The Use of System Codes in Scaling Studies: Relevant Techniques for Qualifying NPP Nodalizations for Particular Scenarios

System codes along with necessary nodalizations are valuable tools for thermal hydraulic safety analysis. Qualifying both codes and nodalizations is an essential step prior to their use in any significant study involving code calculations. Since most existing experimental data come from tests performed on the small scale, any qualification process must therefore address scale considerations. This paper describes the methodology developed at the Technical University of Catalonia in order to contribute to the qualification of Nuclear Power Plant nodalizations by means of scale disquisitions. The techniques that are presented include the so-called Kv-scaled calculation approach as well as the use of “hybrid nodalizations” and “scaled-up nodalizations.” These methods have revealed themselves to be very helpful in producing the required qualification and in promoting further improvements in nodalization. The paper explains both the concepts and the general guidelines of the method, while an accompanying paper will complete the presentation of the methodology as well as showing the results of the analysis of scaling discrepancies that appeared during the posttest simulations of PKL-LSTF counterpart tests performed on the PKL-III and ROSA-2 OECD/NEA Projects. Both articles together produce the complete description of the methodology that has been developed in the framework of the use of NPP nodalizations in the support to plant operation and control

Identification of sex hormone-binding globulin in the human hypothalamus

Gonadal steroids are known to influence hypothalamic functions through both genomic and non-genomic pathways. Sex hormone-binding globulin ( SHBG) may act by a non-genomic mechanism independent of classical steroid receptors. Here we describe the immunocytochemical mapping of SHBG-containing neurons and nerve fibers in the human hypothalamus and infundibulum. Mass spectrometry and Western blot analysis were also used to characterize the biochemical characteristics of SHBG in the hypothalamus and cerebrospinal fluid (CSF) of humans. SHBG-immunoreactive neurons were observed in the supraoptic nucleus, the suprachiasmatic nucleus, the bed nucleus of the stria terminalis, paraventricular nucleus, arcuate nucleus, the perifornical region and the medial preoptic area in human brains. There were SHBG-immunoreactive axons in the median eminence and the infundibulum. A partial colocalization with oxytocin could be observed in the posterior pituitary lobe in consecutive semithin sections. We also found strong immunoreactivity for SHBG in epithelial cells of the choroid plexus and in a portion of the ependymal cells lining the third ventricle. Mass spectrometry showed that affinity-purified SHBG from the hypothalamus and choroid plexus is structurally similar to the SHBG identified in the CSF. The multiple localizations of SHBG suggest neurohypophyseal and neuroendocrine functions. The biochemical data suggest that CSF SHBG is of brain rather than blood origin. Copyright (c) 2005 S. Karger AG, Base

Main Results of Phase IV BEMUSE Project: Simulation of LBLOCA in an NPP

Phase IV of BEMUSE Program is a necessary step for a subsequent uncertainty analysis. It includes the simulation of the reference scenario and a sensitivity study. The scenario is a LBLOCA and the reference plant is Zion 1 NPP, a 4 loop PWR unit. Thirteen participants coming from ten different countries have taken part in the exercise. The BEMUSE (Best Estimate Methods plus Uncertainty and Sensitivity Evaluation) Programhas been promoted by theWorking Group on AccidentManagement and Analysis (WGAMA) and endorsed by the Committee on the Safety of Nuclear Installations (CSNI). The paper presents the results of the calculations performed by participants and emphasizes its usefulness for future uncertainty evaluation, to be performed in next phase. The objectives of the activity are basically to simulate the LBLOCA reproducing the phenomena associated to the scenario and also to build a common, well-known, basis for the future comparison of uncertainty evaluation results among different methodologies and codes. The sensitivity calculations performed by participants are also presented. They allow studying the influence of different parameters such as material properties or initial and boundary conditions, upon the behaviour of the most relevant parameters related to the scenario

PREMIUM, a benchmark on the quantification of the uncertainty of the physical models in the system thermal-hydraulic codes: methodologies and data review

