe

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

Induced disease resistance of satsuma mandarings against penicillium digitatum by gamma irradiation

International Nuclear Information System (INIS)

Jeong, Rae Dong

2017-01-01

Gamma irradiation, which is a type of ionizing radiation, can be used as a fruit inducible factor. In the present study, the effects of gamma irradiation on the resistance of mandarin fruits against Penicillium digitatum, the causal agent of postharvest green mold disease, were investigated. Pretreatment of a low dose of gamma irradiation effectively reduced the disease incidence and lesion diameter of mandarin fruits inoculated with P. digatatum during storage for 14 d. Interestingly, exposed to 400 Gy of gamma irradiation significantly maintained firmness and stimulated the synthesis of defense-related enzymes, (e.g., β-1,3-glucanase, phenylalanine, peroxidase, and polyphenol oxidase) and pathogenesis-related (PR) genes (e.g., PR-1 and PR-2). Therefore, the gamma irradiation-induced resistance against P. digatatum involves both changes of phenolic compounds and the induction of expression of defense-related genes. In addition, scanning electron microscopy analysis revealed that induced disease resistance by gamma irradiation signifcantly inhibits the growth of P. digatatum in mandarin fruits. These results suggest that the exposure of gamma irradiation is a potential methods for inducing the disease resistance of fruit to postharvest fungal pathogens and for extending the postharvest life of mandarin fruit

Induced disease resistance of satsuma mandarings against penicillium digitatum by gamma irradiation

Energy Technology Data Exchange (ETDEWEB)

Jeong, Rae Dong [Dept. of Applied Biology, Institute of Environmentally Friendly Agriculture, Chonnam National University, Gwangju (Korea, Republic of)

2017-06-15

Gamma irradiation, which is a type of ionizing radiation, can be used as a fruit inducible factor. In the present study, the effects of gamma irradiation on the resistance of mandarin fruits against Penicillium digitatum, the causal agent of postharvest green mold disease, were investigated. Pretreatment of a low dose of gamma irradiation effectively reduced the disease incidence and lesion diameter of mandarin fruits inoculated with P. digatatum during storage for 14 d. Interestingly, exposed to 400 Gy of gamma irradiation significantly maintained firmness and stimulated the synthesis of defense-related enzymes, (e.g., β-1,3-glucanase, phenylalanine, peroxidase, and polyphenol oxidase) and pathogenesis-related (PR) genes (e.g., PR-1 and PR-2). Therefore, the gamma irradiation-induced resistance against P. digatatum involves both changes of phenolic compounds and the induction of expression of defense-related genes. In addition, scanning electron microscopy analysis revealed that induced disease resistance by gamma irradiation signifcantly inhibits the growth of P. digatatum in mandarin fruits. These results suggest that the exposure of gamma irradiation is a potential methods for inducing the disease resistance of fruit to postharvest fungal pathogens and for extending the postharvest life of mandarin fruit.

Comparative analysis of the genetic basis of Cry1F resistance in two strains of Spodoptera frugiperda originated from Puerto Rico and Florida.

Science.gov (United States)

Camargo, Ana M; Castañera, Pedro; Farinós, Gema P; Huang, Fangneng

2017-06-01

The fall armyworm, Spodoptera frugiperda (J.E. Smith), is a major target pest of Bacillus thuringiensis (Bt) maize and cotton in America. Since the commercialization of Cry1F maize (event TC1507) in 2003, resistance to Cry1F maize in field populations of S. frugiperda has occurred in Puerto Rico, Brazil and the southeast region of the United States. In this paper, we conducted a comparative analysis of the inheritance of two Cry1F-resistant colonies of S. frugiperda originated from Puerto Rico (PR) and Florida (FL), respectively. The objective of the analysis was to determine if the genetic basis of the resistance was similar in the two different originated colonies. To accomplish the objective, besides PR, FL, and a known Cry1F-susceptible colony, 14 additional colonies were developed by reciprocal crosses among the three parents, F 1 by F 1 crosses, backcrosses, and intercolony-crosses between PR and FL. Larval mortalities of the 17 colonies were assayed on both Cry1F maize leaf tissue and Cry1F-treated diet at the concentrations of 3.16, 10.00, and 31.60µg/g. Resistance to Cry1F in both PR and FL was autosomal and recessive or incompletely recessive. Segregations in F 2 and backcrossed generations associated with FL fitted the Mendelian monogenic model well, while with PR the segregations did not follow the single gene model in some bioassays. Further analyses with the intercolony complementation tests showed a similar level of resistance in the F 1 progeny as their parents FL and PR. Together with the data, it was likely that a single (or a few tightly-linked) gene was involved in FL; PR shared the same locus of the major resistance gene as FL, but the resistance in PR might also be associated with additional minor factors. Information generated from this study should be useful in understanding the origin of Cry1F resistance in the U.S. mainland and developing effective strategies for Bt resistance management in S. frugiperda. Copyright © 2017 Elsevier Inc

