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Cosmic particle flux increases with latitude and altitude and is significantly higher on-board aircraft than at ground level. Furthermore, its intensity depends on solar activity and eruptions. Due to their professional activity, flight crews (FCs) may receive an annual dose of some millisieverts. Therefore, the European directive adopted in 1996 requires the aircraft operators to assess the dose. The effective dose is to be estimated using various experimental and calculation means. In France, it is carried out by the computerized system for flight assessment of exposure to cosmic radiation SIEVERTPN, which sends to SISERI, the national dose registry, the monthly effective dose of each crew member. The average annual effective dose of French FCs was 2.19 mSv in 2019, i.e.between the standard permissible limits set for the public and the limit set for occupationally exposed persons. The effective dose received by the most exposed French FCs increased during the period 2015–2019 and that could be due to the solar cycle effect, changes in the staff flight time or the aircraft model. It can also be noted that more technical flight crews (TFCs) received a dose greater than 5 mSv over the 2016 to 2019 period than commercial flight crew (CFCs). Our study indicates that the number of FCs having received a dose greater than 5 mSv also increased over the period 2016 to 2019. Some parameters, that may affect the assessment of the aircrew effective dose, are not considered in SIEVERTPN calculations, as for example the Forbush decreases and the location in the plane. Lastly, several factors lead us to expect a decrease in the doses received by French aircrew staff in the coming years, such as the peak activity of the 25theleven-year solar cycle expected in July 2025. However, some unexpected events, as for instance the war in Ukraine, can alter this prediction.

La qualité de vie et le bien-être psychologique des patients traités pour un cancer de la thyroïde sont essentiels compte tenu de leur survie très prolongée. Le traitement fait appel à une chirurgie souvent complétée par une thérapie par iode radioactif (RAI). Cette étude vise à examiner les effets potentiels de la thérapie par RAI sur la qualité de vie liée à la santé (Qdv), les symptômes d’anxiété et de dépression, et l’état nutritionnel six mois après traitement.

En 2000, des flux de rayonnement anormalement élevés ont été détectés sur certaines plages du littoral camarguais. Les sables du littoral camarguais ont alors fait l’objet d’une caractérisation radiologique montrant des activités moyennes de quelques dizaines de Bq kg-1en uranium-238 et thorium-232 d’une part, et l’existence de points chauds à plus de 1000 Bq kg-1d’autre part ; voire plus sur deux plages : l’une située à l’Est du phare de Beauduc, l’autre située à l’Est du phare de l’Espiguette. Cette radioactivité, d’origine naturelle, est responsable de l’exposition des personnes fréquentant ces deux dernières plages relativement isolées, mais néanmoins accessibles à tout public. L’Institut de radioprotection et de sûreté nucléaire a réalisé une évaluation des doses susceptibles d’être reçues par des personnes fréquentant ces deux dernières plages, en se basant sur des mesures et des prélèvements effectués in situ, en établissant expérimentalement la solubilité des sables dans les fluides gastrique et intestinal, et en formulant des hypothèses sur la fréquentation des lieux (scénarios). La dose annuelle maximale ainsi évaluée est de l’ordre de 0,8 mSv pour des adultes et 0,5 mSv pour les enfants ; valeurs vraisemblablement très prudentes dans lesquelles la dose par exposition externe prédomine largement.

À la suite d’un accident radiologique dû à une source de gammagraphie survenu au Chili en décembre 2005 et impliquant une victime, l’IRSN a été sollicité pour réaliser la reconstitution dosimétrique par calcul Monte Carlo. Des outils, développés au laboratoire, associant des fantômes anthropomorphes mathématiques et voxélisés au code de calcul Monte Carlo mcnpx ont été mis en œuvre afin de déterminer la distribution de dose au niveau de la fesse gauche de la victime et la dose aux organes critiques. La cartographie dosimétrique réalisée au niveau de la fesse gauche montre que la dose à la surface est importante (1900 Gy) et chute rapidement pour atteindre 20 Gy à 5 cm de profondeur. Les calculs réalisés avec un fantôme mathématique indiquent que les doses moyennes aux organes critiques sont faibles et permettent d’identifier de possibles sites de prélèvement de moelle osseuse. S’appuyant sur la cartographie dosimétrique, une exérèse de 5 cm de profondeur et de 10 cm de diamètre a été pratiquée au niveau de la fesse gauche de la victime.

