A Generic Library for Floating-Point Numbers and Its Application to Exact Computing

International audienceIn this paper we present a general library to reason about floating-point numbers within the Coq system. Most of the results of the library are proved for an arbitrary floating-point format and an arbitrary base. A special emphasis has been put on proving properties for exact computing, i.e. computing without rounding errors

A Generic Library for Floating-Point Numbers and Its Application to Exact Computing

International audienceIn this paper we present a general library to reason about floating-point numbers within the Coq system. Most of the results of the library are proved for an arbitrary floating-point format and an arbitrary base. A special emphasis has been put on proving properties for exact computing, i.e. computing without rounding errors

Clinical practice guidelines for BRCA1 and BRCA2 genetic testing

BRCA1 and BRCA2 gene pathogenic variants account for most hereditary breast cancer and are increasingly used to determine eligibility for PARP inhibitor (PARPi) therapy of BRCA-related cancer. Because issues of BRCA testing in clinical practice now overlap with both preventive and therapeutic management, updated and comprehensive practice guidelines for BRCA genotyping are needed. The integrative recommendations for BRCA testing presented here aim to (1) identify individuals who may benefit from genetic counselling and risk-reducing strategies; (2) update germline and tumour-testing indications for PARPi-approved therapies; (3) provide testing recommendations for personalised management of early and metastatic breast cancer; and (4) address the issues of rapid process and tumour analysis. An international group of experts, including geneticists, medical and surgical oncologists, pathologists, ethicists and patient representatives, was commissioned by the French Society of Predictive and Personalised Medicine (SFMPP). The group followed a methodology based on specific formal guidelines development, including (1) evaluating the likelihood of BRCAm from a combined systematic review of the literature, risk assessment models and expert quotations, and (2) therapeutic values of BRCAm status for PARPi therapy in BRCA-related cancer and for management of early and advanced breast cancer. These international guidelines may help clinicians comprehensively update and standardise BRCA testing practices

Production de protéines recombinantes d'intérêt thérapeutique par les végétaux

TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF

Les plantes transgéniques et leur impact sur la santé

TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF

Etude de l'effet des stress oxydants et des régulateurs de croissance sur la production d'alcaloides indoliques dans des suspensions cellulaires de pervenche tropicale (catharanthus roseus [L] G. Don)

We investigated the mechanisms involved in the regulation of monoterpene indole alkaloid (MIA) production by plant growth regulators in suspension cells (line C20D) of the Madagascar periwinkle (Catharanthus roseus). In these cells, MIA production was induced by the suppression of 2,4-D from the culture medium and enhanced by cytokinin treatment. The importance of the cell redox state was pointed out by studying: (i) the major enzymatic activities of the defence antioxidant systems in cells grown under various hormonal conditions; (ii) the effects of oxidants and antioxidants on MIA production. A search for putative molecular markers of MIA production led to the characterisation of two cDNAs encoding geranyl diphosphate synthase and a CrPS protein belonging to [a]b hydroxylase superfamily, respectively. Studying the expression pattern (Northern blots) of CrPS gene in suspension cells, and the localisation of CrPS mRNA (in situ hybridisation) in developing leaves highly suggested a role of CrPS in the signal transduction pathway leading to MIA production.Nous avons étudié les mécanismes impliqués dans la régulation de la production des alcaloides indoliques monoterpéniques (MIA) par des substances de croissance dans des suspensions cellulaires (lignée C20D) de Pervenche de Madagascar (Catharanthus roseus). Dans ces cellules, la production de MIA est augmentée par la suppression du 2,4-D du milieu et stimulée par un traitement avec une cytokinine. L'importance de l'état rédox a été soulignée par l'étude : (i) des activités enzymatiques principales des systèmes de défense antioxydants dans des cellules sous diverses conditions hormonales; (ii) des effets des oxydants et antioxydants sur la production de MIA. Une recherche de possibles marqueurs moléculaires de la production des MIA a conduit à caractériser deux ADNc codant respectivement une géranyl diphosphate synthase et une protéine CrPS appartenant à la super-famille des [a]b hydroxylases. Des études portant sur le patron d'expression (par Northern blot) du gène CrPS dans des cellules in vitro et sur la localisation des ARNm CrPS (par hybridation in situ) dans des feuilles en développement suggèrent une implication de la protéine CrPS dans la signalisation conduisant à l'induction de la production de MIA.TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF

Voyage botanique dans la Touraine du XIXè siècle (les herborisations et l'herbier du pharmacien Ernest-Henri Tourlet)

TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF

Differential growth dependency of normal and habituated sugarbeet cell lines upon endogenous ethylene production and exogenous ethylene application

A fully habituated (auxin- and cytokinin-independent) nonorganogenic (HNO) sugarbeet (Beta vulgaris) callus produces very little ethylene as compared with a normal (N) hormone-requiring callus of the same strain. Both callus types react by growth changes to application of inhibitors of ethylene biosynthesis and ethylene action, of 1-aminocyclopropane-1-carboxylic acid (ACC) as the immediate precursor of ethylene, to transfer from light to darkness, and also to application of exogenous ethylene or an ethylene trapper. This indicates their growth dependency upon their endogenously biosynthesized ethylene and also their sensitivity to exogenous gas. However, the sensitivity was generally higher for the HNO callus producing naturally less ethylene. The weaker reaction of the HNO callus to the exogenous ethylene was attributed to its hyperhydric status (a water layer surrounding the cells). Because low ethylene production appears as a general characteristic of habituated cell lines, the causal and/or consequential relationships of this low ethylene production with other characteristics of habituated tissues (absence of exogenous hormones in the culture media, deficiency of cell differentiation, accumulation of polyamines in neoplastic tissues) are discussed

Autonomy to plant growth regulators and gene expression in periwinkle cultures in vitro

To better understand the effect of habituation on gene expression in plant cells, we have compared the accumulation of specific mRNAs encoding respectively two proline-rich proteins, a chaperone protein and three enzymes linking primary and secondary metabolisms in two models of in vitro culture of periwinkle. These models consisted of two couples of a 2,4-dichlorophenoxyacetic acid-dependent/2,4-dichlorophenoxyacetic acid independent line in which autonomy to auxin and cytokinin was obtained either through habituation or through transformation with the isopentenyltransferase gene from Agrobacterium tumefaciens. Results showed that gene expression was modified by plant growth regulator autonomy but differently according to the type of autonomy: only the gene encoding a hydroxyproline-rich glycoprotein was regulated similarly in both PGR-independent lines. On the other hand, PGR autonomy did not lead to total insensitivity to exogenously-applied PGRs, and the two PGR autonomous lines did not accumulate indole alkaloids for different reasons

Cytokinins and ethylene stimulate indole alkaloid accumulation in cell suspension cultures of Catharanthus roseus by two distinct mechanisms

peer reviewedThe interactions between cytokinins and ethylene on alkaloid accumulation in a periwinkle cell line have been examined. It was found that (a) either exogenously-applied cytokinins or ethylene (the latter through ethephon degradation) greatly enhanced ajmalicine accumulation in cells subcultured in a 2,4-dichlorophenoxyacetic acid-free medium; (b) the enhancing effect of cytokinin was not mediated by enhancement of endogenous ethylene production contrary to what is found in some plant models, (c) the responses to exogenous cytokinin and ethylene were additive and showed a different pattern of expression. It may be concluded that cytokinin and ethylene can up-regulate the alkaloid production in a periwinkle cells through independent pathways when added exogenously to the cultures. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved