Weakened conditions of admissibility of surface forces applied to linearly elastic membrane shells

International audienceWe consider a family of linearly elastic shells of the first kind (as defined in Ciarlet [2]), also known as non inhibited pure bending shells (Sanchez-Hubert and Sanchez-Palencia [7]). This family is indexed by the half-thickness ε. When ε approaches zero, the averages across the thickness of the shell of the covariant components of the displacement of the points of the shell converge strongly towards the solution of a ”2D generalized membrane shell problem” provided the applied forces satisfy admissibility conditions (Ciarlet and Lods [3], Chapelle and Bathe [1]). The identification of the admissible applied forces usually requires delicate analysis. In the first part of this paper we simplify the general admissibility conditions when applied forces h are surface forces only, and obtain conditions that no longer depend on ε (Luce, Poutous and Thomas [5]) : find hαβ = hβα in L2 (ω) such that for all η = (ηi ) in V(ω), ω hi ηi dω = ω hαβ γαβ (η)dω where ω is a domain of R2 , θ is in C 3 (ω, R3 ) and S = θ(ω) is the middle surface of the shells, where (γαβ (η)) is the linearized strain tensor of S and V(ω) = η ∈ H1 (ω), η = 0 on γ0 , the shells being clamped along Γ0 = θ(γ0 ). In the second part, since the simplified admissibility formulation does not allow to conclude directly to the existence of hαβ , we seek sufficient conditions on h for hαβ to exist in L2 (ω). In order to get them, we impose more regularity to hαβ and boundary conditions. Under these assumptions, we can obtain from the weak formulation a system of PDE with hαβ as unknowns. The existence of solutions depends both on the geometry of the shell and on the choice of h. We carry through the study of four representative geometries of shells and identify in each case a special admissibility functional space for

Asymptotic modelling of a fluid-structure coupling in the case of a prestressed inflated orthotropic mebrane shell

International audienceAbstract In this Note, we consider an inflated orthotropic linearly elastic generalized membrane shell submited to an outer surface perturbation. We obtain the strong convergence towards the solution of a wellposed ”2D” problem of the mean value in the membrane thickness 2ε of the ”3D” scaled displacements, as ε approaches zero

Differential Transcriptional Response To Staphylococcus aureus Infection In Two Divergent Lines Of Sheep Selected On Milk Somatic Cell Score

The milk somatic cell score (SCS) is an indirect indicator of mastitis, currently used as a selection criterion of dairy ruminants that leads to decreased intra-mammary infection prevalence. In the present study, gene expression profiles after Staphylococcus stimulations were determined in three cell types of mastitis resistant and susceptible ewes. The comparisons of the lists of the differentially-expressed genes allowed identification of commonly-regulated genes among cell types. These results lead to identify a subset of genes involved in pathogen-related receptor signaling. These genes may play an important role in recognition of pathogens and may improve resistance to intramammary infections

Processivity and Coupling in Messenger RNA Transcription

The complexity of messenger RNA processing is now being uncovered by experimental techniques that are capable of detecting individual copies of mRNA in cells, and by quantitative real-time observations that reveal the kinetics. This processing is commonly modelled by permitting mRNA to be transcribed only when the promoter is in the on state. In this simple on/off model, the many processes involved in active transcription are represented by a single reaction. These processes include elongation, which has a minimum time for completion and processing that is not captured in the model.In this paper, we explore the impact on the mRNA distribution of representing the elongation process in more detail. Consideration of the mechanisms of elongation leads to two alternative models of the coupling between the elongating polymerase and the state of the promoter: Processivity allows polymerases to complete elongation irrespective of the promoter state, whereas coupling requires the promoter to be active to produce a full-length transcript. We demonstrate that these alternatives have a significant impact on the predicted distributions. Models are simulated by the Gillespie algorithm, and the third and fourth moments of the resulting distribution are computed in order to characterise the length of the tail, and sharpness of the peak. By this methodology, we show that the moments provide a concise summary of the distribution, showing statistically-significant differences across much of the feasible parameter range.We conclude that processivity is not fully consistent with the on/off model unless the probability of successfully completing elongation is low--as has been observed. The results also suggest that some form of coupling between the promoter and a rate-limiting step in transcription may explain the cell's inability to maintain high mRNA levels at low noise--a prediction of the on/off model that has no supporting evidence