Les activités de recherche et d’expertise en dosimétrie de l’Institut de radioprotection et de sûreté nucléaire (IRSN) sont les héritières de celles commencées dans les années soixante au CEA. Les premiers laboratoires créés dans les années soixante étaient destinés à développer les techniques dosimétriques des rayonnements externes pour la protection du personnel. Aujourd’hui, les laboratoires de dosimétrie externe et interne de l’institut couvrent assez largement les différentes problématiques liées à la dosimétrie des rayonnements ionisants, que ce soit pour la mesure et le suivi des doses en situation normale d’exploitation ou pour la reconstitution des doses à la suite d’une situation accidentelle. En 1984, la création des LARD est intervenue sous l’impulsion du chef du service de dosimétrie Portal et de Blanc dans le but de favoriser les contacts entre les divers laboratoires et notamment de les aider à pénétrer les arcanes de la commission européenne pour s’intégrer aux programmes de recherche soutenus par la commission. Après un bref rappel historique, trois des champs d’activité actuellement traités par l’IRSN sont présentés, la reconstitution dosimétrique suite à une irradiation externe accidentelle, la caractérisation dosimétrique et spectrométrique des postes de travail exposés aux neutrons et la recherche pour l’amélioration de la mesure directe en dosimétrie interne.

This study aimed to determine the physiological role of laminin (LN) and its receptor, alpha(6)beta(1) integrin, in controlling the functions of granulosa cells (GC) during follicular development in sheep ovary. Immunohistochemistry experiments showed the presence of increasing levels of LN (P<0.0001), and high levels of mature alpha(6)beta(1) integrin in GC layers of healthy antral follicles during the follicular and the preovulatory phases of the estrous cycle. In vitro, the addition of a function-blocking antibody raised against alpha(6) subunit (anti-alpha(6) IgG) to the medium of ovine GC cultured on LN impaired cell spreading (P<0.0001), decreased the proliferation rate (P<0.05) and increased the apoptosis rate (P<0.05). Furthermore, addition of anti-alpha(6) IgG enhanced estradiol (E2) secretion by GC in the presence or absence of follicle-stimulating hormone (FSH), luteinizing hormone or insulin-like growth factor-I in culture medium (P<0.0001), and inhibited progesterone (P4) secretion in basal conditions or in the presence of low (0.5 ng/ml) FSH concentrations only (P<0.0001). The anti-alpha(6) IgG effect was specific to an interaction of LN with alpha(6)beta(1) integrin since it was ineffective on GC cultured on heat-denatured LN, RGD (arginine-glycine-aspartic acid) peptides and non-coated substratum. Hence, this study established that alpha(6)beta(1) integrin 1) was expressed in GC of antral follicles, 2) mediated the actions of LN on survival, proliferation and steroidogenesis of GC, and 3) was able to dramatically modulate P4 and E2 secretion by GC in vitro. It is suggested that during the follicular and the preovulatory phases of the estrous cycle, the increasing levels of LN in GC of large antral follicles might support their final development to ovulation.

