Strasbourg, France
Strasbourg, France

The University of Strasbourg in Strasbourg, Alsace, France, is the second largest university in France , with about 43,000 students and over 4,000 researchers. The present-day French university traces its history to the earlier German language Universität Straßburg, which was founded in 1538, and was divided in the 1970s into three separate institutions: Louis Pasteur University, Marc Bloch University, and Robert Schuman University. On 1 January 2009, the fusion of these three universities reconstituted a united University of Strasbourg, which is now amongst Europe's best in the League of European Research Universities. Wikipedia.

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University of Strasbourg and French National Center for Scientific Research | Date: 2015-05-18

The subject matter of the present invention concerns the preparation of a coated solid surface wherein the coating contains at least one in-plane oriented layer of anisotropic shaped objects through a specific spraying method, and the device enabling this method.

University of Strasbourg, French National Center for Scientific Research and French Atomic Energy Commission | Date: 2015-05-15

The present invention relates to a process for the preparation of a first compound of interest C1 functionalized with a sydnone compound and to the corresponding functionalized C1 compound of interest. The present invention also relates to a process for the preparation of a conjugate of two compounds of interest C1 and C2 implying a sydnone compound and to the obtained conjugate. The present invention also relates to a process for preparing a compound of interest C2 comprising a strained alkyne moiety functionalized with a sydnone and to the corresponding functionalized compound of interest C2. It also relates to novel sydnone compounds substituted in position 4, which may be used in the above processes.

Pompon J.,University of Strasbourg | Pompon J.,National University of Singapore | Levashina E.A.,University of Strasbourg | Levashina E.A.,Max Planck Institute for Infection Biology
PLoS Biology | Year: 2015

Thioester-containing protein 1 (TEP1) is a key immune factor that determines mosquito resistance to a wide range of pathogens, including malaria parasites. Here we report a new allele-specific function of TEP1 in male fertility. We demonstrate that during spermatogenesis TEP1 binds to and removes damaged cells through the same complement-like cascade that kills malaria parasites in the mosquito midgut. Further, higher fertility rates are mediated by an allele that renders the mosquito susceptible to Plasmodium. By elucidating the molecular and genetic mechanisms underlying TEP1 function in spermatogenesis, our study suggests that pleiotropic antagonism between reproduction and immunity may shape resistance of mosquito populations to malaria parasites. © 2015 Pompon, Levashina.

Le May N.,University of Strasbourg | Iltis I.,University of Strasbourg | Ame J.-C.,CNRS Biotechnology and Cell Signaling Laboratory | Zhovmer A.,University of Strasbourg | And 4 more authors.
Molecular Cell | Year: 2012

Poly-(ADP-ribose) glycohydrolase (PARG) is a catabolic enzyme that cleaves ADP-ribose polymers synthesized by poly-(ADP-ribose) polymerases. Here, transcriptome profiling and differentiation assay revealed a requirement of PARG for retinoic acid receptor (RAR)-mediated transcription. Mechanistically, PARG accumulates early at promoters of RAR-responsive genes upon retinoic acid treatment to promote the formation of an appropriate chromatin environment suitable for transcription. Silencing of PARG or knockout of its enzymatic activity maintains the H3K9me2 mark at the promoter of the RAR-dependent genes, leading to the absence of preinitiation complex formation. In the absence of PARG, we found that the H3K9 demethylase KDM4D/JMJD2D became PARsylated. Mutation of two glutamic acids located in the Jumonji N domain of KDM4D inhibited PARsylation. PARG becomes dispensable for ligand-dependent transcription when either a PARP inhibitor or a non-PARsylable KDM4D/JMJD2D mutant is used. Our results define PARG as a coactivator regulating chromatin remodeling during RA-dependent gene expression. © 2012 Elsevier Inc.

Wright J.E.,Friedrich Miescher Institute for Biomedical Research | Gaidatzis D.,Friedrich Miescher Institute for Biomedical Research | Senften M.,Friedrich Miescher Institute for Biomedical Research | Farley B.M.,University of Massachusetts Medical School | And 3 more authors.
EMBO Journal | Year: 2011

RNA-binding proteins (RBPs) are critical regulators of gene expression. To understand and predict the outcome of RBP-mediated regulation a comprehensive analysis of their interaction with RNA is necessary. The signal transduction and activation of RNA (STAR) family of RBPs includes developmental regulators and tumour suppressors such as Caenorhabditis elegans GLD-1, which is a key regulator of germ cell development. To obtain a comprehensive picture of GLD-1 interactions with the transcriptome, we identified GLD-1-associated mRNAs by RNA immunoprecipitation followed by microarray detection. Based on the computational analysis of these mRNAs we generated a predictive model, where GLD-1 association with mRNA is determined by the strength and number of 7-mer GLD-1-binding motifs (GBMs) within UTRs. We verified this quantitative model both in vitro, by competition GLD-1/GBM-binding experiments to determine relative affinity, and in vivo, by ĝ€̃ transplantationĝ €™ experiments, where ĝ€̃ weakĝ€™ and ĝ€̃ strongĝ€™ GBMs imposed translational repression of increasing strength on a non-target mRNA. This study demonstrates that transcriptome-wide identification of RBP mRNA targets combined with quantitative computational analysis can generate highly predictive models of post-transcriptional regulatory networks. © 2011 European Molecular Biology Organization | All Rights Reserved.

Burton A.,University of Strasbourg | Muller J.,Agency for Science, Technology and Research Singapore | Tu S.,Howard Hughes Medical Institute | Padilla-Longoria P.,National Autonomous University of Mexico | And 3 more authors.
Cell Reports | Year: 2013

Cell plasticity or potency is necessary for the formation of multiple cell types. The mechanisms underlying this plasticity are largely unknown. Preimplantation mouse embryos undergo drastic changes in cellular potency, starting with the totipotent zygote through to the formation of the pluripotent inner cell mass (ICM) and differentiated trophectoderm in the blastocyst. Here, we set out to identify and functionally characterize chromatin modifiers that define the transitions of potency and cell fate in the mouse embryo. Using a quantitative microfluidics approach in single cells, we show that developmental transitions are marked by distinctive combinatorial profiles of epigenetic modifiers. Pluripotent cells of the ICM are distinct from their differentiated trophectoderm counterparts. We show that PRDM14 is heterogeneously expressed in 4-cell-stage embryos. Forced expression of PRDM14 at the 2-cell stage leads to increased H3R26me2 and can induce a pluripotent ICM fate. Our results shed light on the epigenetic networks that govern cellular potency and identity invivo

Klosen P.,University of Strasbourg | Sebert M.-E.,University of Strasbourg | Rasri K.,Rangsit University | Laran-Chich M.-P.,University of Strasbourg | Simonneaux V.,University of Strasbourg
FASEB Journal | Year: 2013

In mammals, melatonin is the pivotal messenger synchronizing biological functions, notably reproductive activity, with annual daylength changes. Recently, two major findings clarified melatonin's mode of action. First, melatonin controls the production of thyroid stimulating hormone (TSH) by the pars tuberalis of the adenohypophysis. This TSH regulates local thyroid hormone availability in the mediobasal hypothalamus. Second, the RF-amides kisspeptin and RFRP-3, recently discovered regulators of the gonadotropic axis, are involved in the melatonin control of reproduction. This study aims to establish a mechanistic link between the melatonin-driven TSH and the RF-amide control of reproduction. We treated short-day-adapted male Djungarian and Syrian hamsters with a chronic central infusion of TSH. In both hamster species, the central administration of 5 mIU/d TSH for 4 to 6 wk restored the summer phenotype of both testicular activity and kisspeptin and RFRP expression. Vehicle treated hamsters remain sexually inactive. Furthermore, the TSH treatment increased the body weight of lean short-day-adapted Djungarian hamsters and reduced hypothalamic somatostatin expression to the summer phenotype. In summary, our study demonstrates the pivotal role of melatonin-driven TSH for the seasonal regulation of reproduction and body weight, and uncovers the neuropeptides relaying this signal within the hypothalamus. © FASEB.

Kemp J.,University of Strasbourg | Despres O.,University of Strasbourg | Sellal F.,CMRR de Strasbourg Colmar | Dufour A.,University of Strasbourg
Ageing Research Reviews | Year: 2012

This paper reviews findings in three subcomponents of social cognition (i.e., Theory of Mind, facial emotion recognition, empathy) during ageing. Changes over time in social cognition were evaluated in normal ageing and in patients with various neurodegenerative pathologies, such as Alzheimer's disease, mild cognitive impairment, frontal and temporal variants of frontotemporal lobar degeneration and Parkinson's disease. Findings suggest a decline in social cognition with normal ageing, a decline that is at least partially independent of a more general cognitive or executive decline. The investigation of neurodegenerative pathologies showing specific deficits in Theory of Mind in relation to damage to specific cerebral regions led us to suggest a neural network involved in Theory of Mind processes, namely a fronto-subcortical loop linking the basal ganglia to the regions of the frontal lobes. © 2011 Elsevier B.V.

Masiero S.,University of Milan | Colombo L.,University of Milan | Colombo L.,CNR Institute of Biophysics | Grini P.E.,University of Oslo | And 2 more authors.
Plant Cell | Year: 2011

Based on their evolutionary origin, MADS box transcription factor genes have been divided into two classes, namely, type I and II. The plant-specific type II MIKC MADS box genes have been most intensively studied and shown to be key regulators of developmental processes, such as meristem identity, flowering time, and fruit and seed development. By contrast, very little is known about type I MADS domain transcription factors, and they have not attracted interest for a long time. A number of recent studies have now indicated a key regulatory role for type I MADS box factors in plant reproduction, in particular in specifying female gametophyte, embryo, and endosperm development. These analyses have also suggested that type I MADS box factors are decisive for setting reproductive boundaries between species. © American Society of Plant Biologists.

Bura T.,CNRS The Institute of Chemistry and Processes for Energy, Environment and Health | Leclerc N.,University of Strasbourg | Fall S.,University of Strasbourg | Leveque P.,University of Strasbourg | And 5 more authors.
Journal of the American Chemical Society | Year: 2012

Green-absorbing dipyrromethene dyes engineered from bis-vinyl-thienyl modules are planar molecules, exhibiting strong absorption in the 713-724 nm range and displaying comparable electron and hole mobilities in thin films (maximum value 1 × 10 -3 cm 2/(Vs)). Bulk heterojunction solar cells assembled with these dyes and a fullerene derivative (PC 61BM) at a low ratio give a power conversion efficiency as high as 4.7%, with short-circuit current values of 14.2 mA/cm 2, open-circuit voltage of 0.7 V, and a broad external quantum efficiency ranging from 350 to 920 nm with a maximum value of 60%. © 2012 American Chemical Society.

Bienayme O.,University of Strasbourg | Traven G.,University of Ljubljana
Astronomy and Astrophysics | Year: 2013

We determine approximate numerical integrals of motion of 2D symmetric Hamiltonian systems. We detail for a few gravitational potentials the conditions under which quasi-integrals are obtained as polynomial series. We show that each of these potentials has a wide range of regular orbits that are accurately modelled with a unique approximate integral of motion. © ESO 2013.

Drug-induced agranulocytosis (neutrophil count <0·5 × 109/l) is a rare haematological complication with an incidence of no more than 10 cases per million inhabitants per year in Europe. Over the past few years there has been a steady decline in mortality rate, (currently at <5%), which can be partly explained by earlier recognition and the improved clinical management of associated intercurrent infections that may lead to severe sepsis if left untreated. The true impact of the use of haematopoietic growth factors, such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), on the decreased mortality rate remains unknown. Yet, most studies show that these molecules, especially G-CSF, reduce the duration of agranulocytosis, antibiotic course and length of hospital stay. Their use is particularly recommended in patients with poor prognostic factors, such as a neutrophil count <0·1 × 109/l, age over 65 years, severe infection or multiple co-morbidities. In all cases, the drug responsible for causing the agranulocytosis must be discontinued and remain permanently contraindicated. The appropriate Medicines Regulatory Agency must also be notified of the adverse event. © 2010 Blackwell Publishing Ltd.

Minkina A.,University of Minnesota | Matson C.K.,University of Minnesota | Matson C.K.,Fred Hutchison Cancer Research Center | Lindeman R.E.,University of Minnesota | And 3 more authors.
Developmental Cell | Year: 2014

Mammalian sex determination initiates in the fetal gonad with specification of bipotential precursor cells into male Sertoli cells or female granulosa cells. This choice was long presumed to be irreversible, but genetic analysis in the mouse recently revealed that sexual fates must be maintained throughout life. Somatic cells in the testis or ovary, even in adults, can be induced to transdifferentiate to their opposite-sex equivalents by loss of a single transcription factor, DMRT1 in the testis or FOXL2 in the ovary. Here, we investigate what mechanism DMRT1 prevents from triggering transdifferentiation. We find that DMRT1 blocks testicular retinoic acid (RA) signaling from activating genes normally involved in female sex determination and ovarian development and show that inappropriate activation of these genes can drive sexual transdifferentiation. By preventing activation of potential feminizing genes, DMRT1 allows Sertoli cells to participate in RA signaling, which is essential for reproduction, without being sexually reprogrammed. © 2014 Elsevier Inc.

Ball V.,University of Strasbourg | Ball V.,French National Institute for Agricultural Research
Physical Chemistry Chemical Physics | Year: 2013

Polyelectrolyte multilayer films are a versatile surface functionalization method of solid-liquid interfaces and appear to be interesting reservoirs to load/release drugs and to act as permselective membranes. For the latter applications critical parameters are the porosity of the film and its Donnan potential. In this investigation the Donnan potential of PEI-(PGA-PAH) n (PEI, PGA and PAH stand for polyethyleneimine, poly-l-glutamic acid and polyallylamine) films will be determined as a function of the number of deposition steps and the concentration of the redox probe, hexacyanoferrate anions, for films made from 10 layer pairs. Complementarily, it will be shown that the retention of the redox probe in the films in the presence of 150 mM NaCl electrolyte depends on both the film thickness and the scan rates at which the electrochemical experiments are performed. © 2013 the Owner Societies.

Amstutz S.,University of Strasbourg | Novotny A.A.,Laboratorio Nacional Of Computacao Cientifica Lncc Mct | De Souza Neto E.A.,University of Swansea
Computer Methods in Applied Mechanics and Engineering | Year: 2012

An algorithm for topology optimization of elastic structures under plane stress subject to the Drucker-Prager stress constraint is presented. The algorithm is based on the use of the topological derivative of the associated objective functional in conjunction with a level-set representation of the structure domain. In this context, a penalty functional is proposed to enforce the point-wise stress constraint and a closed formula for its topological derivative is derived. The resulting algorithm is of remarkably simple computational implementation. It does not require post-processing procedures of any kind and features only a minimal number of user-defined algorithmic parameters. This is in sharp contrast with current procedures for topological structural optimization with local stress constraints. The effectiveness and efficiency of the algorithm presented here are demonstrated by means of numerical examples. The examples show, in particular, that it can easily handle structural optimization problems with underlying materials featuring strong asymmetry in their tensile and compressive yield strengths. © 2012 Elsevier B.V.

Udy D.B.,University of Oregon | Belcher S.,University of Oregon | Williams-Carrier R.,University of Oregon | Gualberto J.M.,University of Strasbourg | Barkan A.,University of Oregon
Plant Physiology | Year: 2012

Chloroplasts and other members of the plastid organelle family contain a small genome of bacterial ancestry. Young chloroplasts contain hundreds of genome copies, but the functional significance of this high genome copy number has been unclear. We describe molecular phenotypes associated with mutations in a nuclear gene in maize (Zea mays), white2 (w2), encoding a predicted organellar DNA polymerase. Weak and strong mutant alleles cause a moderate (approximately 5-fold) and severe (approximately 100-fold) decrease in plastid DNA copy number, respectively, as assayed by quantitative PCR and Southern-blot hybridization of leaf DNA. Both alleles condition a decrease in most chloroplast RNAs, with the magnitude of the RNA deficiencies roughly paralleling that of the DNA deficiency. However, some RNAs are more sensitive to a decrease in genome copy number than others. The rpoB messenger RNA (mRNA) exhibited a unique response, accumulating to dramatically elevated levels in response to a moderate reduction in plastid DNA. Subunits of photosynthetic enzyme complexes were reduced more severely than were plastid mRNAs, possibly because of impaired translation resulting from limiting ribosomal RNA, transfer RNA, and ribosomal proteinmRNA. These results indicate that chloroplast genome copy number is a limiting factor for the expression of a subset of chloroplast genes in maize.Whereas in Arabidopsis (Arabidopsis thaliana) a pair of orthologous genes function redundantly to catalyze DNA replication in both mitochondria and chloroplasts, the w2 gene is responsible for virtually all chloroplast DNA replication in maize. Mitochondrial DNA copy number was reduced approximately 2-fold in mutants harboring strong w2 alleles, suggesting that w2 also contributes to mitochondrial DNA replication. © 2012 American Society of Plant Biologists.

Robert I.,University of Strasbourg | Karicheva O.,CNRS Biotechnology and Cell Signaling Laboratory | Reina San Martin B.,University of Strasbourg | Schreiber V.,CNRS Biotechnology and Cell Signaling Laboratory | Dantzer F.,CNRS Biotechnology and Cell Signaling Laboratory
Molecular Aspects of Medicine | Year: 2013

To cope with the devastating insults constantly inflicted to their genome by intrinsic and extrinsic DNA damaging sources, cells have evolved a sophisticated network of interconnected DNA caretaking mechanisms that will detect, signal and repair the lesions. Among the underlying molecular mechanisms that regulate these events, PARylation catalyzed by Poly(ADP-ribose) polymerases (PARPs), appears as one of the earliest post-translational modification at the site of the lesion that is known to elicit recruitment and regulation of many DNA damage response proteins. In this review we discuss how the complex PAR molecule operates in stress-induced DNA damage signaling and genome maintenance but also in various physiological settings initiated by developmentally programmed DNA breakage. To illustrate the latter, particular emphasis will be placed on the emerging contribution of PARPs to B cell receptor assembly and diversification. © 2013 Elsevier Ltd. All rights reserved.

Sondergaard T.,University of Aalborg | Bozhevolnyi S.I.,University of Southern Denmark | Novikov S.M.,University of Southern Denmark | Beermann J.,University of Southern Denmark | And 2 more authors.
Nano Letters | Year: 2010

We demonstrate that the phenomenon of extraordinary optical transmission (EOT) through perforated metal films can be further boosted up by utilizing nanofocusing of radiation in tapered slits. For one-dimensional arrays of tapered slits in optically thick suspended gold films, we show that the maximum transmission at resonance is achieved for taper angles in the range of 7-10° increasing significantly in comparison with the transmission by straight slits. Transmission spectroscopy of fabricated 500 and 700 nm period tapered slits in a 180 nm thick gold film on a glass substrate demonstrates the enhanced EOT with the resonance transmission being as high as ∼0.18 for the filling ratio of ∼0.13 and showing good correspondence with theoretical results. It is also shown that the enhanced transmission can be achieved with either weak (2.5%) or strong (43%) reflection depending on the direction of light (normal) incidence. © 2010 American Chemical Society.

Fimmel E.,Mannheim University of Applied Sciences | Michel C.J.,University of Strasbourg | Strungmann L.,Mannheim University of Applied Sciences
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2016

The circular code theory proposes that genes are constituted of two trinucleotide codes: the classical genetic code with 61 trinucleotides for coding the 20 amino acids (except the three stop codons {TAA, TAG,TGA}) and a circular code based on 20 trinucleotides for retrieving, maintaining and synchronizing the reading frame. It relies on two main results: the identification of a maximal C3 self-complementary trinucleotide circular code X in genes of bacteria, eukaryotes, plasmids and viruses (Michel 2015 J. Theor. Biol. 380, 156-177. (doi:10.1016/j.jtbi.2015.04.009); Arquès &Michel 1996 J. Theor. Biol. 182, 45-58. (doi:10.1006/jtbi.1996.0142)) and the finding of X circular code motifs in tRNAs and rRNAs, in particular in the ribosome decoding centre (Michel 2012 Comput. Biol. Chem. 37, 24-37. (doi:10.1016/j.compbiolchem.2011.10.002); El Soufi &Michel 2014 Comput. Biol. Chem. 52, 9-17. (doi:10.1016/j.compbiolchem.2014.08.001)). The univerally conserved nucleotides A1492 and A1493 and the conserved nucleotide G530 are included in X circular code motifs. Recently, dinucleotide circular codes were also investigated (Michel &Pirillo 2013 ISRN Biomath. 2013, 538631. (doi:10.1155/2013/538631); Fimmel et al. 2015 J. Theor. Biol. 386, 159-165. (doi:10.1016/j.jtbi.2015.08.034)). As the genetic motifs of different lengths are ubiquitous in genes and genomes, we introduce a new approach based on graph theory to study in full generality n-nucleotide circular codes X, i.e. of length 2 (dinucleotide), 3 (trinucleotide), 4 (tetranucleotide), etc. Indeed, we prove that an n-nucleotide code X is circular if and only if the corresponding graph G(X) is acyclic. Moreover, the maximal length of a path in G(X) corresponds to the window of nucleotides in a sequence for detecting the correct reading frame. Finally, the graph theory of tournaments is applied to the study of dinucleotide circular codes. It has full equivalence between the combinatorics theory (Michel &Pirillo 2013 ISRN Biomath. 2013, 538631. (doi:10.1155/2013/538631)) and the group theory (Fimmel et al. 2015 J. Theor. Biol. 386, 159-165. (doi:10.1016/j.jtbi.2015.08.034)) of dinucleotide circular codes while its mathematical approach is simpler. © 2016 The Author(s) Published by the Royal Society. All rights reserved.

Hipper C.,French National Institute for Agricultural Research | Brault V.,French National Institute for Agricultural Research | Ziegler-Graff V.,University of Strasbourg | Revers F.,French National Institute for Agricultural Research
Frontiers in Plant Science | Year: 2013

Phloem transport of plant viruses is an essential step in the setting-up of a complete infection of a host plant. After an initial replication step in the first cells, viruses spread from cell-to-cell through mesophyll cells, until they reach the vasculature where they rapidly move to distant sites in order to establish the infection of the whole plant. This last step is referred to as systemic transport, or long-distance movement, and involves virus crossings through several cellular barriers: bundle sheath, vascular parenchyma, and companion cells for virus loading into sieve elements (SE). Viruses are then passively transported within the source-to-sink flow of photoassimilates and are unloaded from SE into sink tissues. However, the molecular mechanisms governing virus long-distance movement are far from being understood. While most viruses seem to move systemically as virus particles, some viruses are transported in SE as viral ribonucleoprotein complexes (RNP). The nature of the cellular and viral factors constituting these RNPs is still poorly known. The topic of this review will mainly focus on the host and viral factors that facilitate or restrict virus long-distance movement. © 2013 Hipper, Brault, Ziegler-Graff and Revers.

Aw S.J.,National University of Singapore | Hamamura Y.,Nagoya University | Chen Z.,National University of Singapore | Schnittger A.,University of Strasbourg | Berger F.,National University of Singapore
Development | Year: 2010

Fertilization in flowering plants involves two sperm cells and two female gametes, the egg cell and the central cell, progenitors of the embryo and the endosperm, respectively. The mechanisms triggering zygotic development are unknown and whether both parental genomes are required for zygotic development is unclear. In Arabidopsis, previous studies reported that loss-of-function mutations in CYCLIN DEPENDENT KINASE A1 (CDKA;1) impedes cell cycle progression in the pollen leading to the production of a single sperm cell. Here, we report that a significant proportion of single cdka;1 pollen delivers two sperm cells, leading to a new assessment of the cdka;1 phenotype. We performed fertilization of wild-type ovules with cdka;1 mutant sperm cells and monitored in vivo the fusion of the male and female nuclei using fluorescent markers. When a single cdka;1 sperm was delivered, either female gamete could be fertilized leading to similar proportions of seeds containing either a single endosperm or a single embryo. When two cdka;1 sperm cells were released, they fused to each female gamete. Embryogenesis was initiated but the fusion between the nuclei of the sperm cell and the central cell failed. The failure of karyogamy in the central cell prevented incorporation of the paternal genome, impaired endosperm development and caused seed abortion. Our results thus support that the paternal genome plays an essential role during early seed development. However, sperm entry was sufficient to trigger central cell mitotic division, suggesting the existence of signaling events associated with sperm cell fusion with female gametes.

Risquez-Cuadro R.,University of Seville | Garcia Fernandez J.M.,University of Seville | Nierengarten J.-F.,University of Strasbourg | Ortiz Mellet C.,University of Seville
Chemistry - A European Journal | Year: 2013

Concerted functioning of lectins and carbohydrate-processing enzymes, mainly glycosidases, is essential in maintaining life. It was commonly assumed that the mechanisms by which each class of protein recognizes their cognate sugar partners are intrinsically different: multivalency is a characteristic feature of carbohydrate-lectin interactions, whereas glycosidases bind to their substrates or substrate-analogue inhibitors in monovalent form. Recent observations on the glycosidase inhibitory potential of multivalent glycomimetics have questioned this paradigm and led to postulate an inhibitory multivalent effect. Here the mechanisms at the origin of this phenomenon have been investigated. A D-gluco-configured sp2-iminosugar glycomimetic motif, namely 1-amino-5N,6O-oxomethylydenenojirimycin (1N-ONJ), behaving, simultaneously, as a ligand of peanut agglutinin (PNA) lectin and as an inhibitor of several glycosidases, has been identified. Both the 1N-ONJ-lectin- and 1N-ONJ-glycosidase-recognition processes have been found to be sensitive to multivalency, which has been exploited in the design of a lectin-glycosidase competitive assay to explore the implication of catalytic and non-glycone sites in enzyme binding. A set of isotropic dodecavalent C60-fullerene- sp2-iminosugar balls incorporating matching or mismatching motifs towards several glycosidases (inhitopes) was synthesized for that purpose, thereby preventing differences in binding modes arising from orientational preferences. The data supports that: 1) multivalency allows modulating the affinity and selectivity of a given inhitope towards glycosidases; 2) multivalent presentation can switch on the inhibitory capacity for some inhitope-glycosidase pairs, and 3) interactions of the multivalent inhibitors with non-glycone sites is critical for glycosidase recognition. The ensemble of results point to a shift in the binding mode on going from monovalent to multivalent systems: in the first case a typical "key-lock" model involving, essentially, the high-affinity active site can be assumed, whereas in the second, a lectin-like behavior implying low-affinity non-glycone sites probably operates. The differences in responsiveness to multivalency for different glycosidases can then be rationalized in terms of the structure and accessibility of the corresponding carbohydrate-binding regions. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Moulin E.,Charles Sadron Institute | Cid J.-J.,Charles Sadron Institute | Cid J.-J.,University of Seville | Giuseppone N.,Charles Sadron Institute | Giuseppone N.,University of Strasbourg
Advanced Materials | Year: 2013

Supramolecular organic electronics rests on the use of bottom-up chemical self-assembly processes in order to design conducting components on the 5-100 nm scale. The challenges in this field are both the construction of 1D-nanostructures displaying optimized transport properties and their precise connections to electrodes. The present Research News highlights important advances in such materials regarding their electrical performances, from semiconductors to organic metals, but also regarding their processability. In particular, by externally controlling light-responsive supramolecular polymerization processes, and by using appropriate methods of casting with an applied electric field, it becomes possible to pre-determine the accurate positioning of organic interconnects within patterned nano-circuitry. These strategies using external stimuli to obtain addressability, thus hold promising alternatives to other conducting materials such as carbon nanotubes for further technological applications in nanosciences. Recent advances in supramolecular electronics show that self-assembled nanowires made of π-stacked molecules can achieve electrical properties competing with those encountered in the other categories of conducting materials, including carbon nanotubes. In addition, by externally controlling the supramolecular polymerization processes with light and electric field, it becomes possible to accurately position these electroactive wires at nanoscale. The graphical abstract represents triarylamine-based supramolecular interconnects of 80 nm length specifically linking two gold electrodes in a pre-determined position. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Schepetilnikov M.,University of Strasbourg | Kobayashi K.,Iwate Biotechnology Research Center | Geldreich A.,University of Strasbourg | Caranta C.,French National Institute for Agricultural Research | And 3 more authors.
EMBO Journal | Year: 2011

The protein kinase TOR (target-of-rapamycin) upregulates translation initiation in eukaryotes, but initiation restart after long ORF translation is restricted by largely unknown pathways. The plant viral reinitiation factor transactivator-viroplasmin (TAV) exceptionally promotes reinitiation through a mechanism involving retention on 80S and reuse of eIF3 and the host factor reinitiation-supporting protein (RISP) to regenerate reinitiation-competent ribosomal complexes. Here, we show that TAV function in reinitiation depends on physical association with TOR, with TAV-TOR binding being critical for both translation reinitiation and viral fitness. Consistently, TOR-deficient plants are resistant to viral infection. TAV triggers TOR hyperactivation and S6K1 phosphorylation in planta. When activated, TOR binds polyribosomes concomitantly with polysomal accumulation of eIF3 and RISP-a novel and specific target of TOR/S6K1-in a TAV-dependent manner, with RISP being phosphorylated. TAV mutants defective in TOR binding fail to recruit TOR, thereby abolishing RISP phosphorylation in polysomes and reinitiation. Thus, activation of reinitiation after long ORF translation is more complex than previously appreciated, with TOR/S6K1 upregulation being the key event in the formation of reinitiation-competent ribosomal complexes. © 2011 European Molecular Biology Organization. All Rights Reserved.

Solovei I.,Ludwig Maximilians University of Munich | Wang A.S.,Singapore Institute of Medical Biology | Wang A.S.,National University of Singapore | Thanisch K.,Ludwig Maximilians University of Munich | And 14 more authors.
Cell | Year: 2013

Eukaryotic cells have a layer of heterochromatin at the nuclear periphery. To investigate mechanisms regulating chromatin distribution, we analyzed heterochromatin organization in different tissues and species, including mice with mutations in the lamin B receptor (Lbr) and lamin A (Lmna) genes that encode nuclear envelope (NE) proteins. We identified LBR- and lamin-A/C-dependent mechanisms tethering heterochromatin to the NE. The two tethers are sequentially used during cellular differentiation and development: first the LBR- and then the lamin-A/C-dependent tether. The absence of both LBR and lamin A/C leads to loss of peripheral heterochromatin and an inverted architecture with heterochromatin localizing to the nuclear interior. Myoblast transcriptome analyses indicated that selective disruption of the LBR- or lamin-A-dependent heterochromatin tethers have opposite effects on muscle gene expression, either increasing or decreasing, respectively. These results show how changes in NE composition contribute to regulating heterochromatin positioning, gene expression, and cellular differentiation during development. © 2013 Elsevier Inc.

Des Georges A.,Columbia University | Dhote V.,SUNY Downstate Medical Center | Kuhn L.,French National Center for Scientific Research | Hellen C.U.T.,SUNY Downstate Medical Center | And 3 more authors.
Nature | Year: 2015

During eukaryotic translation initiation, 43S complexes, comprising a 40S ribosomal subunit, initiator transfer RNA and initiation factors (eIF) 2, 3, 1 and 1A, attach to the 5′-terminal region of messenger RNA and scan along it to the initiation codon. Scanning on structured mRNAs also requires the DExH-box protein DHX29. Mammalian eIF3 contains 13 subunits and participates in nearly all steps of translation initiation. Eight subunits having PCI (proteasome, COP9 signalosome, eIF3) or MPN (Mpr1, Pad1, amino-terminal) domains constitute the structural core of eIF3, to which five peripheral subunits are flexibly linked. Here we present a cryo-electron microscopy structure of eIF3 in the context of the DHX29-bound 43S complex, showing the PCI/MPN core at ∼ 6 Å resolution. It reveals the organization of the individual subunits and their interactions with components of the 43S complex. We were able to build near-complete polyalanine-level models of the eIF3 PCI/MPN core and of two peripheral subunits. The implications for understanding mRNA ribosomal attachment and scanning are discussed. © 2015 Macmillan Publishers Limited.