Développement d'une méthode de recherche de dose modélisant un score de toxicité pour les essais cliniques de phase I en Oncologie

Le but principal d'un essai de phase I en oncologie est d'identifier, parmi un nombre fini de doses, la dose à recommander d'un nouveau traitement pour les évaluations ultérieures, sur un petit nombre de patients.Le critère de jugement principal est classiquement la toxicité. Bien que la toxicité soit mesurée pour différents organes sur une échelle gradée, elle est généralement réduite à un indicateur binaire appelé "toxicité dose-limitante" (DLT). Cette simplification très réductrice est problématiqu, en particulier pour les thérapies, dites "thérapies ciblées", associées à peu de DLTs.Dans ce travail, nous proposons un score de toxicité qui résume l'ensemble des toxicités observées chez un patient. Ce score, appelé TTP pour Total Toxicity Profile, est défini par la norme euclidienne des poids associés aux différents types et grades de toxicités possibles. Les poids reflètent l'importance clinique des différentes toxicités.\\ Ensuite, nous proposons la méthode de recherche de dose, QLCRM pour Quasi-Likelihood Continual Reassessment Method, modélisant la relation entre la dose et le score de toxicité TTP à l'aide d'une régression logistique dans un cadre fréquentiste.A l'aide d'une étude de simulation, nous comparons la performance de cette méthode à celle de trois autres approches utilisant un score de toxicité : i) la méthode de Yuan et al. (QCRM) basée sur un modèle empirique pour estimer, dans un cadre bayésien, la relation entre la dose et le score, ii) la méthode d'Ivanova et Kim (UA) dérivée des méthodes algorithmiques et utilisant une régression isotonique pour estimer la dose à recommander en fin d'essai, iii) la méthode de Chen et al. (EID) basée sur une régression isotonique pour l'escalade de dose et l'identification de la dose à recommander. Nous comparons ensuite ces quatre méthodes utilisant le score de toxicité aux méthodes CRM basées sur le critère binaire DLT. Nous étudions également l'impact de l'erreur de classement des grades pour les différentes méthodes, guidées par le score de toxicité ou par la DLT.Enfin, nous illustrons le processus de construction du score de toxicité ainsi que l'application de la méthode QLCRM dans un essai réel de phase I. Dans cette application, nous avons utilisé une approche Delphi pour déterminer avec les cliniciens la matrice des poids et le score de toxicité jugé acceptable.Les méthodes QLCRM, QCRM, UA et EID présentent une bonne performance en termes de capacité à identifier correctement la dose à recommander et de contrôle du surdosage. Dans un essai incluant 36 patients, le pourcentage de sélection correcte de la dose à recommander obtenu avec les méthodes QLCRM et QCRM varie de 80 à 90% en fonction des situations. Les méthodes basées sur le score TTP sont plus performantes et plus robustes aux erreurs de classement des grades que les méthodes CRM basées sur le critère binaire DLT.Dans l'application rétrospective, le processus de construction du score apparaît faisable facilement. Cette étude nous a conduits à proposer des recommandations pour guider les investigateurs et faciliter l'utilisation de cette approche dans la pratique.En conclusion, la méthode QLCRM prenant en compte l'ensemble des toxicités s'avère séduisante pour les essais de phase I évaluant des médicaments associés à peu de DLTs a priori, mais avec des toxicités multiples modérées probables.The aim of a phase I oncology trial is to identify a dose with an acceptable safety level. Most phase I designs use the Dose-Limiting Toxicity (DLT), a binary endpoint, to assess the level of toxicity. DLT might be an incomplete endpoint for investigating molecularly targeted therapies as a lot of useful toxicity information is discarded.In this work, we propose a quasi-continuous toxicity score, the Total Toxicity Profile (TTP), to measure quantitatively and comprehensively the overall burden of multiple toxicities. The TTP is defined as the Euclidean norm of the weights of toxicities experienced by a patient, where the weights reflect the relative clinical importance of each type and grade of toxicity.We propose then a dose-finding design, the Quasi-Likelihood Continual Reassessment Method (QLCRM), incorporating the TTP-score into the CRM, with a logistic model for the dose-toxicity relationship in a frequentist framework. Using simulations, we compare our design to three existing designs for quasi-continuous toxicity scores: i) the QCRM design, proposed by Yuan et al., with an empiric model for the dose-toxicity relationship in a Bayesian framework, ii) the UA design of Ivanova and Kim derived from the "up-and-down" methods for the dose-escalation process and using an isotonic regression to estimate the recommended dose at the end of the trial, and iii) the EID design of Chen et al. using the isotonic regression for the dose-escalation process and for the identification of the recommended dose.We also perform a simulation study to evaluate the TTP-driven methods in comparison to the classical DLT-driven CRM. We then evaluate the robustness of these designs in a setting where grades can be misclassified.In the last part of this work, we illustrate the process of building the TTP-score and the application of the QLCRM method through the example of a paediatric trial. In this study, we have used the Delphi method to elicit the weights and the target toxicity-score considered as an acceptable toxicity measure.All designs using the TTP-score to identify the recommended dose had good performance characteristics for most scenarios, with good overdosing control. For a sample size of 36, the percentage of correct selection for the QLCRM ranged from 80 to 90%, with similar results for the QCRM design. Simulation study demonstrates also that score-driven designs present an improved performance and robustness compared to conventional DLT-driven designs. In the retrospective application of erlotinib trial, the consensus weights as well as the target-TTP were easily obtained, confirming the feasibility of the process. Some guidelines to facilitate the process in a real clinical trial for a better practice of this approach are suggested.The QLCRM method based on the TTP-endpoint combining multiple graded toxicities is an appealing alternative to the conventional dose-finding designs, especially in the context of molecularly targeted agents.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF

Rapport de la campagne PROPPAC 04 à bord du N.O. Le Suroît (30 octobre au 26 novembre 1989)

La campagne PROPPAC 4, dont l'ORSTOM était maître d'oeuvre, s'est déroulée du 30 octobre au 26 novembre 1989 entre 20°S (nord de la Nouvelle-Calédonie) et 5°S le long de 165°E. L'objectif était de décrire en deux points fixes de 8 jours la variabilité à court terme des paramètres hydrologiques et planctoniques, leur répartition le long de la colonne d'eau, la distribution des différentes classes d'organismes et de mesurer l'intensité des flux : advection et mélanges, taux de sédimentation, production primaire et secondaire. Ces informations, recueillies dans deux situations oligotrophes considérées comme typiques, doivent permettre de compléter les données rudimentaires de biologie qui sont collectées au cours des stations de courte durée des radiales bi-annuelles SURTROPAC depuis 1984 et servir à la définition de la relation production-hydrologie dans le Pacifique occidental. La première station de 8 jours, dont la position a été choisie à l'issue d'une radiale préliminaire, était située à 7-8°S et caractérisée par une pycnocline profonde (75 m) et marquée, avec un maximum de chlorophylle vers 80-100 m. La seconde, située à 16°S, correspondrait à une structure hydrologique avec un faible gradient et des sels nutritifs vers 140 m, le maximum de chlorophylle se situant à 120-140 m. (Résumé d'auteur

Serological diagnosis of toxoplasmosis: evaluation of the commercial test recomLine Toxoplasma IgG immunoblot (Mikrogen) based on recombinant antigens

Background: IgG detection to determine immune status to Toxoplasma gondii infection and seroconversion mainly relies on ELISA techniques and, if necessary, on a confirmatory test, Western blot. This study evaluated the performance of the recomLine Toxoplasma IgG immunoblot (IB-recomLine) (Mikrogen) as a confirmatory test on a large number of sera. A total of 171 sera were selected (113 patients) and had previously been analyzed by two ELISA tests, ARCHITECT (Abbott) and VIDAS (bioMérieux) ± LDBIO-Toxo II IgG Western blot (WB-LDBIO) (LDBio). The sera were classified into three groups: group 1 included 50 sera without difficulty in interpreting the IgG results (patients with documented past infection or uninfected); group 2 included 47 sera with difficulty in interpreting the ELISA results; and group 3 included 74 sequential sera from 25 pregnant women with seroconversion. Results: In group 1, overall IgG agreements were 94% and 90% with ARCHITECT and VIDAS, respectively. In group 2, low agreement was observed between IB-recomLine and WB-LDBIO, with eight false-positive and 13 false-negative results. In group 3, 4/13 seroconversions were detected earlier with IB-recomLine compared to other tests. Conclusions: IB-recomLine allowed for earlier diagnosis of toxoplasmic seroconversion compared to both ELISA tests and WB-LDBIO but led to insufficient performance to confirm the immune status when ELISA results were discordant or equivocal