The extracellular matrix (ECM), constituting the follicular basal lamina and present also between follicular cells and in the follicular fluid, is believed to regulate granulosa cell (GC) function during follicular development. Ovine GCs isolated from small (1-3 mm in diameter) or large (4-7 mm in diameter) antral follicles were cultured on various pure ECM components (type I collagen, fibronectin, laminin), synthetic substrata enhancing (RGD peptides) or impairing (poly 2-hydroxyethylmethacrylate (poly-hema)) cell adhesion, or in the presence of heparin. The effects of these factors, used alone or in combination with IGF-I and/or FSH, were evaluated in terms of GC spread, survival, proliferation and steroidogenesis. When grown on type I collagen (CI) gel, poly-hema or heparin, GCs from both large and small follicles exhibited a round shape and a low proliferation rate. Compared with non-coated plastic substratum as a control, these ECM or synthetic compounds enhanced estradiol secretion and reduced progesterone secretion by large-follicle GCs. In contrast, GCs from both large and small follicles spread extensively on CI coating, fibronectin, laminin and RGD peptides. Fibronectin and laminin dramatically increased the proliferation rate and enhanced survival of GCs from both origins. Moreover, fibronectin, laminin and RGD peptides reduced estradiol secretion by large-follicle GCs. Unexpectedly, CI coating increased estradiol secretion and reduced progesterone secretion by large-follicle GCs, suggesting that type I collagen was able to maintain estradiol secretion independently of GC shape. Finally, GC responsiveness to IGF-I and FSH, in terms of proliferation and steroidogenesis, was generally maintained when cells were grown on ECM components, RGD peptides and in the presence of heparin. However, when large-follicle GCs were grown as non-adherent clusters (as observed on poly-hema) basal and IGF-I- and/or FSH-stimulated progesterone secretions were totally abolished. Overall, this study shows that GC shape, survival, proliferation and steroidogenesis can be modulated in vitro by pure ECM components in a specific and coordinated manner. It is suggested that, in vivo, fibronectin and laminin would sustain follicular development by enhancing the survival and proliferation of GCs, whereas type I collagen might participate in the maintenance of estradiol secretion in large antral follicles.

ADAM12 belongs to the transmembrane metalloprotease ADAM ("a disintegrin and metalloprotease") family. ADAM12 has been implicated in muscle cell differentiation and fusion, but its precise function remains unknown. Here, we show that ADAM12 is dramatically up-regulated in regenerated, newly formed fibers in vivo. In C2C12 cells, ADAM12 is expressed at low levels in undifferentiated myoblasts and is transiently up-regulated at the onset of differentiation when myoblasts fuse into multinucleated myotubes, whereas other ADAMs, such as ADAMs 9, 10, 15, 17, and 19, are expressed at all stages of differentiation. Using the yeast two-hybrid screen, we found that the muscle-specific alpha-actinin-2 strongly binds to the cytoplasmic tail of ADAM12. In vitro binding assays with GST fusion proteins confirmed the specific interaction. The major binding site for alpha-actinin-2 was mapped to a short sequence in the membrane-proximal region of ADAM12 cytoplasmic tail; a second binding site was identified in the membrane-distal region. Co-immunoprecipitation experiments confirm the in vivo association of ADAM12 cytoplasmic domain with alpha-actinin-2. Overexpression of the entire cytosolic ADAM12 tail acted in a dominant negative fashion by inhibiting fusion of C2C12 cells, whereas expression of a cytosolic ADAM12 lacking the major alpha-actinin-2 binding site had no effect on cell fusion. Our results suggest that interaction of ADAM12 with alpha-actinin-2 is important for ADAM12 function.

Suite au traitement par radioiode (I131) du cancer différencié de la thyroïde, les glandes salivaires peuvent être le siège d’inflammations, provoquant des troubles salivaires (TbS). L’incidence des TbS est mal connue ainsi que les facteurs de risque cliniques et génétiques. L’étude START vise à estimer l’incidence des TbS après traitement par radioiode, individualiser les facteurs de risque cliniques, biomoléculaires et biochimiques, et valider une méthode d’estimation dosimétrique pour calculer la dose reçue au niveau des glandes salivaires et analyser les relations dose-réponse.

Villin is an evolutionarily well conserved, Ca2+ regulated actin‐binding protein, and a major structural component of the brush border of specialized absorptive cells. Using paraffin sections and an affinity purified polyclonal anti‐villin antibody, we have investigated the early expression of villin during mouse embryogenesis. Villin is first detectable at the early post‐implantation stage in visceral endodermal cells at the periphery of the egg cylinder. In this extra embryonic layer, the expression of villin increases and then persists until full term gestation. In the embryo, villin first appears in gut anlage during the axial rotation. Using the same methodology, villin expression is also demonstrated in differentiating embryoid bodies from a teratocarcinoma. Both in extra embryonic and embryonic extracts, villin expression is confirmed by immunoblot and Northern blot analysis which reveal, respectively, a single polypeptide of 93 kd and an mRNA of 3.4 kb in length, two well defined parameters for adult mouse villin gene expression. The results presented here show that paraffin sections allow very sensitive and highly resolutive detection of antigens in early embryogenesis. They provide a detailed developmental profile of villin expression and demonstrate the usefulness of villin as a marker for epithelial cells involved in absorptive processes.

