On micromechanical damage modeling in geomechanics: influence of numerical integration scheme

Tunnel excavations in deep rocks provide stress perturbations which initiate diffuse and/or localized damage propagation in the material. This damage phenomenon can lead to significant irreversible deformations and changes in rock properties. In this paper, we propose to model such behavior by considering a micromechanically-based damage approach. The resulting micromechanical model, which also accounts for initial stress, is described and assessed through the numerical analysis of a synthetic tunnel drilling in Opalinus Clay. A particular emphasis is put on the numerical integration of the model. In particular, an appropriate choice of the latter is required to ensure the numerical stability and a confident prediction of excavation damaged zone around tunnels

A two scale anisotropic damage model accounting for initial stresses in microcracked materials

In a recent study [15], we proposed a class of isotropic damage models which account for initial stresses. The present paper extends this approach to anisotropic damage due to growth of an arbitrarily penny-shaped microcracks system. The basic principle of the upscaling technique in the presence of initial stress is first recalled. Then, we derive a closed-form expression of the elastic energy potential corresponding to a system of arbitrarily oriented microcracks. It is shown that the coupling between initial stresses and damage is strongly dependent of the microcracks density and orientation. Predictions of the proposed model are illustrated through the investigation of the influence of initial stresses on the material response under non monotonous loading paths. Finally, by considering a particular distribution ofmicrocracks orientation, described by a second order damage tensor, it is shown that the model is a generalization of the macroscopic damage model of Halm and Dragon [9], for which a physically-based interpretation is then proposed

Conserved Usage of Alternative 5′ Untranslated Exons of the GATA4 Gene

BACKGROUND:GATA4 is an essential transcription factor required for the development and function of multiple organs. Despite this important role, our knowledge of how the GATA4 gene is regulated remains limited. To better understand this regulation, we characterized the 5' region of the mouse, rat, and human GATA4 genes. METHODOLOGY/PRINCIPAL FINDINGS:Using 5' RACE, we identified novel transcription start sites in all three species. GATA4 is expressed as multiple transcripts with varying 5' ends encoded by alternative untranslated first exons. Two of these non-coding first exons are conserved between species: exon 1a located 3.5 kb upstream of the GATA4 ATG site in exon 2, and a second first exon (exon 1b) located 28 kb further upstream. Expression of both mRNA variants was found in all GATA4-expressing organs but with a preference for the exon 1a-containing transcript. The exception was the testis where exon 1a- and 1b-containing transcripts were similarly expressed. In some tissues such as the intestine, alternative transcript expression appears to be regionally regulated. Polysome analysis suggests that both mRNA variants contribute to GATA4 protein synthesis. CONCLUSIONS/SIGNIFICANCE:Taken together, our results indicate that the GATA4 gene closely resembles the other GATA family members in terms of gene structure where alternative first exon usage appears to be an important mechanism for regulating its tissue- and cell-specific expression

Investigation of the function of delta-cadinene synthase with aza-analogues and site directedmutagenesis

Terpenes are one of the most structurally varied families of natural products with extraordinary chemical properties that have been exploited for numerous applications. Sesquiterpene synthases are a family of metal-dependent enzymes that catalyse the cyclisation of farnesyl diphosphate (FDP) into a myriad of complex C15-isoprenoid hydrocarbons, the sesquiterpenes. δ-Cadinene synthase (DCS) from Gossypium arboreum (cotton tree) catalyses the formation of δ-cadinene (DCN), a bicyclic intermediate in the biosynthesis of important phytoalexins such us gossypol. Two mechanistic proposals have been made for the formation of δ-cadinene: a 1,10-ring closure mechanism leading to the key intermediate germacradienyl cation, or a 1,6-ring closure leading to thealpha-bisabolyl carbocation. Previous investigation with fluorinated FDP analogues were in partial agreement with both scenarios and hence it was not possible to distinguish unambiguously between the two possible cyclisation reactions. To investigate the catalytic mechanism of DCS, enantiopure samples of the azaanalogues of alpha-bisabolyl cation and germacradienyl cation were needed. These compounds are designed as stable structural and electrostatic mimics of the putative short-lived carbocationic intermediates generated by terpene synthases, and hence often act as potent reversible competitive inhibitors (low Ki) of these enzymes. Here, the enantioselective total synthesis of R- and S- aza-analogues of the alpha-bisabolyl cation are described as well as the partial racemic synthesis of azagermacradienyl cation. Both enantiomers of aza-bisabolyl cation were goodmimics of α-bisabolene. They were competitive inhibitors of DCS, providing evidence for a 1,6-cyclisation closure. The second part of the project involved the investigation of the role of tryptophan 279 for the desolvation of the active site of DCS and therefore for the formation of DCN. Seven mutants of W279 were created. The data obtained showed that W279 is essential to prevent water from entering the active site and form the hydroxylate terpenoid germacradien-4-ol (GD4ol). Mutagenesis studies yielded a mutant, W279A, capable of making GD4ol as the sole product