State diagram of Pr-Bi system

International Nuclear Information System (INIS)

Abulkhaev, V.L.; Ganiev, I.N.

1994-01-01

By means of thermal differential analysis, X-ray and microstructural analysis the state diagram of Pr-Bi system was studied. Following intermetallic compounds were defined in the system: Pr 2 Bi, Pr 5 Bi 3 , Pr 4 Bi 3 , Pr Bi, PrBi 2 , Pr 2 Bi, Pr 5 Bi 3 , Pr 4 Bi 3 and PrBi 2 . The data analysis on Ln-Bi diagram allowed to determine the regularity of change of properties of intermetallic compounds in the line of rare earth elements of cerium subgroup.

Brain delivery of AAV9 expressing an anti-PrP monovalent antibody delays prion disease in mice.

Science.gov (United States)

Moda, Fabio; Vimercati, Chiara; Campagnani, Ilaria; Ruggerone, Margherita; Giaccone, Giorgio; Morbin, Michela; Zentilin, Lorena; Giacca, Mauro; Zucca, Ileana; Legname, Giuseppe; Tagliavini, Fabrizio

2012-01-01

Prion diseases are caused by a conformational modification of the cellular prion protein (PrP (C)) into disease-specific forms, termed PrP (Sc), that have the ability to interact with PrP (C) promoting its conversion to PrP (Sc). In vitro studies demonstrated that anti-PrP antibodies inhibit this process. In particular, the single chain variable fragment D18 antibody (scFvD18) showed high efficiency in curing chronically prion-infected cells. This molecule binds the PrP (C) region involved in the interaction with PrP (Sc) thus halting further prion formation. These findings prompted us to test the efficiency of scFvD18 in vivo. A recombinant Adeno-Associated Viral vector serotype 9 was used to deliver scFvD18 to the brain of mice that were subsequently infected by intraperitoneal route with the mouse-adapted scrapie strain RML. We found that the treatment was safe, prolonged the incubation time of scrapie-infected animals and decreased the burden of total proteinase-resistant PrP (Sc) in the brain, suggesting that scFvD18 interferes with prion replication in vivo. This approach is relevant for designing new therapeutic strategies for prion diseases and other disorders characterized by protein misfolding.

Effects of annealing on the microstructure, corrosion resistance, and mechanical properties of RE{sub 65}Co{sub 25}Al{sub 10} (RE=Ce, La, Pr, Sm, and Gd) bulk metallic glasses

Energy Technology Data Exchange (ETDEWEB)

Zheng, Zhou [School of Materials Science and Engineering, University of Jinan, No. 336, West Road of Nan Xinzhuang, Jinan 250022 (China); Shandong Provincial Key Laboratory of Preparation and Measurement of Building Materials, University of Jinan, No. 336, West Road of Nan Xinzhuang, Jinan 250022 (China); Xing, Qi; Sun, Zhenxi; Xu, Jing; Zhao, Zhengfeng [School of Materials Science and Engineering, University of Jinan, No. 336, West Road of Nan Xinzhuang, Jinan 250022 (China); Chen, Shuying; Liaw, Peter K. [Department of Materials Science and Engineering, University of Tennessee, Knoxville, TN (United States); Wang, Yan, E-mail: mse_wangy@ujn.edu.cn [School of Materials Science and Engineering, University of Jinan, No. 336, West Road of Nan Xinzhuang, Jinan 250022 (China); Shandong Provincial Key Laboratory of Preparation and Measurement of Building Materials, University of Jinan, No. 336, West Road of Nan Xinzhuang, Jinan 250022 (China)

2015-02-25

The effects of annealing on the microstructure, corrosion resistance and mechanical properties of the RE{sub 65}Co{sub 25}Al{sub 10} (RE=Ce, La, Pr, Sm, and Gd) bulk metallic glasses (BMGs) were studied. Microstructural changes are induced after annealing below the onset crystallization temperature of 484 K, resulting in the variation of thermal stability and crystallization behavior. A proper annealing enhances the corrosion resistance in 3.5 wt% NaCl solution, which can be attributed to reduction of the electrochemical activity and galvanic coupling effects in the chloride solution. Moreover, the RE-based BMG annealed at 484 K possesses the higher corrosion potential and lower corrosion current density, combined with the corrosion morphologies, which suggests the best corrosion resistance. Annealing can also obviously change the mechanical properties and fracture morphologies. It presents that free volume annihilation can cause more difficulty in the elastic atom rearrangement for the as-annealed RE-based BMGs.

Israel: a crise próxima

Directory of Open Access Journals (Sweden)

Peter DEMANT

2014-12-01

Full Text Available Apesar de êxitos indisputáveis, o Estado de Israel enfrenta problemas estruturais decorrentes do conflito com o mundo árabe. O texto analisa cinco vulnerabilidades subestimadas: (1 demografia: o crescimento dos ultraortodoxos e dos árabes israelenses, ambos antissionistas, que arrisca tornar minoria os judeus sionistas; (2 estratégia: novas formas de resistência usadas pelos árabes, tanto militares, como os mísseis, quanto pacíficas, como a resistência não violenta, estão progressivamente se tornando contraproducentes à ocupação israelense de territórios inimigos; (3 regional: a Primavera Árabe, apesar dos fracassos, é uma etapa na democratização e modernização das sociedades árabes que acabará erodindo a vantagem qualitativa-educacional israelense; (4 internacional: Israel depende, militar e economicamente, do apoio ocidental, mas, movidos por seus próprios desenvolvimentos demográficos e culturais, os europeus se mostram cada vez mais indiferentes ou hostis a Israel; e até nos EUA, último reduto de simpatia pró-israelense, a identificação com o Estado judaico pode se tornar mais frágil; (5 mundo judaico: devido à orientação cada vez mais particularista de Israel, há, em vez de legitimação recíproca, ameaça de alienação entre as diásporas judaicas e Israel. O artigo conclui que, a termo, as custas políticas, militares e socioculturais que a beligerância permanente impõe a Israel podem constituir um risco existencial para este país. Eventualmente, os dilemas podem se tornar perigosos para sua sobrevivência como Estado judaico.

The Pr and Ca substitution in GdBa2Cu3O7-8

International Nuclear Information System (INIS)

Shakeri, H.; Akhavan, M.

2002-01-01

The granular Gd 1 -x-zPr x Ca z Ba 2 Cu 3 O 7 -8 (Gd Pr Ca-123) high-temperature cuprate samples with 0.0≤x≤0.3 and 0.0≤z≤0.35 are prepared by standard solid state reaction and characterized by XRD and SEM techniques. The BaCuO 2 and impurity phases are less than 1% in the samples having high levels of Pr and Ca concentrations. The electrical resistivity measurements show a nonlinear reduction in T c (x,z=etc) versus x. Moreover, the T c (z) curve with x=0 is nonlinear and a plateau appears at z≅0.05-0.015. For Pr-Ca-doped samples with a constant concentration of Pr, T c increases with the increase of Ca up to an optimum value of Ca doping and then in decreases. Based on these observations, we suggest that hole filling and hole localization the main effects of Pr ion substitution. The magnetic measurements indicate that the value of H C 1 is in the order of 10 m T. The magnetoresistance measurements have been measured and analyzed. The superconducting transition region is broadened by the application of magnetic field. The experimental data near the on sen of superconductivity are fitted with the Ambegakor and Halperin (A H) phase-slip model. We observe that the A H parameter, γ(H), depends not only on the temperature and the magnetic field, but also on the Pr and Ca ions concentrations. It is observed that the critical current density increases with Ca substitution and decreases with pr substitution in Gd-123 system. We suggest that the pr ion substitution probably enhances the weak link, but the Ca ion acts as flux pinning center in the Gd Pr Ca-123 system

Oxidation reduces the fibrillation but not the neurotoxicity of the prion peptide PrP106-126

DEFF Research Database (Denmark)

Bergstrøm, Linda Alice; Chabry, J.; Bastholm, L.

