Éditeur(s) : HAL CCSD American Chemical Society
Résumé : International audience
Constitutive activation of the PI3K/mTOR signaling pathway contributes to carcinogenesis and metastasis in most, if not all, breast cancers. From a chromene backbone reported to inhibit class I PI3K catalytic subunits, several rounds of chemical syntheses led to the generation of a new collection of chromologues that showed enhanced ability to kill PI3K-addicted cancer cells and to inhibit Akt phosphorylation at serine 473, a hallmark of PI3K/mTOR activation. This initial screen uncovered a chromene designated DHM25 that exerted potent antitumor activity against breast tumor cell lines. Strikingly, DHM25 was shown to be a selective and covalent inhibitor of mTOR using biochemical and cellular analyses, modeling, and a large panel of kinase activity assays spanning the human kinome (243 kinases). Finally, in vivo, this novel drug was an efficient inhibitor of growth and metastasis of triple-negative breast cancer cells, paving the way for its clinical application in oncology
ISSN: 0022-2623

hal-01187307
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01187307
DOI : 10.1021/acs.jmedchem.5b00991
PUBMED : 26237138

Éditeur(s) : HAL CCSD
Résumé : International audience
Conférence MISTRALS PAELOMEX
Montpellier, France

hal-01683548
https://hal-univ-tlse2.archives-ouvertes.fr/hal-01683548

Éditeur(s) : HAL CCSD
Résumé : Shoreline and upper beach dynamics under extreme events: the KUNSHEN experiment (Wan Tzu Liao barrier, Taiwan)
PARALIA génie civil & génie côtier

hal-00861950
https://hal.archives-ouvertes.fr/hal-00861950

Éditeur(s) : HAL CCSD
Résumé : LPSC14037
Scientific data collected with modern sensors or dedicated detectors exceed very often the perimeter of the initial scientific design. These data are obtained more and more frequently with large material and human efforts. A large class of scientific experiments are in fact unique because of their large scale, with very small chances to be repeated and to superseded by new experiments in the same domain: for instance high energy physics and astrophysics experiments involve multi-annual developments and a simple duplication of efforts in order to reproduce old data is simply not affordable. Other scientific experiments are in fact unique by nature: earth science, medical sciences etc. since the collected data is "time-stamped" and thereby non-reproducible by new experiments or observations. In addition, scientific data collection increased dramatically in the recent years, participating to the so-called "data deluge" and inviting for common reflection in the context of "big data" investigations. The new knowledge obtained using these data should be preserved long term such that the access and the re-use are made possible and lead to an enhancement of the initial investment. Data observatories, based on open access policies and coupled with multi-disciplinary techniques for indexing and mining may lead to truly new paradigms in science. It is therefore of outmost importance to pursue a coherent and vigorous approach to preserve the scientific data at long term. The preservation remains nevertheless a challenge due to the complexity of the data structure, the fragility of the custom-made software environments as well as the lack of rigorous approaches in workflows and algorithms. To address this challenge, the PREDON project has been initiated in France in 2012 within the MASTODONS program: a Big Data scientific challenge, initiated and supported by the Interdisciplinary Mission of the National Centre for Scientific Research (CNRS). PREDON is a study group formed by researchers from different disciplines and institutes. Several meetings and workshops lead to a rich exchange in ideas, paradigms and methods. The present document includes contributions of the participants to the PREDON Study Group, as well as invited papers, related to the scientific case, methodology and technology. This document should be read as a "facts finding" resource pointing to a concrete and significant scientific interest for long term research data preservation, as well as to cutting edge methods and technologies to achieve this goal. A sustained, coherent and long term action in the area of scientific data preservation would be highly beneficial.
http://hal.in2p3.fr/in2p3-00959072

in2p3-00959072
http://hal.in2p3.fr/in2p3-00959072
http://hal.in2p3.fr/in2p3-00959072/document
http://hal.in2p3.fr/in2p3-00959072/file/PREDON_Scientific_Data_Preservation_2014.pdf