Pelsy F.,French National Institute for Agricultural Research | Pelsy F.,University of Strasbourg
Heredity | Year: 2010

A grapevine variety consists of an array of clones descended by vegetative propagation from a single selected vine grown from a single seedling. A majority of the clones within a variety are identical, but some can show divergent genotypes and, to some extent, divergent phenotypes. Polymorphism results mainly from somatic mutations that occur naturally during plant growth. Various types of mutations were shown to be responsible for genetic diversity among clones: point mutations, large deletions, illegitimate recombination or variable number of repeats in microsatellite sequences. In most cases, somatic mutations do not affect the whole plant; rather, they affect only one cell layer, leading to periclinal chimeras. Such structures do not threaten the plant's fitness and are stable through vegetative propagation. Occasionally, cellular rearrangements in the chimera lead to homogenization of the genotype of the whole plant. Through these molecular and cellular mechanisms, the genotypes of clones drift over time and grapevine varieties evolve. © 2010 Macmillan Publishers Limited All rights reserved.

Agency: Cordis | Branch: FP7 | Program: CPCSA | Phase: ICT-2013.9.9 | Award Amount: 74.61M | Year: 2013

This Flagship aims to take graphene and related layered materials from a state of raw potential to a point where they can revolutionize multiple industries from flexible, wearable and transparent electronics, to new energy applications and novel functional composites.\nOur main scientific and technological objectives in the different tiers of the value chain are to develop material technologies for ICT and beyond, identify new device concepts enabled by graphene and other layered materials, and integrate them to systems that provide new functionalities and open new application areas.\nThese objectives are supported by operative targets to bring together a large core consortium of European academic and industrial partners and to create a highly effective technology transfer highway, allowing industry to rapidly absorb and exploit new discoveries.\nThe Flagship will be aligned with European and national priorities to guarantee its successful long term operation and maximal impact on the national industrial and research communities.\nTogether, the scientific and technological objectives and operative targets will allow us to reach our societal goals: the Flagship will contribute to sustainable development by introducing new energy efficient and environmentally friendly products based on carbon and other abundant, safe and recyclable natural resources, and boost economic growth in Europe by creating new jobs and investment opportunities.

Agency: Cordis | Branch: H2020 | Program: SGA-RIA | Phase: FETFLAGSHIP | Award Amount: 89.00M | Year: 2016

This project is the second in the series of EC-financed parts of the Graphene Flagship. The Graphene Flagship is a 10 year research and innovation endeavour with a total project cost of 1,000,000,000 euros, funded jointly by the European Commission and member states and associated countries. The first part of the Flagship was a 30-month Collaborative Project, Coordination and Support Action (CP-CSA) under the 7th framework program (2013-2016), while this and the following parts are implemented as Core Projects under the Horizon 2020 framework. The mission of the Graphene Flagship is to take graphene and related layered materials from a state of raw potential to a point where they can revolutionise multiple industries. This will bring a new dimension to future technology a faster, thinner, stronger, flexible, and broadband revolution. Our program will put Europe firmly at the heart of the process, with a manifold return on the EU investment, both in terms of technological innovation and economic growth. To realise this vision, we have brought together a larger European consortium with about 150 partners in 23 countries. The partners represent academia, research institutes and industries, which work closely together in 15 technical work packages and five supporting work packages covering the entire value chain from materials to components and systems. As time progresses, the centre of gravity of the Flagship moves towards applications, which is reflected in the increasing importance of the higher - system - levels of the value chain. In this first core project the main focus is on components and initial system level tasks. The first core project is divided into 4 divisions, which in turn comprise 3 to 5 work packages on related topics. A fifth, external division acts as a link to the parts of the Flagship that are funded by the member states and associated countries, or by other funding sources. This creates a collaborative framework for the entire Flagship.

Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: NMP-2007-2.2-1 | Award Amount: 27.17M | Year: 2009

The call 4.2.2-1 organic materials for electronics and photonics is based on the observation that the limited availability of high-performance multi-functional materials is a roadblock to further industrial progress. To address the wide scope of the call, we have identified specific materials bottlenecks to the fields of electronics and photonics. They constitute the focal points of our project. One-P main objective is: to invent, design, synthesize, characterize, process, and to supply the missing materials in the fields of organic electronics and photonics and to develop appropriate patterning methods for micro- and nano-structuring of these materials that can be up-scaled to roll-to-roll technologies. The work plan is composed of five technical workpackages, each one addressing current materials challenges: 1) charge transport and injection, 2) detection and sensing, 3) light emission, 4) functional self-assembled monolayers, 5) continuous processing and technology. Computer-aided design of materials and the use of advanced characterization tools are transversal activities that are integrated in technical workpackages. The sixth workpackage is devoted to dissemination, exploitation, and management of intellectual properties that are essential for the project success. To carry out this multi-disciplinary project, a cross-sectorial consortium has been formed at the European level. It is composed of strong academic and industrial teams with necessary and complementary expertises to cover all scientific, technological and exploitation aspects. The project will generate fundamental knowledge and help to develop unprecedented technologies. They will have a positive impact on competitiveness of European industries, environment, job creation, health, security, safety, and welfare of European citizens

Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2007-2.3.2-6 | Award Amount: 15.92M | Year: 2008

There is now an increasingly solid body of scientific evidence which demonstrates that the binding of small molecular weight compounds, peptides and antibodies (Abs) to fusion-intermediate conformations of gp41 leads to an inhibition of HIV cell entry. The principal aim of this project is to exploit this information by establishing a platform where gp41-derived vaccine candidates will be designed to elicit neutralising Abs. Several families of immunogens which mimic gp41 in its fusion intermediate conformations are already available and others will be designed using modelisation approaches. Candidates will be submitted to a thorough biophysical characterisation followed by a preclinical development in order to identify the most promising for clinical evaluation. A crucial selection parameter is the capacity of antigens to elicit neutralising Abs using internationally standardized assays. Since sexual transmission accounts for more than 90% of HIV infection, the capacity of Abs to inhibit infection at the mucosal level will also be determined. This cross-disciplinary project gathers top European scientists with expertise in protein engineering and characterisation, adjuvantation, formulation for systemic and mucosal delivery, evaluation of functional antibody response, efficacy testing in animal models, medium to large scale vaccine production as well as conduct of clinical trials in both developed and third-world countries. In contrast to previous more empirical attempts, this project is based on the rational exploitation of the knowledge on the mechanism of HIV entry and is thus a promising approach to generate a protective vaccine. It will be the first European project targeting intermediate conformations of gp41 and it could complement/synergize other international strategies focusing on the membrane proximal region of gp41 or gp140 trimer to induce neutralising Abs or aiming at reducing the viral load by eliciting a cellular immunity against HIV.

Human life and the entire ecosystem of South East Asia depend upon the monsoon climate and its predictability. More than 40% of the earths population lives in this region. Droughts and floods associated with the variability of rainfall frequently cause serious damage to ecosystems in these regions and, more importantly, injury and loss of human life. The headwater areas of seven major rivers in SE Asia, i.e. Yellow River, Yangtze, Mekong, Salween, Irrawaddy, Brahmaputra and Ganges, are located in the Tibetan Plateau. Estimates of the Plateau water balance rely on sparse and scarce observations that cannot provide the required accuracy, spatial density and temporal frequency. Fully integrated use of satellite and ground observations is necessary to support water resources management in SE Asia and to clarify the roles of the interactions between the land surface and the atmosphere over the Tibetan Plateau in the Asian monsoon system. The goal of this project is to: 1. Construct out of existing ground measurements and current / future satellites an observing system to determine and monitor the water yield of the Plateau, i.e. how much water is finally going into the seven major rivers of SE Asia; this requires estimating snowfall, rainfall, evapotranspiration and changes in soil moisture; 2. Monitor the evolution of snow, vegetation cover, surface wetness and surface fluxes and analyze the linkage with convective activity, (extreme) precipitation events and the Asian Monsoon; this aims at using monitoring of snow, vegetation and surface fluxes as a precursor of intense precipitation towards improving forecasts of (extreme) precipitations in SE Asia. A series of international efforts initiated in 1996 with the GAME-Tibet project. The effort described in this proposal builds upon 10 years of experimental and modeling research and the consortium includes many key-players and pioneers of this long term research initiative.

Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: KBBE-2009-3-2-01 | Award Amount: 7.90M | Year: 2010

Biodiversity in the seas is only partly explored, although marine organisms are excellent sources for many industrial products. Through close co-operation between industrial and academic partners, the MAREX project will collect, isolate and classify marine organisms, such as micro- and macroalgae, cyanobacteria, sea anemones, tunicates and fish from the Atlantic, Pacific and Indian Oceans as well as from the Mediterranean, Baltic and Arabian Seas. Extracts and purified compounds of these organisms will be studied for several therapeutically and industrially significant biological activities, including anticancer, anti-inflammatory, antiviral and anticoagulant activities by applying a wide variety of screening tools, as well as for ion channel/receptor modulation and plant growth regulation. Chromatographic isolation of bioactive compounds will be followed by structural determination. Sustainable cultivation methods for promising organisms, and biotechnological processes for selected compounds will be developed, as well as biosensors for monitoring the target compounds. The work will entail sustainable organic synthesis of selected active compounds and new derivatives, and development of selected hits to lead compounds. The project will expand marine compound libraries. MAREX innovations will be targeted for industrial product development in order to improve the growth and productivity of European marine biotechnology. MAREX aims at a better understanding of environmentally conscious sourcing of marine biotechnology products and increased public awareness of marine biodiversity and potential. Finally, MAREX is expected to offer novel marine-based lead compounds for European industries and strengthen their product portfolios related to pharmaceutical, nutraceutical, cosmetic, agrochemical, food processing, material and biosensor applications.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: SPA.2013.1.1-06 | Award Amount: 3.22M | Year: 2013

The Rapid Analysis and Spatialisation Of Risk (RASOR) project will develop a platform to perform multi-hazard risk analysis to support the full cycle of disaster management, including targeted support to critical infrastructure monitoring and climate change impact assessment, exploiting internally produced and available services. RASOR adapts the newly developed 12m resolution TanDEM-X Digital Elevation Model (DEM) to risk management applications, using it as a base layer to interrogate data sets and develop specific disaster scenarios. RASOR overlays archived and near-real time very-high resolution optical and radar satellite data, combined with in-situ data for both global and local applications. A scenario-driven query system allows users to project situations into the future and model multi-hazard risk both before and during an event. Managers can determine the extent of flooding in a given area and determine, for example, the risk pending on Critical Infrastructure Systems in terms of their residual functionality as a basis for a systemic vulnerability analysis. Public authorities can determine the impact of coastal subsidence on flood defence over several years given various sea surge scenarios and based on actual, accurate subsidence information. RASOR allows managers to use real scenarios when determining new mitigation or prevention measures, and integrate new, real-time data into their operational system when organising response activities.

Agency: GTR | Branch: AHRC | Program: | Phase: Research Grant | Award Amount: 4.16M | Year: 2012

Over the last decade, the creative industries have been revolutionised by the Internet and the digital economy. The UK, already punching above its weight in the global cultural market, stands at a pivotal moment where it is well placed to build a cultural, business and regulatory infrastructure in which first movers as significant as Google, Facebook, Amazon or iTunes may emerge and flourish, driving new jobs and industry. However, for some creators and rightsholders the transition from analogue to digital has been as problematic as it has been promising. Cultural heritage institutions are also struggling to capitalise upon new revenue streams that digitisation appears to offer, while maintaining their traditional roles. Policymakers are hampered by a lack of consensus across stakeholders and confused by partisan evidence lacking robust foundations. Research in conjunction with industry is needed to address these problems and provide support for legislators. CREATe will tackle this regulatory and business crisis, helping the UK creative industry and arts sectors survive, grow and become global innovation pioneers, with an ambitious programme of research delivered by an interdisciplinary team (law, business, economics, technology, psychology and cultural analysis) across 7 universities. CREATe aims to act as an honest broker, using open and transparent methods throughout to provide robust evidence for policymakers and legislators which can benefit all stakeholders. CREATe will do this by: - focussing on studying and collaborating with SMEs and individual creators as the incubators of innovation; - identifying good, bad and emergent business models: which business models can survive the transition to the digital?, which cannot?, and which new models can succeed and scale to drive growth and jobs in the creative economy, as well as supporting the public sector in times of recession?; - examining empirically how far copyright in its current form really does incentivise or reward creative work, especially at the SME/micro level, as well as how far innovation may come from open business models and the informal economy; - monitoring copyright reform initiatives in Europe, at WIPO and other international fora to assess how they impact on the UK and on our work; - using technology as a solution not a problem: by creating pioneering platforms and tools to aid creators and users, using open standards and released under open licences; - examining how to increase and derive revenues from the user contribution to the creative economy in an era of social media, mash-up, data mining and prosumers; - assessing the role of online intermediaries such as ISPs, social networks and mobile operators to see if they encourage or discourage the production and distribution of cultural goods, and what role they should play in enforcing copyright. Given the important governing role of these bodies should they be subject to regulation like public bodies, and if so, how?; - consider throughout this work how the public interest and human rights, such as freedom of expression, privacy, and access to knowledge for the socially or physically excluded, may be affected either positively or negatively by new business models and new ways to enforce copyright. To investigate these issues our work will be arranged into seven themes: SMEs and good, bad and emergent business models; Open business models; Regulation and enforcement; Creators and creative practice; Online intermediaries and physical and virtual platforms; User creation, behaviour and norms; and, Human rights and the public interest. Our deliverables across these themes will be drawn together to inform a Research Blueprint for the UK Creative Economy to be launched in October 2016.

Agency: Cordis | Branch: FP7 | Program: CSA-SA | Phase: FP7-PEOPLE-2013-NIGHT | Award Amount: 485.18K | Year: 2013

In France, few people usually attend science events. We propose an original and innovative programme in order to raise peoples interest in research. We intend to reach a large audience with many first-time visitors: a total of 25000 attendees and a broader audience of 6 million people. Our strategy will be to point out that the Researchers Night is the only nation-wide event entirely dedicated to researchers, where a direct and extensive dialogue is possible. In order to attract the public, we will offer them to discover the researchers Unknown Worlds. This theme is catchy and linked with the profession of researcher. The unknown worlds in research are many and cover all fields of science: brain, infinitely small, unknown societies, etc. On September 27th, in 15 cities of France, unknown worlds will be created. In museum, libraries, and cinemas, various sceneries will be set up in relation with the researchers topics of interest. Moreover, each city will propose surprising meetings based on original ideas: playful participation to research, games with researchers, facilitators interventions, etc. Those best practices have been successfully tested during the previous researchers nights we organised. Researchers and the public will gather for a playful, surprising, festive, and beautiful evening of enriching meetings. We think the chosen theme and the set up will allow long conversations with researchers, and that people will be seduced by these extraordinary explorations. They will feel much closer to the researchers thanks to the contact they will have with them. To organise this event in the French regions, we are a consortium of 12 partners specialised in scientific vulgarisation, and who are used to work with researchers. We frequently exchange on how to train researchers and on how to create original facilities and devices. We will also have two qualitative enquiries on the researchers image and on the efficiency of our awareness campaign made.

Agency: Cordis | Branch: FP7 | Program: CSA-SA | Phase: FP7-PEOPLE-2011-NIGHT | Award Amount: 432.52K | Year: 2011

Promoting cross and complementary projects, Real Researchers for Real meetings (RRRM) part of a dynamic coaching and preparation of meetings between researchers and the public at the European event of 23 September 2011 favoring atmosphere of conviviality and exhange. 11 partners, including universities, science centers, associations, located throughout the country, from East to West, from North to South have been working on a common project in the desire to give a better exposure to the Researchers night It will build on the skills of mediators, designers implementing features unique to the specific venue and audience expected. The devices chosen should enable researchers to disconnect from their work environment. Researchers will be put in a situation of dialogue, sharing and exchange with citizens. Upstream work will present their demonstration, the specific focus and to facilitate the meeting as the focus of events. Priority should be given in this approach features highlighting the human person and how to approach his craft at the expense of handling and animations that may conflict with the very purpose of the event, namely to amend the representation citizens of the researchers. A job coaching and complementarity may be conducted with artists in a dynamic view of a put, a fresh perspective on science. These approaches must be part of the pathways of the event and its programming leading visitors through a process of questioning the role of the researcher in our societies, and conversely how researchers articulate their jobs in our societies.

Agency: Cordis | Branch: FP7 | Program: CP-TP | Phase: KBBE.2012.3.4-02 | Award Amount: 9.94M | Year: 2012

SYNPOL aims to propel the sustainable production of new biopolymers from feedstock. SYNPOL will thereto establish a platform that integrates biopolymer production through modern processing technologies, with bacterial fermentation of syngas, and the pyrolysis of highly complex biowaste (e.g., municipal, commercial, sludge, agricultural). The R&D activities will focus on the integration of innovative physico-chemical, biochemical, downstream and synthetic technologies to produce a wide range of new biopolymers. The integration will engage novel and mutually synergistic production methods as well as the assessment of the environmental benefits and drawbacks. This integrative platform will be revolutionary in its implementation of novel microwave pyrolytic treatments together with systems-biology defined highly efficient and physiologically balanced recombinant bacteria. The latter will produce biopolymer building-blocks and polyhydroxyalkanoates that will serve to synthesize novel bio-based plastic prototypes by chemical and enzymatic catalysis. Thus, the SYNPOL platform will empower the treatment and recycling of complex biological and chemical wastes and raw materials in a single integrated process. The knowledge generated through this innovative biotechnological approach will not only benefit the environmental management of terrestrial wastes, but also reduce the harmful environmental impact of petrochemical plastics. This project offers a timely strategic action that will enable the EU to lead worldwide the syngas fermentation technology for waste revalorisation and sustainable biopolymer production.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: SST.2008.4.1.1. | Award Amount: 3.47M | Year: 2009

The development of adaptive safety systems addressing vehicle occupant protection requires the use of in depth knowledge of various occupant features, specifically those related to the risk of injury. All occupants in passenger vehicles are at risk of sustaining whiplash injuries in a low severity crash. Whiplash associated disorders (WAD), so called whiplash injuries, resulting from car crashes, are a serious traffic safety issue, resulting in over 4 billion costs to European society. Yearly more than 300 000 European citizens suffer neck problems from these injuries and 15 000 result in long terms consequences. In the population, the females are at higher risk of these injuries than the males. The difference in risk between the robust, male, population and the vulnerable, female, part of the population is between 40-100%. This has been reported from epidemiological studies from all over the world since the end of the 1960s until today. Yet still, when assessing the vehicle safety the only available occupant model for these impact scenarios is an average male. Adaptive anti-whiplash systems need to be evaluated for their benefits both for males and females. If there are no improved protective systems, further rising costs for the European Society can be expected. This project aims at establishing the properties for a model of an average female and to implement those in a computational model in order to provide an improved tool for the development and evaluation of adaptive systems with special focus on protection against whiplash injuries. The project will result in a computational model of a female, in addition to the male model that already exists, for low severity testing. In addition, the computational models will be used in the design and evaluation of adaptive seat systems in order to provide enhanced neck injury protection from the seat.

Agency: Cordis | Branch: FP7 | Program: CSA-SA | Phase: FP7-PEOPLE-2012-NIGHT | Award Amount: 497.02K | Year: 2012

Under the banner of EU 2020 innovation initiative, the Researchers Night 2012 will be run in France around the theme: Imagine the Future. Over 15 sites across the country will allow nearly 20,000 visitors to meet and exchange with over 400 researchers working on a multidisciplinary range of scientific disciplines, ranging from Social Sciences to fundamental and applied sciences. The RIF project has been specifically designed to overcome the stereotype of researchers working alone in their laboratories without any further contact with the real world. By following a new and innovative way of discovering science through art and entertainment this project aims at enhancing public recognition of the researchers, their role in society and the importance of scientific research to the public day-to-day life. In a relaxed and friendly atmosphere, visitors will have the opportunity to express their feelings, and opinions about both the researchers work and their role in society. Reciprocally, researchers will have the opportunity to express their concerns about their work. Furthermore, as if they were in front of a crystal ball, participant researchers will be asked to imagine what the future will be like in 30 years. They will have to imagine the evolution of their research, and the effects it will be likely to have on the world and society.Special attention will be paid to young public, using an accessible language adapted for non scientists. Activities foreseen throughout the RIFs project range from treasure hunting, face-to-face meeting, to the creation of a surprising universe of projected lights and lasers. RIF project proposes to discover how researchers imagine future societies and try to shape them, to discover talented juniors researchers work and cutting-edge research. Researchers Night 2012 will focus on the diversity and cross existing research, while putting out that Researchers are also ordinary people working for a better future for all of us.

Agency: Cordis | Branch: FP7 | Program: CSA-SA | Phase: FP7-PEOPLE-2009-NIGHT | Award Amount: 501.59K | Year: 2010

Researchers night calls to meet and exchange across Europe. For the third time in France, 13 partners spread throughout the country came together to establish this event in over 20 cities in the country. Inviting well over 400 researchers to speak to citizens to show the reality of their job. The consortium is working to set up evening can be shared with family, in particular environments, surprising and exciting to engage in discussions. For 2010, work will be undertaken ahead of the event by highlighting the website and a forum for discussion forum.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: Fission-2007-1.2-01 | Award Amount: 23.78M | Year: 2008

Actinide recycling by separation and transmutation is considered worldwide and particularly in several European countries as one of the most promising strategies to reduce the inventory of radioactive waste, thus contributing to make nuclear energy sustainable. Consistently with potentially viable recycling strategies, the Collaborative Project ACSEPT will provide a structured R&D framework to develop chemical separation processes compatible with fuel fabrication techniques, with a view to their future demonstration at the pilot level. Considering technically mature aqueous separation processes, ACSEPT will optimise and select the most promising ones dedicated to actinide partitioning and those featuring a group separation. These developments will be appropriately balanced with an exploratory research focused on the design of new molecules. In parallel, promising group actinide separation pyro-processes will be developed beyond the current state-of-the-art, as an alternative option, for a longer term. ACSEPT will also pave the way towards more integration between Partitioning and Transmutation by carrying dissolution as well as actinide conversion studies. All experimental results will be integrated by carrying out engineering and systems studies on aqueous and dry (pyro) processes to prepare for future demonstration at a pilot level. A training and education programme will also be implemented to share the knowledge among partitioning community and present and future generations of researchers. The challenging objectives of ACSEPT will be addressed by a multi-disciplinary consortium composed of European universities, nuclear research bodies and major industrial players. This consortium will generate fundamental improvements for a future design of an Advanced Processing Pilot Unit. ACSEPT will thus be an essential contribution to the demonstration, in the long term, of the potential benefits of actinide recycling to minimise the burden on the geological repositories.

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: EO-3-2016 | Award Amount: 1.85M | Year: 2016

E2mC aims at demonstrating the technical and operational feasibility of the integration of social media analysis and crowdsourced information within both the Mapping and Early Warning Components of Copernicus Emergency Management Service (EMS). The Project will develop a prototype of a new EMS Service Component (Copernicus Witness), designed to exploit social media analysis and crowdsourcing capabilities to generate a new Product of the EMS Portfolio. The purpose of the new Copernicus Witness Service Component is to improve the timeliness and accuracy of geo-spatial information provided to Civil Protection authorities, on a 24/7 basis, during the overall crisis management cycle and, particularly, in the first hours immediately after the event. This will result in an early confirmation of alerts from running Early Warning Systems as well as first rapid impact assessment from the field. The technological enabler of the Copernicus Witness is the innovative and scalable Social&Crowd (S&C) Platform, developed by E2mC. Heterogeneous social media data streams (Twitter, Facebook, Instagram, and different data: text, image, video, ) will be analysed and sparse crowdsourcing communities will be federated (crisis specific as Tomnod, HOT, SBTF and generic as Crowdcrafting, EpiCollect,). Two demonstration loops will validate the usefulness of Copernicus Witness and the S&C Platform suitability to allow EC to evaluate possible Copernicus EMS evolution options. E2mC will perform demonstrations within realistic and operational scenarios designed by the Users involved within the Project (Civil Protection Authorities and Humanitarian Aid operators, including their volunteer teams) and by the current Copernicus EMS Operational Service Providers that are part of the E2mC Consortium. The involvement of social media and crowdsourcing communities will foster the engagement of a large number of people in supporting crisis management; many more citizens will become aware of Copernicus.

Agency: Cordis | Branch: H2020 | Program: IA | Phase: LCE-03-2015 | Award Amount: 25.07M | Year: 2016

DESTRESS is aimed at creating EGS (Enhanced geothermal systems) reservoirs with sufficient permeability, fracture orientation and spacing for economic use of underground heat. The concepts are based on experience in previous projects, on scientific progress and developments in other fields, mainly the oil & gas sector. Recently developed stimulation methods will be adapted to geothermal needs, applied to new geothermal sites and prepared for the market uptake. Understanding of risks in each area (whether technological, in business processes, for particular business cases, or otherwise), risk ownership, and possible risk mitigation will be the scope of specific work packages. The DESTRESS concept takes into account the common and specific issues of different sites, representative for large parts of Europe, and will provide a generally applicable workflow for productivity enhancement measures. The main focus will be on stimulation treatments with minimized environmental hazard (soft stimulation), to enhance the reservoir in several geological settings covering granites, sandstones, and other rock types. The business cases will be shown with cost and benefit estimations based on the proven changes of the system performance, and the environmental footprint of treatments and operation of the site will be controlled. In particular, the public debate related to fracking will be addressed by applying specific concepts for the mitigation of damaging seismic effects while constructing a productive reservoir and operating a long-term sustainable system. Industrial participation is particularly pronounced in DESTRESS, including large energy suppliers as well as SMEs in the process of developing their sites. The composition of the consortium involving major knowledge institutes as well as key industry will guarantee the increase in technology performance of EGS as well as an accelerated time to market.

Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-ITN-2008 | Award Amount: 3.79M | Year: 2009

SUPERIOR aims at providing top-quality cross-disciplinary and supra-sectoral training to a pool of promising young researchers, in an area at the interface between Supramolecular Chemistry, Materials- and Nano-Science, Physics and Electrical Engineering. SUPERIOR appointees will be formally trained in lecture courses, dedicated schools and workshops, and through an ambitious and carefully planned research activity that benefits both from the expertise of world-leading senior investigators and of younger and energetic PIs with remarkable track records in both training and research. SUPERIOR is designed to generate new scientific and technological knowledge by combining supramolecularly-engineered nanostructured materials (SENMs), mostly based on organic semiconductors, with tailor-made interfaces to solid substrates and electrodes, for fabricating prototypes of optoelectronic devices. We are particularly interested in developing multiscale SENMs for transistors (FETs), in-plane diodes single-photon emitters, and especially solar cells (PVDs) and organic light-emitting diodes, OLEDs. The specific training and research objectives are: 1. Supramolecular synthetic chemistry of electrically/optically 1D and 2D (macro)molecules 2. Hierarchical self-organisation of multifunctional SENMs at surfaces. Multiscale SPMs studies of physico-chemical properties 3. Time-resolved photophysical studies of single-molecules and SENMs 4. Time-resolved spectroscopy of materials and devices 5. Modelling the geometric and electronic structures and the optical properties of SENMs 6. Advanced devices processing/(nano)fabrication 7. Formation of controlled interfaces of SENMs with substrate and electrodes 8. Devices I: FETs: Measurement of charge mobility in stacks, also upon photodoping. 9. Devices II: PVDs addressing the charge collection problem. 10. Devices III: Emissive devices - Single photon emitters and OLEDs 11. Dissemination and strategic development 12. Management

Agency: Cordis | Branch: FP7 | Program: | Phase: | Award Amount: 4.66M | Year: 2008

ITER is the next generation of fusion devices and is intended to demonstrate the scientific and technical feasibility of fusion as a sustainable energy source for the future. To exploit the full potential of the device and to guarantee optimal operation for the device a high degree of physics modelling and simulation is needed already in the current construction phase of the ITER project. First principles modelling tools that are needed for an adequate description of the underlying physics cover both a wide range of timescales and spatial orderings and are in general very demanding from a computational point of view. Current modelling activities relies on local or national computational resources and an improved access to computing infrastructures will be instrumental in advancing a pan-European modelling activity for ITER to a very competitive status in relation to the ITER partners. The EUFORIA project will provide a comprehensive framework and infrastructure for core and edge transport and turbulence simulation, linking grid and High Performance Computing (HPC), to the fusion modelling community. The project will enhance the modelling capabilities for ITER and DEMO sized plasmas through the adaptation, optimization and integration of a set of critical applications for edge and core transport modelling targeting different computing paradigms as needed (serial and parallel grid computing and HPC). Deployment of both a grid service and a High Performance computing services are essential to the project. A novel aspect is the dynamic coupling and integration of codes and applications running on a set of heterogeneous platforms into a single coupled framework through a workflow engine a mechanism needed to provide the necessary level integration in the physics applications. This strongly enhances the integrated modelling capabilities of fusion plasmas and will at the same time provide new computing infrastructure and tools to the fusion community in general.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.3.2-1 | Award Amount: 3.26M | Year: 2008

Although HIV-1 Nef was originally named negative factor, it has been shown to be critical for efficient persistance of HIV-1 infected humans thus playing a major role in the progression to AIDS. Remarkably; until now Nef has not been evaluated as an antiretroviral drug target. It is well established that Nef promotes HIV-1 replication and facilitates viral immune evasion by interacting with various host factors. Disrupting these essential interactions may delay or even prevent disease progression. Partners in this consortium have already identified small molecule inhibitors targeting Nef function. The first objective of this project is therefore to validate the molecular events elicited by these molecules in both virus-free as well as in HIV infection in vitro assays. In a complementing approach, small compound libraries already available to the consortium will be used and adapted to screen for inhibitors of Nef induced modulation of cellular receptors, NFAT activation and the Nef SH3 binding domain, that likely contribute to the importance of Nef in HIV-1 pathogenicity. In addition, functional screenings to discover drugable cellular Nef partners using RNA interference libraries will be performed. After validation of their importance in relation to the established host proteins co-interacting in the Nef cellular pathways, a selection will be additionally targeted by the developed small molecule inhibitors. Our ultimate goal is to deliver a complementary portfolio of candidate drugs that target the most important parameters in the Nef-host interaction pathway. Critical cellular interaction partners are much more conserved than viral enzymes that are usually targeted in highly-active-antiretroviral therapy (HAART). Therefore, it is believed by the partners that the novel approach presented in this project proposal will yield compounds less likely to be subject to the occurrence of drug resistance

Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: SSH-2007-1.1-01 | Award Amount: 4.28M | Year: 2009

The proposed research project will study the interactions between knowledge, economic growth and social wellbeing in Europe. It focuses on knowledge-intensive entrepreneurship as a necessary mechanism and an agent of change mediating between the creation of knowledge and its transformation into economic activity. Knowledge-intensive entrepreneurship is perceived herein as a core interface between two interdependent systems: the knowledge generation and diffusion system, on the one hand, and the productive system, on the other. Both systems shape and are shaped by the broader social context including customs, culture, and institutions thus also pointing at the linkage of entrepreneurship to that context. The project has three main objectives (research thrusts). At the micro level, it purports to study in depth the very act of knowledge-intensive entrepreneurship, its defining characteristics, boundaries, scope and incentives. At the macro level, it will study the link between knowledge entrepreneurship, economic growth and social wellbeing, also extending to the socio-economic processes that help transform the animal spirits (John Maynard Keynes) into a self-reinforcing process for broader societal prosperity. The way the broader socio-economic environment stokes animal spirits and benefits from them will be studied within the contexts of various shades of capitalism in Europe and elsewhere, expanding beyond the growth accounting and endogenous growth approaches and issues to novel concepts of knowledge-intensive entrepreneurship in growth and, further, into the underlying issues of social wellbeing such as inclusion, cohesion, equity, opportunities, and social care. Finally, at the policy level, the project will take a systemic approach aiming at an organic integration of diverse sets of policies that influence the creation and growth of innovative entrepreneurial ventures based on knowledge generation and diffusion.

