Acquired and naturally occurring resistance of thyroid follicular cells to the growth inhibitory action of transforming growth factor-beta 1 (TGF-beta 1)

While the multifunctional proteins of the transforming growth factor-beta (TGF-beta) family have a potent antiproliferative effect on thyroid follicular cell growth, increased expression of TGF-beta in proliferating thyroid cells and in thyroid tumours has recently been described, suggesting a secondary counter-regulatory role of these proteins. We have studied further this apparent paradox in vitro using FRTL-5 cells, 5 continuous cell strains from feline multinodular goitres (MNG) and 29 primary cultures prepared from human MNG. While dose dependent inhibition of FRTL-5 cell growth was confirmed, a variable fraction of these cells was naturally resistant towards TGF-beta 1, thus explaining the large interassay variability of growth inhibition (36 to 98% within 2 days, n = 19). After 40 days of continuous exposure, FRTL-5 cells became fully refractory towards TGF-beta 1 inhibition, due to the selective growth of naturally resistant subclones, as demonstrated for example by microscopic observation of three-dimensionally growing collagen-embedded cell clusters. The refractoriness could still be demonstrated even after several cell passages. In addition, 2 out of 5 feline thyroid cell strains obtained from feline MNG and 18 out of 29 primary cultures from human MNG showed a high degree of refractoriness towards TGF-beta. We conclude that constitutively TGF-beta resistant cells may occur in thyroid glands and that persistent TGF-beta refractoriness may secondarily be acquired. Resistant cells may escape regular growth control mechanisms and hence may contribute to the notorious heterogeneity of thyroid growth and to nodular transformation.     

Argumentation-Based Ontology Engineering

The Diligent argumentation framework helps capture design deliberations in ontology-engineering discussions. It makes consensus-building tasks more efficient and provides detailed guidance for nonexperts. The semantic Web envisions an infrastructure in which humans and machines seamlessly exchange information on the Web. During the discussions participants raise new issues or elaborate on existing ones. Once a discussion evolves, participants can group issues and act on them accordingly.     

CAST3M/ARCTURUS: A coupled heat transfer CFD code for thermal–hydraulic analyzes of gas cooled reactors

The safety of gas cooled reactors (High Temperature Reactors (HTR), Very High Temperature Reactors (VHTR) or Gas Cooled Fast Reactors (GFR)) must be ensured by systems (active or passive) which maintain loads on component (fuel) and structures (vessel, containment) within acceptable limits under accidental conditions. To achieve this objective, thermal–hydraulics computer codes are necessary tools to design, enhance the performance and ensure a high safety level of the different reactors. Some key safety questions are related to the evaluation of decay heat removal and containment pressure and thermal loads. This requires accurate simulations of conduction, convection, thermal radiation transfers and energy storage. Coupling with neutronics is also an important modeling aspect for the determination of representative parameters such as neutronics coefficient (Doppler coefficient, Moderator coeffcient, …), critical position of control rods, reactivity insertion aspects, …. For GFR, the high power density of the core and its necessary reduced dimension cannot rely only on passive systems for decay heat removal. Therefore, forced convection using active safety systems (gas blowers, heat exchangers, …) are highly recommended. Nevertheless, in case of station black-out, the safety demonstration of the concept should be guaranteed by natural circulation heat removal. This could be performed by keeping a relatively high back-up pressure for pure helium convection and also by heavy gas injection. So, it is also necessary to model mixing of different gases, the on-set of natural convection and the pressure and thermal loads onto the proximate or guard containment. In this paper, we report on the developments of the CAST3M/ARCTURUS thermal–hydraulics (Lumped Parameter and CFD) code developed at CEA, including its coupling to the neutronics code CRONOS2 and the system code CATHARE. Elementary validation cases are detailed, as well as application of the code to benchmark problems such as the HTR-10 thermal–hydraulic exercise. Examples of containment thermal–hydraulics calculations for fast reactor design (GFR) are also detailed.     

Direct observation of liquid crystals using cryo‐TEM: Specimen preparation and low‐dose imaging

Liquid crystals (LCs) represent a challenging group of materials for direct transmission electron microscopy (TEM) studies due to the complications in specimen preparation and the severe radiation damage. In this paper, we summarize a series of specimen preparation methods, including thin film and cryo‐sectioning approaches, as a comprehensive toolset enabling high‐resolution direct cryo‐TEM observation of a broad range of LCs. We also present comparative analysis using cryo‐TEM and replica freeze‐fracture TEM on both thermotropic and lyotropic LCs. In addition to the revisits of previous practices, some new concepts are introduced, e.g., suspended thermotropic LC thin films, combined high‐pressure freezing and cryo‐sectioning of lyotropic LCs, and the complementary applications of direct TEM and indirect replica TEM techniques. The significance of subnanometer resolution cryo‐TEM observation is demonstrated in a few important issues in LC studies, including providing direct evidences for the existence of nanoscale smectic domains in nematic bent‐core thermotropic LCs, comprehensive understanding of the twist‐bend nematic phase, and probing the packing of columnar aggregates in lyotropic chromonic LCs. Direct TEM observation opens ways to a variety of TEM techniques, suggesting that TEM (replica, cryo, and in situ techniques), in general, may be a promising part of the solution to the lack of effective structural probe at the molecular scale in LC studies. Microsc. Res. Tech. 77:754–772, 2014. © 2014 Wiley Periodicals, Inc.     

Electron beam-induced changes in vitreous sections of biological samples

Nonpretreated high pressure frozen samples of Zea mays, cartilage and human erythrocytes were cryosectioned and observed at 110 K in a cryoelectron microscope. Changes induced by medium doses of electron irradiation (< 10 ke nm^?2) are described. After some ke nm^?2, the most conspicuous cutting artefacts are erased to a large extent and the visibility of the cell organelles is improved. The sections, compressed in the cutting direction by the sectioning process, shrink once more, in the same direction, when irradiated. This shrinkage depends on the section support and on how the section is adsorbed to it. Shrinkage is not uniform; it is most pronounced in mitochondria, condensed chromatin and nucleolus. This differential shrinkage improves the visibility of major structures on the section and, as a result, ‘nicer’ images are recorded. However, this apparent improvement is a beam-induced artefact that must be paired with a loss of high resolution information.     

High pressure hydrogen fires

Within the scope of the French national project DRIVE and European project HyPER, high pressure jet flames of hydrogen were produced and instrumented.The experimental technique and measurement strategy are presented. Many aspects are original developments like the direct measurement of the mass flow rate by weighing continuously the hydrogen container, the image processing to extract the flame geometry, the heat flux measurement device, the thermocouples arrangement…Flames were observed from 900 bar down to 1 bar with orifices ranging from 1 to 3 mm. An original set of data is now available about the main flame characteristics and about some thermodynamic aspects of hydrogen releases under high pressure.A brief comparison of some available models is presented.