Éditeur(s) : HAL CCSD American Society for Microbiology
Résumé : International audience
Human leishmaniasis are widely spread diseases with different clinical forms caused by about 20 species within the Leishmania genus. Leishmania species identification is relevant for therapeutic management and prognosis, especially for cutaneous and muco-cutaneous forms. Several methods are available to identify Leishmania species from culture, but they have not been standardized for the majority of the currently described species, with the exception of MultiLocus Enzyme Electrophoresis. Moreover, these techniques are expensive, time-consuming and not available in all laboratories. Within the last decade, mass spectrometry (MS) has been adapted for microorganism identification, including Leishmania However, no commercial reference mass spectral database is available. In this study, a reference mass spectral library (MSL) for Leishmania isolates, accessible through a free web-based application (mass spectral identification, MSI), was constructed and tested. It includes mass spectral data for 33 different Leishmania species, including species that infect humans, animals and phlebotomine vectors. Four laboratories on two continents evaluated MSI performance using 268 samples of which 231 were Leishmania strains. All Leishmania strains, but one, were correctly identified at least at the complex level. A risk of species misidentification within the L. donovani, L. guyanensis and L. braziliensis complexes was observed, as already reported with other techniques. The tested application was reliable, with identification results comparable to those obtained with reference methods, but with a more favorable cost-efficiency ratio. This free online identification system relies on a scalable database and can be implemented directly in the user's computers.
ISSN: 0095-1137

hal-01571305
https://hal.archives-ouvertes.fr/hal-01571305
DOI : 10.1128/JCM.00845-17
PUBMED : 28724559

Éditeur(s) : HAL CCSD
Résumé : International audience
This paper shows how the notion of “local site of a question” helps the teacher to get into this question in order to teach it. We discuss the relationship between the description of what has to be deeply known to answer the difficulties or the obstacles which arise for the pupils during the study of a question, and what Shulman, and his successors, model under the name of pedagogical content knowledge. A survey, conducted among current French teachers, shows how they are powerless when facing the difficulties of their pupils and a study of some old teaching books shows how this problem was addressed in former teaching practices. Based on these results, we open the discussion of the training of the teachers.
L’article montre l’usage possible de la notion de « site local d’une question » dans le travail du professeur se préparant à enseigner cette question. On discute à cette occasion les proximités entre la description de ce qu’il y a à savoir profondément, pour répondre aux difficultés ou obstacles que rencontreront les élèves au cours de l’étude d’une question, et ce que Shulman et ses successeurs modélisent sous le terme de « pedagogical content knowledge ». Une enquête auprès de professeurs actuels montre comment ils sont démunis face aux difficultés des élèves, et une enquête dans des ouvrages d’enseignement anciens montre comment le problème soulevé a été traité en pratique par l’enseignement traditionnel. L’article discute alors le problème de la formation que les professeurs seraient en droit d’attendre.
Education & Didactique

hal-01530862
https://hal.univ-antilles.fr/hal-01530862

Éditeur(s) : HAL CCSD Coastal Education and Research Foundation (CERF) Coastal Education and Research Foundation
Résumé : International audience
Current profiles
ISSN: 0749-0208