Agency: Cordis | Branch: FP7 | Program: CP-CSA-Infra | Phase: INFRA-2010-1.1.9 | Award Amount: 9.24M | Year: 2011

Biomedical research depends on the availability of living non-human primates and biological material with primate origin. The need for animal research using non-human primates is therefore recognised by all governments that support internationally competitive biomedical research aimed at addressing the worlds most pressing medical challenges. While essential for biomedical research owing to their similarity to humans, non-human primates are more than other animals endowed with high sensory and cognitive abilities. This is the basis of an international consensus that the use of primates in research has to comply with the highest ethical standards and should be restricted to cases where no alternatives exist. Research with primates has to follow the 3R-concept of Refinement, Reduction and Replacement. Meeting this requirement necessitates a commitment to substantial investments into appropriate facilities, specialized equipment and extensive training of personnel, which has been realised by the establishment of the I3-project EUPRIM-Net in the 6th framework programme. The aim of EUPRIM-Net is to contribute to European science by improving the ability of its participants to provide the best services, support the best science that meets the highest ethical standards for primate-based animal research. With the funding of EUPRIM-Net II we will build on the successes of the starting phase of EUPRIM-Net to focus on the following overarching core objectives: - advancing the 3Rs (refinement, reduction, replacement) in primate research - develop, refine and ensure best practice in primate research - extend the network in Europe to include commercial partners and extend the network to include non-European primate centres to insure a global sharing of available resources. Additionally, EUPRIM-Net places a focus on moving away from EU funding and implementing self-sustaining structures.

Agency: Cordis | Branch: FP7 | Program: CPCSA | Phase: INFRA-2008-1.2.2 | Award Amount: 6.76M | Year: 2009

The overall objective of the Geo-Seas project is to effect a major and significant improvement in the overview and access to marine geological and geophysical data and data-products from national geological surveys and research institutes in Europe by upgrading and interconnecting their present infrastructures.The Geo-Seas partnership has taken a strategic decision to adopt the SeaDataNet interoperability principles, architecture and components wherever possible. This approach allows the Geo-Seas upgrading to gain instant traction and momentum whilst avoiding wasteful duplicative effort. It is envisaged that the SeaDataNet infrastructure will provide a core platform that will be adaptively tuned in order to cater for the specific requirements of the geological and geophysical domains. A range of additional activities for developing and providing new products and services is also undertaken in order to fulfill the diverse needs of end-user communities.

Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 2.65M | Year: 2015

Nanotechnology has been identified as a key enabling technology of economic growth and the value of nanomaterials in the global market is forecast to grow to 2 trillion by 2015. In order to be a market leader in this area, it is imperative that Europe invest in research where the gap between knowledge creation and successful commercialisation is bridged, and in training the next generation of highly skilled researchers in nanotechnology. This ETN will increase innovation capacity and strengthen doctoral training in nanotechnology on a European level. The ETN will push research into applications at the cutting-edge of nanotechnology by uniting leading experts from both the academic and non-academic sectors under the theme Multi-Stimuli Responsive Molecular Systems and Materials. The objective of the research programme is to prepare new smart molecular systems and materials in a bottom-up approach from low molecular weight building blocks by exploiting dynamic covalent chemistry and supramolecular interactions. Close collaboration between the academic and industrial members in this ETN will ensure immediate commercialisation of any new technology or materials developed by the network. This ETN provides a highly structured and comprehensive training programme in nanotechnology, a subject not specifically taught in many European universities. Early-stage researchers will be recruited and trained so they are equipped with a balance of research-related and transferable skills to enhance their career perspectives in both the academic and non-academic sectors. Thus, the network will produce highly skilled, creative, innovative and entrepreneurial researchers who will contribute to European innovation capacity in nanotechnology.

News Article | October 5, 2016

A tiny lift, artificial muscles and miniscule motors. The Nobel Prize in Chemistry 2016 is awarded to Jean-Pierre Sauvage, Sir J. Fraser Stoddart and Bernard L. Feringa for their design and production of molecular machines. They have developed molecules with controllable movements, which can perform a task when energy is added. The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry 2016 to “for the design and synthesis of molecular machines”​ The development of computing demonstrates how the miniaturisation of technology can lead to a revolution. The 2016 Nobel Laureates in Chemistry have miniaturized machines and taken chemistry to a new dimension. The first step towards a molecular machine was taken by Jean-Pierre Sauvage in 1983, when he succeeded in linking two ring-shaped molecules together to form a chain, called a catenane. Normally, molecules are joined by strong covalent bonds in which the atoms share electrons, but in the chain they were instead linked by a freer mechanical bond. For a machine to be able to perform a task it must consist of parts that can move relative to each other. The two interlocked rings fulfilled exactly this requirement. The second step was taken by Fraser Stoddart in 1991, when he developed a rotaxane. He threaded a molecular ring onto a thin molecular axle and demonstrated that the ring was able to move along the axle. Among his developments based on rotaxanes are a molecular lift, a molecular muscle and a molecule-based computer chip. Bernard Feringa was the first person to develop a molecular motor; in 1999 he got a molecular rotor blade to spin continually in the same direction. Using molecular motors, he has rotated a glass cylinder that is 10,000 times bigger than the motor and also designed a nanocar. 2016’s Nobel Laureates in Chemistry have taken molecular systems out of equilibrium’s stalemate and into energyfilled states in which their movements can be controlled. In terms of development, the molecular motor is at the same stage as the electric motor was in the 1830s, when scientists displayed various spinning cranks and wheels, unaware that they would lead to electric trains, washing machines, fans and food processors. Molecular machines will most likely be used in the development of things such as new materials, sensors and energy storage systems. Jean-Pierre Sauvage, born 1944 in Paris, France. Ph.D. 1971 from the University of Strasbourg, France. Professor Emeritus at the University of Strasbourg and Director of Research Emeritus at the National Center for Scientific Research (CNRS), France. Sir J. Fraser Stoddart, born 1942 in Edinburgh, UK. Ph.D. 1966 from  Edinburgh University, UK. Board of Trustees Professor of Chemistry at Northwestern University, Evanston, IL, USA. Bernard L. Feringa, born 1951 in Barger-Compascuum, the Netherlands. Ph.D.1978 from the University of Groningen, the Netherlands. Professor in Organic Chemistry at the University of Groningen, the Netherlands.

News Article | October 12, 2016

Three chemists who created tiny molecular machines have won the 2016 Nobel Prize in Chemistry for their intricate designs. Jean-Pierre Sauvage, at the University of Strasbourg in France; Fraser Stoddart, a Scottish-born chemist at Northwestern University in Evanston, Illinois; and Bernard Feringa, at the University of Groningen in the Netherlands, share the award for their work in the 1980s and 1990s, when they pioneered efforts to miniaturize motors. “I’m a bit shocked because it was such a great surprise. And I’m so honoured,” said Feringa in an interview with the Nobel Committee just after winning the prize. The three have made molecular knots, shuttles, rotors, chains, pumps, axles, switches, memory devices and even a nanocar — all at the scale of molecules (see 'Nano machines'). The nanoscale machines are yet to find application, but researchers hope that their uses could range from delivering drugs to computer memory. “It’s early days, of course,” Feringa told the Nobel Committee. “But once you are able to control movement, you have a motor, you can think of all kinds of functions.” He suggested that the machines could be used as tiny robots in the body to deliver drugs or detect cancerous cells; or as smart materials that could adapt or change depending on external signals. "I applaud the fact that — for once in chemistry — Stockholm [where the Nobels are announced] has recognized a piece of chemistry that is fundamental in its making and being," Stoddart said at a press conference at Northwestern University, held later in the day. Only a handful of laboratories are currently actively engaged in making nanomachines, says Dean Astumian, who studies the theory of molecular motors at the University of Maine in Orono. But he thinks the field will get a boost from the award. “The recognition that is afforded by a Nobel Prize is going to attract the best young people,” he says. Astumian thinks the work will provide applications within 25 years. “There’s no device that you can buy that’s made out of molecular machines. But they’re coming.” In 1983, Sauvage’s group was the first to create molecular interlocking chains and rings — called catenanes — which were the first steps to creating the connected parts needed for molecular motors. By creating interlocking rings, Stoddart noted at his press conference, Sauvage's group effectively invented a new way to bind molecules together — a mechanical bond, rather than a chemical one. "New bonds are few and far between. They are really the blue moons," Stoddart said. Stoddart himself, in 1991, created the first molecular shuttle: a ring-shaped molecule threaded onto an ‘axle’, called a rotaxane. The ring could shunt back and forth between two sites on the axle, which was capped at each end by stoppers, and Stoddart and other chemists figured out how to control that process, using changes in acidity, light or temperature. Since then, Stoddart’s team has used similar rotaxanes to make a molecular ‘lift’, which can raise itself (by less than a nanometre) above a surface, and an artificial ‘muscle’, in which rotaxanes bend a thin sheet. The researchers have also used millions of rotaxanes to make a high-density memory device — in which the shuttles flick from an ‘on’ state to an ‘off’ state. And in 1999, Feringa was the first to develop a synthetic molecular motor — a single molecule with paddle units connected by a carbon–carbon double bond. The paddles rotated, and kept on spinning, when the bond was broken with light. Feringa showed that the motors could have macroscale effects, such as rotating a glass rod sitting on top of them. Perhaps most famously, Feringa has also created a four-wheel-drive ‘nanocar’ out of the motors. The Nobel winners' work — and other chemists' nanomachines — have also had an impact on researchers’ understanding of nature, Astumian says. In particular, the artificial systems have helped to demonstrate that all chemically-powered molecular machines, whether synthetic or biological, work according to the same principles: by selectively harvesting the random jiggles of Brownian motion, rather than pushing against them. Asked by reporters at the Nobel press conference whether his machines would find a use, Feringa likened the creators of minuscule machines to the Wright Brothers, who made their maiden flight in a powered aircraft more than 100 years ago. “People were saying, why do we need a flying machine? Now we have a Boeing 747 and an Airbus. That’s a little bit how I feel. The opportunities are great.” During his own press conference, Stoddart also took political swipes, both at recent UK anti-immigration rhetoric and at US Presidential candidate Donald Trump. He said that his old country, the United Kingdom, was “in a real mess because it thinks it can raise borders to people coming in". And referring to Trump's comment in his first debate with Hillary Clinton that not paying federal taxes would be "smart", Stoddart said that one-third of his Nobel earnings would go to taxes, because, he said, "I am not smart".

News Article | October 5, 2016

This year's Nobel Prize for Chemistry goes to a team of scientists who contributed to molecular medicine. The treatments they worked on could one day be injected to treat patients suffering from different types of cancer, or to create new types of materials and energy storing devices. Jean-Pierre Sauvage, J. Fraser Stoddart and Bernard Feringa have created molecules that respond to a stimulus creating a mechanical motion that allows to perform certain tasks. The $931,000 prize represents a reward for the possibility of creating smart medicines that look for the disease or the tissue damage in the body and send the attributed drugs to fix the problem. These types of smart materials will be created to be adaptable to changes of stimuli, such as in response to light or temperature. The Nobel committee explained that the molecular medicine was "at the same stage as the electric motor was in the 1830s" before the team's approach. Similarly to the creation of electric trains and washing machines, this discovery unveils an endless number of uses and possibilities to incorporate this breakthrough into various aspects of technological development. "Think of a tiny micro-robot that a doctor in the future will inject into your blood and that goes to search for a cancer cell or goes to deliver a drug, for instance," said Feringa, a professor of organic chemistry at the University of Groningen in the Netherlands. Sauvage is a professor emeritus at the University of Strasbourg and director of research emeritus at the National Center for Scientific Research in France. He started this line of research in 1983, when he linked two ring-shaped molecules to form a chain (catenane), through a mechanical bond. He was followed by Stoddart, who threaded a molecular ring through a molecular axle, proving that the first would move along the latter. Feringa was, in 1999, the first person to create a molecular motor. Together, the team managed to bring the molecular systems intro energy-filled states where their motion can be controlled, instead of just being in a state of equilibrium. Chemistry is the third of this year's Nobel Prizes. The first two were awarded to Yoshinori Ohsumi for Medicine and a team of British scientists for Physics. "The development of computing demonstrates how the miniaturization of technology can lead to a revolution. The 2016 Nobel Laureates in Chemistry have miniaturized machines and taken chemistry to a new dimension," said the Royal Swedish Academy of Science. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.

News Article | October 5, 2016

The world’s most minuscule machines operate on the molecular level and have won their creators the 2016 Nobel Prize in chemistry. The prize is shared between Jean-Pierre Sauvage of the University of Strasbourg in France, J. Fraser Stoddart of Northwestern University in Evanston, Ill., and Bernard Feringa of the University of Groningen in the Netherlands. Sauvage and colleagues first linked two ring-shaped molecules together in 1983 to form a necklacelike chain. In 1991, Stoddart’s team created an atom-scale axle, paving the way to build molecular “muscles” and “elevators.” Through electrochemistry, Feringa and colleagues powered up the first light-powered molecular motor in 1999 and even designed a four-wheel drive, nano-sized car. These fantastic machines have opened up the molecular world to manipulating and moving objects at the smallest levels imaginable. There are “endless opportunities,” Feringa said in a phone interview during the announcement ceremony.

News Article | October 5, 2016

STOCKHOLM/LONDON (Reuters) - A trio of European scientists has won the 2016 Nobel Prize for Chemistry for developing molecular machines that could one day be injected to fight cancer or used to make new types of materials and energy storage devices. Frenchman Jean-Pierre Sauvage, Scotland's J. Fraser Stoddart and Dutchman Bernard Feringa developed molecules that produce mechanical motion in response to a stimulus, allowing them to perform specific tasks, the Nobel Academy said on Wednesday in awarding the 8 million Swedish crown ($931,000) prize. Such molecular machines can be developed in smart medicines that seek out disease or damage and deliver drugs to fight or fix it, and in smart materials that can adapt in response to external triggers such as changes in light or temperature. "There are endless opportunities," Feringa, a professor of organic chemistry at the University of Groningen in the Netherlands, told reporters when asked to predict what his work could eventually be used for. "Think of a tiny micro-robot that a doctor in the future will inject into your blood and that goes to search for a cancer cell or goes to deliver a drug, for instance." Goran Hansson, a member of the Royal Swedish Academy of Sciences which conferred the award, said this year's recognition was "all about the world's tiniest machines". "The sky's the limit," he said when asked where the discovery could lead. The Nobel committee's statement said the science of molecular machinery was now "at the same stage as the electric motor was in the 1830s" - when scientists displayed various spinning cranks and wheels, unaware that they would lead to electric trains, washing machines, fans and food processors. "We can still only guess at the thrilling developments ahead of us," it said. "However, we do have a definite answer to (the) initial question - how small can you make machinery?: At least 1,000 times thinner than a strand of hair." Sauvage is professor emeritus at the University of Strasbourg and director of research emeritus at France's National Center for Scientific Research. Stoddart, born in Edinburgh and now professor of chemistry at Northwestern University in the United States, said the prize was "quite unexpected". "When it happens, it takes your breath away," he said in a phone interview as he watched the ceremony live from his home outside Chicago. Chemistry is the third of this year's Nobels. Japan's Yoshinori Ohsumi won the medicine award on Monday, while three British-born scientists, including two Scots, took the physics prize on Tuesday. The prizes are named after dynamite inventor Alfred Nobel and have been awarded since 1901 for achievements in science, literature and peace, in accordance with his will.

News Article | November 16, 2016

Kenji Ohmori (Institute for Molecular Science, National Institutes of Natural Sciences, Japan) has collaborated with Matthias Weidemüller (University of Heidelberg), Guido Pupillo (University of Strasbourg), Claudiu Genes (University of Innsbruck) and their coworkers to develop the world's fastest simulator that can simulate quantum mechanical dynamics of a large number of particles interacting with each other within one billionths of a second. The dynamics of many electrons interacting with each other governs a variety of important physical and chemical phenomena such as superconductivity, magnetism, and chemical reactions. An ensemble of many particles thus interacting with each other is referred to as a "strongly correlated system." Understanding the properties of strongly correlated systems is thus one of the central goals of modern sciences. It is extremely difficult, however, to predict theoretically the properties of a strongly correlated system even if one uses the post-K supercomputer, which is one of the world's fastest supercomputers planned to be completed by the year 2020 in a national project of Japan. For example, the post-K cannot exactly calculate even the energy, which is the most basic property of matter, when the number of particles in the system is more than 30. Instead of calculating with a classical computer such as the post-K, an alternative concept has been proposed and referred to as a "quantum simulator," in which quantum mechanical particles such as atoms are assembled into an artificial strongly correlated system whose properties are known and controllable. The latter is then used to simulate and understand the properties of a different strongly correlated system, whose properties are not known. Huge investment to the development of quantum simulators has therefore been started recently in national projects of various countries including US, EU, and China. The team has developed a completely new quantum simulator that can simulate the dynamics of a strongly correlated system of more than 40 atoms within one billionths of a second. This has been realized by introducing a novel approach in which an ultrashort laser pulse whose pulse-width is only 100 billionths of a second is employed to control a high-density ensemble of atoms cooled down to temperatures close to absolute zero. Furthermore they have succeeded in simulating the motion of electrons of this strongly correlated system that is modulated by changing the strength of interactions among many atoms in the ensemble. This "ultrafast quantum simulator" is expected to serve as a basic tool to investigate the origin of physical properties of matter including magnetism and, possibly, superconductivity.

News Article | November 19, 2015

Astronomers at Caltech may have stumbled up the highest dark matter concentration in any known galaxy—and it happens to be just next door. At first glance, there isn't all that much to Triangulum II. With around 1,000 stars calling it home, the dwarf galaxy is a fleck of dust compared to our Milky Way, which is thought to contain some 200 to 400 billion stars. That's fine though: Triangulum II is a "dead" galaxy. It's long-since stopped producing new stars and soon enough what's left will blink away. Triangulum II might not be such an empty place, however. As described in a paper posted to the arXiv pre-print server and set for publication in the Astrophysical Journal Letters, the galaxy is seemingly overloaded with dark matter. This is so much so that the ratio of dark matter to regular matter within Triangulum II might prove to be the highest ever seen, making it an excellent quarry for directly detecting the stuff—a frustratingly elusive astrophysics milestone. Determining how much dark matter in a galaxy is simple enough in theory. It's just a comparison between all of the stuff you can see and how much mass that should add up to, and the actual observed mass of the galaxy. The difference can be assumed to be dark matter. To calculate their estimates, the Caltech team used the Low Resolution Imaging Spectrometer instrument at Hawaii's Keck Observatory. They were able to come up with a mass-to-light ratio—galactic mass compared to visible matter—of around 3500 (compared to 100 for the universe as a whole). Which is a lot of dark matter. The claim that Triangulum II has the highest mass-to-light ratio of any known galaxy is dependent on it being in a state of dynamic equilibrium—that is, there isn't some huge external force mucking things up. So, we're going on a pretty big assumption here. "It is unclear whether Tri II is in dynamical equilibrium," the Caltech group writes. "With a total luminosity of only 450 L⊙ [the unit of solar luminosity], the galaxy has very few stars available to measure its shape very precisely. Even fewer stars are available for spectroscopy." Another group of astronomers, this one at the University of Strasbourg in France, has been measuring the velocities of stars around Tri II, finding that the further away from the galaxy's center they are, the faster they're moving. This is the opposite of what would be expected from a galaxy in equilibrium. The gravity of the Milky Way might be pulling it apart. “My next steps are to make measurements to confirm that other group’s findings,” offers astronomer Evan Kirby, the study's lead author, in a statement. “If it turns out that those outer stars aren’t actually moving faster than the inner ones, then the galaxy could be in what’s called dynamic equilibrium. That would make it the most excellent candidate for detecting dark matter with gamma rays.”

News Article | October 5, 2016

Chemists who envisioned and built machines on the molecular scale have won the 2016 Nobel Prize in Chemistry. The award of nearly $1 million will be shared equally between Jean-Pierre Sauvage, J. Fraser Stoddart, and Ben L. Feringa “for the design and synthesis of molecular machines.” Molecular machines are single-molecules that behave much like the machines people encounter every day: They have controllable movements and can perform a task with the input of energy. Examples include a tiny elevator that goes up and down with changes in pH and a super-small motor that spins in one direction when exposed to light and heat. Many in the field speculate that molecular machines could find use in computing, novel materials, and energy storage. Building machines on the molecular scale takes clever chemistry. Both University of Strasbourg’s Sauvage and Northwestern University’s Stoddart were recognized for their work in the 1980s and 1990s creating molecules linked by a mechanical bond—components that are mechanically interlocked rather than covalently attached. These include catenanes, ring-shaped moieties hooked together like links in a chain, and rotaxanes, ring-shaped moieties wrapped around a rod-shaped one. In 1999 University of Groningen’s Feringa created the first molecular motor—a molecule that spins in one direction based on the light- and heat-driven isomerization of a double bond. In subsequent years a menagerie of molecular machines has been built in the laboratories of these three chemists and many others working in the field, including a motorized molecular car from Feringa’s lab that scoots along a surface. “Chemistry is about creating objects and new things,” said Stoddart reached at home in the early hours this morning. This award, he said, recognizes chemists—scientists who make, model, and measure. The Nobel Committee, he noted, has “recognized three people whose hearts and souls are in chemistry” “The recipients are an outstanding choice,” says Boston College chemistry professor T. Ross Kelly, who works in the field of molecular machines. “Creating molecules from scratch with function is something only chemists and nature can do.” The body is full of molecular machines, Kelly notes, and being able to understand how they work and then build them from scratch may allow scientists to repair them when they malfunction. “The Nobel Prize is way beyond a gift to three scientists,” notes ACS President Donna Nelson. “Each year it inspires work in a different area of science.” Nelson, who is also an organic chemistry professor at the University of Oklahoma, says that she appreciates the difficulty of creating molecular machines. Not only does the work present a synthetic challenge, she says, “but being able to prove that you’ve made your target molecules and that they have the desired functionality…it’s an amazing feat. This prize is well deserved.”

News Article | November 2, 2016

Motors too small to see with the eye may soon have the power to drive innovations in chemistry, biology and computing. Three creators of such nanoscopic machines were honored October 5 with the Nobel Prize in chemistry. Sharing the prize of 8 million Swedish kronor (about $930,000) equally are Jean-Pierre Sauvage, J. Fraser Stoddart and Bernard Feringa. “If you had to choose three people at the top of the field, that’s it. These are the men,” says James Tour, a nanomachines chemist at Rice University in Houston. ”It is a well-warranted prize.” Recognition of the burgeoning field of molecular motors will draw more money and inspire children to become scientists, says Donna Nelson, an organic chemist at the University of Oklahoma in Norman and the president of the American Chemical Society. “It will benefit not only these three chemists, it will benefit the entire field of chemistry.” Chemists and physicists have envisioned molecular machines since at least the 1960s, but were never able to reliably produce complex structures. Then in 1983, Sauvage, of the University of Strasbourg in France, devised a method for making interlocking molecular rings, or catenanes. Sauvage’s molecular chain set the stage for the rest of the field (SN: 9/8/90, p. 149). Stoddart, of Northwestern University in Evanston, Ill., improved the efficiency so that he could produce large quantities of molecular machines, starting in 1991 with rings clipped around a central axle. That structure is known as a rotaxane. He and colleagues learned to control the slide of the rings along the axle, making a simple molecular switch. Such switches could be used to create molecular computers or drug delivery systems. Stoddart showed in 2000 that it was possible to make molecular “muscles” using interlocking rings and axles. Stoddart and colleagues have since devised molecular elevators and pumps based on the same molecules. Feringa, of the University of Groningen in the Netherlands, ramped things up another notch in 1999 by building the first molecular motor. Things move so differently at the molecular scale that many researchers weren’t sure anyone could precisely control the motion of molecular motors, says R. Dean Astumian of the University of Maine in Orono. Feringa’s innovation was to devise asymmetric molecules that would spin in one direction when hit with a pulse of light. Up to 50,000 of the motors could span the width of a human hair, says Tour. Alone, one of the spinning motors doesn’t pack much punch (SN: 2/7/04, p. 94), but harnessed together in large numbers the little motors can do big work, he says. Groups of the whirring motors powered by light can rotate a glass rod thousands of times their size and do other work on a macroscopic scale. Feringa also harnessed his motors into a four-wheel-drive “nanocar” (SN: 12/17/11, p. 8). The process of making molecular machines has improved drastically over recent decades, thanks in large part to the work of the three newly christened laureates, says Rigoberto Advincula, a chemist at Case Western Reserve University in Cleveland. Scientists have a better understanding of how to construct molecules that more reliably bend, loop and connect to form shapes. “You don’t have tweezers to put them together,” he says. “You template the reaction so that the thread to goes through the ring. That then makes it easier for the two thread ends to meet each other.” New techniques have also allowed the production of more intricate shapes. Further development will bring these processes to even bigger scales, allowing for the design of molecular machines for everything from energy harvesting to building protein complexes, Advincula says. Such applications are still on the horizon and no one really knows what sorts of machines chemists can make from molecules yet. When people question Feringa about what his molecular motors can be used for, he “feels a bit like the Wright brothers” when people asked them after their first flight why they needed a flying machine, he said during a telephone call during the announcement of the prize. There are “endless opportunities,” including nanomachines that can seek and destroy tumor cells or deliver drugs to just the cells that need them, Feringa speculated. Stoddart, who was born in Edinburgh and moved to the United States in 1997, applauded the Nobel committee for recognizing “a piece of chemistry that is extremely fundamental in its making and being.” Sauvage, in particular, created a new type of molecular bond in order to forge his chain, Stoddart said during a news conference. “New chemical compounds are probably several thousand a day worldwide,” he said. “New chemical reactions, well, maybe a dozen or two a month. Maybe I go over the top there. But new bonds, they are few and far between. They are really the blue moons. So I think that’s what’s being recognized, more than anything.”

News Article | October 5, 2016

STOCKHOLM/LONDON (Reuters) - A trio of European scientists has won the 2016 Nobel Prize for Chemistry for developing molecular machines that could one day be injected to fight cancer or used to make new types of materials and energy storage devices. Frenchman Jean-Pierre Sauvage, Scotland's J. Fraser Stoddart and Dutchman Bernard Feringa developed molecules that produce mechanical motion in response to a stimulus, allowing them to perform specific tasks, the Nobel Academy said on Wednesday in awarding the 8 million Swedish crown (731,618 pound) prize. Such molecular machines can be developed in smart medicines that seek out disease or damage and deliver drugs to fight or fix it, and in smart materials that can adapt in response to external triggers such as changes in light or temperature. "There are endless opportunities," Feringa, a professor of organic chemistry at the University of Groningen in the Netherlands, told reporters when asked to predict what his work could eventually be used for. "Think of a tiny micro-robot that a doctor in the future will inject into your blood and that goes to search for a cancer cell or goes to deliver a drug, for instance." Goran Hansson, a member of the Royal Swedish Academy of Sciences which conferred the award, said this year's recognition was "all about the world's tiniest machines". "The sky's the limit," he said when asked where the discovery could lead. The Nobel committee's statement said the science of molecular machinery was now "at the same stage as the electric motor was in the 1830s" - when scientists displayed various spinning cranks and wheels, unaware that they would lead to electric trains, washing machines, fans and food processors. "We can still only guess at the thrilling developments ahead of us," it said. "However, we do have a definite answer to (the) initial question - how small can you make machinery?: At least 1,000 times thinner than a strand of hair." Sauvage is professor emeritus at the University of Strasbourg and director of research emeritus at France's National Center for Scientific Research. Stoddart, born in Edinburgh and now professor of chemistry at Northwestern University in the United States, said the prize was "quite unexpected". "When it happens, it takes your breath away," he said in a phone interview as he watched the ceremony live from his home outside Chicago. Chemistry is the third of this year's Nobels. Japan's Yoshinori Ohsumi won the medicine award on Monday, while three British-born scientists, including two Scots, took the physics prize on Tuesday. The prizes are named after dynamite inventor Alfred Nobel and have been awarded since 1901 for achievements in science, literature and peace, in accordance with his will.

News Article | October 26, 2016

Miniature robots that doctors could guide through a patient’s body to kill cancer cells are closer to reality thanks to winners of this year’s Nobel Prize for Chemistry. Three winners share the £727,000 prize for developing nanoscale machines—1000th the width of a human hair—that pave the way for applications in medicine, computing and engineering. The winners were Jean-Pierre Sauvage of the University of Strasbourg in France, Fraser Stoddart of Northwestern University in Illinois, USA, and Bernard Feringa of the University of Groningen in the Netherlands. Each devised different groups of molecules with moving parts that they could control remotely, despite their tiny size. “It’s early days, but once you can control movement, you have many possibilities,” said Feringa, interviewed after receiving notification of the prize. “We think of transporters, and of microrobots that doctors could inject into veins to search for cancer cells, or deliver drugs, or maybe smart materials that can change in response to a signal.” Since 1994, Feringa has devised a multitude of molecular machines that can rotate. They include a molecular version of a 4-wheel drive car, and a rotating molecular motor that can actually drive the rotation of a rod that’s 10,000 times larger. But the ground was laid as early as 1983 when Sauvage and his colleagues in France made a machine formed from two interlinked molecular rings. Called catenanes, the machines worked by rotating one of the rings relative to the other with the help of a copper atom that served as an on-switch. A decade later in 1991, Fraser Stoddart and his colleagues had pioneered another family of molecular machines called rotaxanes in which ring shaped molecules could be guided remotely to different points along a molecular axle. From that, Stoddart produced molecules that work like those in muscles. “They can extend and contract dramatically, mimicking the function of muscle tissue,” said  Olof Ramström of the Swedish Royal Institute of Technology in Stockholm, describing the trio’s achievements at the ceremony today. After that, Stoddart even made a molecular elevator that can move up and down between two stages. Ramström cautioned, however, that big practical breakthroughs are yet to come. “This is very fundamental science, and the future will show what these molecular machines can do,” he said. “The development stage is the same as the stage a century ago when scientists first demonstrated electrical machines and now look, they’re everywhere.” Stoddart wrote about his work in New Scientist in 1994.