2007-01-01

There is increasing evidence that soluble oligomers of misfolded protein may play a role in the pathogenesis of protein misfolding diseases including the transmissible spongiform encephalopathies (TSE) where the protein involved is the prion protein, PrP. The effect of oxidation on fibrillation...... tendency and neurotoxicity of different molecular variants of the prion peptide PrP106-126 was investigated. It was found that methionine oxidation significantly reduced amyloid fibril formation and proteinase K resistance, but it did not reduce (but rather increase slightly) the neurotoxicity...

Effects of posture on upper and lower limb peripheral resistance following submaximal cycling.

Science.gov (United States)

Swan, P D; Spitler, D L; Todd, M K; Maupin, J L; Lewis, C L; Darragh, P M

1989-09-01

The purpose of this study was to determine postural effects on upper and lower limb peripheral resistance (PR) after submaximal exercise. Twelve subjects (six men and six women) completed submaximal cycle ergometer tests (60% age-predicted maximum heart rate) in the supine and upright seated positions. Each test included 20 minutes of rest, 20 minutes of cycling, and 15 minutes of recovery. Stroke volume and heart rate were determined by impedance cardiography, and blood pressure was measured by auscultation during rest, immediately after exercise, and at minutes 1-5, 7.5, 10, 12.5, and 15 of recovery. Peripheral resistance was calculated from values of mean arterial pressure and cardiac output. No significant (p less than 0.05) postural differences in PR were noted during rest for either limb. Immediately after exercise, PR decreased (55% to 61%) from resting levels in both limbs, independent of posture. Recovery ankle PR values were significantly different between postures. Upright ankle PR returned to 92% of the resting level within four minutes of recovery, compared to 76% of the resting level after 15 minutes in the supine posture. Peripheral resistance values in the supine and upright arm were not affected by posture and demonstrated a gradual pattern of recovery similar to the supine ankle recovery response (85% to 88% of rest within 15 minutes). The accelerated recovery rate of PR after upright exercise may result from local vasoconstriction mediated by a central regulatory response to stimulation from gravitational pressure on lower body circulation.

Prion protein (PrP) gene-knockout cell lines: insight into functions of the PrP

Science.gov (United States)

Sakudo, Akikazu; Onodera, Takashi

2015-01-01

Elucidation of prion protein (PrP) functions is crucial to fully understand prion diseases. A major approach to studying PrP functions is the use of PrP gene-knockout (Prnp−/−) mice. So far, six types of Prnp−/− mice have been generated, demonstrating the promiscuous functions of PrP. Recently, other PrP family members, such as Doppel and Shadoo, have been found. However, information obtained from comparative studies of structural and functional analyses of these PrP family proteins do not fully reveal PrP functions. Recently, varieties of Prnp−/− cell lines established from Prnp−/− mice have contributed to the analysis of PrP functions. In this mini-review, we focus on Prnp−/− cell lines and summarize currently available Prnp−/− cell lines and their characterizations. In addition, we introduce the recent advances in the methodology of cell line generation with knockout or knockdown of the PrP gene. We also discuss how these cell lines have provided valuable insights into PrP functions and show future perspectives. PMID:25642423

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

Science.gov (United States)

Wilson, John W; Tsukayama, Dean T

2016-04-01

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

Optimization of Drilling Resistance Measurement (DRM) user-controlled variables

OpenAIRE

Tudor, Dumitrescu; Pesce, Giovanni; Ball, Richard

2017-01-01

Drilling Resistance Measurement (DRM) is recognised as an important on-site micro-invasive procedure for assessment of construction materials. This paper presents a detailed investigation of user-controlled variables and their influence on drilling resistance. The study proves that the ratio of penetration rate/rotational speed (PR/RPM) is proportional to drilling resistance. Data from Bath stone and an artificial reference stone demonstrates how different materials can be compared using thei...