hal-01122783
https://hal.archives-ouvertes.fr/hal-01122783

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
BACKGROUND: The RH blood group system has many RHCE variant alleles that have arisen through gene conversion or nucleotide changes. Two probands, with red blood cells (RBCs) that were D+C+E-c+(w) e+ were sent to our laboratories to resolve the weak c expression. STUDY DESIGN AND METHODS: Hemagglutination tests were performed by automated and manual procedures. Genomic DNA analysis was performed by sequencing of Exons 1 to 10 of RHCE and RHD. RESULTS: The probands' RBCs did not react with standard monoclonal anti-E reagents from Bio-Rad, Diagast, DiaMed, Immucor, Ortho, and Quotient. The RBCs reacted variably with anti-c reagents from Diagast, DiaMed, Immucor, or Ortho and did not react with the Quotient anti-c reagent. Surprisingly, sequencing results of RHCE showed the presence of C/G at Position 676 (E/e polymorphism) and the association of the E polymorphism with a 734T>C transition in Exon 5 of the RHCE, encoding a Leu245Pro amino acid substitution in the mature RhcE polypeptide. Replacement of leucine 245 by proline in the eighth transmembrane domain of the RhcE protein may have a steric effect on the protein such that most anti-E reagents do not bind and the interaction between anti-c and c antigen is also affected. CONCLUSION: We report a novel RHCE*cE allele, RHCE*cE734C, which was assigned the provisional ISBT allele name RHCE*cE.14 or RHCE*03.14. It was found in two probands whose RBCs had weakened c expression and typed E- with conventional anti-E reagents. These data, once again, highlight the fact that the genotype does not always reflect the phenotype.
ISSN: 0041-1132

hal-00839022
https://hal.archives-ouvertes.fr/hal-00839022
DOI : 10.1111/j.1537-2995.2012.03860.x
PUBMED : 22958092

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
ISSN: 0003-4975

hal-01563338
http://hal.univ-brest.fr/hal-01563338
DOI : 10.1016/j.athoracsur.2016.03.093
PUBMED : 27262916

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
The CoPanFlu-France cohort of households was set up in 2009 to study the risk factors for infection by the pandemic influenza virus (H1N1pdm) in the French general population. The authors developed an integrative data-driven approach to identify individual, collective and environmental factors associated with the post-seasonal serological H1N1pdm geometric mean titer, and derived a nested case-control analysis to identify risk factors for infection during the first season. This analysis included 1377 subjects (601 households). The GMT for the general population was 47.1 (95% confidence interval (CI): 45.1, 49.2). According to a multivariable analysis, pandemic vaccination, seasonal vaccination in 2009, recent history of influenza-like illness, asthma, chronic obstructive pulmonary disease, social contacts at school and use of public transports by the local population were associated with a higher GMT, whereas history of smoking was associated with a lower GMT. Additionally, young age at inclusion and risk perception of exposure to the virus at work were identified as possible risk factors, whereas presence of an air humidifier in the living room was a possible protective factor. These findings will be interpreted in light of the longitudinal analyses of this ongoing cohort.
ISSN: 1932-6203

Droits : http://creativecommons.org/licenses/by-sa/
hal-01122215
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122215
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122215/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122215/file/journal.pone.0060127.pdf
PUBMED : 23613718

Éditeur(s) : HAL CCSD Centers for Disease Control and Prevention
Résumé : International audience
ISSN: 1080-6040

hal-01447667
https://hal.archives-ouvertes.fr/hal-01447667
DOI : 10.3201/eid2210.160052

Éditeur(s) : HAL CCSD
Résumé : International audience
o abstract
34th International Conference on Coastal Engineering ICCE2014 in Seoul, Korea

hal-01426584
https://hal.archives-ouvertes.fr/hal-01426584

Éditeur(s) : HAL CCSD Taylor & Francis: SSH Journals
Résumé : International audience
We investigated the oxygen-conserving potential of the human diving response by comparing trained breath-hold divers (BHDs) to non-divers (NDs) during simulated dynamic breath-holding (BH). Changes in haemodynamics [heart rate (HR), stroke volume (SV), cardiac output (CO)] and peripheral muscle oxygenation [oxyhaemoglobin ([HbO2]), deoxyhaemoglobin ([HHb]), total haemoglobin ([tHb]), tissue saturation index (TSI)] and peripheral oxygen saturation (SpO2) were continuously recorded during simulated dynamic BH. BHDs showed a breaking point in HR kinetics at mid-BH immediately preceding a more pronounced drop in HR (−0.86 bpm.%−1) while HR kinetics in NDs steadily decreased throughout BH (−0.47 bpm.%−1). By contrast, SV remained unchanged during BH in both groups (all P > 0.05). Near-infrared spectroscopy (NIRS) results (mean ± SD) expressed as percentage changes from the initial values showed a lower [HHb] increase for BHDs than for NDs at the cessation of BH (+24.0 ± 10.1 vs. +39.2 ± 9.6%, respectively; P < 0.05). As a result, BHDs showed a [tHb] drop that NDs did not at the end of BH (−7.3 ± 3.2 vs. −3.0 ± 4.7%, respectively; P < 0.05). The most striking finding of the present study was that BHDs presented an increase in oxygen-conserving efficiency due to substantial shifts in both cardiac and peripheral haemodynamics during simulated BH. In addition, the kinetic-based approach we used provides further credence to the concept of an “oxygen-conserving breaking point” in the human diving response.
ISSN: 0264-0414