News Article | November 16, 2016

Okazaki, Japan - Kenji Ohmori (Institute for Molecular Science, National Institutes of Natural Sciences, Japan) has collaborated with Matthias Weidemüller (University of Heidelberg), Guido Pupillo (University of Strasbourg), Claudiu Genes (University of Innsbruck) and their coworkers to develop the world's fastest simulator that can simulate quantum mechanical dynamics of a large number of particles interacting with each other within one billionths of a second. The dynamics of many electrons interacting with each other governs a variety of important physical and chemical phenomena such as superconductivity, magnetism, and chemical reactions. An ensemble of many particles thus interacting with each other is referred to as a "strongly correlated system". Understanding the properties of strongly correlated systems is thus one of the central goals of modern sciences. It is extremely difficult, however, to predict theoretically the properties of a strongly correlated system even if one uses the post-K supercomputer, which is one of the world's fastest supercomputers planned to be completed by the year 2020 in a national project of Japan. For example, the post-K cannot exactly calculate even the energy, which is the most basic property of matter, when the number of particles in the system is more than 30. Instead of calculating with a classical computer such as the post-K, an alternative concept has been proposed and referred to as a "quantum simulator", in which quantum mechanical particles such as atoms are assembled into an artificial strongly correlated system whose properties are known and controllable. The latter is then used to simulate and understand the properties of a different strongly correlated system, whose properties are not known. Huge investment to the development of quantum simulators has therefore been started recently in national projects of various countries including US, EU, and China. The team has developed a completely new quantum simulator that can simulate the dynamics of a strongly correlated system of more than 40 atoms within one billionths of a second. This has been realized by introducing a novel approach in which an ultrashort laser pulse whose pulse-width is only 100 billionths of a second is employed to control a high-density ensemble of atoms cooled down to temperatures close to absolute zero. Furthermore they have succeeded in simulating the motion of electrons of this strongly correlated system that is modulated by changing the strength of interactions among many atoms in the ensemble. This "ultrafast quantum simulator" is expected to serve as a basic tool to investigate the origin of physical properties of matter including magnetism and, possibly, superconductivity. This result will be published in Nature Communications, an online scientific journal of UK, on 16th November 2016. Journal: Nature Communications Title: Direct observation of ultrafast many-body electron dynamics in an ultracold Rydberg gas Authors: Nobuyuki Takei, Christian Sommer, Claudiu Genes, Guido Pupillo, Haruka Goto, Kuniaki Koyasu, Hisashi Chiba, Matthias Weidemüller, and Kenji Ohmori Date: 2016/11/16 DOI: 10.1038/NCOMMS13449 Kenji Ohmori Professor and Chairman, Department of Photo-Molecular Science, Institute for Molecular Science, National Institutes of Natural Sciences 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan Tel?+81-564-55-7361?Fax?+81-564-54-2254 E-mail: URL: https:/

News Article | October 7, 2016

Both the Chemistry and Physics Nobel Prizes this year share the distinction of being material and molecular studies that have revealed much about the nature of matter but both also hint at new technology with a wide range of implications. Tuesday, 4th October 2016, saw the announcement of the Physics prize, with half going to David J. Thouless of the University of Washington, Seattle, WA, and the other half to F. Duncan M. Haldane Princeton University, NJ and J. Michael Kosterlitz Brown University, Providence, Rhode Island, USA. The prize recognizes their theoretical discoveries of topological phase transitions and topological phases of matter. All three scientists are British born. The scientists unlocked the secrets of exotics phases of matter using mathematics to help us understand the behavior and properties of superconductors, superfluids, and thin magnetic films. More specifically, they used topology, the branch of mathematics that describes continuous transitions from one shape or structure to another, that are preserved, deformations such as stretching and bending as opposed to tearing or gluing. The mathematics applies equally to abstract entities such as spacetime and black holes as well as everyday objects such as teacups and doughnuts as well as materials at the molecular and atomic levels. In the early 1970s, Kosterlitz and Thouless overturned the theory that superconductivity or superfluidity could not exist in thin layers. They showed that superconductivity could occur at low temperatures and also explained the mechanism, a phase transition, that leads to the loss of superconductivity as the temperature rises above a critical point. In the 1980s, Thouless also explained earlier experiments with very thin electrically conducting layers and showed that topology could explain this too. Meanwhile, Haldane discovered how topology could explain the magnetic properties of certain materials. A day later, the Chemistry prize was announced and will be shared by Jean-Pierre Sauvage of the University of Strasbourg, France, British-born Sir J. Fraser Stoddart, of Northwestern University, Evanston, Illinois, USA, and Bernard L. Feringa of the University of Groningen, the Netherlands. The prize this year is in recognition of the design and synthesis of molecular machines. Such a terse phrase belies the true enormity of their efforts of many years wherein they are laying the foundations for devices that work on a scale much smaller than any manufactured system and in some sense on a par with the machinery of living cells. Sauvage took his first step towards a molecular machine in 1983 when he linked two ring-shaped molecules to form a catenane. Stoddart's work then extended this concept in 1991 to the so-called rotaxanes, a ring on a string, molecular system. And, in 1999 Feringa built a molecular motor. Together these three developments operating in parallel could one day allow technologists to build devices from the successors to these molecules. David Bradley blogs at Sciencebase Science Blog and tweets @sciencebase, he is author of the popular science book "Deceived Wisdom".

News Article | October 5, 2016

The creators of the world's tiniest machines have received the world's greatest recognition, having been awarded the 2016 Nobel Prize for Chemistry. The molecular machines are a thousand times thinner than a strand of hair, as BBC reports. Their small size allows for easy insertion into the human body to administer drugs, directly target cancer cells, or contribute to the functioning of "smart" technologies. The 8 million Swedish kronor, or $930,000, prize will be shared among the machine's designers, Jean-Pierre Sauvage, Sir Fraser Stoddart, and Bernard Feringa. Sauvage, who is emeritus professor at the University of Strasbourg and director of research emeritus at the French National Centre for Scientific Research (CNRS), has studied the relationship between sunlight and chemical reactions, which helped him understand how to link molecules in a chain. Stoddart, affiliated with Northwestern University, had threaded a molecular ring onto a microscopic rod, acting as an axle, and then added to heat to make it go backwards and forwards. The discovery was the foundation of his group building various molecular machines. Feringa, a professor of organic chemistry at the University of Groningen, the Netherlands, began research into molecular motors in 1999, and eventually built a four-wheel-drive nano-car in 2011. "I feel a little bit like the Wright Brothers who were flying 100 years ago for the first time and people were saying why do we need a flying machine and now we have a Boeing 747 and an Airbus," Feringa said of the Nobel prize in the BBC interview. "In terms of development, the molecular motor is at the same stage as the electric motor was in the 1830s, when scientists displayed various spinning cranks and wheels, unaware that they would lead to electric trains, washing machines, fans, and food processors," the Royal Swedish Academy of Sciences told The New York Times as they announced the Nobel prize. The academy awarded the prize to these three scientists because they were the frontrunners in the second wave of nanotechnology, which had been initially pioneered by physicist Richard Feynman beginning in the 1950s. The implications of nanotechnology for medicine and smart materials are only just beginning to be understood, but as stated already, this is only the commencement of something that could become a fundamental technology in decades to come. Get six of our favorite Motherboard stories every day by signing up for our newsletter.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: SPA-2007-1.1-01 | Award Amount: 40.31M | Year: 2009

SAFER aims at implementing preoperational versions of the Emergency Response Core Service. SAFER will reinforce European capacity to respond to emergency situations: fires, floods, earthquakes, volcanic eruptions, landslides, humanitarian crisis. The main goal is the upgrade of the core service and the validation of its performance with 2 priorities: First priority is the short term improvement of response when crisis occurs, with the rapid mapping capacity after disastrous events, including the relevant preparatory services (reference maps). For validation purposes, the project will deliver as from 2008 services at full scale for real events or during specific exercises. The main performance criterion is the response time. RTD work addresses technical, operational and organisational issues. The content of this first action is consistent with the definition of the preparatory action recently decided. The second priority is the extension to core service components before and after the crisis. It targets the longer term service evolution, through the provision of thematic products, to be added in the portfolio of services. The main performance criterion is the added-value of products with risk-specific information. In SAFER, thematic products will cover mainly the meteorological and geophysical risks. SAFER includes also some transverse RDT actions, with the objective to increase added-value of the overall service chain. Users involvement is a key driver and a specific task addresses the federation of the key users, both for interventions in Europe and outside Europe. The emphasis put on quality assurance and validation methodology is reflected in the work plan. The consortium is built around a core team of European service providers, already involved in the former or ongoing projects, in the frame of FP6 or ESA programmes. A wide network of scientific partners and service providers will extend the European dimension, in particular in the new member states.

Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: PEOPLE-2007-1-1-ITN | Award Amount: 2.40M | Year: 2008

This project intends to use directed evolution as tool to reproduce Natures remarkable ability to generate molecular machines - in particular enzymes that perform at levels near perfection. By harnessing the forces of Darwinian evolution in the laboratory we want to (i) screen large and diverse genome libraries for protein with new and useful functions, (ii) optimize existing proteins for applications in medicine, biotechnology and cell biology and (iii) provide a better understanding of how existing enzymes evolved and study enzyme mechanisms in general. The proposed Network brings together leading academic and industrial groups with diverse and complementary skills: the development of a variety of innovative biotechnology tools for the generation and exploitation of large genomic and man-made libraries, expertise in mechanistic enzymology and an unrivalled technology platform including phage display, in vitro compartmentalization, ribosome display, selective protein labelling and high-throughput screening that will be key to achieve the ambitious goals of this project. The project is a continuation of a highly successful framework 5 network. The partnership has now been extended by two successful SMEs at different stages of their development and one of Europes premier medium-sized biotech companies that are keen to utilise and market the expected results of this collaborative effort.

Agency: Cordis | Branch: FP7 | Program: CPCSA | Phase: INFRA-2007-2.2-02 | Award Amount: 20.38M | Year: 2008

ESFRI has identified High Performance Computing (HPC) as a strategic priority for Europe. Scientists and engineers must be provided with access to capability computers of leadership class in Europe to remain competitive internationally and to maintain or regain leadership. Supercomputers are an indispensable tool to solve the most challenging problems through simulations.\n\nPACE, the Partnership for Advanced Computing in Europe, has the overall objective to prepare the creation of a persistent pan-European HPC service, consisting of three to five centres, similar to the US HPC infrastructure. PACE will be the tier-0 level of the European HPC ecosystem. It will build on the experience of the partners and use concepts and services from EC-funded projects like GEANT2 and DEISA.\n\nThe hosting centres of the planned tier-0 systems will provide the expertise, competency, and the required infrastructure for comprehensive services to meet the challenging demands of excellent users from academia and industry.\n\nPACE will prepare for the implementation of the infrastructure in 2009/2010 by defining and setting up a legal and organisational structure involving HPC centres, national funding agencies, and scientific user communities to ensure adequate funding for the continued operation and periodic renewal of leadership systems, coordinated procurements, efficient use and fair access.\n\nIn parallel PACE will prepare the deployment of Petaflop/s systems in 2009/2010. This includes the procurement of prototype systems for the evaluation of software for managing the distributed infrastructure, the selection, benchmarking, and scaling of libraries and codes from major scientific user communities, the definition of technical requirements and procurement procedures, as well as collaborations with the European IT-industry to influence the development of new technologies and components for architectures that are promising for Petaflop/s systems to be procured after 2010.

News Article | September 1, 2016

The legacy of World War II and the Holocaust continues to be unearthed, 70 years after the final bombs were dropped, the gates to the extermination camps opened. Body parts and brains of the victims of Nazi doctors were found at the Max Planck Psychiatric Institute during renovations last year, according to The Daily Mail. The remains are believed to have come from the work of Josef Mengele, the “Angel of Death” of Auschwitz infamous for his sadistic experiments on twins and children. The gruesome discovery was found during renovation work at the Munich facility. In a separate ongoing dig, skulls and bones with glue on them have been found in Berlin, about 100 yards away from what was the Kaiser Wilhelm Institute for Human Heredity and Eugenics during the Nazi regime, according to The Associated Press. Mengele, the most infamous SS doctor at the death camp in Poland from 1943 until the end of World War II, escaped Allied investigators and justice for decades, until his remains were disinterred in Brazil and identified in 1985. The Munich and Berlin discoveries also follow a revelation in France: the identification of the remains of 86 victims of the Holocaust on the shelves of the University of Strasbourg last year. Some of those victims were identified, based on tattoos and biometrics on file in the World War II records. The Mack Planck Society ordered a complete review of its specimens, since the discovery of the brains in its Munich-based collection. "The Max Planck Society has accepted a difficult legacy of its predecessor organziation, the Kaiser Wilhelm Society," said Martin Stratmann, the current president of the organization. "We are well aware of the special responsibility that it entails." Mengele remained in Germany and under the radar of war crimes prosecutors until 1949, when he crossed the border to Austria and then fled to Argentina. He lived under his real name in Buenos Aires for about a decade, until the Israeli capture of fellow Nazi Adolf Eichmann prompted his escape to Paraguay and then Brazil. German sympathizers hosted him and kept his identity a secret. Mengele had a stroke and drowned while swimming in 1979. He was buried under the pseudonym Wolfgang Gerhard. His remains were identified in 1985. The Nazi doctor's remains have been stored in a sack at a Brazilian police moruge for decades. In a twist, they are going to be used to teach medical students in the South American country, a doctor announced earlier this year.

News Article | November 16, 2016

Abstract: Kenji Ohmori (Institute for Molecular Science, National Institutes of Natural Sciences, Japan) has collaborated with Matthias Weidemüller (University of Heidelberg), Guido Pupillo (University of Strasbourg), Claudiu Genes (University of Innsbruck) and their coworkers to develop the world's fastest simulator that can simulate quantum mechanical dynamics of a large number of particles interacting with each other within one billionths of a second. The dynamics of many electrons interacting with each other governs a variety of important physical and chemical phenomena such as superconductivity, magnetism, and chemical reactions. An ensemble of many particles thus interacting with each other is referred to as a "strongly correlated system". Understanding the properties of strongly correlated systems is thus one of the central goals of modern sciences. It is extremely difficult, however, to predict theoretically the properties of a strongly correlated system even if one uses the post-K supercomputer, which is one of the world's fastest supercomputers planned to be completed by the year 2020 in a national project of Japan. For example, the post-K cannot exactly calculate even the energy, which is the most basic property of matter, when the number of particles in the system is more than 30. Instead of calculating with a classical computer such as the post-K, an alternative concept has been proposed and referred to as a "quantum simulator", in which quantum mechanical particles such as atoms are assembled into an artificial strongly correlated system whose properties are known and controllable. The latter is then used to simulate and understand the properties of a different strongly correlated system, whose properties are not known. Huge investment to the development of quantum simulators has therefore been started recently in national projects of various countries including US, EU, and China. The team has developed a completely new quantum simulator that can simulate the dynamics of a strongly correlated system of more than 40 atoms within one billionths of a second. This has been realized by introducing a novel approach in which an ultrashort laser pulse whose pulse-width is only 100 billionths of a second is employed to control a high-density ensemble of atoms cooled down to temperatures close to absolute zero. Furthermore they have succeeded in simulating the motion of electrons of this strongly correlated system that is modulated by changing the strength of interactions among many atoms in the ensemble. This "ultrafast quantum simulator" is expected to serve as a basic tool to investigate the origin of physical properties of matter including magnetism and, possibly, superconductivity. This result will be published in Nature Communications, an online scientific journal of UK, on 16th November 2016. ### (Information of the paper) Journal: Nature Communications Title: Direct observation of ultrafast many-body electron dynamics in an ultracold Rydberg gas Authors: Nobuyuki Takei, Christian Sommer, Claudiu Genes, Guido Pupillo, Haruka Goto, Kuniaki Koyasu, Hisashi Chiba, Matthias Weidemüller, and Kenji Ohmori Date: 2016/11/16 DOI: 10.1038/NCOMMS13449 For more information, please click Contacts: Kenji Ohmori Professor and Chairman, Department of Photo-Molecular Science, Institute for Molecular Science, National Institutes of Natural Sciences 38 Nishigo-Naka, Myodaiji, Okazaki 444-8585, Japan Tel?+81-564-55-7361?Fax?+81-564-54-2254 URL: (Press contact) Public Relations, Institute for Molecular Science, Natural Institutes of Natural Sciences TEL/FAX?+81-564-55-7262 If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Home > Press > A Northwestern Nobel Prize: Sir Fraser Stoddart of Northwestern University is awarded the Nobel Prize in Chemistry Abstract: Sir Fraser Stoddart, Board of Trustees Professor of Chemistry in the Weinberg College of Arts and Sciences at Northwestern University, today (Oct. 5) was awarded the Nobel Prize in Chemistry. The Royal Swedish Academy of Sciences announced it has awarded the Nobel Prize in Chemistry 2016 to Professor Stoddart as well as Jean-Pierre Sauvage, University of Strasbourg, France, and Bernard L. Feringa, University of Groningen, the Netherlands, "for the design and synthesis of molecular machines." The academy credited them with developing “molecules with controllable movements, which can perform a task when energy is added." “The development of computing demonstrates how the miniaturization of technology can lead to a revolution. The 2016 Nobel Laureates in Chemistry have miniaturized machines and taken chemistry to a new dimension,” the academy said. Read the academy’s announcement. For his part, Professor Stoddart was awarded the prize because, the academy said, in 1991 he developed “a rotaxane. He threaded a molecular ring onto a thin molecular axle and demonstrated that the ring was able to move along the axle. Among his developments based on rotaxanes are a molecular lift, a molecular muscle and a molecule-based computer chip.” By introducing an additional type of bond (the mechanical bond) into chemical compounds, Stoddart became one of the few chemists to have opened up a new field of chemistry during the past 25 years. His work on molecular recognition and self-assembly and his subsequent introduction of template-directed routes to mechanically interlocked molecules has changed dramatically the way chemists go about making soft materials. Stoddart’s introduction of the mechanical bond, which has led to the fabrication of artificial molecular switches and motors, has been responsible for putting chemists at the forefront of the burgeoning field of molecular nanotechnology, with implications ranging all the way from information technology to health care. “This is a tremendous honor for Professor Stoddart and Northwestern University,” Northwestern President Morton Schapiro said. “Fraser is a pioneer in the fields of chemistry and integrated nanosystems and a member of an outstanding chemistry department. The University is proud of his many accomplishments.” Stoddart’s achievements include raising the bar for molecular electronics (using molecules on the nanoscale as the tiniest of switches, which have been incorporated into the densest of memory chips in a device that can hold the Declaration of Independence but is only the size of a white blood cell) and giving practical expression to artificial molecular switches (using nanovalves planted on the surfaces of mesoporous glass nanoparticles to create controllable and targeted drug delivery systems for the treatment of cancer and other degenerative diseases). In 2007, The Sunday Times in the U.K. wrote that Stoddart “is to nanotechnology what J.K. Rowling is to children’s literature.” A common theme of Stoddart’s research is the quest for a better fundamental understanding of self-assembly and molecular recognition processes in chemical systems. He has been working for more than three decades on using this growing understanding to develop template-directed protocols that rely upon such processes to create artificial molecular machines. Underlying his bottom-up approach to the construction of integrated nanosystems is Stoddart’s philosophy of transferring concepts from biology into chemistry. “My research on mechanically interlocked molecules, which has taken the field of supramolecular chemistry, i.e., chemistry beyond the molecule, back into the molecular domain, heralds a game-changer for molecular nanotechnology,” Stoddart said. The exquisite interplay between the classical (covalent and noncovalent) chemical bonds and the contemporary mechanical bond provides chemists with a blueprint and platform to start designing and making artificial molecular motors that operate far away from equilibrium in much the same way as do the motor-proteins that drive living systems to perform work in a multitude of different settings. A native of Edinburgh, Scotland, Stoddart received the Royal Medal in 2010 from His Royal Highness the Duke of Edinburgh at the Royal Society of Edinburgh (RSE), Scotland’s national academy of arts and sciences. He was appointed by Her Majesty Queen Elizabeth II as a Knight Bachelor in her 2007 New Year’s Honours List for his services to chemistry and molecular nanotechnology. He was elected to the fellowship of the American Academy of Arts and Sciences in 2012 and membership of the National Academy of Sciences in 2014. During his career, Stoddart has received many other prestigious national and international awards and honors. They include being elected an honorary fellow of both the RSE and the Royal Society of Chemistry (RSC) and receiving the Davy Medal from the Royal Society, the national academy of science of the United Kingdom and the Commonwealth, of which he is also a Fellow. Other awards include the Nagoya Gold Medal in Organic Chemistry, the American Chemical Society’s Arthur C. Cope Award, the Feynman Prize in Nanotechnology, the King Faisal International Prize in Science, the Tetrahedron Prize for Creativity in Organic Chemistry, the Albert Einstein World Award of Science and the RSC’s Centenary Prize. Stoddart serves on the international advisory boards of numerous journals, including Chemistry World, Organic Letters and ChemPlusChem. He has published 1,080 scientific papers and trained more than 500 graduate and postdoctoral students. Before joining the Northwestern faculty in January 2008, Stoddart was Fred Kavli Chair in Nanosystems Sciences at the University of California at Los Angeles and director of the California NanoSystems Institute. He came to UCLA in 1997 from England’s University of Birmingham, where he had been a professor of organic chemistry since 1990 and had headed the university’s School of Chemistry since 1993. Born in Edinburgh in 1942, Stoddart received his bachelor of science (1964), Ph.D. (1966) and D.Sc. (1980) degrees from the University of Edinburgh. In 1967, he moved to Queen’s University in Ontario, Canada, where he was a National Research Council postdoctoral fellow and then, in 1970, to England’s University of Sheffield, where he was first an Imperial Chemical Industries (ICI) research fellow before becoming a faculty lecturer (assistant professor) in chemistry. After spending a three-year “secondment” (1978 to 1981) at the ICI Corporate Laboratory in Runcorn, England, he returned full time to the University of Sheffield, where he was promoted to a readership (associate professorship). He moved to the University of Birmingham in 1990 to take up the Chair of Organic Chemistry in 1990. This is the second Nobel Prize winner from Northwestern’s department of chemistry. The late John A. Pople received the 1998 Nobel Prize in Chemistry. A video of Stoddart speaking at a nanotechnology town hall meeting about his background, his research and his “15 seconds worth of contact” with Her Majesty Queen Elizabeth II can be viewed on Northwestern’s YouTube channel. (Sir Fraser Stoddart is a resident of Evanston, Illinois.) For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Thunis P.,European Commission - Joint Research Center Ispra | Clappier A.,University of Strasbourg
Atmospheric Environment | Year: 2014

Air quality models are useful tools for the assessment and forecast of pollutant concentrations in the atmosphere. Most of the evaluation process relies on the "operational phase" or in other words the comparison of model results with available measurements which provides insight on the model capability to reproduce measured concentrations for a given application. But one of the key advantages of air quality models lies in their ability to assess the impact of precursor emission reductions on air quality levels. Models are then used in a dynamic mode (i.e. response to a change in a given model input data) for which evaluation of the model performances becomes a challenge. The objective of this work is to propose common indicators and diagrams to facilitate the understanding of model responses to emission changes when models are to be used for policy support. These indicators are shown to be useful to retrieve information on the magnitude of the locally produced impacts of emission reductions on concentrations with respect to the "external to the domain" contribution but also to identify, distinguish and quantify impacts arising from different factors (different precursors). In addition information about the robustness of the model results is provided. As such these indicators might reveal useful as first screening methodology to identify the feasibility of a given action as well as to prioritize the factors on which to act for an increased efficiency. Finally all indicators are made dimensionless to facilitate the comparison of results obtained with different models, different resolutions, or on different geographical areas. © 2014 The Authors.

Lenzi S.M.,University of Padua | Nowacki F.,University of Strasbourg | Poves A.,Autonomous University of Madrid | Sieja K.,University of Strasbourg
Physical Review C - Nuclear Physics | Year: 2010

We study the development of collectivity in the neutron-rich nuclei around N=40, where the experimental and theoretical evidence suggest a rapid shape change from the spherical to the rotational regime, in analogy to what happens at the island of inversion surrounding Na31. Theoretical calculations are performed within the interacting shell-model framework in a large valence space, based on a Ca48 core, which encompasses the full pf shell for the protons and the 0f5/2, 1p3/2, 1p1/2, 0g9/2, and 1d5/2 orbits for the neutrons. The effective interaction is based on a G matrix obtained from a realistic nucleon-nucleon potential whose monopole part is corrected empirically to produce effective single-particle energies compatible with the experimental data. We find a good agreement between the theoretical results and the available experimental data. We predict the onset of deformation at different neutron numbers for the various isotopic chains. The maximum collectivity occurs in the chromium isotopes where the large deformation regime already starts at N=38. The shell evolution responsible for the observed shape changes is discussed in detail, in parallel to the situation in the N=20 region. © 2010 The American Physical Society.

Rotstein Y.,University of Strasbourg | Rotstein Y.,Us Israel Bi Ational Science Foundation | Schaming M.,University of Strasbourg
Tectonics | Year: 2011

Although the Upper Rhine Graben (URG) has been studied extensively for years, the origin of some of its first-order structures is still under debate, particularly the relatively young uplift of the Vosges Mountains (VM) and Black Forest Mountains (BFM). Their uplift appears to be temporally related to the change of the URG into a continental transform, the rapid subsidence of its deep northern basin, and the onset of erosional and nondepositional phase south of the Northern Basin. Recent observations from newly released seismic reflection data, coupled with older geologic and seismic observations, are used to explain this correlation. We suggest that when the URG turned into a continental transform during the early Miocene, not only was its northern basin transtensionally subsiding as previously suggested, but the VM and BFM were transpressionally uplifted. Transpression became weaker with growing distance from the Alpine front, and north of Baden-Baden the transpression is expressed only by down-buckling of the sediments, forming a deep, elongated syncline. The largest uplifts and erosion associated with this event occurred along both boundaries of the southern URG. However, the center of the graben was also affected to some extent, causing widespread erosion of pre-early Miocene sediments and subsequent nondeposition. The arcuate Vosges and Black Forest fault systems, which formed the boundary faults of the URG during the Oligocene, became mechanically unfavorable during the Miocene transpressional regime. Instead, more linear normal faults took over as the dominant boundary faults, forming the western and eastern Rhine Fault systems and assuming a strike-slip component of motion. Copyright 2011 by the American Geophysical Union.

Gutierrez-Marco J.C.,Complutense University of Madrid | Ghienne J.-F.,University of Strasbourg | Bernardez E.,Complutense University of Madrid | Hacar M.P.,Ferrovial Agroman S.A.
Geology | Year: 2010

Paleovalleys and their infilling successions are described from outcrops and drill cores of the Cantabrian Range (northern Spain). A Hirnantia fauna and associated diamictites with striated lonestones indicate that the paleovalleys are related to the Hirnantian (latest Ordovician) glacial event. Based on overall geometry, depositional facies, and associated deformation structures, the paleovalleys are interpreted as subglacial tunnel valleys. They were most likely related to the North Gondwana ice sheet. The ice sheet therefore reached the Ibero-Armorican domain that was still attached to the Gondwana landmass at least until the latest Ordovician. © 2010 Geological Society of America.

Sadoc J.-F.,University Paris - Sud | Rivier N.,University of Strasbourg | Charvolin J.,University Paris - Sud
Acta Crystallographica Section A: Foundations of Crystallography | Year: 2012

Phyllotaxis, the search for the most homogeneous and dense organizations of small discs inside a large circular domain, was first developed to analyse arrangements of leaves or florets in plants. It has since become an object of study not only in botany, but also in mathematics, computer simulations and physics. Although the mathematical solution is now well known, an algorithm setting out the centres of the small discs on a Fermat spiral, the very nature of this organization and its properties of symmetry remain to be examined. The purpose of this paper is to describe a phyllotactic organization of points through its Voronoi cells and Delaunay triangulation and to refer to the concept of defects developed in condensed matter physics. The topological constraint of circular symmetry introduces an original inflation-deflation symmetry taking the place of the translational and rotational symmetries of classical crystallography. © 2012 International Union of Crystallography Printed in Singapore - all rights reserved.

Graille M.,University Paris - Sud | Graille M.,Ecole Polytechnique - Palaiseau | Seraphin B.,Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire Igbmc | Seraphin B.,French National Center for Scientific Research | And 2 more authors.
Nature Reviews Molecular Cell Biology | Year: 2012

Living cells require the continuous production of proteins by the ribosomes. Any problem enforcing these protein factories to stall during mRNA translation may then have deleterious cellular effects. To minimize these defects, eukaryotic cells have evolved dedicated surveillance pathways: non-stop decay (NSD), no-go decay (NGD) and non-functional 18S-rRNA decay (18S-NRD). Recent studies support a general molecular framework for these surveillance pathways, the mechanisms of which are intimately related to translation termination. © 2012 Macmillan Publishers Limited. All rights reserved.

Millevoi S.,University Paul Sabatier | Moine H.,University of Strasbourg | Vagner S.,French Institute of Health and Medical Research | Vagner S.,University Paris - Sud
Wiley Interdisciplinary Reviews: RNA | Year: 2012

G-quadruplexes are noncanonical structures formed by G-rich DNA and RNA sequences that fold into a four-stranded conformation. Experimental studies and computational predictions show that RNA G-quadruplexes are present in transcripts associated with telomeres, in noncoding sequences of primary transcripts and within mature transcripts. RNA G-quadruplexes at these specific locations play important roles in key cellular functions, including telomere homeostasis and gene expression. Indeed, RNA G-quadruplexes appear as important regulators of pre-mRNA processing (splicing and polyadenylation), RNA turnover, mRNA targeting and translation. The regulatory mechanisms controlled by RNA G-quadruplexes involve the binding of protein factors that modulate G-quadruplex conformation and/or serve as a bridge to recruit additional protein regulators. In this review, we summarize the current knowledge on the role of G-quadruplexes in RNA biology with particular emphasis on the molecular mechanisms underlying their specific function in RNA metabolism occurring in physiological or pathological conditions. © 2012 John Wiley & Sons, Ltd.

Caurier E.,University of Strasbourg | Nowacki F.,University of Strasbourg | Poves A.,Autonomous University of Madrid
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2012

We study in this Letter the double beta decay of 136Xe with emission of two neutrinos which has been recently measured by the EXO-200 Collaboration. We use the same shell model framework, valence space, and effective interaction that we have already employed in our calculation of the nuclear matrix element (NME) of its neutrinoless double beta decay. Using the quenching factor of the Gamow-Teller operator which is needed to reproduce the very recent high resolution 136Xe ( 3He, t) 136Cs data, we obtain a nuclear matrix element M 2ν=0.025 MeV -1 compared with the experimental value M 2ν=0.019(2) MeV -1. © 2012 Elsevier B.V.

Hergeth S.P.,Medizinweltenservices GmbH | Schneider R.,University of Strasbourg
EMBO Reports | Year: 2015

The linker histone H1 family members are a key component of chromatin and bind to the nucleosomal core particle around the DNA entry and exit sites. H1 can stabilize both nucleosome structure and higher-order chromatin architecture. In general, H1 molecules consist of a central globular domain with more flexible tail regions at both their N- and C-terminal ends. The existence of multiple H1 subtypes and a large variety of posttranslational modifications brings about a considerable degree of complexity and makes studying this protein family challenging. Here, we review recent progress in understanding the function of linker histones and their subtypes beyond their role as merely structural chromatin components. We summarize current findings on the role of H1 in heterochromatin formation, transcriptional regulation and embryogenesis with a focus on H1 subtypes and their specific modifications. © 2015 The Authors.

Felden B.,French Institute of Health and Medical Research | Vandenesch F.,University of Lyon | Bouloc P.,University Paris - Sud | Romby P.,University of Strasbourg
PLoS Pathogens | Year: 2011

Staphylococcus aureus is a major human pathogen causing a wide spectrum of nosocomial and community-associated infections with high morbidity and mortality. S. aureus generates a large number of virulence factors whose timing and expression levels are precisely tuned by regulatory proteins and RNAs. The aptitude of bacteria to use RNAs to rapidly modify gene expression, including virulence factors in response to stress or environmental changes, and to survive in a host is an evolving concept. Here, we focus on the recently inventoried S. aureus regulatory RNAs, with emphasis on those with identified functions, two of which are directly involved in pathogenicity. © 2011 Felden et al.

Wu D.,Beckman Institute | Freund J.B.,University of Illinois at Urbana - Champaign | Fraser S.E.,Beckman Institute | Vermot J.,University of Strasbourg
Developmental Cell | Year: 2011

Otoliths, which are connected to stereociliary bundles in the inner ear, serve as inertial sensors for balance. In teleostei, otolith development is critically dependent on flow forces generated by beating cilia; however, the mechanism by which flow controls otolith formation remains unclear. Here, we have developed a noninvasive flow probe using optical tweezers and a viscous flow model in order to demonstrate how the observed hydrodynamics influence otolith assembly. We show that rotational flow stirs and suppresses precursor agglomeration in the core of the cilia-driven vortex. The velocity field correlates with the shape of the otolith and we provide evidence that hydrodynamics is actively involved in controlling otolith morphogenesis. An implication of this hydrodynamic effect is that otolith self-assembly is mediated by the balance between Brownian motion and cilia-driven flow. More generally, this flow feature highlights an alternative biological strategy for controlling particle localization in solution. © 2011 Elsevier Inc.

Bura T.,Laboratoire Of Chimie Moleculaire | Leclerc N.,CNRS Institute of Chemistry | Bechara R.,University of Strasbourg | Leveque P.,University of Strasbourg | And 2 more authors.
Advanced Energy Materials | Year: 2013

Photovoltaic solar energy conversion has attracted considerable interest of the scientifi c community due to the urgent need for alternative and renewable energy sources. Solar cells using solution-processed organic semiconductors as a photoactive layer have appeared as a particularly promising technology due to the prospective for low cost, light weight modules and roll-to-roll processing. [ 1 ] A signifi cant increase in the power conversion effi ciency (PCE) of solution-processed organic photovoltaic (OPV) devices has been achieved over the last decade, and results largely from the development of new electron-donating conjugated polymers. Intensive research on solution-processed small conjugated molecules, as an alternative to semiconducting polymers, started more recently and is driven by potential advantages, such as the mono-disperse nature, easier purifi cation, better reproducibility and excellent light-harvesting properties of molecular dyes. Small molecules have already been used effi ciently in vapor-deposited OPV devices and allowed the development of tandem cells with PCEs around 12%. [ 2 ] For solution-processed devices, however, the performances are still lower and limited by the diffi-culty in achieving high quality thin fi lms with a controlled and thermally stable nanomorphology (interpenetrated network of donor and acceptor domains), good charge carrier transport and low recombination rates.© 2013 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim.