The actin binding sites of actobindin and thymosin beta 4, two small polypeptides that inhibit actin polymerization by interacting with monomeric actin, have been localized using peptide mimetics. Both sites are functionally similar and extend over 20 residues and are located in the NH2‐terminus of the polypeptides. They can be dissected into two functional entities: a conserved hexapeptide motif (LKHAET or LKKTET), which forms the major contact site through electrostatic interactions with actin, and a non‐conserved NH2‐terminal segment preceding the motif, which exerts the inhibitory activity on actin polymerization probably by steric hindrance. The introduction of a glutamic acid at the third position in the motif, creating LKEAET or LKETET sequences, which are similar to those found in some F‐actin binding proteins, converts the peptide's inhibitory phenotype into an F‐actin stimulatory property. These results allow the proposal of a simple model for G‐ to F‐actin modulation.

Comme on le fait couramment en Thermodynamique des processus irréversibles, nous proposons d'inclure explicitement le bilan entropique dans la mise en équation des problèmes de thermodynamique des milieux continus, mais sans faire appel à une équation de Gibbs, dont nous avons montré par ailleurs qu'elle ne tient pas en variables observables.

Survey of results recently obtained by the author about hereditary behaviour, Gibbs equation, caloric equation of state, local equilibrium, reversible accessibility, use of internal variables, behaviour classification. Toward a new and unified approach: thermodynamics in natural variables.

The amino acid composition of coconut calli under somatic embryogenesis induction conditions was compared with that of calli under multiplication conditions. Six amino acids were detected: proline, valine, leucine, serine, alanine and threonine. Calli were classified into five groups according to their amino acid composition by a clustering method taking into account the morphogenetic stage of each callus. A discriminant analysis and an analysis of variance revealed that the groups had been classified correctly. The first group comprised all calli sampled at the beginning of culture (TO). Thereafter, two major phases were detected. The first phase concerned analysis times T8 and T15 and corresponded to a latency phase as regards growth and adaptation to culture conditions. Calli on the multiplication medium were significantly different from calli on the induction medium, characterized by a drop in proline, valine and serine contents. This drop was an initial reaction to the increase in 2,4-D and mineral element concentrations in the media to initiate unicellular type embryogenesis. The second phase, regrouping analysis times T28, T42 and T60, corresponded to callus growth. Heterogeneity was detected in calli on the induction medium and was confirmed by a histological study. Some calli adapted to the changes in the medium by remaining at the meristematic stage; their amino acid composition became similar to that of calli on the multiplication medium. The others tended well towards embryogenesis and were characterized by increases in the proline, valine and leucine contents and an unchanged alanine content; these increases were concomitant with the formation of storage proteins observed histologically at the time of embryogenesis initiation.

Abstract: Rappel d'un algorithme numérique dû à Bazant, et permettant la résolution pas à pas des équations de Volterra de la visco-élasticité linéaire avec vieillissement. Application de cet algorithme au calcul pas à pas de l'évolution de la déformation moyenne et de la courbure dans une structure hétérogène du type multilame (stratifié ou fibré assimilable à des poutres hétérogènes chargées dans un plan de symétrie avec conservation des sections planes). Calcul pas à pas des déformations et contraintes dans chaque lame au niveau des interfaces. Calcul des flèches, en une section pour différentes portées ramené à celui d'une portée type et décomposé en deux cas d'importance pratique: courbure parabolique (charge transversale uniforme) et courbure constante (moment constant, charge axiale excentrée sans effets, du2 c ordre; variations dimensionnelles des matériaux constitutifs). Prise en compte de la précontrainte qui entre dans le formalisme génèral moyennant l'attribution à l'acier d'une prédéformation égale à l'opposé du quotient de la précontrainte initiale par le module d'élasticité instantané de l'acier. Indications pratiques sur le programme MULTIVIBAZ et exemple de résultats.