The objective of the Post-BEMUSE Reflood Model Input Uncertainty Methods (PREMIUM) benchmark is to progress on the issue of the quantification of the uncertainty of the physical models in system thermalhydraulic codes by considering a concrete case: the physical models involved in the prediction of core reflooding. The present document was initially conceived as a final report for the Phase I “Introduction and Methodology Review” of the PREMIUM benchmark. The objective of Phase I is to refine the definition of the benchmark and publish the available methodologies of model input uncertainty quantification relevant to the objectives of the benchmark. In this initial version the document was approved by WGAMA and has shown its usefulness during the subsequent phases of the project. Once Phase IV was completed, and following the suggestion of WGAMA members, the document was updated adding a few new sections, particularly the description of four new methodologies that were developed during this activity. Such developments were performed by some participants while contributing to PREMIUM progress (which is why this report arrives after those of other phases). After this revision the document title was changed to “PREMIUM methodologies and data review”. The introduction includes first a chapter devoted to contextualization of the benchmark in nuclear safety research and licensing, followed by a description of the PREMIUM objectives. Next, a description of the Phases in which the benchmark is divided and its organization is explained. Chapter two consists of a review of the involvement of the different participants, making a brief explanation of the input uncertainty quantification methodologies used in the activity. The document ends with some conclusions on the development of Phase I, some more general remarks and some statements on the benefits of the benchmark, which can be briefly summarized as it follows: - Contribution to development of tools and experience related to uncertainty calculation and promotion of the use of BEPU approaches for licensing and safety assessment purposes; - Contribution to prioritization of improvements to thermal-hydraulic system codes; - Contribution to a fluent and close interaction between the scientific community and regulatory organizations. Appendices include the complete description of the experimental data FEBA/SEFLEX used in the benchmark and the methodologies CIRCÉ and FFTBM and the general requirements and description specification used for Phase I. Due to the revision of the document, four extra appendixes have been added related to the methods developed during the activity, MCDA DIPE, Tractebel IUQ and PSI methods

Molecular profiling of circulating tumor cells links plasticity to the metastatic process in endometrial cancer

Background: About 20% of patients diagnosed with endometrial cancer (EC) are considered high-risk with unfavorable prognosis. In the framework of the European Network for Individualized Treatment in EC (ENITEC), we investigated the presence and phenotypic features of Circulating Tumor Cells (CTC) in high-risk EC patients. Methods: CTC isolation was carried out in peripheral blood samples from 34 patients, ranging from Grade 3 Stage IB to Stage IV carcinomas and recurrences, and 27 healthy controls using two methodologies. Samples were subjected to EpCAM-based immunoisolation using the CELLection™ Epithelial Enrich kit (Invitrogen, Dynal) followed by RTqPCR analysis. The phenotypic determinants of endometrial CTC in terms of pathogenesis, hormone receptor pathways, stem cell markers and epithelial to mesenchymal transition (EMT) drivers were asked. Kruskal-Wallis analysis followed by Dunn's post-test was used for comparisons between groups. Statistical significance was set at p < 0.05. Results: EpCAM-based immunoisolation positively detected CTC in high-risk endometrial cancer patients. CTC characterization indicated a remarkable plasticity phenotype defined by the expression of the EMT markers ETV5, NOTCH1, SNAI1, TGFB1, ZEB1 and ZEB2. In addition, the expression of ALDH and CD44 pointed to an association with stemness, while the expression of CTNNB1, STS, GDF15, RELA, RUNX1, BRAF and PIK3CA suggested potential therapeutic targets. We further recapitulated the EMT phenotype found in endometrial CTC through the up-regulation of ETV5 in an EC cell line, and validated in an animal model of systemic dissemination the propensity of these CTC in the accomplishment of metastasis. Conclusions: Our results associate the presence of CTC with high-risk EC. Gene-expression profiling characterized a CTC-plasticity phenotype with stemness and EMT features. We finally recapitulated this CTC-phenotype by over-expressing ETV5 in the EC cell line Hec1A and demonstrated an advantage in the promotion of metastasis in an in vivo mouse model of CTC dissemination and homing

International training Program: 3D S.UN.COP – Scaling, Uncertainty and 3D thermal-hydraulics/neutron-kinetics CouPled Codes Seminar

Thermal-hydraulic system computer codes are extensively used worldwide for analysis of nuclear facilities by utilities, regulatory bodies, nuclear power plant designers and vendors, nuclear fuel companies, research organizations, consulting companies, and technical support organizations. The computer code user represents a source of uncertainty that can influence the results of system code calculations. This influence is commonly known as the ‘user effect’ and stems from the limitations embedded in the codes as well as from the limited capability of the analysts to use the codes. Code user training and qualification is an effective means for reducing the variation of results caused by the application of the codes by different users. This paper describes a systematic approach to training code users who, upon completion of the training, should be able to perform calculations making the best possible use of the capabilities of best estimate codes. In other words, the program aims at contributing towards solving the problem of user effect. The 3D S.UN.COP (Scaling, Uncertainty and 3D COuPled code calculations) seminars have been organized as follow-up of the proposal to IAEA for the Permanent Training Course for System Code Users [1]. Five seminars have been held at University of Pisa (2003, 2004), at The Pennsylvania State University (2004), at University of Zagreb (2005) and at the School of Industrial Engineering of Barcelona (2006). It was recognized that such courses represented both a source of continuing education for current code users and a mean for current code users to enter the formal training structure of a proposed ‘permanent’ stepwise approach to user training. The 3D S.UN.COP 2006 was successfully held with the attendance of 33 participants coming from 18 countries and 28 different institutions (universities, vendors, national laboratories and regulatory bodies). More than 30 scientists (coming from 13 countries and 23 different institutions) were involved in the organization of the seminar, presenting theoretical aspects of the proposed methodologies and holding the training and the final examination. A certificate (LA Code User grade) was released to participants that successfully solved the assigned problems. A sixth seminar will be organized in 2007 at the Texas A&M University involving more than 30 scientists between lecturers and code developers