Prunus domestica pathogenesis-related protein-5 activates the defense response pathway and enhances the resistance to fungal infection.

Directory of Open Access Journals (Sweden)

Ashraf El-kereamy

Full Text Available Pathogenesis-related protein-5 (PR-5 has been implicated in plant disease resistance and its antifungal activity has been demonstrated in some fruit species. However, their roles, especially their interactions with the other defense responses in plant cells, are still not fully understood. In this study, we have cloned and characterized a new PR-5 cDNA named PdPR5-1 from the European plum (Prunus domestica. Expression of PdPR5-1 was studied in different cultivars varying in resistance to the brown rot disease caused by the necrotrophic fungus Monilinia fructicola. In addition transgenic Arabidopsis, ectopically expressing PdPR5-1 was used to study its role in other plant defense responses after fungal infection. We show that the resistant cultivars exhibited much higher levels of transcripts than the susceptible cultivars during fruit ripening. However, significant rise in the transcript levels after infection with M. fructicola was observed in the susceptible cultivars too. Transgenic Arabidopsis plants exhibited more resistance to Alternaria brassicicola. Further, there was a significant increase in the transcripts of genes involved in the phenylpropanoid biosynthesis pathway such as phenylalanine ammonia-lyase (PAL and phytoalexin (camalexin pathway leading to an increase in camalexin content after fungal infection. Our results show that PdPR5-1 gene, in addition to its anti-fungal properties, has a possible role in activating other defense pathways, including phytoalexin production.

Prion protein (PrP) gene-knockout cell lines: insight into functions of the PrP

OpenAIRE

Sakudo, Akikazu; Onodera, Takashi

2015-01-01

Elucidation of prion protein (PrP) functions is crucial to fully understand prion diseases. A major approach to studying PrP functions is the use of PrP gene-knockout (Prnp ?/?) mice. So far, six types of Prnp ?/? mice have been generated, demonstrating the promiscuous functions of PrP. Recently, other PrP family members, such as Doppel and Shadoo, have been found. However, information obtained from comparative studies of structural and functional analyses of these PrP family proteins do not ...

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

Science.gov (United States)

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

2014-08-01

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

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

DEFF Research Database (Denmark)

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

2004-01-01

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

Avaliação da resistência de união metalocerâmica em função de diferentes tempos de oxidação prévia Evaluation of the bond resistance between metal and ceramics, resulting from different previous oxidation times

Directory of Open Access Journals (Sweden)

Stefan Fiuza de Carvalho DEKON

1999-01-01

Full Text Available Avaliou-se a resistência de união metal/porcelana utilizando-se uma liga de Ni-Cr, submetida a diferentes tempos de oxidação prévia com o sistema cerâmico Vita-VMK, através do teste preconizado por CHIODI NETTO3. A análise dos resultados permitiu as seguintes conclusões: a ausência da oxidação prévia possibilitou os melhores resultados, sendo que a diferença foi estatisticamente significante; diferentes tempos de oxidação prévia provocaram redução acentuada nos valores obtidos e foram semelhantes entre si; o grupo submetido ao processo de jateamento após a oxidação prévia por cinco minutos mostrou resultados similares aos grupos que também passaram pelo processo de oxidação e não sofreram jateamento posterior.The objective of this research was to evaluate the porcelain-alloy bonding strength using a local-made alloy under different times of pre-oxidation with a ceramic system. The test used was preconized by CHIODI NETTO. The results lead to the following conclusions: the control group (no pre-oxidation showed the best values, statistically significant, when compared with others groups. The different times of pre-oxidation procedures reduced the values significantly, and the groups were similar to each other. The group submitted to the sandblasting process after a pre-oxidation of 5 minutes, showed similar values when compared with the other groups treated with pre-oxidation without sandblasting.

Oxygen diffusion in Y sub 1 sub - sub x Pr sub x Ba sub 2 Cu sub 3 O sub 7 sub - subdelta observed by resistivity measurements

CERN Document Server

Diosa, J E; Mellander, B E

1997-01-01

In situ resistivity measurements have been used to monitor the oxygen uptake and removal for the ceramic system Y sub 1 sub - sub x Pr sub x Ba sub 2 Cu sub 3 O sub 7 sub - subdelta (YPBCO) in the temperature range 300 - 1000 K. The study of the out-diffusion of oxygen was performed by annealing the oxygenated samples in ambient air at constant heating rates. We found that, independently of x, the oxygen concentration O sub 7 sub - subdelta is preserved up to 600 K, and that oxygen diffuses out of the oxides at temperatures higher than 600 K. However, the rate of oxygen removal from PrBa sub 2 Cu sub 3 O sub 7 sub - subdelta (PBCO) is greatly reduced as compared to the rate for pure YBa sub 2 Cu sub 3 O sub 7 sub - subdelta (YBCO), and decreases with increasing x in YPBCO. The study of the in-diffusion of oxygen was performed by annealing the deoxygenated samples in ambient air at constant heating rates. We found that, independently of x, the oxygen uptake takes place in the temperature range 550 - 750 K, whe...

Relationship between electrical and structural properties in Pr2/3+xTiO3±y

International Nuclear Information System (INIS)

Kirsanov, N.A.; Bazuev, G.V.

1987-01-01

Synthesis conditions results of X-ray diffraction investigations and electric properties of oxide titanium bronzes (OTB) of praseodymium Pr 2/3+x TiO 3±y in homogeneity region are presented. Change of crystal lattice symmetry in the region of existence of oxide titanium bronzes Pr 2/3+x TiO 3 ± y (O ≤ x ≤ 1/3) was revealed. Specific electrical resistance measurements enabled to conclude that d-electrons of Ti 3+ cations were characterized by collectivized behaviour, conditioned by formation of harrow, partially occupied π*-zone

Phase diagram of Pr-P system

International Nuclear Information System (INIS)

Mironov, K.E.

1981-01-01

An area of the Pr-P system, adjoining to the Pr ordinate, is plotted up by the DTA method. Presence of P solid solution in Pr is established. Data on thermal stability of PrP, PrP 2 , PrP 5 and PrP 7 are generalized. The diagram of phase transformations in Pr-P system is plotted up proceeding from the whole complex of the data, presented. A supposition is made on a possible formation of solid solutions between the highest polyphosphide and phosphorus [ru

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

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Xiao Chen

2017-08-01

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

Cu4Pr6(MoO4)11-Pr2(MoO4)3 system

International Nuclear Information System (INIS)

Arzumanyan, G.A.

1982-01-01

Existence boundaries and Dalton compositions (CuPr(MoO 4 ) 2 , CuPr 3 (MoO 4 ) 5 ) of solid solutions that in the mojority are of shcheelite dsitored structure have been determined in the Cu 4 Pr 6 (MoO 4 ) 11 -Pr 2 (MoO 4 ) 3 system. It has been revealed that regions of homogeneity near the CuPr(MoO 4 ) 2 composition have a horseshoeshaped profile

Revealing the importance of meristems and roots for the development of hypersensitive responses and full foliar resistance to Phytophthora infestans in the resistant potato cultivar Sarpo Mira

DEFF Research Database (Denmark)

Orlowska, Elzbieta Zofia; Basile, Alessio; Kandzia, Izabela

2012-01-01

The defence responses of potato against Phytophthora infestans were studied using the highly resistant Sarpo Mira cultivar. The effects of plant integrity, meristems, and roots on the hypersensitive response (HR), plant resistance, and the regulation of PR genes were analysed. Sarpo Mira shoots a...

Study of the enterotoxigenicity of enterobacteria and their resistance to antibiotics in postirradiation abacteriosis

International Nuclear Information System (INIS)

Korshunov, V.M.; Bodryagina, A.B.; Pinegin, B.V.

1981-01-01

Qualitative and quantitative composition of Enterobacteriaceal family was studied and the percentage of enterotoxigenic and antibiotic resistant strains was determined in the large intestine cavity of intact mice of CBA line as well as in the cavity and wall of the small intestine of those animals on the 7 day after γ-irradiation (900 R). It was ascertained that postirradiation abacteriosis was characterized by the penetration in quantity of Esub(coli,Pr. morganii) into the small intestine and by the emergence in the small intestine of non-determinable in the intestinal tract intact animals: Pr. vulgaris, Pr. mirabilis, Pr. rettgeri, Ent. aerogenes, Ent. cloacae, Ent. hafniae, Citrobacter freundii, Providencia alcalifaciens; all revealed representatives of enterobacteria were capable of establishing associative bond with the mucous membrane of the intestine. Enterobacteria synthesizing resistant to antibiotics enterotoxins were revealed in quantity in the wall and lumen of the small intestine of irradiated mice [ru

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.)

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.

Transport and ordering of polarons in CER manganites PrCaMnO

International Nuclear Information System (INIS)

Schramm, S; Hoffmann, J; Jooss, Ch

2008-01-01

The temperature-dependent resistivity and the colossal resistance effect induced by strong electric fields of the small-band Pr 1-x Ca x MnO 3 (PCMO) manganites are analysed with respect to the influence of the Ca doping, post-annealing, the prehistory of the electric stimulation, and the physical dimensions of the sample. Despite the phase separation between charge and orbital ordered and disordered phases, PCMO reveals the properties of a homogeneous medium with a conductivity governed by the hopping of small polarons if the electric field is not too strong. In contrast, high electric fields induce a structural transition which gives rise to a glassy behaviour in the transient regime. In the low resistance state the small activation energy of charge carrier hopping implies a transition to large polaron hopping

The genetic basis of resistance and matching-allele interactions of a host-parasite system: The Daphnia magna-Pasteuria ramosa model.

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Gilberto Bento

2017-02-01

Full Text Available Negative frequency-dependent selection (NFDS is an evolutionary mechanism suggested to govern host-parasite coevolution and the maintenance of genetic diversity at host resistance loci, such as the vertebrate MHC and R-genes in plants. Matching-allele interactions of hosts and parasites that prevent the emergence of host and parasite genotypes that are universally resistant and infective are a genetic mechanism predicted to underpin NFDS. The underlying genetics of matching-allele interactions are unknown even in host-parasite systems with empirical support for coevolution by NFDS, as is the case for the planktonic crustacean Daphnia magna and the bacterial pathogen Pasteuria ramosa. We fine-map one locus associated with D. magna resistance to P. ramosa and genetically characterize two haplotypes of the Pasteuria resistance (PR- locus using de novo genome and transcriptome sequencing. Sequence comparison of PR-locus haplotypes finds dramatic structural polymorphisms between PR-locus haplotypes including a large portion of each haplotype being composed of non-homologous sequences resulting in haplotypes differing in size by 66 kb. The high divergence of PR-locus haplotypes suggest a history of multiple, diverse and repeated instances of structural mutation events and restricted recombination. Annotation of the haplotypes reveals striking differences in gene content. In particular, a group of glycosyltransferase genes that is present in the susceptible but absent in the resistant haplotype. Moreover, in natural populations, we find that the PR-locus polymorphism is associated with variation in resistance to different P. ramosa genotypes, pointing to the PR-locus polymorphism as being responsible for the matching-allele interactions that have been previously described for this system. Our results conclusively identify a genetic basis for the matching-allele interaction observed in a coevolving host-parasite system and provide a first insight into

The genetic basis of resistance and matching-allele interactions of a host-parasite system: The Daphnia magna-Pasteuria ramosa model.

Science.gov (United States)

Bento, Gilberto; Routtu, Jarkko; Fields, Peter D; Bourgeois, Yann; Du Pasquier, Louis; Ebert, Dieter

2017-02-01

Negative frequency-dependent selection (NFDS) is an evolutionary mechanism suggested to govern host-parasite coevolution and the maintenance of genetic diversity at host resistance loci, such as the vertebrate MHC and R-genes in plants. Matching-allele interactions of hosts and parasites that prevent the emergence of host and parasite genotypes that are universally resistant and infective are a genetic mechanism predicted to underpin NFDS. The underlying genetics of matching-allele interactions are unknown even in host-parasite systems with empirical support for coevolution by NFDS, as is the case for the planktonic crustacean Daphnia magna and the bacterial pathogen Pasteuria ramosa. We fine-map one locus associated with D. magna resistance to P. ramosa and genetically characterize two haplotypes of the Pasteuria resistance (PR-) locus using de novo genome and transcriptome sequencing. Sequence comparison of PR-locus haplotypes finds dramatic structural polymorphisms between PR-locus haplotypes including a large portion of each haplotype being composed of non-homologous sequences resulting in haplotypes differing in size by 66 kb. The high divergence of PR-locus haplotypes suggest a history of multiple, diverse and repeated instances of structural mutation events and restricted recombination. Annotation of the haplotypes reveals striking differences in gene content. In particular, a group of glycosyltransferase genes that is present in the susceptible but absent in the resistant haplotype. Moreover, in natural populations, we find that the PR-locus polymorphism is associated with variation in resistance to different P. ramosa genotypes, pointing to the PR-locus polymorphism as being responsible for the matching-allele interactions that have been previously described for this system. Our results conclusively identify a genetic basis for the matching-allele interaction observed in a coevolving host-parasite system and provide a first insight into its molecular basis.