Possible Effects of Volcanic Eruptions on the Modern Atmosphere of Venus

This work reviews possible signatures and potential detectability of present-day volcanically emitted material in the atmosphere of Venus. We first discuss the expected composition of volcanic gases at present time, addressing how this is related to mantle composition and atmospheric pressure. Sulfur dioxide, often used as a marker of volcanic activity in Earth’s atmosphere, has been observed since late 1970s to exhibit variability at the Venus’ cloud tops at time scales from hours to decades; however, this variability may be associated with solely atmospheric processes. Water vapor is identified as a particularly valuable tracer for volcanic plumes because it can be mapped from orbit at three different tropospheric altitude ranges, and because of its apparent low background variability. We note that volcanic gas plumes could be either enhanced or depleted in water vapor compared to the background atmosphere, depending on magmatic volatile composition. Non-gaseous components of volcanic plumes, such as ash grains and/or cloud aerosol particles, are another investigation target of orbital and in situ measurements. We discuss expectations of in situ and remote measurements of volcanic plumes in the atmosphere with particular focus on the upcoming DAVINCI, EnVision and VERITAS missions, as well as possible future missions

Cannabis and benzodiazepines as determinants of methadone trough plasma concentration variability in maintenance treatment: a transnational study

Purpose: To assess tobacco, alcohol, cannabis and benzodiazepine use in methadone maintenance treatment (MMT) as potential sources of variability in methadone pharmacokinetics. Methods: Trough plasma (R)- and (S)-methadone concentrations were measured on 77 Australian and 74 Swiss MMT patients with no additional medications other than benzodiazepines. Simple and multiple regression analyses were performed for the primary metric, plasma methadone concentration/dose. Results: Cannabis and methadone dose were significantly associated with lower 24-h plasma (R)- and (S)-methadone concentrations/dose. The models containing these variables explained 14-16% and 17-25% of the variation in (R)- and (S)-methadone concentration/dose, respectively. Analysis of 61 patients using only CYP3A4 metabolised benzodiazepines showed this class to be associated with higher (R)-concentration/dose, which is consistent with a potential competitive inhibition of CYP3A4. Conclusion: Cannabis use and higher methadone doses in MMT could in part be a response to—or a cause of—more rapid methadone clearance. The effects of cannabis and benzodiazepines should be controlled for in future studies on methadone pharmacokinetics in MM

Arabidopsis TFL2/LHP1 Specifically Associates with Genes Marked by Trimethylation of Histone H3 Lysine 27

TERMINAL FLOWER 2/LIKE HETEROCHROMATIN PROTEIN 1 (TFL2/LHP1) is the only Arabidopsis protein with overall sequence similarity to the HETEROCHROMATIN PROTEIN 1 (HP1) family of metazoans and S. pombe. TFL2/LHP1 represses transcription of numerous genes, including the flowering-time genes FLOWERING LOCUS T (FT) and FLOWERING LOCUS C (FLC), as well as the floral organ identity genes AGAMOUS (AG) and APETALA 3 (AP3). These genes are also regulated by proteins of the Polycomb repressive complex 2 (PRC2), and it has been proposed that TFL2/LHP1 represents a potential stabilizing factor of PRC2 activity. Here we show by chromatin immunoprecipitation and hybridization to an Arabidopsis Chromosome 4 tiling array (ChIP-chip) that TFL2/LHP1 associates with hundreds of small domains, almost all of which correspond to genes located within euchromatin. We investigated the chromatin marks to which TFL2/LHP1 binds and show that, in vitro, TFL2/LHP1 binds to histone H3 di- or tri-methylated at lysine 9 (H3K9me2 or H3K9me3), the marks recognized by HP1, and to histone H3 trimethylated at lysine 27 (H3K27me3), the mark deposited by PRC2. However, in vivo TFL2/LHP1 association with chromatin occurs almost exclusively and co-extensively with domains marked by H3K27me3, but not H3K9me2 or -3. Moreover, the distribution of H3K27me3 is unaffected in lhp1 mutant plants, indicating that unlike PRC2 components, TFL2/LHP1 is not involved in the deposition of this mark. Rather, our data suggest that TFL2/LHP1 recognizes specifically H3K27me3 in vivo as part of a mechanism that represses the expression of many genes targeted by PRC2

Detecting Venus’ volcanic gas plumes with VenSpec-H

International audienceThe VenSpec-H instrument is part of the EnVision payload which is currently being evaluated by ESA for mission selection. EnVision is a medium class mission to determine the nature and current state of geological activity on Venus, and its relationship with the atmosphere, to understand how Venus and Earth could have evolved so differently. VenSpec-H is part of the VenSpec suite [1], including also an IR mapper and a UV spectrometer [2] suite. The science objectives of this suite are to search for temporal variations in surface temperatures and tropospheric concentrations of volcanically emitted gases, indicative of volcanic eruptions; and study surface-atmosphere interactions and weathering by mapping surface emissivity and tropospheric gas abundances. Recent and perhaps ongoing volcanic activity has been inferred in data from both Venus Express an