hal-01325466
https://hal-univ-perp.archives-ouvertes.fr/hal-01325466
DOI : 10.1080/02640414.2016.1183809

Éditeur(s) : HAL CCSD Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists
Résumé : International audience
Hepatic periportal fibrosis, which affects 5–10% of subjects infected by Schistosoma mansoni, is caused by the T cell-dependent granuloma that develop around schistosome eggs. Experimental models of infection have shown that granuloma and fibrosis are tightly regulated by cytokines. However, it is unknown why advanced periportal fibrosis occurs only in certain subjects. The goal of the present study was to evaluate the cytokine response of S. mansoni-infected subjects with advanced liver disease in an attempt to relate susceptibility to periportal fibrosis with an abnormal production of cytokines that regulate granuloma and fibrosis. Fibrosis was evaluated by ultrasound on 795 inhabitants of a Sudanese village in which S. mansoni is endemic: advanced periportal fibrosis was observed in 12% of the population; 35% of the affected subjects exhibited signs of portal hypertension. Age (odds ratio (OR), 11.5), gender (OR, 4.2), and infection levels (OR, 2.2) were significantly (p < 0.01) associated with hepatic fibrosis. Cytokines produced by egg-stimulated blood mononuclear cells from 99 subjects were measured (75 with no or mild fibrosis; 24 subjects with advanced fibrosis). Multivariate analysis of cytokine levels showed that high IFN-γ levels were associated with a marked reduction of the risk of fibrosis (p = ‫OR, 0.1); in contrast, high TNF-α levels were associated with an increased risk (p = 0.05; OR, 4.6) of periportal fibrosis. Moreover, infection levels were negatively associated with IFN-γ production. These results with observations in experimental models strongly suggest that IFN-γ plays a key role in the protection of S. mansoni-infected patients against periportal fibrosis, whereas TNF-α may aggravate the disease.
ISSN: 0022-1767

Droits : http://creativecommons.org/licenses/by-nc-nd/
hal-01211587
https://hal.archives-ouvertes.fr/hal-01211587
https://hal.archives-ouvertes.fr/hal-01211587/document
https://hal.archives-ouvertes.fr/hal-01211587/file/929.full.pdf
DOI : 10.4049/jimmunol.169.2.929

Éditeur(s) : HAL CCSD Seismological Society of America
Résumé : With the assistance of the ASTER team (M. Arnold, G. Aumaître, D. Bourlès, and K. Keddadouche)
International audience
The Bulnay earthquake of 23 July 1905 (Mw 8.3–8.5), in north‐central Mongolia, is one of the world’s largest recorded intracontinental earthquakes and one of four great earthquakes that occurred in the region during the twentieth century. The 375 km long surface rupture of the left‐lateral, strike‐slip, N095°E‐trending Bulnay fault associated with this earthquake is remarkable for its pronounced expression across the landscape and for the size of features produced by previous earthquakes. Our field observations suggest that in many areas the width and geometry of the rupture zone is the result of repeated earthquakes; however, in those areas where it is possible to determine that the geomorphic features are the result of the 1905 surface rupture alone, the size of the features produced by this single earthquake are singular in comparison to most other historical strike‐slip surface ruptures worldwide. Along the 80 km stretch, between 97.18° E and 98.33° E, the fault zone is characterized by several meters width and the mean left‐lateral 1905 offset is 8.9±0.6  m with two measured cumulative offsets that are twice the 1905 slip. These observations suggest that the displacement produced during the penultimate event was similar to the 1905 slip. Morphotectonic analyses carried out at three sites along the eastern part of the Bulnay fault allow us to estimate a mean horizontal slip rate of 3.1±1.7  mm/yr over the Late Pleistocene–Holocene period. In parallel, paleoseismological investigations show evidence for two earthquakes prior to the 1905 event, with recurrence intervals of ∼2700–4000  yrs.
ISSN: 0037-1106

hal-01179837
https://hal.archives-ouvertes.fr/hal-01179837
https://hal.archives-ouvertes.fr/hal-01179837v2/document
https://hal.archives-ouvertes.fr/hal-01179837/file/rizza2015.pdf
DOI : 10.1785/0120140119

Éditeur(s) : HAL CCSD Microbiology Society
Résumé : International audience
An actinobacterial strain, designated ViU22(T), was isolated from a natural uranium-rich soil and was studied using a polyphasic approach. Cells formed orange-pigmented colonies, were rod-shaped, Gram-positive (non-staining method), non-motile and non-spore-forming. This organism grew in 0-4.5 % (w/v) NaCl and at 15-37 °C, with optimal growth occurring in 0.5 % (w/v) NaCl and at 30 °C. Comparative 16S rRNA gene sequence analysis revealed that the strain ViU22(T) belonged to the genus Microbacterium. It exhibited highest 16S rRNA gene sequence similarity with the type strains of Microbacterium testaceum (98.14 %) and Microbacterium binotii (98.02 %). The DNA-DNA relatedness of strains ViU22(T) with the most closely related type strains Microbacterium testaceum and Microbacterium binotii DSM 19164(T) was 20.10 % (± 0.70) and 28.05 % (± 0.35), respectively. Strain ViU22(T) possessed a type B2β peptidoglycan with partial substitution of glutamic acid by 3-hydroxy glutamic acid. The major menaquinones were MK-11 and MK-12. Major polar lipids detected in the strain ViU22(T) were diphosphatidylglycerol, phosphatidylglycerol, an unknown phospholipid and unknown glycolipids. The predominant fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0, a pattern reported for other Microbacterium species. The major cell-wall sugars were galactose, xylose and mannose and the DNA G+C content was 71 mol%. Together, the DNA-DNA hybridization results and the differentiating phenotypic characteristics, showed that strain ViU22(T) should be classified as the type strain of a novel species within the genus Microbacterium, for which the name Microbacterium lemovicicum sp. nov. is proposed. The type strain is ViU22(T) ( = ATCC BAA-2396(T) = CCUG 62198(T) = DSM 25044(T)).
ISSN: 1466-5026

hal-01561095
https://hal-amu.archives-ouvertes.fr/hal-01561095
PUBMED : 23264499
DOI : 10.1099/ijs.0.048454-0

Éditeur(s) : HAL CCSD Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists
Résumé : International audience
Schistosome infection is a major public health concern affecting millions of people living in tropical regions of Africa, Asia, and South America. Schistosomes cause mild clinical symptoms in most subjects, whereas a small proportion of individuals presents severe clinical disease (as periportal fibrosis (PPF)) that may lead to death. Severe PPF results from an abnormal deposition of extracellular matrix proteins in the periportal spaces due to a chronic inflammation triggered by eggs and schistosome Ags. Extracellular matrix protein production is regulated by a number of cytokines, including IFN-gamma. We have now screened putative polymorphic sites within this gene in a population living in an endemic area for Schistosoma mansoni. Two polymorphisms located in the third intron of the IFN-gamma gene are associated with PPF. The IFN-gamma +2109 A/G polymorphism is associated with a higher risk for developing PPF, whereas the IFN-gamma +3810 G/A polymorphism is associated with less PPF. The polymorphisms result in changes in nuclear protein interactions with the intronic regions of the gene, suggesting that they may modify IFN-gamma mRNA expression. These results are consistent with the results of previous studies. Indeed, PPF is controlled by a major locus located on chromosome 6q22-q23, closely linked to the gene encoding the alpha-chain of the IFN-gamma receptor, and low IFN-gamma producers have been shown to have an increased risk of severe PPF. Together, these observations support the view that IFN-gamma expression and subsequent signal transduction play a critical role in the control of PPF in human hepatic schistosome infection (S. mansoni).
ISSN: 0022-1767