Inhibitory efficacy of bufadienolides on Na+,K+-pump activity versus cell proliferation.

Science.gov (United States)

Xu, Yinfang; Liu, Xuan; Schwarz, Silvia; Hu, Lihong; Guo, Dean; Gu, Quanbao; Schwarz, Wolfgang

2016-07-01

Bufadienolides are cytotoxic drugs that may form the basis for anticancer agents. Due to structural and functional similarity to cardiotonic glycosides, application is restricted. We, therefore, investigated correlation of their putative anticancer effects with inhibition of Na + ,K + pumps. The natural bufalin and three derivatives were tested. The anticancer effects of the drugs were checked by observing their inhibitory effects on proliferation of rat liver cancer cells using MTT assay. Inhibition of Na + ,K + -pump was determined by measuring pump-mediated current of rat α1/β1 and α2/β1 Na + ,K + pumps expressed in Xenopus oocytes. All tested bufadienolides inhibited cell proliferation and Na + ,K + pump activity. An activity coefficient A =100x IC 50 Na,K pump /IC 50 pr o liferation was used to describe drug effectivity as anticancer drug. Natural bufalin exhibited lowest effectivity on cell proliferation, and also the A value for rat α1 isoform was the lowest (0.08), the α2 isoform was much less sensitive ( A =1.00). The highest A values were obtained for the BF238 derivative with A =0.88 and 2.64 for the α1 and α2 isoforms, respectively. Therefore, we suggest that search for bufalin derivatives with high anticancer effect and low affinity for both Na + ,K + pump isoforms may be a promising strategy for development of anticancer drugs.

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

Directory of Open Access Journals (Sweden)

Vanita Vanas

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

Prion subcellular fractionation reveals infectivity spectrum, with a high titre-low PrPres level disparity

Directory of Open Access Journals (Sweden)

Lewis Victoria

2012-04-01

Full Text Available Abstract Background Prion disease transmission and pathogenesis are linked to misfolded, typically protease resistant (PrPres conformers of the normal cellular prion protein (PrPC, with the former posited to be the principal constituent of the infectious 'prion'. Unexplained discrepancies observed between detectable PrPres and infectivity levels exemplify the complexity in deciphering the exact biophysical nature of prions and those host cell factors, if any, which contribute to transmission efficiency. In order to improve our understanding of these important issues, this study utilized a bioassay validated cell culture model of prion infection to investigate discordance between PrPres levels and infectivity titres at a subcellular resolution. Findings Subcellular fractions enriched in lipid rafts or endoplasmic reticulum/mitochondrial marker proteins were equally highly efficient at prion transmission, despite lipid raft fractions containing up to eight times the levels of detectable PrPres. Brain homogenate infectivity was not differentially enhanced by subcellular fraction-specific co-factors, and proteinase K pre-treatment of selected fractions modestly, but equally reduced infectivity. Only lipid raft associated infectivity was enhanced by sonication. Conclusions This study authenticates a subcellular disparity in PrPres and infectivity levels, and eliminates simultaneous divergence of prion strains as the explanation for this phenomenon. On balance, the results align best with the concept that transmission efficiency is influenced more by intrinsic characteristics of the infectious prion, rather than cellular microenvironment conditions or absolute PrPres levels.

Magnetic and electromagnetic properties of Pr doped strontium ferrite/polyaniline composite film

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Huang, Ying; Li, Yuqing; Wang, Yan, E-mail: wangyan287580632@126.com

2014-11-15