Villin is an evolutionarily well conserved, Ca2+ regulated actin‐binding protein, and a major structural component of the brush border of specialized absorptive cells. Using paraffin sections and an affinity purified polyclonal anti‐villin antibody, we have investigated the early expression of villin during mouse embryogenesis. Villin is first detectable at the early post‐implantation stage in visceral endodermal cells at the periphery of the egg cylinder. In this extra embryonic layer, the expression of villin increases and then persists until full term gestation. In the embryo, villin first appears in gut anlage during the axial rotation. Using the same methodology, villin expression is also demonstrated in differentiating embryoid bodies from a teratocarcinoma. Both in extra embryonic and embryonic extracts, villin expression is confirmed by immunoblot and Northern blot analysis which reveal, respectively, a single polypeptide of 93 kd and an mRNA of 3.4 kb in length, two well defined parameters for adult mouse villin gene expression. The results presented here show that paraffin sections allow very sensitive and highly resolutive detection of antigens in early embryogenesis. They provide a detailed developmental profile of villin expression and demonstrate the usefulness of villin as a marker for epithelial cells involved in absorptive processes.

The actin binding sites of actobindin and thymosin beta 4, two small polypeptides that inhibit actin polymerization by interacting with monomeric actin, have been localized using peptide mimetics. Both sites are functionally similar and extend over 20 residues and are located in the NH2‐terminus of the polypeptides. They can be dissected into two functional entities: a conserved hexapeptide motif (LKHAET or LKKTET), which forms the major contact site through electrostatic interactions with actin, and a non‐conserved NH2‐terminal segment preceding the motif, which exerts the inhibitory activity on actin polymerization probably by steric hindrance. The introduction of a glutamic acid at the third position in the motif, creating LKEAET or LKETET sequences, which are similar to those found in some F‐actin binding proteins, converts the peptide's inhibitory phenotype into an F‐actin stimulatory property. These results allow the proposal of a simple model for G‐ to F‐actin modulation.

Summary Brush borders which are localized at the apical face of enterocytes, are composed of thousands of stiff microvilli containing bundles of microfilaments made of actin. Their assembly occurs during terminal differentiation of the enterocytes when these cells migrate along the villus of the intestinal mucosa. The cell line HT 29 derived from a human colonic adenocarcinoma whose differentiation can be induced, can also be used as a model to study in culture the assembly of the intestinal brush border.

An actin-binding protein of M(r) 105,000 has been isolated from anuran amphibian intestinal mucosa. Polyclonal antibodies directed against chicken and pig intestinal villins and anti-porcine villin headpiece monoclonal antibody crossreact with the amphibian M(r) 105,000 protein. Furthermore, the latter possesses an NH2-terminal sequence that is very homologous to those of avian and mammalian villins. In addition, polyclonal antibodies directed against amphibian intestinal M(r) 105,000 protein crossreact with chicken and mouse intestinal epithelial cell villins. These data indicate that the amphibian intestinal M(r) 105,000 protein is immunologically and structurally related to villin, an actin-binding protein expressed in specific epithelial tissues in vertebrates. Morphological, immunocytochemical and immunoblotting techniques were then used to investigate the expression of villin during embryonic and larval intestinal development of Xenopus laevis. Villin is not found in the egg or the endoderm of the early embryo. It is first detected just before hatching in the apical domain of endodermal cells at a time when few surface microvilli are visible by transmission electron microscopy. In the newly hatched larva, villin accumulates as these cells differentiate. These results provide a detailed developmental profile of Xenopus intestinal villin expression and demonstrate that this protein is a useful marker for the presumptive intestinal endoderm.

An actin-binding protein of M(r) 105,000 has been isolated from anuran amphibian intestinal mucosa. Polyclonal antibodies directed against chicken and pig intestinal villins and anti-porcine villin headpiece monoclonal antibody crossreact with the amphibian M(r) 105,000 protein. Furthermore, the latter possesses an NH2-terminal sequence that is very homologous to those of avian and mammalian villins. In addition, polyclonal antibodies directed against amphibian intestinal M(r) 105,000 protein crossreact with chicken and mouse intestinal epithelial cell villins. These data indicate that the amphibian intestinal M(r) 105,000 protein is immunologically and structurally related to villin, an actin-binding protein expressed in specific epithelial tissues in vertebrates. Morphological, immunocytochemical and immunoblotting techniques were then used to investigate the expression of villin during embryonic and larval intestinal development of Xenopus laevis. Villin is not found in the egg or the endoderm of the early embryo. It is first detected just before hatching in the apical domain of endodermal cells at a time when few surface microvilli are visible by transmission electron microscopy. In the newly hatched larva, villin accumulates as these cells differentiate. These results provide a detailed developmental profile of Xenopus intestinal villin expression and demonstrate that this protein is a useful marker for the presumptive intestinal endoderm.