Droits : http://creativecommons.org/licenses/by-nc-nd/
hal-01211760
https://hal.archives-ouvertes.fr/hal-01211760
https://hal.archives-ouvertes.fr/hal-01211760/document
https://hal.archives-ouvertes.fr/hal-01211760/file/J%20Immunol-2003-Chevillard-5596-601.pdf
DOI : 10.4049/jimmunol.171.10.5596

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
In this paper we present a new local remeshing algorithm that is dedicated to the problem of erosion in finite element models whose grid follows the movement of the free surface. The method, which we name Surface Lagrangian Remeshing (SLR), is adapted to 2D Lagrangian models which couple surface erosion with deformation of Earth materials. The remeshing procedure preserves nodes defining the surface submitted to erosion and removes nodes belonging to surface elements whose internal angles or area is critically low. This algorithm is ideally suited to track long term surface evolution. To validate the method we perform a set of numerical tests, using triangular finite elements, which compare the results obtained with the SLR algorithm with global remeshing and with analytical results. The results show good agreements with analytical solutions. Interpolation errors associated with remeshing are generated locally and numerical diffusion is restricted to the remeshed domain itself. In addition this method is computationally costless compared to classical global remeshing algorithm. We propose to couple the SLR method with the Dynamical Lagrangian Remeshing (DLR) algorithm to enable local remeshing only of Lagrangian models coupling large deformation of Earth materials with large erosion.
ISSN: 0098-3004

hal-00639472
https://hal.archives-ouvertes.fr/hal-00639472
DOI : 10.1016/j.cageo.2010.05.023

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
ISSN: 1752-0894

hal-01667978
https://hal.archives-ouvertes.fr/hal-01667978
DOI : 10.1038/s41561-017-0028-x

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Evidence of a changing environment in the catchment area of a small pond (Lansquenet, Lorraine, France) during the last millennium was provided by coupling palynology data and organic ratios [terrestrial to aquatic ratio: TAR(HC); the C29 vs. C27 sterols, C29/C27(ST); average chain length, ACL and aquatic/macrophytes ratio, Paq]. The depositional and alteration conditions of organic matter (OM) were provided by the 5α(H)-stanols/Δ5-sterols ratio. This study shows that quite simple organic ratios clearly allow identification of the different evolution steps of a watershed, from a swamp to the progressive settlement of a pond. During the swampy period, the C/N(at) (ca. 11.1), TAR(HC) (ca. 36.8), C29/C27(ST) (ca. 8.7) and Paq (<0.3) show a high contribution of allochthonous OM associated with the presence of particular aquatic and mesohygrophilous species. A woody level dated to the XIIIth century reflects the period of the settlement of the pond in a more oxic environment [5α(H)-stanol/Δ5sterol ratio <0.2]. Then, the progressive increase in aquatic input and the development of submerged and floating macrophytes are evidenced by low C/N(at) (<7.6), TAR(HC) (ca. 2.7), C29/C27(ST) (ca. 2) and high Paq (ca. 0.5), suggesting an increase in the water level and eutrophication of the pond. A second oxic event [5α(H)-stanols/Δ5sterols ratio averaging 0.16], associated with extensive OM degradation, corresponds to the most recent dredging in 2002 and reflects an important disturbance of sediments due to pond management.
ISSN: 0146-6380

hal-00758066
https://hal.archives-ouvertes.fr/hal-00758066
DOI : 10.1016/j.orggeochem.2012.06.004