Mariette X.,University Paris - Sud | Gottenberg J.-E.,University of Strasbourg
Current Opinion in Rheumatology | Year: 2010

Purpose Of Review: To summarize recent findings on new pathogenic mechanisms of interaction between genetic and environmental factors and between innate and adaptive immunity in primary Sjögren's syndrome and to reconcile pathogenesis and treatment by focusing on the crucial pathogenic steps that could be targeted by emerging therapies. Recent Findings: Regarding genetic predisposition, the functional relevance of IRF5 and STAT4 gene polymorphisms in the activation of type I interferon pathways has been demonstrated. It has also been shown that the isolated stimulation of innate immunity in mice can result in dryness, which precedes lymphocytic infiltrates in salivary glands. In animal models, possible environmental triggers of the disease, such as oestrogen deficiency and/or infection by Epstein-Barr virus, can lead to innate immune followed by autoimmune epithelitis. The IFN-BAFF-B lymphocyte pathogenic axis is, therefore, targeted by numerous drugs currently in evaluation. The development of consensus disease activity scores and patient-related outcomes might help to initiate new controlled trials. The first positive randomized controlled trial with rituximab has been recently published. Summary: Hopefully, persistent and joint efforts by many teams to improve the knowledge on the pathogenesis of the disease may allow identification of new therapeutic targets in Sjögren's syndrome. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Roy N.,University of Strasbourg | Buhler E.,CNRS Complex Systems and Materials Laboratory | Lehn J.-M.,University of Strasbourg
Polymer Chemistry | Year: 2013

We describe a novel approach to the generation of a supramolecular polymer and its assembly into microcapsules by the aerial oxidation of a supramolecular building block. It involves the initial build-up of a ditopic supramolecular component by hydrogen bonding association of two complementary subunits, followed by its covalent polymerization through oxidative formation of C-C linkages. The supramolecular component itself was selectively formed from a dynamic covalent library of hydrazone isomers by target specific amplification of a single library constituent. The polymer obtained condenses into supramolecular aggregates of micrometric size and capsular-type morphology, presenting multilayered walls, which have been characterized by STEM, SEM and AFM imaging methods. The present design methodology implements the covalent polycondensation of non-covalent monomers towards the formation of supramolecular polymers, in a sequence opposite to the usual non-covalent polyassociation of covalent complementary monomers. It can be envisaged as a proactive step towards forming adaptive smart materials through manipulation of the sequence of supramolecular/non-covalent and molecular/covalent steps for the generation of supramolecular polymers by suitable selection of receptor and substrate moieties. © 2013 The Royal Society of Chemistry.

Kolesnikova O.,University of Strasbourg | Back R.,Ecole Polytechnique - Palaiseau | Graille M.,Ecole Polytechnique - Palaiseau | Graille M.,University Paris - Sud | Seraphin B.,University of Strasbourg
Nucleic Acids Research | Year: 2013

In the yeast Saccharomyces cerevisiae, the Edc3 protein was previously reported to participate in the auto-regulatory feedback loop controlling the level of the RPS28B messenger RNA (mRNA). We show here that Edc3 binds directly and tightly to the globular core of Rps28 ribosomal protein. This binding occurs through a motif that is present exclusively in Edc3 proteins from yeast belonging to the Saccharomycetaceae phylum. Functional analyses indicate that the ability of Edc3 to interact with Rps28 is not required for its general function and for its role in the regulation of the YRA1 pre-mRNA decay. In contrast, this interaction appears to be exclusively required for the autoregulatory mechanism controlling the RPS28B mRNA decay. These observations suggest a plausible model for the evolutionary appearance of a Rps28 binding motif in Edc3. © The Author(s) 2013. Published by Oxford University Press.

Caurier E.,University of Strasbourg | Nowacki F.,University of Strasbourg | Poves A.,Autonomous University of Madrid | Poves A.,CERN
Physical Review C - Nuclear Physics | Year: 2014

The N=20 and N=28 "islands of inversion" are described by large scale shell model calculations with an extension of the interaction SDPF-U that makes it possible to mix configurations with different N ω or equivalently with different numbers of particles promoted from the sd shell to the pf shell. It allows to connect the classical sd-shell calculations below N=18 with the sd (protons)-pf (neutrons) calculations beyond N=24-26, for all the isotopes from oxygen to sulfur, using the same interaction. For some isotopes this range contains all the nuclei between the proton and the neutron drip lines and includes the N=20 and N=28 islands of inversion. We pay particular attention to the properties of the states at fixed N ω which turn out to be the real protagonists of the physics at N=20. The existence of islands of inversion or deformation are explained as the result of the competition between the spherical mean field which favors the 0 ω configurations and the nuclear correlations which favor the deformed N ω configurations. The magnesium chain is exceptional because in it the N=20 and N=28 islands of inversion merge, enclosing all the isotopes between N=19 and N=30. Indeed, this would be also the case for the neon and sodium chains if their drip lines would reach N=28. © 2014 American Physical Society.

Grosjean H.,University Paris - Sud | Westhof E.,University of Strasbourg
Nucleic Acids Research | Year: 2016

The principles of mRNA decoding are conserved among all extant life forms. We present an integrative view of all the interaction networks between mRNA, tRNA and rRNA: the intrinsic stability of codon-anticodon duplex, the conformation of the anticodon hairpin, the presence of modified nucleotides, the occurrence of non-Watson-Crick pairs in the codon-anticodon helix and the interactions with bases of rRNA at the A-site decoding site. We derive a more information-rich, alternative representation of the genetic code, that is circular with an unsymmetrical distribution of codons leading to a clear segregation between GC-rich 4-codon boxes and AU-rich 2:2-codon and 3:1-codon boxes. All tRNA sequence variations can be visualized, within an internal structural and energy framework, for each organism, and each anticodon of the sense codons. The multiplicity and complexity of nucleotide modifications at positions 34 and 37 of the anticodon loop segregate meaningfully, and correlate well with the necessity to stabilize AU-rich codon-anticodon pairs and to avoid miscoding in split codon boxes. The evolution and expansion of the genetic code is viewed as being originally based on GC content with progressive introduction of A/U together with tRNA modifications. The representation we present should help the engineering of the genetic code to include non-natural amino acids. © 2016 The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Calderon M.A.,Imperial College London | Linneberg A.,Glostrup University Hospital | Linneberg A.,Copenhagen University | Kleine-Tebbe J.,Allergy and Asthma Center Westend Outpatient Clinic Hanf | And 4 more authors.
Journal of Allergy and Clinical Immunology | Year: 2015

The house dust mite (HDM) is a major perennial allergen source and a significant cause of allergic rhinitis and allergic asthma. However, awareness of the condition remains generally low. This review assesses the links between exposure to HDM, development of the allergic response, and pathologic consequences in patients with respiratory allergic diseases. We investigate the epidemiology of HDM allergy to explore the interaction between mites and human subjects at the population, individual, and molecular levels. Core and recent publications were identified by using "house dust mite" as a key search term to evaluate the current knowledge of HDM epidemiology and pathophysiology. Prevalence data for HDM allergen sensitization vary from 65 to 130 million persons in the general population worldwide to as many as 50% among asthmatic patients. Heterogeneity of populations, terminology, and end points in the literature confound estimates, indicating the need for greater standardization in epidemiologic research. Exposure to allergens depends on multiple ecological strata, including climate and mite microhabitats within the domestic environment, with the latter providing opportunity for intervention measures to reduce allergen load. Inhaled mite aeroallergens are unusually virulent: they are able to activate both the adaptive and innate immune responses, potentially offering new avenues for intervention. The role of HDM allergens is crucial in the development of allergic rhinitis and asthma, but the translation of silent sensitization into symptomatic disease is still incompletely understood. Improved understanding of HDMs, their allergens, and their microhabitats will enable development of more effective outcomes for patients with HDM allergy. © 2014 The Authors.

Garcia-Vidal F.J.,Autonomous University of Madrid | Martin-Moreno L.,University of Zaragoza | Ebbesen T.W.,University of Strasbourg | Kuipers L.,FOM Institute for Atomic and Molecular Physics
Reviews of Modern Physics | Year: 2010

This review provides a perspective on the recent developments in the transmission of light through subwavelength apertures in metal films. The main focus is on the phenomenon of extraordinary optical transmission in periodic hole arrays, discovered over a decade ago. It is shown that surface electromagnetic modes play a key role in the emergence of the resonant transmission. These modes are also shown to be at the root of both the enhanced transmission and beaming of light found in single apertures surrounded by periodic corrugations. This review describes both the theoretical and experimental aspects of the subject. For clarity, the physical mechanisms operating in the different structures considered are analyzed within a common theoretical framework. Several applications based on the transmission properties of subwavelength apertures are also addressed. © 2010 The American Physical Society.

Mas-Torrent M.,CSIC - Institute of Materials Science | Mas-Torrent M.,CIBER ISCIII | Crivillers N.,CSIC - Institute of Materials Science | Crivillers N.,CIBER ISCIII | And 5 more authors.
Chemical Reviews | Year: 2012

Organic/inorganic hybrid materials based on attaching functional molecules to a surface are attracting great attention due to the wide range of novel properties and applications that these new materials can bring. Additionally, the use of organic molecules for surface functionalization opens the possibility to tune the material properties and molecular assembly through synthetic chemistry. A particularly appealing field is focused on employing as an active molecular unit an organic free radical to anchor on a substrate either chemically or by physisorption. However, and unavoidably, the first question that arises when an organic free radical is deposited/grafted on a surface is what is the implication of their organization and relative arrangement of the neighboring radicals as well as their orientation with respect to the surface on their properties. Thus, a crucial issue is whether in these surface radical organizations, especially when conducting surfaces are employed, the magnetic properties of the molecules are preserved. This has prompted the application to these systems of several magnetic characterization techniques as well as theoretical studies, and in most of the cases, it has been found that the spin of the molecule is maintained after surface grafting. To further progress in this area, it is imperative to not only synthesize promising functionalmolecules able to form stable and robust surface assemblies but also to develop sensitive characterization techniques to read, or even modify (i.e., write), the surface properties. In most of the reported cases in which the radicals were covalently attached to a surface, hybrid materials exhibiting high robustness were achieved, offering wide perspectives for these materials. Hence, some of the traditional applications of organic free radicals have already been transferred to SAMs of these molecules on surfaces, such as spinprobe and spin-label functions, preparation ofmagneticmaterials, and as catalysts in oxidation processes of organicmolecules. In addition, an emerging and potential application that is growing large expectations is their use for the fabrication of spintronic devices, where the unpaired electron of the free radical could favor spin polarization conservation during the electron transport process. Further, the magnetic properties of bistable radicals have also been successfully exploited as an output signal in surface-confined molecular switches that could in the future lead to single molecule switching devices. In all likelihood, these novel hybrid materials based on attaching organic free radicals on surfaces will continue to arouse the interest of materials scientists in the coming years, since a wide range of interdisciplinary applications are foreseen. © 2011 American Chemical Society.

Biniek L.,Charles Sadron Institute | Leclerc N.,CNRS The Institute of Chemistry and Processes for Energy, Environment and Health | Heiser T.,University of Strasbourg | Bechara R.,University of Strasbourg | Brinkmann M.,Charles Sadron Institute
Macromolecules | Year: 2013

A large-scale alignment method is used to orient the conjugated polymer poly(2,5-bis(3-dodecyl-2-yl)thieno[3,2-b]thiophene) (C12-pBTTT). This fast one-step alignment method does not use any alignment layer and does not necessarily require postalignment annealing of the films. It exploits the increased plasticity of the conjugated polymer films for 50 °C ≤ T ≤ 125 °C to obtain high in-plane orientations by mechanical rubbing of the films. As visualized by HR-TEM, the in-plane alignment of C12-pBTTT chains and size of the oriented domains increase with the temperature of the film during rubbing (Tr). The domains have a preferential face-on orientation; i.e., the π-stacking direction is along the film normal and the chain direction parallel to the rubbing direction. Postrubbing annealing at T < 200°C can further improve in-plane alignment whereas for T ≥ 200°C, edge-on oriented C12-pBTTT crystals are formed. The anisotropy of hole transport for highly in-plane oriented face-on as well as edge-on oriented films was measured in OFET devices. Depending on the annealing conditions, this anisotropy of hole mobility varies in the range 7-70 with the highest mobilities along the rubbing direction and the highest anisotropies for the oriented face-on films. © 2013 American Chemical Society.

Foy J.T.,University of Strasbourg | Ray D.,Shiv Nadar University | Aprahamian I.,Dartmouth College
Chemical Science | Year: 2014

Proton relay plays an important role in many biocatalytic pathways. In order to mimic such processes in the context of molecular switches, we developed coordination-coupled deprotonation (CCD) driven signaling and signal enhancement sequences. This was accomplished by using the zinc(ii)-initiated CCD of a hydrazone switch to instigate an acid catalyzed imine bond hydrolysis that separates a quencher from a fluorophore thus leading to emission amplification. Because CCD is a reversible process, we were able to show that the catalysis can be regulated and turned "on" and "off" using a metalation/demetalation cycle. This journal is © The Royal Society of Chemistry.

Thuery P.,CEA Saclay Nuclear Research Center | Riviere E.,University Paris - Sud | Harrowfield J.,University of Strasbourg
Inorganic Chemistry | Year: 2015

The reaction of 1,3-adamantanedicarboxylic acid (LH2) with uranyl nitrate under solvo-hydrothermal conditions, either alone or in the presence of additional metal cations (Co2+, Ni2+, or Cu2+) gives a series of nine complexes displaying a wide range of architectures. While [UO2(L)(H2O)]·1.25CH3CN (1) and [UO2(L)(DMF)] (2) are one-dimensional (1D) species analogous to that previously known, [H2NMe2]2[(UO2)2(L)3]·1.5H2O (3), which includes dimethylammonium counterions generated in situ, is a three-dimensional (3D) framework, and [UO2(L)(NMP)] (4) (NMP = N-methyl-2-pyrrolidone) is a braid-shaped 1D polymer. When 3d block metal ions are present and bound to 2,2′-bipyridine (bipy) coligands, their role is reduced to that of decorating species attached to uranyl-containing 1D polymers, as in [UO2M(L)2(bipy)2]·0.5H2O with M = Co (5) or Ni (6), and [(UO2)2Cu2(L)3(NO3)2(bipy)2]·0.5H2O (9), or of counterions, as in [Ni(bipy)3][(UO2)4(O)2(L)3]·3H2O (7), in which a two-dimensional (2D) assembly is built from tetranuclear uranyl-containing building units. In contrast, the heterometallic 3D framework [UO2Cu(L)2] (8) can be isolated in the absence of bipy. The emission spectra measured in the solid state display the usual uranyl vibronic fine structure, with various degrees of resolution and quenching, except for that of complex 7, which shows emission from the nickel(II) centers. The magnetic properties of complexes 5, 6, 8, and 9 were investigated, showing, in particular, the presence of zero-field splitting effects in 6 and weak antiferromagnetic interactions in 9. © 2015 American Chemical Society.

Mariette X.,University Paris - Sud | Gottenberg J.-E.,University of Strasbourg | Ravaud P.,French Institute of Health and Medical Research | Combe B.,Montpellier University
Rheumatology | Year: 2011

Objectives. Clinical registries have shown their effectiveness in capturing the long-term benefit of drugs in routine care. In France, two types of registry have been established to analyse the safety and efficacy of biological agents. Methods. The Research Axed on Tolerance of Biotherapies (RATIO) registry was designed to prospectively collect all cases of lymphoma and opportunistic infections occurring in patients receiving anti-TNF blockers for any indication. We also examined the results from nationwide prospective cohorts in order to investigate the safety and efficacy of rituximab (RTX), abatacept (ABA) and tocilizumab in RA and other autoimmune diseases. Results. Analysis of the RATIO registry demonstrated an increased risk of Legionella pneumophila infection in patients receiving anti-TNF therapy, a higher risk of tuberculosis [odds ratio (OR) (95% CI): 13.3 (2.6, 69.0) and 17.1 (3.6, 80.6) for infliximab and adalimumab vs etanercept, respectively], opportunistic infections and incidence of lymphoma, with mAb than with soluble-receptor anti-TNF. The characteristics of RA patients in RTX and ABA registries showed that some patients did not receive previous TNF blockers [20% in autoimmunity and RTX (AIR) and 13% in Orencia and RA (ORA)] and one-third of them were treated without concomitant DMARDs. Patients receiving RTX showed an increased proportion of severe infections (5.0/100 patient-years). Lung and cardiac comorbidities, extra-articular involvement and low immunoglobulin G before RTX were predictive factors of severe infections. In addition, the AIR registry suggested the effectiveness of RTX in patients with SLE. Conclusion. The establishment of biological registries in rheumatic diseases, in France, with their different methods, has already provided additional data to controlled trials, mainly on the risk of severe infections and lymphoma. © The Author 2010. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

Reilly P.T.,National Cancer Center Singapore | Yu Y.,Shanghai JiaoTong University | Hamiche A.,University of Strasbourg | Wang L.,Shanghai JiaoTong University
BioEssays | Year: 2014

The acidic (leucine-rich) nuclear phosphoprotein 32kDa (ANP32) family is composed of small, evolutionarily conserved proteins characterized by an N-terminal leucine-rich repeat domain and a C-terminal low-complexity acidic region. The mammalian family members (ANP32A, ANP32B, and ANP32E) are ascribed physiologically diverse functions including chromatin modification and remodelling, apoptotic caspase modulation, protein phosphatase inhibition, as well as regulation of intracellular transport. In addition to reviewing the widespread literature on the topic, we present a concept of the ANP32s as having a whip-like structure. We also present hypotheses that ANP32C and other intronless sequences should not currently be considered bona fide family members, that their disparate necessity in development may be due to compensatory mechanisms, that their contrasting roles in cancer are likely context-dependent, along with an underlying hypothesis that ANP32s represent an important node of physiological regulation by virtue of their diverse biochemical activities. © 2014 The Authors. Bioessays published by WILEY Periodicals, Inc.

Franchi J.,University of Strasbourg | Jan Y.L.,University Paris - Sud
Communications in Mathematical Physics | Year: 2011

We define and study on Lorentz manifolds a family of covariant diffusions in which the quadratic variation is locally determined by the curvature. This allows the interpretation of the diffusion effect on a particle by its interaction with the ambient space-time. We will focus on the case of warped products, especially Robertson-Walker manifolds, and analyse their asymptotic behaviour in the case of Einstein-de Sitter-like manifolds. © 2011 Springer-Verlag.

Beaulieu M.,Albert Ludwigs University of Freiburg | Thierry A.-M.,University of Strasbourg | Gonzalez-Acuna D.,University of Concepción | Polito M.J.,Woods Hole Oceanographic Institution
Conservation Physiology | Year: 2013

Ecologists have recently shown great interest in using physiological markers as indicators of the health of animal populations. In this context, the measurement of markers of oxidative balance, such as antioxidant defences and oxidative damage, may be a valuable tool. Indeed, at the individual level, antioxidant defences are positively associated with fertility and survival probability, while elevated oxidative damage during reproduction or growth may negatively affect recruitment and survival. Therefore, variation in oxidative balance is likely to influence demographic processes. This suggests that conservationists may be able to use oxidative markers to monitor population health. Yet, the connection between these markers and demographic parameters first needs to be established. We present here preliminary results obtained in colonies of breeding Gentoo (Pygoscelis papua) and Adélie penguins (Pygoscelis adeliae), showing that antioxidant defences strongly reflect population trends. However, population trend was not related to oxidative damage. This suggests that in the context of the emerging field of conservation physiology, antioxidant defences may represent a key parameter to monitor population health. We therefore exhort other research teams to assess the generality of this finding in other biological models, especially in species of conservation concern. © The Author 2013.

Lehmann J.,University Paris - Sud | Jossinet F.,University of Strasbourg | Gautheret D.,University Paris - Sud
Nucleic Acids Research | Year: 2013

The structure and function of conserved motifs constituting the apex of Stem I in T-box mRNA leaders are investigated. We point out that this apex shares striking similarities with the L1 stalk (helices 76-78) of the ribosome. A sequence and structure analysis of both elements shows that, similarly to the head of the L1 stalk, the function of the apex of Stem I lies in the docking of tRNA through a stacking interaction with the conserved G19:C56 base pair platform. The inferred structure in the apex of Stem I consists of a module of two T-loops bound together head to tail, a module that is also present in the head of the L1 stalk, but went unnoticed. Supporting the analysis, we show that a highly conserved structure in RNAse P formerly described as the J11/12-J12/11 module, which is precisely known to bind the elbow of tRNA, constitutes a third instance of this T-loop module. A structural analysis explains why six nucleotides constituting the core of this module are highly invariant among all three types of RNA. Our finding that major RNA partners of tRNA bind the elbow with a same RNA structure suggests an explanation for the origin of the tRNA L-shape. © 2013 The Author(s) 2013.

This proposal aims at a compact version of a gasifier by integrating the fluidized bed steam gasification of biomass and the hot gas cleaning and conditioning system into one reactor vessel. Such arrangement will guarantee the conversion of tar, elimination of trace elements and an efficient abatement of the particulate, delivering high purity syngas, suitable to assure a substantial share of power generation even in small- to medium-scale (few MWth) CHP and power plants, and to increase the overall economic revenue, in line with the FP7 energy directives. It is expected that this innovation will provide a concrete contribution to the target fixed in the work programme of reducing the cost of electricity obtained by means of advanced gasification systems below 0.04 /kWh in 2020. The strategy of the work plan is designed to: (i) carry out systematic investigations into the development of catalytic and sorbent materials and verify their effectiveness to improve gas quality at real gasification conditions with tests at bench- to pilot-scale (up to 100kWth); (ii) evaluate the purity of syngas against existing cleaning and conditioning systems, by means of a proof of concept in the Gssing gasification plant, and the compatibility towards advanced power generation systems, by means of electricity production tests with a SOFC unit; (iii) assess technical feasibility of process simplification and intensification actions by means of design and operation of an integrated gasification and hot gas cleaning and conditioning fluidized bed prototype reactor (1 MWth), at a significant scale to provide sufficient and reliable information for industrial applications. This ambitious project relates well to the complementary expertises of applicants. Consortium also includes the stakeholders relevant to assure the necessary impact for dissemination and exploitation of the results, and to promote in the medium term industrial applications for the commercialisation of the innovation.

French National Center for Scientific Research, University of Burgundy, University of Strasbourg and Synthelor Sas | Date: 2015-10-06

Novel P-chirogenic organophosphorus compounds of general formula (I), a process for the synthesis of the compounds of formula (I), and intermediate products of general formulae (II), (III) and (IV), as shown below, are involved in the synthesis of compounds (I). Metal complexes including compounds (I) as ligands are also described. The novel compounds and complexes are useful in asymmetric catalysis by transition metal complexes or organocatalysis, especially for asymmetric hydrogenation or allylation. Compounds of general formula (I) may be useful as agrochemical and therapeutic substances, or as reagents or intermediates for fine chemistry.

Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2010.2.1.2-1 | Award Amount: 11.94M | Year: 2011

Amyotrophic Lateral Sclerosis is one of the most devastating diseases in neurology affecting in Europe 50,000 individuals at any time, and causing around 10,000 deaths each year. ALS is characterized by progressive degeneration of motor neurons in brain and spinal cord leading to muscle weakness. ALS affects otherwise healthy people at any time in adulthood. The patient becomes paralyzed and dies as the result of respiratory failure on average 3 years after onset of symptoms. There is no cure for ALS. The only available drug (Riluzole) is marginally effective in extending the lifespan of ALS patients with 3 to 6 months. Despite recent scientific breakthroughs in the discovery of (1) multiple ALS associated genes, (2) evidence for metabolic dysregulation, (3) environmental risk factors, and (4) the protein TDP43 in aggregates of 95% of ALS patients, mechanistic models applicable to patients are still unknown. This shows that ALS can best be tackled through a systems biology approach which can only be achieved in a large integrative effort at the European level. Euro-MOTOR unites a multidisciplinary partnership of world-leading experts of clinicians, basic scientists and bioinformaticians, and is able to exploit excellent infrastructures for patient sampling, -omics platforms, disease modelling and bioinformatics. Euro-MOTOR will integrate large quantitative -omics data sets from new functional models and from patients in two prospective European, population-based inception cohorts. By leveraging on the variation in the multilevel -omics data, Euro-MOTOR aims to detect key genetic drivers of disease susceptibility/progression, while parametric modelling of the causal connections in identified molecular networks will generate a model of disease. Major findings will be validated in a second prospective patient cohort and adequate functional models, resulting in robust targets that pave the way for novel therapeutic interventions for this disabling and fatal disease.

French National Center for Scientific Research, University of Strasbourg and University of Illinois at Urbana - Champaign | Date: 2010-01-22

The present invention relates to a method for tightly temporally controlling the biological activity of a protein of interest in a vertebrate, upon induction of the activity of a fusion protein comprising said protein of interest and an ERM polypeptide containing a mutated ligand binding domain of the human oestrogen receptor , with a synthetic ligand that does not interfere with oestrogen signalling. In particular, the present invention concerns a method for generating tightly temporally-controlled targeted somatic mutations in a vertebrate, preferably a mouse, by inducing the activity of a fusion protein comprising a site-specific recombinase protein and an ERM polypeptide, with a synthetic ligand devoid of oestrogenic and anti-oestrogenic activities.

Agency: Cordis | Branch: H2020 | Program: MSCA-RISE | Phase: MSCA-RISE-2015 | Award Amount: 328.50K | Year: 2016

Finding a CURE for 35 Million individuals living with HIV/AIDS is one of the great global health challenges of the 21st century. The major obstacle to HIV eradication is the persistence of latent HIV cellular reservoirs, where the integrated viral genome is transcriptionally silenced but replication-competent and can escape both Anti-Retroviral Therapy and Immune Responses. The development of novel strategies aimed at eliminating these reservoirs have become paramount in HIV research, if we want to achieve an HIV/AIDS CURE. To accelerate the State of the Art in HIV CURE research in Europe, our EU4HIVCURE consortium brings together an intersectoral and interdisciplinary collaboration between 3 Universities, 3 Hospitals, 1 International Research Organisation from 4 European countries and 1 University from Canada. Our aim is to dissect the intricate mechanisms controlling HIV-1 latency and identify new druggable targets to develop novel latency-reversing strategies and eradicate persistent viral reservoirs by forcing HIV-1 gene expression. To facilitate continuum for translation to the clinic, we have developed an operational framework, which maximises exchange of knowledge and expertise via secondements, networking and training activities.

French Institute of Health, Medical Research, University of Strasbourg, French National Center for Scientific Research and Stichting Dienst Landbouwkundig Onderzoek | Date: 2012-05-04

The present invention provides materials and methods for DNA amplification, in particular linear amplification methods using RNA polymerase. These methods permit high-throughput sequencing of pictogram amounts of DNA and are of use in a range of applications including genome-wide profiling of transcription factors and epigenetic DNA and histone modifications, global transcript profiling, mapping of chromatin conformations, as well as for forensic use and archaeological studies.

Agency: Cordis | Branch: FP7 | Program: CSA-SA | Phase: FP7-2008-PEOPLE-NIGHT | Award Amount: 476.39K | Year: 2008

For the fourth year of the European demonstration the Night of the Researchers, 13 French partners met to propose projects having to bring the citizen and the researcher to be met.The diversity of the operators will offer to the visitors a diversity of proposal, participant in a discovery of this individual who is the researcher. We will find ourselves in the cities like Strasbourg, Mulhouse, Besancon, Dijon, Lille, Rennes, Bordeaux, Toulouse, Angers, Montpellier, Nimes, Brest, Nice and Paris and the area Ile de France.For this edition 2008, each partner will offer a festive demonstration. The importance will be put on the meeting of the public with the researchers present. It will be produced by a setting in scene particular, an accompaniment of the visitor during the evening, the use of particular places and specific in order to produce a real event participative and opened with the greatest number.During these various evenings, the goal is to lead the researcher to be an actor of the demonstration. To present themselves as being a citizen, and to identify the magic which its work can cause. It is in the sense that the aesthetic approach of the evenings will be an essential point, in order to immerse the visitor in an environment enabling him to plunge itself in an unknown universe in its eyes.

Agency: Cordis | Branch: FP7 | Program: CSA-SA | Phase: FP7-PEOPLE-2009-NIGHT | Award Amount: 475.31K | Year: 2009

RaCeN results on the work develop between 12 French partners that for the second time work on only one project to have a bigger impact on the public. It is not only an event, is a preparation, discussion with all partners before the venue, and it is an observation, an analysis of the different proposition after the 25th September. The aim is to offer large public and researchers an unique opportunity to directly meet and get closer to one another. Events will be organised in the cities of Strasbourg, Mulhouse, Besancon, Dijon, Lille, Rennes, Brest, Bordeaux, Toulouse, Angers, Montpellier, Nimes, Lyon as well as Paris and the region Ile de France. All the events will focus on the researchers as human beings: their will act advisers during the hands on experiments and demos, will be available to all the potential questions raised by the audience and in particular share with the public interests and fun, and act as normal citizens while unveiling the magic of their work to the participants. We chose to mobilize the PhD student to show them the necessity to discuss with citizens, to prepare these researchers of tomorrow to participate at the debate science and society, and to show at young visitors that their big sister or brother engage in a career in research.

Agency: Cordis | Branch: FP7 | Program: CSA-SA | Phase: PEOPLE-2007-5-1.NIGHT | Award Amount: 138.85K | Year: 2007

For the third issue of the Researchers night , five partners from the North and East of France decided to work together in order to offer their scientific and human richness to a large territory. Thus researchers will be in the heart of the events that will be organised during the night of the Friday 28th of September in five large French cities: Besanon, Dijon, Lille, Mulhouse and Strasbourg. The international Polar year was chosen as a main theme for the events programmed in the North-East of France. These five events will have various forms: a polar station with numerous workshops built in the core of the city, special night guided tours in museums, evening of ice sliding, dancing in a synthetic igloo, food sampling, discussion meetings between researchers and public on the image and the role of the researcher in society, meetings in unusual places like an ice rink, giant igloo or historical monuments... By involving researchers in all these events we want the general public to be confronted with a more human face of the researcher and make it realise that scientists are people like them who can share the same interests. A special attention will be put on young public. For instance, each city will participate to the European drawing contest and will organise its own regional awards during the night. The European dimension of research will be particularly underline by having researchers from various European countries some of them having received European funds to participate to the various events in the different cities. Last but not least, the communication tools used for all this events will be homogeneous, as a common graphic charter will be agreed on between all the partners involved. This will include one common national bookmark and website. This national communication will be reinforced by specific regional communication by the coordinator and local communication by each city.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: GC.SST.2012.1-4. | Award Amount: 3.11M | Year: 2012

In the next 20 years the number of small and light-weight full electric vehicles will substantially increase especially in urban areas. These Small Electric Vehicles (SEVs) shows distinctive design differences compared to the traditional car (e.g. no bonnets, vertical windscreens, outstanding wheels). Thus the consequences of impacts of SEVs with vulnerable road users (VRU) and other (heavier) vehicles will be different from traditional collisions. These fundamental changes are not adequately addressed by current vehicle safety evaluation methods and regulations. VRU protection, compatibility with heavier opponents and the introduction of active safety systems have to be appropriately taken into account in order to avoid any SEV over-engineering (e.g. heavy or complex vehicle body) by applying current regulations and substantially impair the SEVs (environmental) efficiency. Therefore the project SafeEV aims based on future accident scenarios to define advanced test scenarios and evaluation criteria for VRU, occupant safety and compatibility of SEVs. Moreover, industrial applicable methods for virtual testing of these scenarios and criteria (e.g. a method for active occupant safety assessment) will be developed. These methods are applied in order to derive protection systems for enhanced VRU and occupant safety for SEVs. The evaluation of one developed hardware system will be used to demonstrate the potential and applicability of these new methods. Dedicated best practice guidelines for VRU and occupant safety evaluation of SEVs will ensure a sustainable impact for industry and regulative organisations beyond the project duration. With the new evaluation methods developed, vehicle safety for SEV on urban roads in the next decade will be adequately addressed resulting in less fatalities and injuries without compromising vehicle efficiency. Moreover cost-efficient development of SEVs will be made possible by the new virtual testing methodologies developed.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: Fission-2012-2.3.1 | Award Amount: 10.27M | Year: 2013

Nuclear power plays a key role in limiting EUs greenhouse gases emissions, and makes an important contribution to improve European Unions independence, security and diversity of energy supply. However, its social acceptance is closely linked to an enhanced safety in the management of long-lived radioactive waste contributing to resource efficiency and cost-effectiveness of this energy and ensuring a robust and socially acceptable system of protection of man and environment. Among the different strategies, partitioning and transmutation (P&T) allows a reduction of the amount, the radiotoxicity and the thermal power of these wastes, leading to an optimal use of geological repository sites. In line with the Strategic Research Agenda of SNE-TP, the SACSESS collaborative project will provide a structured framework to enhance the fuel cycle safety associated to P&T. In addition, safety studies will be performed for each selected process to identify weak points to be studied further. These data will be integrated to optimise flowsheets and process operation conditions. A training and education programme will be implemented in close collaboration with other European initiatives, addressing safety issues of nuclear energy industry. The multidisciplinary consortium composed of European universities, nuclear research bodies, TSOs and industrial stakeholders will generate fundamental safety improvements on the future design of an Advanced Processing Unit. SACSESS will thus be an essential contribution to the demonstration of the potential benefits of actinide partitioning to the global safety of the long-lived waste management.

Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2011-ITN | Award Amount: 3.19M | Year: 2011

Peritoneal dialysis (PD) and haemodialysis (HD) are life-saving renal replacement therapies for more than 200,000 patients with chronic kidney disease in Europe, and this number increases annually. Although PD and HD have similar mortality rates, PD offers major advantages in terms of quality of life, costs, home-based treatment opportunities and early patient survival. Moreover, PD, rather than HD, offers opportunities for improvements. Nevertheless, only 10% of patients in Europe are treated with PD. Presently, PD research faces a significant shortage in workforce, probably through competition with other specialisations, the absence of a coherent training program and limited trans-European collaboration. The EuTRiPD consortium consists of eight research institutes, an SME and a large private company throughout eight of the EU Member States. Additionally, one multi-national company and three (inter)national organizations that promote education, scholarly excellence and public awareness will be associate partners. Each partner has internationally recognized expertise in PD, ranging from basic to bedside research and from raising awareness on kidney diseases to commercialisation of project results. By providing an inter-disciplinary and intersectoral long lasting training programme in PD research, EuTRiPD will address this need for researchers and clinicians in renal diseases. The scientific goal of EuTRiPD is to advance the current state of the art in PD by carrying out bench to bedside research, focused on the identification of biomarkers and interventions that promote survival and function of the peritoneal membrane. This will finally result in the clinical implementation of new therapeutic approaches. EuTRiPD will deliver twelve skilled ESRs with excellent career opportunities in nephrology and PD research. The unique set up of this training program will equip them with the skills to pursue a career in other disciplines and sectors should they choose to do so.

Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2010-ITN | Award Amount: 4.32M | Year: 2010

GENIUS aims at offering highest-quality supra-sectoral and cross-disciplinary training to a pool of promising young researchers, in an area at the interface between Supramolecular Chemistry, Materials- and Nano-Science, Physics and Electrical Engineering. GENIUS appointees will be trained in lecture courses, dedicated schools and workshops, and through an ambitious and carefully planned research activity that benefits both from the expertise of world-leading PIs with remarkable track records in both training and research. GENIUS is designed to generate new scientific and technological knowledge on the production, processing and characterization of graphene based supramolecular architectures, taking advantage of the outstanding physical and electronic properties of graphene. We are particularly interested in developing and studying a new graphene-organic hybrid material (GOH) for applications in microelectronics; the new material proposed, while maintaining the excellent properties of classical graphene, will have improved processability in solution, chemical functionalization and tunable optoelectronic properties. We will use supramolecular interactions to cover single graphene sheets with polycyclic aromatic hydrocarbon molecules, i.e. nano-graphenes (NG), which are composed of i) an aromatic core able to interact strongly with graphene, and ii) flexible side chains to provide solubility in organic solvents. NGs adsorb reversibly on graphene by pi-pi interactions, forming ordered adlayers on its surface with pre-programmed molecule spacing and orientation, ultimately modulating the electronic properties of the GOH. The interaction of NG and graphene will be studied at macroscopic scale by optical, Raman and current-voltage spectroscopy, and at molecular and microscopic scales primarily by Scanning Probe Microscopies. As a proof of principle, field effect transistors and photovoltaics devices based on graphene-NG composites will be tested.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: ENERGY.2009.2.4.1 | Award Amount: 7.12M | Year: 2010

The project contributes to the improvement of the concept of Enhanced Geothermal Systems by investigating the role of induced seismicity, which is twofold: (i) an instrument to image fluid pathways induced by hydraulic stimulation treatments, which has been done to some extent in previous projects; and (ii) an implication of such treatments to potential seismic hazards. The mitigation of induced seismicity to an acceptable level is the major intent of this project. For this purpose, we set as our goals (1) to understand why seismicity is induced in some cases but not in others; (2) to determine the potential hazards depending on geological setting and geographical location; (3) to work out licensing and monitoring guidelines for local authorities, which should include a definition of what level of ground motion is acceptable; and (4) to develop strategies to fulfil the task of the stimulation and improve the hydraulic properties of the geothermal reservoir without producing large magnitude events. To accomplish the project goals a high quality database of case studies will be assembled. This will include data on seismicity and ground motion, geomechanics, reservoir characteristics, injection/production, and surface deformation, as well as information on the local stress field and local geology. The interpretation will be based on data from the sites: Soultz-sous-forts (France), Basel (Switzerland), Gro Schnebeck (Germany), KTB (Germany), Larderello/Latera (Italy), Campi Flegrei (Italy), Hengill, Krafla, Reykjanes (Iceland), Groningen (Netherlands), and others (Berlin, El Salvador; The Geysers, USA). The GEISER-project will overcome shortcomings of previous work by including model based forecast of stimulation and/or production induced seismicity. Developing soft stimulation strategies and guidelines on how to react on induced seismicity will support the acceptance of geothermal applications.

Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 3.83M | Year: 2015

iSwitch will offer top-level multi-disciplinary and supra-sectorial training to a pool of talented young researchers, involving contributions from different scientific and technological fields such as, supramolecular chemistry, materials, nanoscience, physics and engineering. iSwitchs appointees will be trained through lecture courses, dedicated international schools and workshops, topical conferences, secondments to other consortium nodes and an ambitious and carefully planned research activities benefiting from the expertise of world-leading senior PIs and of younger but well-established PIs with outstanding track records in training and research. Additionally, iSwitch will generate new ground-breaking S&T knowledge needed to obtain efficient and fast switching in supramolecular electro- and opto-active materials as a response to external stimuli. This will be accomplished via controlled self-assembly of multicomponent architectures incorporating molecular switches, for fabricating responsive and multifunctional optoelectronic supramolecular devices. We are particularly interested in developing nano- and macro-scale switchable transistors and light-emitting devices as new solutions to (nanoscale) multifunctional organic-based logics. The specific training and research objectives are: - Design and synthesis of a (macro)molecular toolbox including electroactive and responsive systems as well as semiconducting and metallic nanostructures - Controlled interfaces of switches on (non)planar surfaces - Self-assembly of multicomponent systems into multifunctional architectures and materials - Multiscale structural, optical and electrical characterization of systems including Scanning Probe studies and time-resolved spectroscopy - Fabrication and characterization of switchable devices, i.e., transistors for logics and light-emitting devices for photonics, and related applications (optical illumination, optical filtering/landscaping, optical sensors, photovoltaics, etc.)

Zafeiratos S.,University of Strasbourg | Piccinin S.,CNR Institute of Materials | Teschner D.,Fritz Haber Institute of the Max Planck Society
Catalysis Science and Technology | Year: 2012

Alloys play a crucial role in several heterogeneous catalytic processes, and their applications are expected to rise rapidly. This is essentially related to the vast number of configurations and type of surface sites that multi-component materials can afford. It is well established that the chemical composition at the surface of an alloy usually differs from that in the bulk. This phenomenon, referred to as surface segregation, is largely controlled by the surface free energy. However, surface energy alone cannot safely predict the active surface state of a solid catalyst, since the contribution of other parameters such as size and support effects, as well as influence of the adsorbates, play a major role. This can lead to numerous surface configurations as for example over the length of a catalytic reactor, as the chemical potential of the gas phase changes continuously over the catalyst bed and hence different reactions may prevail at different catalyst bed segments. Thanks to the rapid improvement of the analytical surface science characterization techniques and theoretical methodologies, the potential effects induced by alloyed catalysts are better understood. For catalysis, the relevance of measurements performed on well-defined surfaces under idealized ultrahigh vacuum conditions has been questioned and studies in environments that closely resemble conditions of working alloy catalysts are needed. In this review we focus on experimental and theoretical studies related to in situ (operando) observations of surface segregation and phase separation phenomena taking place on the outermost surface layers of alloy catalysts. The combination of first principles theoretical treatment and in situ observation opens up new perspectives of designing alloy catalysts with tailored properties. © 2012 The Royal Society of Chemistry.

Porquet D.,University of Strasbourg | Dubau J.,University Paris - Sud | Grosso N.,University of Strasbourg
Space Science Reviews | Year: 2010

We review X-ray plasma diagnostics based on the line ratios of He-like ions. Triplet/singlet line intensities can be used to determine electronic temperature and density, and were first developed for the study of the solar corona. Since the launches of the X-ray satellites Chandra and XMM-Newton, these diagnostics have been extended and used (from C∈v to Si∈xiii) for a wide variety of astrophysical plasmas such as stellar coronae, supernova remnants, solar system objects, active galactic nuclei, and X-ray binaries. Moreover, the intensities of He-like ions can be used to determine the ionization process(es) at work, as well as the distance between the X-ray plasma and the UV emission source for example in hot stars. In the near future thanks to the next generation of X-ray satellites (e.g., Astro-H and IXO), higher-Z He-like lines (e.g., iron) will be resolved, allowing plasmas with higher temperatures and densities to be probed. Moreover, the so-called satellite lines that are formed closed to parent He-like lines, will provide additional valuable diagnostics to determine electronic temperature, ionic fraction, departure from ionization equilibrium and/or from Maxwellian electron distribution. © 2010 Springer Science+Business Media B.V.

French Institute of Health, Medical Research, French National Center for Scientific Research, University of Strasbourg, Cornell University, University Paris - Sud and Assistance Publique Hopitaux De Paris Aphp | Date: 2015-05-21

A method for preventing or treating cardiomyopathy due to energy failure in a subject in need thereof is provided. The method comprises administering to the subject a therapeutically effective amount of a vector which comprises a nucleic acid sequence encoding a gene that can reverse energy failure. An exemplary cardiomyopathy is that which is associated with Friedreich ataxia and an exemplary nucleic acid sequence comprises a nucleic acid that encodes frataxin (FXN).

Bouchon M.,Joseph Fourier University | Durand V.,Joseph Fourier University | Durand V.,University of Savoy | Marsan D.,University of Savoy | And 2 more authors.
Nature Geoscience | Year: 2013

Many earthquakes are preceded by foreshocks. However, the mechanisms that generate foreshocks and the reason why they occur before some earthquakes and not others are unknown. Here we use seismic catalogues from the best instrumented areas of the North Pacific to analyse the foreshock sequences preceding all earthquakes there between 1999 and 2011, of magnitude larger than 6.5 and at depths shallower than 50 km. The data set comprises 31 earthquakes at plate boundaries, and 31 in plate interiors. We find that there is a remarkable contrast between the foreshock sequences of interplate compared with intraplate earthquakes. Most large earthquakes at plate interfaces in the North Pacific were preceded by accelerating seismic activity in the months to days leading up to the mainshock. In contrast, foreshocks are much less frequent in intraplate settings. We suggest that at plate boundaries, the interface between the two plates begins to slowly slip before the interface ruptures in a large earthquake. This relatively long precursory phase could help mitigate earthquake risk at plate boundaries. © 2013 Macmillan Publishers Limited. All rights reserved.

Lengline O.,University of Strasbourg | Got J.-L.,University of Savoy
Geophysical Research Letters | Year: 2011

The direction of propagation is an important factor that affects the pattern of ground motion generated by an earthquake. Characterizing factors favoring a potential rupture propagation direction is thus an important task. Here we analyze the earthquake directivity of repeating earthquake sequences located on the San Andreas fault near Parkfield, California. All earthquakes of a sequence have very similar waveforms and have overlapping surface ruptures. We show that subtle variations of the transfer function between earthquakes of a common sequence can be interpreted as a change of apparent rupture duration. Relative apparent rupture durations are computed for all pairs of events at all available stations and for each sequence. We invert these measurements to obtain an estimation of the apparent rupture duration for each individual event of the sequence relative to a reference event. Variation of apparent rupture duration with azimuth attests for the rupture directivity. We show that the majority of analyzed microearthquakes presents a rupture in the south-east direction. We also show that, on a given repeating sequence, most earthquakes tend to show the same rupture direction. Copyright © 2011 by the American Geophysical Union.

Rosat S.,University of Strasbourg | Hinderer J.,University of Strasbourg
Bulletin of the Seismological Society of America | Year: 2011

Since the beginning of the Global Geodynamics Project (GGP) in 1997, the number of superconducting gravimeters (SGs) has increased to reach 30 operating sites today. Data from this network allow a comparison of the noise levels of the different contributing stations. The knowledge of the noise levels at each site is important in any combination of data to determine global Earth parameters, for example, the stacking of the data in the search for elusive signals, like the gravity variations associated with the translational mode of the inner core. We use a standardized procedure based on the computation of the residual power spectral densities (PSDs) over a quiet time period in order to evaluate the combined instrument plus site noise in the long-period seismic band (0.3 mHz-1 mHz). The experience at Strasbourg (France) has shown some improvements from the TT70-T005 full-size instrument to the C026 compact model in terms of noise reduction, while the most recent Observatory SG types, OSG044 at Bad Homburg (Germany) and OSG052 at Sutherland (South Africa), do not show any further improvement with respect to the compact models, respectively CD30 and CD037, operating at the same stations. At Black Forest Observatory (BFO) in Germany, the experience of the dual-sphere OSG with a lower sphere heavier than usual has shown that the instrumental and site conditions make this station the least noisy one at frequencies larger than 0.1 mHz. The noise analysis using the longest time-series available has shown that the noise level at these sites is mostly stable (within 1σ) over the years. The comparison with some seismological noise models shows that the best SG sites are less noisy than longperiod seismometers below 1 mHz. However, the noise level of the best SGs is still at the limit of detection of the subseismic translational mode of the inner core.

Grob M.,University of Strasbourg | Grob M.,University of Alberta | Maggi A.,University of Strasbourg | Stutzmann E.,CNRS Paris Institute of Global Physics
Geophysical Research Letters | Year: 2011

Seismic noise spectra at all seismic stations display two peaks in the 1-20 s period band, called primary and secondary microseisms. They are caused by the coupling of ocean waves into Rayleigh waves. At most locations, microseismic power is greater during local winter (when nearby oceans are stormier) than local summer. This tendency is reversed for stations in Antarctica, where growth of local winter sea ice seems to impede microseism generation in near coastal areas. A decade of continuous data from coastal seismic stations in Antarctica show systematic seasonality in microseismic signal levels, and demonstrate associations with both broad-scale and local sea-ice conditions. Primary microseisms are known to be generated at the coast and the modulation that we observe can be associated with sea-ice variations both in the vicinity of the station and along other Antarctic coasts. The similar modulation of short-period secondary microseisms corroborates their mostly near-coastal origin, while the continued presence of long-period secondary microseisms suggests more distant source regions. These observations could be used to extend the monitoring of climate variability prior to the availability of satellite-derived climate indicators. Copyright © 2011 by the American Geophysical Union.

Ho B.Q.,Vietnam National University, Ho Chi Minh City | Clappier A.,University of Strasbourg
Atmospheric Environment | Year: 2011

A road traffic Emission Inventory (EI) is generated for Ho Chi Minh City (HCMC), Vietnam. For generating the EI for road traffic sources, we used the new EMISENS model, which combines the top-down and bottom-up approaches. The bulk emission factors of traffic stem from another study that estimated the emission factors for HCMC by using an inverse air quality model method. The results show that the motorcycles are responsible for the bulk of traffic emissions (contributing 94% of CO, 68% of NMVOC, 61% of SO2 and 99% of CH4). Four scenarios for reducing of the traffic emissions are designed using the HCMC's plan for reduction of emissions. Two scenarios are the reduction scenarios for the year of 2015 and 2020. In addition, two scenarios are the Business as Usual scenario for the year of 2015 and 2020. If the local government does not have any plan for reduction of emissions (scenario of Business as Usual) the emissions will increase rapidly. If the government follows the planning as set out by the local managers, the emissions of the city will decrease. © 2011.

Bell A.F.,University of Edinburgh | Naylor M.,University of Edinburgh | Heap M.J.,University of Strasbourg | Main I.G.,University of Edinburgh
Geophysical Research Letters | Year: 2011

Power-law accelerations in the mean rate of strain, earthquakes and other precursors have been widely reported prior to material failure phenomena, including volcanic eruptions, landslides and laboratory deformation experiments, as predicted by several theoretical models. The Failure Forecast Method (FFM), which linearizes the power-law trend, has been routinely used to forecast the failure time in retrospective analyses; however, its performance has never been formally evaluated. Here we use synthetic and real data, recorded in laboratory brittle creep experiments and at volcanoes, to show that the assumptions of the FFM are inconsistent with the error structure of the data, leading to biased and imprecise forecasts. We show that a Generalized Linear Model method provides higher-quality forecasts that converge more accurately to the eventual failure time, accounting for the appropriate error distributions. This approach should be employed in place of the FFM to provide reliable quantitative forecasts and estimate their associated uncertainties. Copyright 2011 by the American Geophysical Union.

Bronner A.,University of Strasbourg | Sauter D.,University of Strasbourg | Manatschal G.,University of Strasbourg | Peron-Pinvidic G.,Geological Survey of Norway | Munschy M.,University of Strasbourg
Nature Geoscience | Year: 2011

Continental breakup is usually marked by a sharp contact between continental and oceanic crust. However, in settings with low magma supply, this transition zone is much wider1,2 and exhibits a gradual change from continental crust, to exhumed blocks of continental mantle, to oceanic crust. Traditionally, the timing and location of continental breakup is defined by the first observation of a magnetic anomaly that is generated by magma erupted from the newly formed mid-ocean ridge. As the magma cools to form rock, it preserves a record of the Earth's magnetic field at that time. However, in the broad transitional zone at magma-poor rifted margins, the seafloor-spreading origin of magnetic anomalies is debated3,4. Here we compare seismic 5-10 and drill-hole data11-13 with measurements of the first magnetic anomaly-the J anomaly-formed in the Newfoundland-Iberia rift system. We find that the J anomaly is associated with locally high topography and thickened crust, probably resulting from voluminous magma both erupted at the surface and added beneath blocks of exhumed continental mantle. We therefore argue that the J anomaly did not form during seafloor spreading, but instead represents a pulse of magmatism that may have triggered continental breakup before seafloor spreading. Our findings imply that opening of this part of the North Atlantic may have occurred later than previously thought and may explain inconsistencies in some previous kinematic reconstructions. © 2011 Macmillan Publishers Limited. All rights reserved.

Moreau J.,University of Strasbourg
Basin Research | Year: 2011

Rocks of Late Ordovician to Silurian age are well exposed on the western rim of the Murzuq Basin (Ghat-Tikiumit area, Libya) where seismic-scale exposures allow spectacular insights into the growth and decay of the Late Ordovician (Hirnantian) ice sheet. The final deglaciation left a complex topography with a combination of subglacial morphologies and proglacial depositional systems. This paper documents the glacial and proglacial palaeo-topography that controls the accumulation of a postglacial transgressive depositional system and the Rhuddanian (Early Silurian) shales. The glacial relief directly contributed to an important hiatus, with the Rhuddanian deposits at the base of the remnant glacial troughs being 3Ma older than at the top of the topographic highs. The source-rock in the Murzuq Basin is of Early Rhuddanian age, so it is present only in the deepest part whereas geomorphic traps are formed within the highs of the relict postglacial topography. The transgressive system, recognised for its good reservoir potential, is considered to play a key-role in the petroleum system, linking the source rock deposited in the ancient topographic lows with the reservoir rocks in the topographic highs. This study aims to demonstrate the importance of palaeo-glaciological reconstructions for petroleum exploration of the Ordovician-Silurian in North Africa. © 2011 The Authors. Basin Research © 2011 Blackwell Publishing Ltd, European Association of Geoscientists & Engineers and International Association of Sedimentologists.

Zhu W.,State University of New York at Stony Brook | Baud P.,University of Strasbourg | Wong T.-F.,State University of New York at Stony Brook
Journal of Geophysical Research: Solid Earth | Year: 2010

The analysis of compactant failure in carbonate formations hinges upon a fundamental understanding of the mechanics of inelastic compaction. Microstructural observations indicate that pore collapse in a limestone initiates at the larger pores, and microcracking dominates the deformation in the periphery of a collapsed pore. To capture these micromechanical processes, we developed a model treating the limestone as a dual porosity medium, with the total porosity partitioned between macroporosity and microporosity. The representative volume element is made up of a large pore which is surrounded by an effective medium containing the microporosity. Cataclastic yielding of this effective medium obeys the Mohr-Coulomb or Drucker Prager criterion, with failure parameters dependent on porosity and pore size. An analytic approximation was derived for the unconfined compressive strength associated with failure due to the propagation and coalescence of pore-emanated cracks. For hydrostatic loading, identical theoretical results for the pore collapse pressure were obtained using the Mohr-Coulomb or Drucker-Prager criterion. For nonhydrostatic loading, the stress state at the onset of shear-enhanced compaction was predicted to fall on a linear cap according to the Mohr-Coulomb criterion. In contrast, nonlinear caps in qualitative agreement with laboratory data were predicted using the Drucker-Prager criterion. Our micromechanical model implies that the effective medium is significantly stronger and relatively pressureinsensitive in comparison to the bulk sample. Copyright 2010 by the American Geophysical Union.

Kondo J.,Sophia University | Westhof E.,University of Strasbourg
Nucleic Acids Research | Year: 2011

Nucleotide bases are recognized by amino acid residues in a variety of DNA/RNA binding and nucleotide binding proteins. In this study, a total of 446 crystal structures of nucleotide-protein complexes are analyzed manually and pseudo pairs together with single and bifurcated hydrogen bonds observed between bases and amino acids are classified and annotated. Only 5 of the 20 usual amino acid residues, Asn, Gln, Asp, Glu and Arg, are able to orient in a coplanar fashion in order to form pseudo pairs with nucleotide bases through two hydrogen bonds. The peptide backbone can also form pseudo pairs with nucleotide bases and presents a strong bias for binding to the adenine base. The Watson-Crick side of the nucleotide bases is the major interaction edge participating in such pseudo pairs. Pseudo pairs between the Watson-Crick edge of guanine and Asp are frequently observed. The Hoogsteen edge of the purine bases is a good discriminatory element in recognition of nucleotide bases by protein side chains through the pseudo pairing: the Hoogsteen edge of adenine is recognized by various amino acids while the Hoogsteen edge of guanine is only recognized by Arg. The sugar edge is rarely recognized by either the side-chain or peptide backbone of amino acid residues. © The Author(s) 2011. Published by Oxford University Press.

Zhang F.,University of Massachusetts Medical School | Wang J.,University of Massachusetts Medical School | Xu J.,University of Massachusetts Medical School | Zhang Z.,University of Massachusetts Medical School | And 9 more authors.
Cell | Year: 2012

piRNAs silence transposons during germline development. In Drosophila, transcripts from heterochromatic clusters are processed into primary piRNAs in the perinuclear nuage. The nuclear DEAD box protein UAP56 has been previously implicated in mRNA splicing and export, whereas the DEAD box protein Vasa has an established role in piRNA production and localizes to nuage with the piRNA binding PIWI proteins Ago3 and Aub. We show that UAP56 colocalizes with the cluster-associated HP1 variant Rhino, that nuage granules containing Vasa localize directly across the nuclear envelope from cluster foci containing UAP56 and Rhino, and that cluster transcripts immunoprecipitate with both Vasa and UAP56. Significantly, a charge-substitution mutation that alters a conserved surface residue in UAP56 disrupts colocalization with Rhino, germline piRNA production, transposon silencing, and perinuclear localization of Vasa. We therefore propose that UAP56 and Vasa function in a piRNA-processing compartment that spans the nuclear envelope. © 2012 Elsevier Inc.

Sieja K.,University of Strasbourg
Acta Physica Polonica B | Year: 2016

We investigate collective features of nuclei with several valence particles outside the closed cores of 78Ni and 132Sn. Using the pseudo-SU(3) model and large-scale shell model diagonalizations, we show that quadrupole collectivity should develop in N = 54 and N = 86 isotones and that non-axial degrees of freedom may play an important role in both regions.

Li T.,Fudan University | Rao B.,University of Strasbourg
Mathematical Methods in the Applied Sciences | Year: 2015

By means of a non-exact controllability result, we show the necessity of the conditions of compatibility for the exact synchronization by two groups for a coupled system of wave equations with Dirichlet boundary controls. Copyright © 2014 John Wiley & Sons, Ltd.

Recent fieldworks on Comoros, Seychelles and Madagascar have allowed to update the knowledge on Phisidini Jin, 1987 species from these islands and to uncover this tribe on Comoros and Madagascar where it was up to now considered as lacking (Jin & Kevan 1992). In the present article, the new genus Seselphisis n. gen. is proposed for the new species S. praslinensis n. gen., n. sp. from Seychelles; Brachyphisis visenda (Bolivar, 1912) is transferred to this genus. Two new genera are described from Comoros: Comorophisis n. gen. to include C. labati n. gen., n. sp. from Grande Comore and C. mayottensis n. gen., n. sp. from Mayotte; Comorocolya n. gen. to include C. ngazidja n. gen., n. sp. from Grande Comore, C. ndzuwaniensis n. gen., n. sp. from Anjouan and C. mwaliensis n. gen., n. sp. from Mohéli. Malagasyphisis maromizaha n. gen., n. sp. is described from Madagascar. The song of Seselphisis visenda n. comb., Seselphisis praslinensis n. gen., n. sp., Comorophisis labati n. gen., n. sp., Comorophisis mayottensis n. gen., n. sp., Comorocolya ngazidja n. gen., n. sp. and Comorocolya mwaliensis n. gen., n. sp. are described. Now, 15 Phisidini species are known on South Western Indian Ocean (SWIO) islands: one is widespread, the others are endemic to one island or few islands. Endemic SWIO Phisidini species are belonging to archipelago endemic genera. Keys to SWIO Phisidini genera and to Phisidini from Comoros are given. © Publications Scientifiques du Muséum national d'Histoire naturelle, Paris.

Gavira C.,University of Strasbourg | Hofer R.,University of Strasbourg | Lesot A.,University of Strasbourg | Lambert F.,Laboratoire Of Recherche En Biotechnologies | And 2 more authors.
Metabolic Engineering | Year: 2013

Natural nootkatone is a high value ingredient for the flavor and fragrance industry because of its grapefruit flavor/odor, low sensorial threshold and low availability. Valencene conversion into nootkatol and nootkatone is known to be catalyzed by cytochrome P450 enzymes from both prokaryotic and eukaryotic organisms, but so far development of a viable bioconversion process using either native microorganisms or recombinant enzymes was not successful. Using an in silico gene-mining approach, we selected 4 potential candidate P450 enzymes from higher plants and identified two of them that selectively converted (+)-valencene into β-nootkatol with high efficiency when tested using recombinant yeast microsomes in vitro. Recombinant yeast expressing CYP71D51v2 from tobacco and a P450 reductase from arabidopsis was used for optimization of a bioconversion process. Bioconversion assays led to production of β-nootkatol and nootkatone, but with low yields that decreased upon increase of the substrate concentration. The reasons for this low bioconversion efficiency were further investigated and several factors potentially hampering industry-compatible valencene bioconversion were identified. One is the toxicity of the products for yeast at concentrations exceeding 100mgL-1. The second is the accumulation of β-nootkatol in yeast endomembranes. The third is the inhibition of the CYP71D51v2 hydroxylation reaction by the products. Furthermore, we observed that the formation of nootkatone from β-nootkatol is not P450-dependent but catalyzed by a yeast component. Based on these data, we propose new strategies for implementation of a viable P450-based bioconversion process. © 2013 Elsevier Inc.

Rousseau F.,University of Strasbourg
Medical Image Analysis | Year: 2010

Image enhancement is of great importance in medical imaging where image resolution remains a crucial point in many image analysis algorithms. In this paper, we investigate brain hallucination (Rousseau, 2008), or generating a high-resolution brain image from an input low-resolution image, with the help of another high-resolution brain image. We propose an approach for image super-resolution by using anatomical intermodality priors from a reference image. Contrary to interpolation techniques, in order to be able to recover fine details in images, the reconstruction process is based on a physical model of image acquisition. Another contribution to this inverse problem is a new regularization approach that uses an example-based framework integrating non-local similarity constraints to handle in a better way repetitive structures and texture. The effectiveness of our approach is demonstrated by experiments on realistic Brainweb Magnetic Resonance images and on clinical images from ADNI, generating automatically high-quality brain images from low-resolution input. © 2010 Elsevier B.V.

Rochel N.,University of Strasbourg | Moras D.,University of Strasbourg
Anticancer Research | Year: 2012

The plethora of actions of 1α,25-dihydroxyvitamin D 3, the active form of the seco-steroid hormone vitamin D, in various systems suggested wide clinical applications in treatments for renal osteodystrophy, osteoporosis, psoriasis, cancer, autoimmune diseases and prevention of graft rejection. However, the major side-effects of hypercalcemia of VDR ligands limit their use. ZK203278, a novel synthetic analog has been shown to act as a potent immunomodulator and presents dissociated biologic profile with low calcemic sideeffects. Here, we described the crystal structures of the hVDR ligand-binding domain in complex with ZK203278 and determined its correlation with its specific dissociated biologic profile. The VDR/ZK203278 structure, in comparison with VDR/1α,25-dihydroxyvitamin D 3, shows specific interactions of the thiazole group of ZK203278 with residues of H3, H11 and H12. These specific interactions may lead to altered selective interactions with co-regulators and consequently to the dissociated biologic profile of this novel ligand.

The grasshopper genus Hebridea Willemse, 1926 is redefined, the species Hebridea rufotibialis Willemse, 1926 from Espiritu Santo is redescribed and life history traits are given. Hebridea amedegnatoae n. sp. is described from Malekula Island. Examination of its morphology reveals that Hebridea belongs to Catantopinae Brunner von Wattenwyl, 1893 and not to Cyrtacanthacridinae Kirby, 1902. Relations of Hebridea with closely related Catantopinae genera are discussed. © Publications Scientifiques du Muséum national d'Histoire naturelle, Paris.

Mochol I.,University of Strasbourg | Mochol I.,Polish Academy of Sciences | Petri J.,University of Strasbourg
Monthly Notices of the Royal Astronomical Society: Letters | Year: 2015

The population of gamma-ray pulsars, including Crab observed in the TeV range, and Vela detected above 50 GeV, challenges existing models of pulsed high-energy emission. Such models should be universally applicable, yet they should account for spectral differences among the pulsars. We show that the gamma-ray emission of Crab and Vela can be explained by synchrotron radiation from the current sheet of a striped wind, expanding with a modest Lorentz factor G{cyrillic} ≲ 100 in the Crab case, and G{cyrillic} ≲ 50 in the Vela case. In the Crab spectrum, a new synchrotron self-Compton component is expected to be detected by the upcoming experiment CTA. We suggest that the gamma-ray spectrum directly probes the physics of relativistic magnetic reconnection in the striped wind. In the most energetic pulsars, like Crab, with E3/2 38/P-2 ≳ 0.002 (where E˙ is the spin-down power, P is the pulsar period, and X = Xi × 10i in CGS units), reconnection proceeds in the radiative cooling regime and results in a soft power-law distribution of cooling particles; in less powerful pulsars, like Vela, particle energization is limited by the current sheet size, and a hard particle spectrum reflects the acceleration mechanism. A strict lower limit on the number density of radiating particles corresponds to emission close to the light cylinder, and, in units of the GJ density, it is ≳0.5 in the Crab wind, and κ ≳ 0.05 in the Vela wind. © 2015 The Authors.