We have investigated the presence of villin (a Ca2+-regulated actin binding protein) in various tissues (normal or malignant) and in established cell lines by using sensitive immunochemical techniques on cell extracts and immunofluorescence analysis on frozen sections. Our results show that villin is a marker that can be used to distinguish normal differentiated epithelial cells from the simple epithelia lining the gastrointestinal tract and renal tubules. Villin is found in the absorptive cells of the small and large intestines, in the duct cells of pancreas and biliary system, and in the cells of kidney proximal tubules. Furthermore, undifferentiated normal and tumoral cells of intestinal origin in vivo and in cell culture express villin. Therefore, expression of villin is seen in cells that do not necessarily display the morphological features characteristic of their terminally differentiated state, such as the microvilli-lined brush border. We suggest the possible clinical implications of using villin as a marker in the diagnosis of metastatic adenocarcinomas.

Using polyclonal antibodies raised against clathrin, we have developed an enzyme-linked immunoassay that can specifically measure the quantity of clathrin in crude cell extracts. We found that the quantity (weight percent of total protein) of clathrin was similar in cell types that exhibit large differences in their levels of endocytosis and exocytosis (lymphoid cells, 0.11%; liver cells, 0.07%, fibroblasts, 0.18%; myeloma cells, 0.16%). However, the quantity of clathrin was found to be significantly higher in brain cortex (0.75%). Cellular clathrin was separated by high-speed centrifugation into two fractions: an unassembled form present in high-speed supernatants and an assembled form (clathrin coats) present in the pellets. We show that the fraction of clathrin in the unassembled state varies considerably depending on the cell type studied (14% in brain cortex to 70% in lymphocytes). Our data support the view that the amount of clathrin (relative to total cell protein) in eucaryotic cells is not related to the extent of receptor-mediated endocytosis and intracellular membrane traffic. However, the fraction of assembled clathrin seems to be higher in endocytically and/or exocytically active cells.

A clone HT29-18 has been isolated from the parent cell line HT-29, which derived from a human colon adenocarcinoma (Fogh, J., and G. Trempe, 1975, Human Tumor Cells in Vitro, J. Fogh, editor, Plenum Publishing Corp., New York, 115-141). This clone is able to differentiate as the parent cell line does. Differentiation occurs when glucose is replaced by galactose in the culture medium (Pinto, M., M.D. Appay, P. Simon-Assman, G. Chevalier, N. Dracopoli, J. Fogh, and A. Zweibaum, 1982, Biol. Cell., 44:193-196). We demonstrate here that the differentiated cloned population HT29-18/gal is heterogenous: although 90% of the cells show morphological characteristics of "absorptive cells", only 20-30% of them display sucrase-isomaltase in their apical microvillar membranes. About 10% of the entire cell population consists of cells containing mucous granules similar to intestinal goblet cells. We have isolated two subclones, HT29-18-C1 and HT29-18-N2, from the differentiated HT29-18/gal cells. HT29-18-C1 cells show morphological characteristics of polarized absorptive cells, when growing either in glucose- or in galactose-containing media, but the sucrase-isomaltase is not expressed in the cells grown in glucose-containing medium. The clone HT29-18-N2 is also polarized in both culture conditions and is similar to globlet cells in vivo. It grows as a monolayer, exhibits tight junctions, and contains numerous mucous granules whose exocytosis can be triggered by carbachol, a parasympathomimetic drug. We conclude that the clone HT29-18 first isolated was a multipotent cell population from which we isolated several subclones that differentiate either as absorptive (HT29-18-C1) or as mucous (HT29-18-N2) cells. In contrast to the parent HT-29 cell line, the subclones retain most of their differentiated properties in glucose-containing medium.

Coconut calli were cultivated on two somatic embryogenesis induction media (SEIMs), differing in their 2,4-D content. Gain in dry matter weight, composition of soluble sugars within calli, but also pH and contents of glucose and macroelements in media were analysed at 0, 15, 28, and 60 days of culture. Relationships between contents of endogenous sugars, on the one hand, and between contents of media macroelements, on the other hand, were analysed. Comparison was made with calli maintained on a control multiplication medium.

Brush border in enterocytes is a cell surface specialization intimately associated with terminal differentiation of these cells. HT29-18, a clone derived from the HT-29 human colonic adenocarcinoma cell line, and HT29-18-C1, a subclone from HT29-18 described in the companion paper (Huet, C., C. Sahuquillo-Merino, E. Coudrier, and D. Louvard, 1987, J. Cell Biol., 105:345-357), undergo terminal differentiation with brush borders in the absence of glucose or upon replacement of glucose by galactose in the medium. Taking advantage of this clone and its subclone which can be manipulated in vitro, we have studied the synthesis and subcellular distribution of villin, one major protein in the microvillus core of the brush border. For this study, a monoclonal antibody against villin (BDID2C3) has been isolated and characterized in detail. In addition an ELISA has been set up to measure villin accurately in total cell extracts. Villin content in differentiated HT29-18 cells is close to that seen in normal human colonic cells but 10 times lower in undifferentiated HT29-18 cells. The rate of villin synthesis is dramatically increased in the course of enterocytic differentiation, while villin is remarkably stable after synthesis. We have recently shown, using a cDNA probe for villin, that this change is controlled either at the transcription level or by RNA stabilization (Pringault, E., M. Arpin, A. Garcia, J. Finidori, and D. Louvard, 1986, EMBO (Eur. Mol. Biol. Organ.) J., 5:3119-3124). As shown by immunofluorescence and immunogold labelings, villin is targeted to the brush border area of differentiated HT29-18 cells but remains diffusely distributed in undifferentiated ones.

Résumé Nous présentons une tentative pour étendre à la viscoélasticité non linéaire les méthodes du calcul symbolique, dont on sait qu'ils ramènent, dans le cas linéaire, tous les problèmes de viscoélasticité, tant dynamiques que statiques, à des problèmes d'élastostatique (Mandel, 1955).

A parameter uncertainty analysis has been performed to derive the probability distribution of the weighted equivalent dose to lung for an adult (wlung Hlung) per unit exposure to radon progeny in the home. The analysis was performed using the ICRP Publication 66 human respiratory tract model (HRTM) with tissue weighting factor for the lung, wlung = 0.12 and the radiation weighting factor for alpha particles, wR = 20. It is assumed that the HRTM is a realistic representation of the physical and biological processes, and that the parameter values are uncertain. The parameter probability distributions used in the analysis were based on a combination of experimental results and expert judgement from several prominent European scientists. The assignment of the probability distributions describing the uncertainty in the values of the assigned fractions (ABB, Abb, AAI) of the tissue weighting factor proved difficult in practice due to lack of quantitative data. Because of this several distributions were considered. The results of the analysis give a mean value of wlung Hlung per unit exposure to radon progeny in the home of 15 mSv per working level month (WLM) for a population. For a given radon gas concentration, the mean value of wlung Hlung per unit exposure is 13 mSv per 200 Bq.m-3.y of 222Rn. Parameters characterising the distributions of wlung Hlung per unit exposure are given. If the ICRP weighting factors are fixed at their default values (ABB, Abb, AAI = 0.333, 0.333, 0.333; wlung = 0.12; and wr = 20) then on the basis of this uncertainty analysis it is extremely unlikely (P " 0.0007) that a value of Hw/Pp for exposure in the home is as low as 4 mSv per WLM, the value determined with the epidemiological approach. Even when the uncertainties in the ABB, Abb, AAI values are included then this probability is predicted to be between 0.01 to 0.08 depending upon the distribution assumed for describing the uncertainties in the ABB, Abb, AAI values. Thus, it is concluded that the uncertainties in the HRTM parameters considered in this study cannot totally account for the discrepancy between the dosimetric and epidemiological approaches.