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

Derivados de metales alcalinos y metales de transición de hidrocarburos acetilénicos

Tesis - Universidad Complutense de Madrid, 1974.Fac. de Ciencias QuímicasTRUEProQuestpu

International Training Program in Support of Safety Analysis: 3C 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. Eleven 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), at the Royal Institute of Technology, Stockholm (October 2009) and in Petten, The Netherlands (October 2010) 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 2010 at IE-JRC was successfully held with the attendance of 23 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. The eleventh seminar has been held (March 2011) in Wilmington, North Carolina, involving more than 30 scientists between lecturers and code developers (http://www.nrgspg.ing.unipi.it/3dsuncop/)

Derivados de metales alcalinos y metales de transición de hidrocarburos acetilénicos

Tesis - Universidad Complutense de Madrid, 1974.Fac. de Ciencias QuímicasTRUEProQuestpu

Main Results of the OECD BEMUSE Programme

The BEMUSE (Best Estimate Methods Uncertainty and Sensitivity Evaluation) Programme promoted by the Working Group on Analysis and Management of Accidents (WGAMA) and endorsed by the Committee on the Safety of Nuclear Installations (CSNI) represents an important step towards reliable application of high-quality best-estimate and uncertainty and sensitivity evaluation methods. The methods used in this activity are considered to be mature for application, including licensing processes. Skill, experience and knowledge of the users about the applied suitable computer code as well as the used uncertainty method are important for the quality of the results

Acquired experience on organizing 3D S.UN.COP: International Course to support Nuclear Licensing by user training in the areas of Scaling, Uncertainty, and 3D Thermalhydraulics/ Neutron-Kinetics CouPled Codes

Thermal-hydraulic system computer codes are extensively used worldwide for analysis of nuclear facilities by utilities, regulatory bodies, nuclear power plant designers, vendors, and research organizations. Computer code user represents a source of uncertainty that may significantly affect the results of system code calculations. Code user training and qualification represent an effective means for reducing the variation of results caused by the application of the codes by different users. This paper describes the experience in applying 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 addition, this paper presents the organization and the main features of the 3D S.UN.COP (scaling, uncertainty, and 3D coupled code calculations) seminars during which particular emphasis is given to practical applications in connection with the licensing process of best estimate plus uncertainty methodologies, showing the designer, utility and regulatory approache

International Course to Support Nuclear Licensing by User Training in the Areas of Scaling, Uncertainty, and 3D Thermal-Hydraulics/Neutron-Kinetics Coupled Codes: 3D S.UN.COP Seminars

Thermal-hydraulic system computer codes are extensively used worldwide for analysis of nuclear facilities by utilities, regulatory bodies, nuclear power plant designers, vendors, and research 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 represent 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. In addition, this paper presents the organization and the main features of the 3D S.UN.COP (scaling, uncertainty, and 3D coupled code calculations) seminars during which particular emphasis is given to the areas of the scaling, uncertainty, and 3D coupled code analysis

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

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

Endometrial carcinoma: molecular alterations involved in tumor development and progression

In the western world, endometrial carcinoma (EC) is the most common cancer of the female genital tract. The annual incidence has been estimated at 10-20 per 100 000 women. Two clinicopathological variants are recognized: the estrogen related (type I, endometrioid) and the non-estrogen related (type II, non-endometrioid).The clinicopathological differences are paralleled by specific genetic alterations, with type I showing microsatellite instability and mutations in phosphatase and tensin homologue deleted on chromosome 70, PIK3CA, K-RAS and CTNNB1 (beta-catenin), and type II exhibiting TP53 mutations and chromosomal instability. Some non-endometrioid carcinomas probably arise from pre-existing endometrioid carcinomas as a result of tumor progression and, not surprisingly, some tumors exhibit combined or mixed features at the clinical, pathological and molecular levels. In EC, apoptosis resistance may have a role in tumor progression. Understanding pathogenesis at the molecular level is essential in identifying biomarkers for successful targeted therapies. In this review, the genetic changes of endometrial carcinogenesis are discussed in the light of the morphological features of the tumors and their precursors