Averous L.,University of Strasbourg | Pollet E.,University of Strasbourg
MRS Bulletin | Year: 2011

In recent years, bio-based products have been of great interest since sustainable development policies have tended to expand with decreasing reserves of fossil fuels and growing concerns for the environment. Consequently, biodegradable and renewable polymers have been the topic of significant research. These polymers can mainly be classified as agro-polymers (starch, chitosan) and biopolyesters (polyhydroxyalkanoates, poly(lactic acid)). Unfortunately, for certain applications, these bio-based polymers cannot be fully competitive with conventional thermoplastics since some of their properties are too weak. Therefore, to extend the range of their applications, current bio-based polymers have to be reformulated. Some of the most promising are nano-biocomposites, where nano-sized fillers are dispersed into a biopolymer matrix, which could yield a range of improved properties (stiffness, permeability). This article reports the most recent developments in renewable nano-biocomposites based on the use of nanoclay fillers. © 2011 Materials Research Society.

Henry M.,University of Strasbourg
Current Opinion in Colloid and Interface Science | Year: 2016

It is suggested that electromagnetic quantum vacuum fluctuations are at the very deep root of the so-called “specific ions effects” in concentrated solutions or in living cells. A many-body quantum-mechanical frame of thinking is proposed based on the concept of quantum coherence taking into account explicitly density and excitation frequencies of molecules and/or ionic species. It is also proposed that Hofmeister phenomena could have a natural explanation in the harmonic relationships between sets of characteristic frequencies ruled by quantum mechanical laws. It then follows that physical chemistry of concentrated media and biology should be ruled more by a quantum “symphony” between indistinguishable constituents rather than localized two-body electrical interactions between molecular or ionic species. © 2016 Elsevier Ltd

The Trigonidiinae crickets of Rodrigues are examined. Two species widespread in South Western Indian Ocean islands are recorded in Rodrigues for the first time: Trigonidium cicindeloides Rambur, 1839 and Natula longipennis (Serville, 1839). Nemobius luteolus Butler, 1876 is a Trigonidiinae and not a Nemobiinae, it is transferred to Metioche Stål, 1877 as Metioche luteolus (Butler, 1876), n. comb. Two new species are described from the restored areas of the island. These new species are tentatively considered as Metioche and included in the new subgenus Superstes n. subgen.: Metioche (Su-perstes) superbus n. subgen., n. sp. and Metioche (Superstes) payendeei n. subgen., n. sp. This new subgenus is charac-terized by the male genitalia asymmetry and the striking hyperthely of the left pseudepiphallic lophi and paramere. Elements of the ecology of endemic Trigonidiinae of Rodrigues are given, and their conservation status is assessed. © 2012 Magnolia Press.

Imfeld G.,CNRS The Institute of Chemistry and Processes for Energy, Environment and Health | Vuilleumier S.,University of Strasbourg
European Journal of Soil Biology | Year: 2012

Extensive application of industrially-produced pesticides in agriculture has resulted in contamination of soil ecosystems. A variety of both cultivation-dependent and cultivation-independent methods can be applied to measure and interpret the effects of pesticide exposure. We review here the expanding panel of these methods in the specific context of responses of the soil bacterial microflora to pesticide exposure, and of ongoing advances in microbial molecular ecology, including metagenomics and new approaches for DNA sequencing. Several issues still need to be addressed in order to routinely evaluate the effect of pesticides on bacterial communities in soil in the future, and to make way for a widely accepted framework for risk assessment in agro-ecosystems that include bacterial indicators. © 2011 Elsevier Masson SAS.

Mortazavi B.,University of Strasbourg | Mortazavi B.,CRP Henri Tudor | Ahzi S.,University of Strasbourg
Solid State Communications | Year: 2012

We investigated the effects of boron atoms substitution on the thermal conductivity and mechanical properties of single-layer graphene using the non-equilibrium molecular dynamics (NEMD) simulations. By performing the uniaxial tension simulations, we observed that substituted boron atoms slightly decrease the elastic modulus and tensile strength of graphene. On the other hand, it was observed that only 0.75% concentration of boron atoms in graphene reduces the thermal conductivity of graphene by more than 60% and leads to vanishing chirality effect. © 2012 Elsevier Ltd. All rights reserved.

Tassy O.,University of Strasbourg | Tassy O.,Stowers Institute for Medical Research | Tassy O.,Howard Hughes Medical Institute | Pourquie O.,University of Strasbourg | And 2 more authors.
Nucleic Acids Research | Year: 2014

The function of genes is often evolutionarily conserved, and comparing the annotation of ortholog genes in different model organisms has proved to be a powerful predictive tool to identify the function of human genes. Here, we describe Manteia, a resource available online at Manteia allows the comparison of embryological, expression, molecular and etiological data from human, mouse, chicken and zebrafish simultaneously to identify new functional and structural correlations and gene-disease associations. Manteia is particularly useful for the analysis of gene lists produced by high-throughput techniques such as microarrays or proteomics. Data can be easily analyzed statistically to characterize the function of groups of genes and to correlate the different aspects of their annotation. Sophisticated querying tools provide unlimited ways to merge the information contained in Manteia along with the possibility of introducing custom user-designed biological questions into the system. This allows for example to connect all the animal experimental results and annotations to the human genome, and take advantage of data not available for human to look for candidate genes responsible for genetic disorders. Here, we demonstrate the predictive and analytical power of the system to predict candidate genes responsible for human genetic diseases. © 2013 The Author(s). Published by Oxford University Press.

Westhof E.,University of Strasbourg
Genome Biology | Year: 2010

The discovery of several new structured non-coding RNAs in bacterial and archaeal genomes and metagenomes raises burning questions about their biological and biochemical functions. © 2010 BioMed Central Ltd.

Transfer RNAs (tRNA) are small RNAs that provide the interface between DNA and ribosome-dependent protein synthesis, besides being involved in many other cellular processes. They interact with an impressive number of small molecule and macromolecular ligands and show structural and functional plasticity far to be deciphered. Here it is shown how tRNA biology was (and still is) idea and technology-driven and why crystallogenesis was at the heart of this science/technology interplay. Thus the quest to understand tRNA recognition/misrecognition by aminoacyl-tRNA synthetases (aaRS) stimulated biologists since the 1960s to crystallize tRNAs and their protein partners under their different functional states. This led to novel crystallization methods (vapor phase diffusion, microdialysis), characterization of system-specific additives (polyamines, metal ions, adenylate analogues), and discovery of ammonium sulfate as a crystallant for tRNA:aaRS complexes. Studies on the physical chemistry of tRNA and aaRS crystal growth, including the role of microgravity, were undertaken, and advanced methods for optimizing crystal quality were validated. As a result, the empiricism in tRNA crystallization was replaced by more rationality and led to the discipline of crystallogenesis. This facilitated tRNA crystallography, culminating with tRNA on the ribosome, thereby providing a robust structural background to better comprehend tRNA biology. © 2013 American Chemical Society.

The injection of fluid into a rock mass results in variations of effective stresses that sometimes generate induced seismicity. These effective stress field variations depend on the diffusion process, which depends, in turn, on the magnitude of the pore pressure variation relative to the total stress. Four diffusion mechanisms are distinguished: diffusion through a poroelastic rock mass, and diffusion in preferential directions controlled either by slip along preexisting fractures, or by the development of fresh shear zones, or by hydraulic fracturing. More importantly, in some instances, this diffusion process also generates non-seismic motions that, in turn, influence the seismic activity, in particular when injection stops. © 2012 Springer-Verlag.

Wittlinger G.,University of Strasbourg | Farra V.,University of Paris Pantheon Sorbonne
Geophysical Journal International | Year: 2012

We analyse seismic data from the broad-band stations located on the Antarctic and Greenland ice sheets to determine the large-scale seismic parameters of the polar ice sheets. The P-to-S converted waves at the ice/rock interface and inside the ice sheets and their multiples (the P receiver functions) are used to estimate the in situ P velocity Vp and the P-to-S velocity ratio Vp/Vs of the polar ice. The thickness of the whole ice layer is precisely known either from radio echo soundings or from ice core drillings allowing thus an accurate determination of Vp and Vp/Vs. At some places in and near the Wilkes Basin, a sedimentary layer is probably squeezed between the ice and the bedrock. We find that the polar ice caps have a two-layer structure, the upper layer of variable thickness about 2/3 of the total thickness with velocities very close to the ice standard values and the lower layer preserving a standard Vp but with about 25 per cent smaller shear wave velocity and a more or less constant thickness. The shear-velocity drop in the lower layer may be the evidence of a strong anisotropy induced by preferred orientation of ice crystals and by fine layering of soft and hard ice layers. A large variation of ice viscosity with depth is therefore expected and heterogeneous flowing of the polar ice sheet. This heterogeneous flowing may invalidate the use at great depth of the ice dating models based on monotonic layer thinning. © 2012 The Authors Geophysical Journal International © 2012 RAS.

Girard F.,University of Strasbourg | Ghienne J.-F.O.,University of Strasbourg | Rubino J.-L.,Total S.A.
Journal of Sedimentary Research | Year: 2012

A Late Ordovician glacially related delta is documented based on architecture and facies from outcrops in the western Murzuq Basin (Libya). Sandstone megabeds highlight clinoform geometries of a proglacial, low-angle, shallow-water delta. The progradational wedge extends over 25 km from the SSE to the NNW and is about 100 m thick. Two types of clinothems have been distinguished, and eleven facies sequences are characterized in relation with their along-slope positions. Sand-prone facies sequences in type 1 clinothems relate to high-magnitude-low-frequency glacial outburst floods generating a freshwater, highly concentrated plunging hyperpycnal flow at the river mouth. During the waxing stage, the slope adjustment of an out-of-grade profile causes significant erosion. The resulting additional sediment charge involves along foresets a downslope flow transformation into a co-genetic sandy debris flow and high-density turbidity flow. Hybrid event beds including linked debrites and turbidites are the resulting deposits. In the lower slope, decreasing sediment concentration of the high-density turbidity flow leads to sediment lofting and to a second flow transformation resulting in a lower-density turbidity flow and a concomitant rising sediment plume. Deposition results in crude ripple cross-stratification. Debrite deposition is temporally restricted to an early segment of the rising limb of the flood hydrograph. During the ensuing waxing stage, uninterrupted, sustained-flow conditions maintain up to the peak flow, permitting the aggradation of thick sandstone successions with crude ripple cross-stratification. During the waning stage, backstepping of the whole depositional system leads to prevailing sedimentation in the delta-plain setting. Mouth-bar development and channel plugs are characterized by climbing-dune crossstratification (CDCS). Shale-prone sedimentation in type 2 clinothems essentially corresponds to background ablation-related sedimentation but also includes minor, debrite-bearing, outburst-related event beds. This study documents the links between glacial outbursts, hyperpycnal flows, and hybrid beds in low-angle delta settings and illustrates a type of proximal, sanddominated hyperpycnite. Dam failure of subglacial lakes is inferred for the outburst generation. Comparison with modern and Pleistocene examples may suggest that outburst events were days to several years in duration (type 1 clinothem), with a 1-40 ky recurrence period (type 2 clinothem). © 2012, SEPM (Society for Sedimentary Geology).

Imler J.-L.,University of Strasbourg | Imler J.-L.,French National Center for Scientific Research
Developmental and Comparative Immunology | Year: 2014

The functional analysis of genes from the model organism Drosophila melanogaster has provided invaluable information for many cellular and developmental or physiological processes, including immunity. The best-understood aspect of Drosophila immunity is the inducible humoral response, first recognized in 1972. This pioneering work led to a remarkable series of findings over the next 30. years, ranging from the identification and characterization of the antimicrobial peptides produced, to the deciphering of the signalling pathways activating the genes that encode them and, ultimately, to the discovery of the receptors sensing infection. These studies on an insect model coincided with a revival of the field of innate immunity, and had an unanticipated impact on the biomedical field. © 2013 Elsevier Ltd.

Hammerstein P.,Humboldt University of Berlin | Noe R.,University of Strasbourg
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2016

Cooperation between organisms can often be understood, like trade between merchants, as a mutually beneficial exchange of services, resources or other ‘commodities’. Mutual benefits alone, however, are not sufficient to explain the evolution of trade-based cooperation. First, organisms may reject a particular trade if another partner offers a better deal. Second, while human trade often entails binding contracts, non-human trade requires unwritten ‘terms of contract’ that ‘self-stabilize’ trade and prevent cheating even if all traders strive to maximize fitness. Whenever trading partners can be chosen, market-like situations arise in nature that biologists studying cooperation need to account for. The mere possibility of exerting partner choice stabilizes many forms of otherwise cheatable trade, induces competition, facilitates the evolution of specialization and often leads to intricate forms of cooperation. We discuss selected examples to illustrate these general points and review basic conceptual approaches that are important in the theory of biological trade and markets. Comparing these approaches with theory in economics, it turns out that conventional models—often called ‘Walrasian’ markets— are of limited relevance to biology. In contrast, early approaches to trade and markets, as found in the works of Ricardo and Cournot, contain elements of thought that have inspired useful models in biology. For example, the concept of comparative advantage has biological applications in trade, signalling and ecological competition. We also see convergence between post-Walrasian economics and biological markets. For example, both economists and biologists are studying ‘principal-agent’ problems with principals offering jobs to agents without being sure that the agents will do a proper job. Finally, we show that mating markets have many peculiarities not shared with conventional economic markets. Ideas from economics are useful for biologists studying cooperation but need to be taken with caution. © 2016 The Author(s) Published by the Royal Society. All rights reserved.

Parisotto M.,University of Strasbourg | Metzger D.,University of Strasbourg
Molecular Oncology | Year: 2013

Despite major improvement in treatment of early stage localised prostate cancer, the distinction between indolent tumors and those that will become aggressive, as well as the lack of efficient therapies of advanced prostate cancer, remain major health problems. Genetically engineered mice (GEM) have been extensively used to investigate the molecular and cellular mechanisms underlying prostate tumor initiation and progression, and to evaluate new therapies. Moreover, the recent development of conditional somatic mutagenesis in the mouse prostate offers the possibility to generate new models that more faithfully reproduce the human disease, and thus should contribute to improve diagnosis and treatments. The strengths and weaknesses of various models will be discussed, as well as future opportunities. © 2013 Federation of European Biochemical Societies.

When family relations are not structured around laws that forbid incest, then prevails violence based on the domination of some over others. This article develops the specificity of the mother-daughter link in incestuous circumstances and how the victim's childhood is experienced as early maternal rejection. Maternal violence is exceptionally expressed through deeds but more so through attitudes of rejection or of lack of engagement to the child. A quest for affection associated to the original distress sets in and the abuser, who does not live by the law but rather in the perversion of the relation, exploits this distress. Through these acts, he reinforces the violence on the other and particularly on the feminine gender. The case study that this article presents highlights that beyond the incestuous act, the entire intra-family links fall within psychopathology. It also shows that violence, which is a consequence of this disorder, persists as a symptom and therefore needs to be voiced. © 2013 Elsevier Masson SAS.

If bereavement is a crossroad phenomenon involving both collective belonging and private attachment, the cultural part in the loss of a kin has progressively been erased since the beginning of the 20th century in France. What remains is the affective dimension. There is a kind of reversal of grief expression in our western societies. One hundred years ago, the social expression of mourning was predominant whereas the intimate expression of grief was hidden behind. But with the two world wars, the disorganization of rituals and the loss of faith in a protective God, the affects came to the forefront. Once collective, bereavement is now solipsist (referred to the self). Faced with a lack of social treatment, bereaved people turn to medicine and try to " cure" their grief. They acclaim " advances" in Medicine and appreciate the individualization in the medicalization of emotional states. On one hand, there is the most frequent bereavement in our societies, which is the loss of their old companions by lonely spouses. But this ordinary loss is cautious and quiet. On the other hand, media are exaggerating exceptional bereavements. But instead of being shared in collective ceremonies, these catastrophic deaths are provoking numbness, even in therapeutic groups and are now included in psychiatry manuals. By 2050, the number of dead people will have increased by 38 % in France. Prospective studies are planning 750,000 dead people in the year of 2050. Bereavement will not be exceptional then. A real demand for psychosocial support will certainly develop in the future, far beyond family propositions and community support. Associations with medical expertise are today centered on complicated grieves and propose special follow up in sanitary institutions (where about 70 % of persons die in France). Although bereaved people have a subjective feeling of a too long and uncertain temporality of grief, unusual bereavements draw outpour of grief in blogs or are searched for on Facebook. But grief is frequently lived alone. It seems that common bereavement is a kind of incongruity that many would like to bypass with a hastened death, a discreet and sober disappearing. Restoring social bonds around the mortality and fragility of existence would give back grief its social place in existence as generating human collective solidarity. Mourning would find again its affective role as a driving force behind individual experience and would find again its legitimate place within family lives, passing down from generation to generation the modalities of attachment and of identification to a lineage. © 2012 Elsevier Masson SAS.

Barnabe-Heider F.,Karolinska Institutet | Goritz C.,Karolinska Institutet | Sabelstrom H.,Karolinska Institutet | Takebayashi H.,Kumamoto University | And 3 more authors.
Cell Stem Cell | Year: 2010

Several distinct cell types in the adult central nervous system have been suggested to act as stem or progenitor cells generating new cells under physiological or pathological conditions. We have assessed the origin of new cells in the adult mouse spinal cord by genetic fate mapping. Oligodendrocyte progenitors self-renew, give rise to new mature oligodendrocytes, and constitute the dominating proliferating cell population in the intact adult spinal cord. In contrast, astrocytes and ependymal cells, which are restricted to limited self-duplication in the intact spinal cord, generate the largest number of cells after spinal cord injury. Only ependymal cells generate progeny of multiple fates, and neural stem cell activity in the intact and injured adult spinal cord is confined to this cell population. We provide an integrated view of how several distinct cell types contribute in complementary ways to cell maintenance and the reaction to injury. © 2010 Elsevier Inc.

Lengline O.,University of Strasbourg | Duputel Z.,University of Strasbourg | Ferrazzini V.,CNRS Paris Institute of Global Physics
Geophysical Research Letters | Year: 2016

We apply a template matching method to detect and locate preeruptive earthquakes at Piton de la Fournaise volcano in 2014 and 2015. This approach enabled the detection of many events and unveiled persistent seismicity features through multiple eruptions. Shallow earthquakes define a ring-shaped structure beneath the main crater. The repetitive occurrence of events along this structure suggests that it corresponds to a preexisting zone of weakness within the edifice. We also show evidence of deep magma transfer in 2015. More than 5000 deep earthquakes define an upward migration immediately followed by the occurrence of shallow events leading to an eruption 20 days later. This suggests the creation of a hydraulic connection between the lower part of the volcanic system and a magma reservoir located near sea level. We can envisage than such replenishments of the shallow reservoir occurred in the past but were undetected because of limited deep earthquake detections. © 2016. American Geophysical Union. All Rights Reserved.

Mendoza-Parra M.-A.,University of Strasbourg | Gronemeyer H.,University of Strasbourg
Seminars in Cell and Developmental Biology | Year: 2013

Nuclear receptors (NRs) are important mediators of the information encoded in the chemical structure of its corresponding ligand, as they interpret such information in the context of the cell identity and physiological status and convert it into sequential transcription regulatory events. At the cell level this can result in temporally coordinated processes such as cell fate transitions, which comprise the regulation of a plethora of gene programs including among others regulation of cell proliferation, metabolism and specific functionalities that are acquired by the differentiated cell. While both the early steps of nuclear receptor function and their impact on animal/organ physiology is rather well understood, little is known about the dynamic gene networks that ultimately cause a particular (cell) physiological phenomenon induced by the cognate NR ligand/hormone.Thanks to advances in massive parallel sequencing and bioinformatics analyses of genome-wide data sets, time has come for the development of NR systems biology. Indeed it is now possible to integrate global transcription factor binding, epigenetic chromatin histone and DNA modification patterns with transcriptomes and 3-dimensional chromatin structures, extract decision points in temporal studies and decipher the temporal control of gene networks that are the ultimate genetic readouts of NR ligand-induced physiological phenomena. In this review we will summarize the chronology of the development of increasingly larger data sets for NR action, with a particular focus on studies performed with the RAR/RXR nuclear receptor family, and discuss the present attempts to integrate a multitude of genome-wide data sets in the ultimate context of the temporal 3-dimensional chromatin structure. © 2013 Elsevier Ltd.

Al Tanoury Z.,University of Strasbourg | Piskunov A.,University of Strasbourg | Rochette-Egly C.,University of Strasbourg
Journal of Lipid Research | Year: 2013

Vitamin A or retinol is arguably the most multifunctional vitamin in the human body, as it is essential from embryogenesis to adulthood. The pleiotropic effects of vitamin A are exerted mainly by one active metabolite, all-trans retinoic acid (atRA), which regulates the expression of a battery of target genes through several families of nuclear receptors (RARs, RXRs, and PPARβ/δ), polymorphic retinoic acid (RA) response elements, and multiple coregulators. It also involves extranuclear and nontranscriptional effects, such as the activation of kinase cascades, which are integrated in the nucleus via the phosphorylation of several actors of RA signaling. However, vitamin A itself proved recently to be active and RARs to be present in the cytosol to regulate translation and cell plasticity. These new concepts expand the scope of the biologic functions of vitamin A and RA. Copyright © 2013 by the American Society for Biochemistry and Molecular Biology, Inc.

Dantzer F.,University of Strasbourg | Santoro R.,University of Zürich
FEBS Journal | Year: 2013

Poly(ADP-ribose) polymerases (PARPs) are enzymes that transfer poly(ADP-ribose) (PAR) groups to target proteins, and thereby affect various nuclear and cytoplasmic processes. The activity of PARP family members, such as PARP1 and PARP2, is tied to cellular signalling pathways, and, through poly(ADP-ribosyl)ation, they ultimately promote changes in chromatin architecture, gene expression, and the location and activity of proteins that mediate signalling responses. A growing body of evidence suggest that PARPs, particularly PARP1 and PARP2, also operate at heterochromatic regions such as the inactive X chromosome, telomeres, pericentric heterochromatin and silent ribosomal RNA (rRNA) genes. Both proteins localize to heterochromatic sites and often associate with or poly(ADP-ribosyl)ate histones and heterochromatin- binding proteins, thereby modulating their activities. In this review, we describe current knowledge concerning the role of PARPs in establishment and inheritance of heterochromatic structures, and highlight how their contribution affects biological outcomes. PARP1 and PARP2 are poly(ADP-ribose) polymerases (PARPs/ARTDs), enzymes that transfer poly(ADP-ribose) groups to target proteins and thereby affect cellular processes. The activity of PARP1 and PARP2 is tied to cellular signalling pathways, and through poly(ADP-ribosyl)ation they promote changes in chromatin architecture and gene expression. Here, we describe the role of PARPs in heterochromatin and their contribution in biological outcomes. © 2013 FEBS.

Fouesneau M.,University of Strasbourg | Fouesneau M.,University of Washington | Lancon A.,University of Strasbourg | Chandar R.,University of Toledo | Whitmore B.C.,US Space Telescope Science Institute
Astrophysical Journal | Year: 2012

The majority of clusters in the universe have masses well below 10 5 M⊙. Hence, their integrated fluxes and colors can be affected by the presence or absence of a few bright stars introduced by stochastic sampling of the stellar mass function. Specific methods are being developed to extend the analysis of cluster energy distributions into the low-mass regime. In this paper, we apply such a method to real observations of star clusters, in the nearby spiral galaxy M83. We reassess the ages and masses of a sample of 1242 clusters for which UBVIHα fluxes were obtained from observations with the Wide Field Camera 3 instrument on board the Hubble Space Telescope. Synthetic clusters with known properties are used to characterize the limitations of the method (valid range and resolution in age and mass, method artifacts). The ensemble of color predictions of the discrete cluster models are in good agreement with the distribution of observed colors. We emphasize the important role of the Hα data in the assessment of the fraction of young objects, particularly in breaking the age-extinction degeneracy that hampers an analysis based on UBVI data only. We find the mass distribution of the cluster sample to follow a power law of index -2.1 ± 0.2, and the distribution of ages a power law of index -1.0 ± 0.2 for log (M/ M ⊙) > 3.5, and ages between 107 and 109 yr. An extension of our main method, which makes full use of the probability distributions of age and mass obtained for the individual clusters of the sample, is explored. It produces similar power-law slopes and will deserve further investigation. Although the properties derived for individual clusters significantly differ from those obtained with traditional, non-stochastic models in about 30% of the objects, the first-order aspect of the age and mass distributions is similar to those obtained previously for this M83 sample in the range of overlap of the studies. We extend the power-law description to lower masses with better mass and age resolution and without most of the artifacts produced by the classical method. © 2012. The American Astronomical Society. All rights reserved.

Smith M.A.,Catholic University of America | Lopes De Oliveira R.,Federal University of Sergipe | Motch C.,University of Strasbourg
Astrophysical Journal | Year: 2012

HD110432 (BZCru; B1Ve) is the brightest member of a small group of "γCas analogs" that emit copious hard X-ray flux, punctuated by ubiquitous "flares." To characterize the X-ray time history of this star, we made a series of six RXTE multi-visit observations in 2010 and an extended observation with the XMM-Newton in 2007. We analyzed these new light curves along with three older XMM-Newton observations from 2002 to 2003. Distributed over five months, the RXTE observations were designed to search for long X-ray modulations over a few months. These observations indeed suggest the presence of a long cycle with P 226days and an amplitude of a factor of two. We also used X-ray light curves constructed from XMM-Newton observations to characterize the lifetimes, strengths, and interflare intervals of 1615 flare-like events in the light curves. After accounting for false positive events, we infer the presence of 955 (2002-2003) and 386 (2007) events we identified as flares. Similarly, as a control we measured the same attributes for an additional group of 541 events in XMM-Newton light curves of γCas, which, after a similar correction, yielded 517 flares. We found that the flare properties of HD110432 are mostly similar to our control group. In both cases the distribution of flare strengths are best fit with log-linear relations. Both the slopes of these distributions and the flaring frequencies themselves exhibit modest fluctuations. We discovered that some flares in the hard X-ray band of HD110432 were weak or unobserved in the soft band and vice versa. The light curves also occasionally show rapid curve drop-offs that are sustained for hours. We discuss the existence of the long cycle and these flare properties in the backdrop of two rival scenarios to produce hard X-rays, a magnetic star-disk interaction, and the accretion of blobs onto a secondary white dwarf. © 2012 The American Astronomical Society. All rights reserved.

Travelletti J.,University of Strasbourg | Travelletti J.,University of Caen Lower Normandy | Malet J.-P.,University of Strasbourg
Engineering Geology | Year: 2012

The geometry of the bedrock, internal layers and slip surfaces control the deformation pattern and the mechanisms of landslides. A challenge to progress in understanding landslide behavior is to construct accurate 3D geometrical models from different surveying techniques. The objective of this work is to present a methodology for integrating multi-source and multi-resolution data in a 3D geometrical model using geostatistical tools. The methodology consists in integrating the data by extracting relevant information on the internal structure of the landslide and in detecting possible incoherencies between different interpretations. A simple method to classify the input data and to control their influence on the model interpolation is proposed through the development of an expert reliability index. The methodology is applied for the creation of a 3D geometrical model of the Super-Sauze mudslide (South French Alps) for which an extensive dataset is available. Error calculation and expert geomorphological interpretation allow one to select the most suitable interpolation algorithm and to define the volumes of each layer. The proposed 3D geometrical model highlights the influence of the bedrock geometry on the observed kinematic pattern. © 2011 Elsevier B.V.

Kebede S.,Science Faculty | Travi Y.,University of Strasbourg
Quaternary International | Year: 2012

Understanding the origin of the δ 18O and δ 2H content of meteoric waters is the initial step in using these isotopes in water resources, hydrological and hydro-climatic investigations. Specifically, isotopes of water are proven tools in a) constraining rate and mechanism of groundwater recharge, b) tracing movement of groundwaters, c) reconstructing past climate (rainfall amount, humidity and temperature) at various time scales, d) quantifying water flux across boundaries (e.g. evaporation rates, mixing), and e) complementing regional and global climate models. The δ 18O and δ 2H values in rainfall waters of Ethiopia have long been recognised as a 'regional anomaly'. Regardless of the station's high altitude (2360 m asl) and the region's low mean annual temperature (16 °C), two conditions that would otherwise lead to relative isotope depletion, the rains show the highest 18O composition with no sign of effect of evaporative enrichment (as revealed by d-excess). This enrichment is also reflected in other local meteoric waters (shallow groundwaters, lakes, ambient vapour and rivers). Here, the δ 18O and δ 2H of 600 lake water samples, 3000 groundwater samples, and rainfall isotope data base from IAEA/WMO stations at Addis Ababa have been used to show the linkage between rainfall derivation processes and isotope signals. The major sources of moisture in Ethiopia are recycled moisture from continental sources for western and northern Ethiopia, and direct moisture from the Southern Indian Ocean for eastern lowlands of Ethiopia. Southern Ethiopia is influenced by South Indian Ocean moisture, which is characterised by relatively depleted 18O and 2H. Spatial variation (altitude and latitude) in 18O and 2H is weak, with altitude effect accounting for 0.1‰/100 m depletion in δ 18O. Detailed investigation of the relation between isotope pattern and isotope effects (amount, seasonality, temperature, etc.) shows that these effects are not pronounced. The -4.5‰ δ 18O shift recorded in deeper groundwaters and other paleo-climate achieves (from the current wt. mean rainfall value of -0.5‰) can only be explained by a shift in source of moisture, such as the northward penetration of the South Indian Ocean moisture into the Ethiopian highlands, or changes in evaporation conditions at the source. © 2011 Elsevier Ltd and INQUA.

Brantut N.,University College London | Baud P.,University of Strasbourg | Heap M.J.,University of Strasbourg | Meredith P.G.,University College London
Journal of Geophysical Research: Solid Earth | Year: 2012

In the upper crust, the chemical influence of pore water promotes time dependent brittle deformation through sub-critical crack growth. Sub-critical crack growth allows rocks to deform and fail at stresses well below their short-term failure strength, and even at constant applied stress ("brittle creep"). Here we provide a micromechanical model describing time dependent brittle creep of water-saturated rocks under triaxial stress conditions. Macroscopic brittle creep is modeled on the basis of microcrack extension under compressive stresses due to sub-critical crack growth. The incremental strains due to the growth of cracks in compression are derived from the sliding wing crack model of Ashby and Sammis (1990), and the crack length evolution is computed from Charles' law. The macroscopic strains and strain rates computed from the model are non linear, and compare well with experimental results obtained on granite, low porosity sandstone and basalt rock samples. Primary creep (decelerating strain) corresponds to decelerating crack growth, due to an initial decrease in stress intensity factor with increasing crack length in compression. Tertiary creep (accelerating strain as failure is approached) corresponds to an increase in crack growth rate due to crack interactions. Secondary creep with apparently constant strain rate arises as an inflexion between those two end-member phases. The minimum strain rate at the inflexion point can be estimated analytically as a function of model parameters, effective confining pressure and temperature, which provides an approximate creep law for the process. The creep law is used to infer the long term strain rate as a function of depth in the upper crust due to the action of the applied stresses: in this way, sub-critical cracking reduces the failure stress in a manner equivalent to a decrease in cohesion. We also investigate the competition with pressure solution in porous rocks, and show that the transition from sub-critical cracking to pressure solution dominated creep occurs with increasing depth and decreasing strain rates. © 2012. American Geophysical Union. All Rights Reserved.