International Training Program in Support of Safety Analysis: 3D S.UN.COP - Scaling, Uncertainty and 3D Thermal-Hydraulics/Neutron kinetics Coupled Codes Seminars

Thermal-hydraulic system computer codes are extensively used worldwide for analysis of nuclear facilities by utilities, regulatory bodies, nuclear power plant designers and vendors, nuclear fuel companies, research organizations, consulting companies, and technical support organizations. The computer code user represents a source of uncertainty that can influence the results of system code calculations. This influence is commonly known as the ‘user effect’ and stems from the limitations embedded in the codes as well as from the limited capability of the analysts to use the codes. Code user training and qualification is an effective means for reducing the variation of results caused by the application of the codes by different users. This paper describes a systematic approach to training code users who, upon completion of the training, should be able to perform calculations making the best possible use of the capabilities of best estimate codes. In other words, the program aims at contributing towards solving the problem of user effect. The 3D S.UN.COP (Scaling, Uncertainty and 3D COuPled code calculations) seminars have been organized as follow-up of the proposal to IAEA for the Permanent Training Course for System Code Users. Nine seminars have been held at University of Pisa (two in 2004), at The Pennsylvania State University (2004), at the University of Zagreb (2005), at the School of Industrial Engineering of Barcelona (January- February 2006), in Buenos Aires, Argentina (October 2006), requested by Autoridad Regulatoria Nuclear (ARN), Nucleoelectrica Argentina S.A (NA-SA) and Comisión Nacional de Energía Atómica (CNEA), at the College Station, Texas A&M, (January-February 2007), in Hamilton and Niagara Falls, Ontario (October 2007) requested by Atomic Energy Canada Limited (AECL), Canadian Nuclear Society (CNS) and Canadian Nuclear Safety Commission (CNSC), in Petten, The Netherlands (October 2008) in cooperation with the Institute of Energy of the Joint Research Center of the European Commission (IE-JRC-EC). It was recognized that such courses represented both a source of continuing education for current code users and a mean for current code users to enter the formal training structure of a proposed ‘permanent’ stepwise approach to user training. The 3D S.UN.COP 2008 at IE-JRC was successfully held with the attendance of 35 participants coming from more than 10 countries and 20 different institutions (universities, vendors and national laboratories). More than 30 scientists (coming from more than 10 countries and 20 different institutions) were involved in the organization of the seminar, presenting theoretical aspects of the proposed methodologies and holding the training and the final examination. A certificate (LA Code User grade) was released to participants that successfully solved the assigned problems. A tenth seminar will be held (October 2009) at the Royal Institute of Technology (KTH) in Amsterdam (Sweden), involving more than 30 scientists between lecturers and code developers (http://dimnp.ing.unipi.it/3dsuncop/2009/index.html)

Consistent code qualification process and application to VVER-1000 NPP

Calculation analysis by application of the system codes are performed to evaluate the NPP or the facility behavior during a postulated transient or to evaluate the code capability. The calculation analysis constitutes a process that involves the code itself, the data of the reference plant, the data about the transient, the nodalization, and the user. All these elements affect one each other and affect the results. A major issue in the use of mathematical model is constituted by the model capability to reproduce the plant or facility behavior under steady state and transient conditions. These aspects constitute two main checks that must be satisfied during the qualification process. The first of them is related to the realization of a schematization of the reference plant; the second one is related to the capability to reproduce the transient behavior. The aim of this paper is to describe the UMAE (Uncertainty Method based on Accuracy Extrapolation) methodology developed at University of Pisa for qualifying a nodalization and analysing the calculated results and to perform the uncertainty evaluation of the system code by the CIAU code (Code with the capability of Internal Assessment of Uncertainty). The activity consists with the re-analysis of the Experiment BL-44 (SBLOCA) performed in the LOBI facility and the analysis of a Kv-scaling calculation of the WWER-1000 NPP nodalization taking as reference the test BL-44. Relap5/Mod3.3 has been used as thermal-hydraulic system code and the standard procedure adopted at University of Pisa has been applied to show the capability of the code to predict the significant aspects of the transient and to obtain a “qualified nodalization” of the WWER-1000 through a systematic qualitative and quantitative accuracy evaluation. The qualitative accuracy evaluation is based on the selection of Relevant Thermal-hydraulic Aspects (RTAs) and is a prerequisite to the application of the Fast Fourier Transform Based Method (FFTBM) which quantifies the error in code predictions related to the measured experimental signals. A reference test scenario (SBLOCA) is then performed with the qualified WWER-1000 NPP nodalization and the CIAU code is applied for the uncertainty evaluation of the calculated results