Sutra E.,University of Strasbourg | Manatschal G.,University of Strasbourg
Geology | Year: 2012

The discovery of hyperthinned continental crust and exhumed mantle on present-day deepwater rifted margins leads to two fundamental questions: (1) in detail, how does the crust thin in extension, and (2) what controls extreme crustal thinning and mantle exhumation? Reflection and refraction seismic lines across the Iberian margin show decoupling levels in the crust cut by structures that eventually transfer deformation to mantle levels. The region of decoupled extension appears to be more broadly distributed on the northern Iberian margin and more localized on the southern margin. Based on drill hole data, the transition from decoupled to coupled deformation occurred during Tithonian time (ca. 145 Ma). This evolution from decoupled to coupled deformation may help explain the crustal architecture of the Iberian margin. An apparent delay of subsidence across the hyperextended coupled zone of the Iberian margin may indicate that crustal thinning had to occur simultaneously with lithospheric necking and the advection of heat related to lithospheric mantle thinning. © 2012 Geological Society of America.

Ai P.,CNRS Coordination Chemistry | Danopoulos A.A.,CNRS Coordination Chemistry | Danopoulos A.A.,University of Strasbourg | Braunstein P.,CNRS Coordination Chemistry | Monakhov K.Y.,RWTH Aachen
Chemical Communications | Year: 2013

A novel N,N′-diphosphanyl-imidazol-2-ylidene acts as a stable, hybrid PCNHCP ligand for M2 or linear M3 (M = Cu, Ag, Au) arrays with metallophilic interactions. © 2014 The Royal Society of Chemistry.

Mahamdallie S.S.,Natural History Museum in London | Pesson B.,University of Strasbourg | Ready P.D.,Natural History Museum in London
Heredity | Year: 2011

Phlebotomus ariasi is one of the two sandflies transmitting the causative agent of zoonotic leishmaniasis, Leishmania infantum, in France and Iberia, and provides a rare case study of the postglacial re-colonization of France by a Mediterranean species. Four DNA sequences were analysedmitochondrial cytochrome b (cyt b), nuclear elongation factor-1α (EF-1α) and two anonymous nuclear locifor 14-15 French populations and single populations from northeast Spain, northwest Spain, Portugal and Morocco. The presence of cryptic sibling species was not revealed by phylogenetic analyses and testing for reproductive isolation between sympatric populations defined by the two most divergent cyt b haplogroups. No locus was shown to be under positive directional or balancing selection and, therefore, molecular variation was explained demographically. Each nuclear locus showed shallow isolation by distance from Portugal to the French Pyrenees, but for both cyt b and EF-1α there was then a step change to the upland Massif Central, where leading-edge populations showed low diversity at all loci. Multiple genetic divergences and population expansions were detected by analyses of cyt b and dated to the Pleistocene. Endemicity of one cyt b sub-lineage suggested the presence of a refuge north of the Pyrenees during the last glacial period. Monopolization of the Massif Central by genetically differentiated populations of P. ariasi might possibly hinder the northwards spread of leishmaniasis. © 2011 Macmillan Publishers Limited All rights reserved 0018-067X/11.

Urzhumtsev A.,University of Strasbourg | Urzhumtsev A.,University of Lorraine | Afonine P.V.,Lawrence Berkeley National Laboratory | Lunin V.Y.,Russian Academy of Sciences | And 3 more authors.
Acta Crystallographica Section D: Biological Crystallography | Year: 2014

Numerical comparison of crystallographic contour maps is used extensively in structure solution and model refinement, analysis and validation. However, traditional metrics such as the map correlation coefficient (map CC, real-space CC or RSCC) sometimes contradict the results of visual assessment of the corresponding maps. This article explains such apparent contradictions and suggests new metrics and tools to compare crystallographic contour maps. The key to the new methods is rank scaling of the Fourier syntheses. The new metrics are complementary to the usual map CC and can be more helpful in map comparison, in particular when only some of their aspects, such as regions of high density, are of interest. © 2014 International Union of Crystallography.

Spenle C.,University of Strasbourg | Simon-Assmann P.,University of Strasbourg | Orend G.,University of Strasbourg | Miner J.H.,University of Washington
Cell Adhesion and Migration | Year: 2013

Laminins (LM) are extracellular matrix molecules that contribute to and are required for the formation of basement membranes. They participate in the modulation of epithelial/mesenchymal interactions and are implicated in organogenesis and maintenance of organ homeostasis. Among the LM molecules, the LM α5 chain (LMα5) is one of the most widely distributed LM in the developing and mature organism. Its presence in some basement membranes during embryogenesis is absolutely required for maintenance of basement membrane integrity and thus for proper organogenesis. LMα5 also regulates the expression of genes important for major biological processes, in part by repressing or activating signaling pathways, depending upon the physiological context. © 2013 Landes Bioscience.

Lithfous S.,University of Strasbourg | Dufour A.,University of Strasbourg | Despres O.,University of Strasbourg
Ageing Research Reviews | Year: 2013

Normal aging and mild Alzheimer's disease (AD) are associated with declines in navigational skills, including allocentric and egocentric representations, cognitive mapping, landmark processing, and spatial memory. These changes, however, are associated with different patterns of structural and functional alterations in the neural network of navigation. In AD, these changes occur in the hippocampus, parahippocampal gyrus, parietal lobe, retrosplenial cortex, prefrontal cortex, and caudate nucleus, whereas in aging, modifications occur mainly in the prefrontal cortex and the hippocampus. The navigation abilities of patients with mild cognitive impairment (MCI) have been found to show different performance patterns, depending on their cognitive profiles. Since patients with MCI do not uniformly develop dementia of the Alzheimer type, it is important to identify reliable early cognitive markers of conversion to AD dementia. In this review, we propose that navigation deficits may help distinguish patients at higher risk of developing AD dementia from individuals with normal cognitive aging and those with other neurodegenerative diseases. © 2012 Elsevier B.V.

Pastore A.,UK National Institute for Medical Research | Puccio H.,Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire | Puccio H.,French Institute of Health and Medical Research | Puccio H.,University of Strasbourg | Puccio H.,Collège de France
Journal of Neurochemistry | Year: 2013

Reduced levels of the protein frataxin cause the neurodegenerative disease Friedreich's ataxia. Pathology is associated with disruption of iron-sulfur cluster biosynthesis, mitochondrial iron overload, and oxidative stress. Frataxin is a highly conserved iron-binding protein present in most organisms. Despite the intense interest generated since the determination of its pathology, identification of the cellular function of frataxin has so far remained elusive. In this review, we revisit the most significant milestones that have led us to our current understanding of frataxin and its functions. The picture that emerges is that frataxin is a crucial element of one of the most essential cellular machines specialized in iron-sulfur cluster biogenesis. Future developments, therefore, can be expected from further advancements in our comprehension of this machine. © 2013 International Society for Neurochemistry.

Collongues N.,French Institute of Health and Medical Research | Collongues N.,University of Strasbourg | De Seze J.,French Institute of Health and Medical Research
Therapeutic Advances in Neurological Disorders | Year: 2011

Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system (CNS) characterized by severe attacks of optic neuritis and myelitis, and which, unlike multiple sclerosis (MS), commonly spares the brain in the early stages. NMO used to be considered as a special form of MS. During the past 10 years, however, the two diseases have been shown to be clearly different. NMO is a B-cell-mediated disease associated with anti-aquaporin-4 antibodies in many cases and its pathophysiology seems to be near the acute lesion of necrotizing vasculitis. Assessment of prevalence shows that NMO is far less frequent than MS, which explains the absence of randomized clinical trials and NMO treatment strategies validated by evidence-based medicine. Recently, many data have been published that suggest that the therapeutic option in NMO should be immunosuppressive rather than immunomodulatory drugs. In the present study, after a brief overview of NMO, we review therapeutic studies and propose new therapeutic strategies in the relapse and disease-modifying fields. © 2011 The Author(s).

Befort K.,University of Strasbourg
Frontiers in Pharmacology | Year: 2015

The opioid system consists of three receptors, mu, delta, and kappa, which are activated by endogenous opioid peptides (enkephalins, endorphins, and dynorphins). The endogenous cannabinoid system comprises lipid neuromodulators (endocannabinoids), enzymes for their synthesis and their degradation and two well-characterized receptors, cannabinoid receptors CB1 and CB2. These systems play a major role in the control of pain as well as in mood regulation, reward processing and the development of addiction. Both opioid and cannabinoid receptors are coupled to G proteins and are expressed throughout the brain reinforcement circuitry. Extending classical pharmacology, research using genetically modified mice has provided important progress in the identification of the specific contribution of each component of these endogenous systems in vivo on reward process. This review will summarize available genetic tools and our present knowledge on the consequences of gene knockout on reinforced behaviors in both systems, with a focus on their potential interactions. A better understanding of opioid-cannabinoid interactions may provide novel strategies for therapies in addicted individuals. © 2015 Befort.

Su B.,University of Strasbourg | Moog C.,University of Strasbourg
Frontiers in Immunology | Year: 2014

HIV antibody (Ab) functions capable of preventing mucosal cell-free or cell-to-cell HIV transmission are critical for the development of effective prophylactic and therapeutic vaccines. In addition to CD4+ T cells, other potential HIV-target cell types including antigen-presenting cells (APCs) (dendritic cells, macrophages) residing at mucosal sites are infected. Moreover, the interactions between APCs and HIV lead to HIV cell-to-cell transmission. Recently discovered broadly neutralizing antibodies (NAbs) are able to neutralize a broad spectrum of HIV strains, inhibit cell-to-cell transfer, and efficiently protect from infection in the experimentally challenged macaque model. However, the 31% protection observed in the RV144 vaccine trial in the absence of detectable NAbs in blood samples pointed to the possible role of additional Ab inhibitory functions. Increasing evidence suggests that IgG Fcγ receptor (FcγR)-mediated inhibition of Abs present at the mucosal site may play a role in protection against HIV mucosal transmission. Moreover, mucosal IgA Abs may be determinant in protection against HIV sexual transmission. Therefore, defining Ab inhibitory functions that could lead to protection is critical for further HIV vaccine design. Here, we review different inhibitory properties of HIV-specific Abs and discuss their potential role in protection against HIV sexual transmission. © 2014 Su and Moog.

Liti G.,University of Nottingham | Schacherer J.,University of Strasbourg
Comptes Rendus - Biologies | Year: 2011

Genome sequences of multiple individuals are essential to determine the forces shaping sequence variation as well as to understand the relationship between genotype and phenotype. Because of their wide ecological, geographical and genetic diversity, yeast species represent an ideal model system for population genomics. Recently, there has been a renewed interest in characterizing the genetic diversity within yeast species such as Saccharomyces cerevisiae and Saccharomyces paradoxus. Here, we review recent progress in the exploration of the intraspecific diversity using large collections of yeast isolates. These recent large-scale polymorphism surveys have increased our understanding of the population structures as well as the evolutionary history of the species. In addition, these resources represent a powerful framework for dissecting the relationship between genotype and phenotype. © 2011 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

Morel O.,University of Strasbourg
Seminars in immunopathology | Year: 2011

Plasma membrane remodeling characterized by phosphatidylserine exposure and consecutive microparticle (MP) shedding is an ubiquitous process enabling the clearance of senescent cells and the maintenance of tissue homeostasis. MPs are released as fragments from the budding plasma membrane of virtually all eukaryotic cell types undergoing stimulation or apoptosis and may be considered a broad primitive response to stress. MP release is dependent on cytoskeleton degradation pathways involving caspases, requires a sustained increase in intracellular calcium triggering K+ and Cl- efflux and is possibly tuned by mitochondria permeability changes. Because they convey a broad spectrum of bioactive molecules, circulating MPs may serve as shuttles promoting cellular cross talk in various pathological settings such as inflammation or immunity-induced thrombotic disorders. If the drastic shedding of procoagulant MPs appears clearly noxious in thrombotic disorders or in some models of inflammation-induced coagulopathy, this does not necessarily endorse their invariably harmful nature. In the vessel, endothelial cytoprotection reported in the early regulation of inflammation-induced coagulopathy is emblematic of the beneficial effects provided by MPs. In addition, MPs would prove beneficial in the prevention of blood leakage. Because of their multiple properties that are characteristic of a private response of the parental cell, MPs could act as cytoprotective and anti-inflammatory agents through the delivery of activated protein C or annexin 1 and could contribute to the limitation of vascular hyporeactivity. Owing to their ability to cargo bioactive signals, MPs could be viewed as an integrated communication network enabling the coordination of complex cellular responses in biological fluids and the maintenance of the homeostasis equation. A better understanding of the molecular mechanisms involved in MP shedding would pave the way of a new pharmacological approach aiming at the control of MP-driven cellular responses.

Eschbach J.,French Institute of Health and Medical Research | Eschbach J.,University of Strasbourg | Eschbach J.,University of Ulm | Dupuis L.,French Institute of Health and Medical Research | Dupuis L.,University of Strasbourg
Pharmacology and Therapeutics | Year: 2011

Cytoplasmic dynein 1 (later referred to as dynein) is the major molecular motor moving cargoes such as mitochondria, organelles and proteins towards the minus end of microtubules. Dynein is involved in multiple basic cellular functions, such as mitosis, autophagy and structure of endoplasmic reticulum and Golgi, but also in neuron specific functions in particular retrograde axonal transport. Dynein is regulated by a number of protein complexes, notably by dynactin. Several studies have supported indirectly the involvement of dynein in neurodegeneration associated with Alzheimer's disease, Parkinson's disease, Huntington's disease and motor neuron diseases. First, axonal transport disruption represents a common feature occurring in neurodegenerative diseases. Second, a number of dynein-dependent processes, including autophagy or clearance of aggregation-prone proteins, are found defective in most of these diseases. Third, a number of mutant genes in various neurodegenerative diseases are involved in the regulation of dynein transport. This includes notably mutations in the P150Glued subunit of dynactin that are found in Perry syndrome and motor neuron diseases. Interestingly, gene products that are mutant in Huntington's disease, Parkinson's disease, motor neuron disease or spino-cerebellar ataxia are also involved in the regulation of dynein motor activity or of cargo binding. Despite a constellation of indirect evidence, direct links between the motor itself and neurodegeneration are few, and this might be due to the requirement of fully active dynein for development. Here, we critially review the evidence of dynein involvement in different neurodegenerative diseases and discuss potential underlying mechanisms. © 2011 Elsevier Inc.

Oertel A.M.,University of Strasbourg | Ritleng V.,University of Strasbourg | Burr L.,University of Strasbourg | Chetcuti M.J.,University of Strasbourg
Organometallics | Year: 2011

Cationic cyclopentadienyl mixed bis-N-heterocyclic carbene (NHC) nickel complexes of the general formula [Ni(NHC)(NHC′)Cp](PF 6) (NHC/NHC′ = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (Mes 2NHC) a, 1,3-dimethylimidazol-2-ylidene (Me 2NHC) b, 1-isopropyl-3-methyl-imidazol-2-ylidene (iPr-NHC-Me) c; Cp = η 5-C 5H 5) were prepared by the reaction of the cationic monocarbene complex [Ni(Mes 2NHC)(NCMe)Cp](PF 6) 1a or [Ni(Me 2NHC)(NCMe)Cp](BF 4) 1b with the appropriate free carbene. The new mixed bis(carbene) complexes [Ni(Mes 2NHC)(Me 2NHC)Cp](PF 6) 2ab, [Ni(Mes 2NHC)(iPr-NHC-Me)Cp](PF 6) 2ac, and [Ni(Me 2NHC)(iPr-NHC-Me)Cp](BF 4) 2bc were obtained in moderate-to-high yields and were fully characterized by 1H and 13C NMR spectroscopies, elemental analyses, and, in the case of 2ab, by a single-crystal X-ray diffraction study. The monocarbene precursor 1b was also structurally characterized. The mixed bis-NHC complexes 2ab and 2ac were tested as catalysts for the Suzuki-Miyaura cross-coupling of phenylboronic acid with 4′-bromoacetophenone, and their activities were compared to that of related monocarbene CpNi complexes. © 2011 American Chemical Society.

Background: The objective of theFALCOFORTEprogramme was to demonstrate the efficacy and safety of 3 months of therapy with the fixed combination perindopril/indapamide in hypertensive patients in everyday medical practice. Design and methods: Patients with blood pressure >140/90mmHgor with blood pressure >130/85mmHgand three or more risk factors were prescribed perindopril/indapamide 2.5/0.625mg or 5/1.25 mg. Dosage could be increased to 10/2.5mg at any time during the study. Results: Of the 2327 patients included, 69% of patients had been unsuccessfully treated with other antihypertensives, 4.6% had not tolerated previous antihypertensive treatments, and 26.8% were newly diagnosed hypertensive patients. Roughly half the cohort was at high or very high cardiovascular risk. After 3 months of therapy, systolic blood pressure decreased from 156.9 ± 13.7 to 132.3 ± 10.6mmHg (p < 0.0001) and diastolic blood pressure from 94.9 ± 8.2 to 81.3 ± 6.3mmHg (p < 0.0001). Target blood pressure was reached by 87.1%of patients. Similar changes from baseline were observed in patients with diabetes mellitus, metabolic syndrome or left ventricular hypertrophy (p < 0.0001).When blood pressure decreaseswere analysed by dose, changes frombaseline increased with increasing doses. Perindopril/indapamide waswell tolerated with no significant changes in laboratory parameters being observed. Quality of life improved significantly. Conclusions: Therapy with fixed combination perindopril/ indapamide was effective and well tolerated in a wide range of patients. © 2011 Adis Data Information BV. All rights reserved.

Munschy M.,University of Strasbourg | Fleury S.,University of Strasbourg
Geophysical Prospecting | Year: 2011

Magnetic surveys for geophysical interpretation will most usefully furnish estimates of the three components of the magnetic field vector. We review methods for obtaining this information based on scalar and tensor magnetic field measurements and point out the advantages of fluxgate vector measurements. Fluxgate vector magnetometers can be powerful instruments in magnetic mapping. The main problems in using fluxgate magnetometers arise from calibration errors and drift but these can be overcome using a quick and simple method of calibration. This method also has the advantage of compensating permanent and induced magnetic fields generated by the airplane. This is illustrated by a new aeromagnetic survey flown in the Vosges area (France). Measurement accuracy is shown to be similar to that obtained with scalar magnetometers. We take advantage of this accuracy to calculate in the Fourier domain other magnetic functions from the total-field anomaly, in particular, the magnetic gradient tensor is obtained without using any superconducting quantum devices. A similar approach is used to introduce a new magnetic anomaly tensor that is the equivalent of the pseudo-gravity tensor. Maps presented in the last sections serve as an example to illustrate the various functions, the goal of the paper being to obtain magnetic vector data from the observations without first postulating the detailed nature of the sources. © 2011 European Association of Geoscientists & Engineers.

Calo M.,University of Strasbourg | Dorbath C.,University of Strasbourg | Cornet F.H.,French National Center for Scientific Research | Cuenot N.,GEIE
Geophysical Journal International | Year: 2011

In 2000, a large water injection (over 23000 m3) has been conducted in granite through a 5-km-deep borehole at Soultz-sous-Forêts, in the Upper Rhine Graben (northeastern France). The microseismicity induced by this hydraulic stimulation was monitored with a network of 14 seismic stations deployed at ground surface. Some 7215 well-located events have been used to conduct a 4-D tomography of P-wave velocities. The method combines a double-difference tomography method with an averaging post-processing that corrects for parameter dependence effects. The total set of 7 215 events has been divided into 14 subsets that explore periods defined with respect to the injection scheme. Particular attention is given to changes in injected flow rates, periods of stationary injection conditions and post-injection periods. Fast changes in VP velocities are identified in large rock mass volumes precisely when the injection flow rate varies while little velocity variation is detected during stationary injection periods. The VP anomalies observed during stationary injection conditions are interpreted as being caused by effective stress variations linked to fluid diffusion, while the fast changes observed concomitantly to changes in flow rate are considered to be caused by non-seismic motions. © 2011 The Authors Geophysical Journal International © 2011 RAS.

Dunoyer P.,University of Strasbourg | Brosnan C.A.,University of Strasbourg | Schott G.,University of Strasbourg | Wang Y.,University of Strasbourg | And 4 more authors.
EMBO Journal | Year: 2010

Recent work on metazoans has uncovered the existence of an endogenous RNA-silencing pathway that functionally recapitulates the effects of experimental RNA interference (RNAi) used for gene knockdown in organisms such as Caenorhabditis elegans and Drosophila. The endogenous short interfering (si)RNA involved in this pathway are processed by Dicer-like nucleases from genomic loci re-arranged to form extended inverted repeats (IRs) that produce perfect or near-perfect dsRNA molecules. Although such IR loci are commonly detected in plant genomes, their genetics, evolution and potential contribution to plant biology through endogenous silencing have remained largely unexplored. Through an exhaustive analysis performed using Arabidopsis, we provide here evidence that at least two such endogenous IRs are genetically virtually indistinguishable from the transgene constructs commonly used for RNAi in plants. We show how these loci can be useful probes of the cellular mechanism and fluidity of RNA-silencing pathways in plants, and provide evidence that they may arise and disappear on an ecotype scale, show highly cell-specific expression patterns and respond to various stresses. IR loci thus have the potential to act as molecular sensors of the local environments found within distinct ecological plant niches. We further show that the various siRNA size classes produced by at least one of these IR loci are functionally loaded into cognate effector proteins and mediate both post-transcriptional gene silencing and RNA-directed DNA methylation (RdDM) of endogenous as well as exogenous targets. Finally, and as previously reported during plant experimental RNAi, we provide evidence that endogenous IR-derived siRNAs of all size classes are not cell-autonomous and can be transported through graft junctions over long distances, in target tissues where they are functional, at least in mediating RdDM. Collectively, these results define the existence of a bona fide, endogenous and systemic RNAi pathway in plants that may have implications in adaptation, epiallelism and trans-generational memory. © 2010 European Molecular Biology Organization.

Hammani K.,University of Strasbourg | Giege P.,University of Strasbourg
Trends in Plant Science | Year: 2014

Mitochondria are essential for the eukaryotic cell and are derived from the endosymbiosis of an α-proteobacterial ancestor. Compared to other eukaryotes, RNA metabolism in plant mitochondria is complex and combines bacterial-like traits with novel features that evolved in the host cell. These complex RNA processes are regulated by families of nucleus-encoded RNA-binding proteins. Transcription is particularly relaxed and is initiated from multiple promoters covering the entire genome. The variety of RNA precursors accumulating in mitochondria highlights the importance of post-transcriptional processes to determine the size and abundance of transcripts. Here we review RNA metabolism in plant mitochondria, from RNA transcription to translation, with a special focus on their unique features that are controlled by trans-factors. © 2013 Elsevier Ltd.

Lazauskas R.,University of Strasbourg | Dufour M.,University of Strasbourg
Physical Review C - Nuclear Physics | Year: 2011

The 12C nucleus is investigated in a nonmicroscopic α-particle model involving local and nonlocal potentials. Faddeev equations formulated in configuration space are used to solve the three-body problem for bound and resonant states. We demonstrate that the nonlocal potential developed by Papp and Moszkowski appears to be particularly well adapted to study 3α clustering. We point out 12C states of positive-parity which share common features with the 02+ Hoyle states. Several negative-parity states revealing a clear bosonic α-particle structure are also obtained. © 2011 American Physical Society.

Belikov I.,University of Strasbourg
Journal of Physics G: Nuclear and Particle Physics | Year: 2011

We present the study of K0 S and Λ production performed with the ALICE experiment at the LHC in Pb-Pb collisions at √sNN = 2.76 TeV and pp collisions at √s = 0.9 and 7 TeV. The K 0 S and Λ particles are reconstructed via their V0 decay topology allowing their identification up to high transverse momenta. The corresponding baryon/meson ratios as a function of transverse momentum are extracted for Pb-Pb collisions in centrality bins and in the transverse momentum range from 1 to 6 GeV/c. They are also compared with those measured in pp events at the LHC energies of 0.9 and 7 TeV as well as in Au-Au collisions at √sNN = 6.24 and 200 GeV from RHIC. © CERN 2011. Published under licence by IOP Publishing Ltd.

Ducros A.,Montpellier University | Wolff V.,University of Strasbourg
Headache | Year: 2016

During the last 10 years, reversible cerebral vasoconstriction syndrome (RCVS) has emerged as the most frequent cause of thunderclap headache (TCH) in patients without aneurysmal subarachnoid hemorrhage, and as the most frequent cause of recurrent TCHs. The typical TCHs of RCVS are multiple, recurring over a few days to weeks, excruciating, short-lived, and brought up by exertion, sexual activities, emotion, Valsalva maneuvers, or bathing, among other triggers. All these triggers induce sympathetic activation. In a minority of cases with RCVS, TCH heralds stroke and rarely death. Early diagnosis of RCVS in patients who present with isolated headache enables proper management and might reduce the risk of eventual stroke. This review describes the characteristics, triggers, diagnosis, and management of TCH in RCVS. One aim is to underline that the TCH pattern of RCVS is so typical that it enables, according to the 2013 revision of the International Classification of Headache Disorders, the diagnosis of "probable RCVS" in patients with such a headache pattern, normal cerebral angiography, and no other cause. Another objective is to discuss the role of physical and emotional stress in RCVS and in other related conditions involving similar triggers. © 2016 American Headache Society.

Renault H.,University of Strasbourg | Renault H.,Albert Ludwigs University of Freiburg | Bassard J.-E.,Copenhagen University | Hamberger B.,Copenhagen University | And 2 more authors.
Current Opinion in Plant Biology | Year: 2014

Cytochromes P450 catalyze a broad range of regiospecific, stereospecific and irreversible steps in the biosynthetic routes of plant natural metabolites with important applications in pharmaceutical, cosmetic, fragrance and flavour, or polymer industries. They are consequently essential drivers for the engineered bioproduction of such compounds. Two ground-breaking developments of commercial products driven by the engineering of P450s are the antimalarial drug precursor artemisinic acid and blue roses or carnations. Tedious optimizations were required to generate marketable products. Hurdles encountered in P450 engineering and their potential solutions are summarized here. Together with recent technical developments and novel approaches to metabolic engineering, the lessons from this pioneering work should considerably boost exploitation of the amazing P450 toolkit emerging from accelerated sequencing of plant genomes. © 2014 The Authors.

Anton N.,University of Strasbourg | Vandamme T.F.,University of Strasbourg
Pharmaceutical Research | Year: 2014

In the last decade, nanomaterials have gained considerable attention and interest in the development of new and efficient molecular probes for medical diagnosis and imaging. Compared to traditional contrast agents used from the 70s, this comes from the new possibilities offered by the increased half-life of nanosystems in blood stream, as well as by the specific accumulation in organ of lesions through passive or active targeting mechanisms. Heavy metal or iodinated-loaded nanoparticles are excellent absorbers of X-rays and can offer excellent improvement in medical diagnosis and X-ray imaging. This review aims to propose an accurate state-of-the-art of the emerging applications of nanotechnology in X-ray imaging. Likewise we will discuss and compare all the solutions proposed, and the impact of their composition, formulation methods, and physicochemical properties on their applications, efficiency, and potential industrial scaling-up. © 2013 Springer Science+Business Media New York.

Song Y.-H.,University of South Carolina | Lazauskas R.,University of Strasbourg | Gudkov V.,University of South Carolina
Physical Review C - Nuclear Physics | Year: 2011

Time reversal invariance-violating (TRIV) effects in low-energy elastic neutron-deuteron scattering are calculated using meson exchange and EFT-type TRIV potentials in a distorted-wave Born approximation with realistic hadronic strong interaction wave functions, obtained by solving the three-body Faddeev equations in configuration space. The relation between TRIV and parity-violating observables is discussed. © 2011 American Physical Society.

Lazauskas R.,University of Strasbourg | Carbonell J.,CEA Saclay Nuclear Research Center
Physical Review C - Nuclear Physics | Year: 2011

A formalism based on the complex-scaling method is developed for solving the few-particle scattering problem, in terms of bound state boundary conditions. Several applications are presented to demonstrate the efficiency of the method for computing the elastic and three-body breakup reactions in systems described by Hamiltonians which may include both short- and long-range interactions. © 2011 American Physical Society.

Hou J.,University of Strasbourg | Friedrich A.,University of Strasbourg | De Montigny J.,University of Strasbourg | Schacherer J.,University of Strasbourg
Current Biology | Year: 2014

Understanding the molecular basis of how reproductive isolation evolves between individuals from the same species offers valuable insight into patterns of genetic differentiation as well as the onset of speciation [1, 2]. The yeast Saccharomyces cerevisiae constitutes an ideal model partly due to its vast ecological range, high level of genetic diversity [3-6], and laboratory-amendable sexual reproduction. Between S. cerevisiae and its sibling species in the Saccharomyces sensu stricto complex, reproductive isolation acts postzygotically and could be attributed to chromosomal rearrangements [7], cytonuclear incompatibility [8, 9], and antirecombination [10, 11], although the implication of these mechanisms at the incipient stage of speciation remains unclear due to further divergence in the nascent species. Recently, several studies assessed the onset of intraspecific reproductive isolation in S. cerevisiae by evaluating the effect of the mismatch repair system [12-14] or by fostering incipient speciation using the same initial genetic background [15-18]. Nevertheless, the overall genetic diversity within this species was largely overlooked, and no systematic evaluation has been performed. Here, we carried out the first species-wide survey for postzygotic reproductive isolation in S. cerevisiae. We crossed 60 natural isolates sampled from diverse niches with the reference strain S288c and identified 16 cases of reproductive isolation with reduced offspring viabilities ranging from 44% to 86%. Using different mapping strategies, we identified reciprocal translocations in a large fraction of all isolates surveyed, indicating that large-scale chromosomal rearrangements might play a major role in the onset of reproductive isolation in this species. © 2014 Elsevier Ltd.

Pauli G.,University of Strasbourg | Malling H.-J.,Copenhagen University
Current Opinion in Allergy and Clinical Immunology | Year: 2010

Purpose Of Review: Subcutaneous immunotherapy is a well documented treatment of allergic rhinitis and asthma. The majority of the disadvantages of the treatment are related to the poor quality of the natural allergen extracts which can contain varying amounts of individual allergens including allergens to which the patient may not be sensitized. Recombinant allergens offer a possibility to use well defined molecules with consistent pharmaceutical quality defined in mass units. The proof of concept of the clinical efficacy of recombinant allergens is based on two studies published as full articles. Recent Findings: One study applied a mixture of five Phleum pratense major allergens in a maximum dose of 40mcg protein. The clinical efficacy showed a significant efficacy with 40% reduction in disease severity. The second study compared a commercial birch extract with both recombinant Bet v 1 and purified Bet v 1 in dosages of 15mcg allergen. The clinical effect was 60% additional efficacy. Systemic side effects occurred more frequently with grass allergens. A third study used hypoallergenic fragments and a trimer of Bet v 1. The study did not show efficacy and a rather high frequency of systemic side effects. Summary: The advantages of using recombinant allergens for immunotherapy are obvious but more studies on a large scale are needed before the overall value in terms of efficacy and safety can be assessed. Clinical trials are also necessary for new combined vaccines based on recombinant allergens that in experimental studies have shown greatly enhanced immunogenicity and low allergen-specific reactivity. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Olivier J.-H.,University of Strasbourg | Harrowfield J.,ISIS | Ziessel R.,University of Strasbourg
Chemical Communications | Year: 2011

Synthetic routes for the construction of 3-substituted 2,4-pentadionate ligands are broadly surveyed. They involve sequential alkylation and arylation by numerous methods, including those based on reactions of coordinated ligands, and can provide access to various rationally designed ligands. Applications of such ligands in the synthesis of multichromophoric complexes are illustrated in some detail. Incorporation of 3-substituted 2,4-pentanedione units into mesomorphic and macromolecular structures is considered in relation to structural control of energy and electron transfer processes in photoactive systems. Aspects of the general supramolecular chemistry of complexes of 3-substituted-2,4-pentadionate ligands are briefly discussed to illustrate the utility of such species within the full range of 1,3-dionate chemistry. © 2011 The Royal Society of Chemistry.

Rochette-Egly C.,University of Strasbourg
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2015

Retinoic acid (RA), the active derivative of vitamin A, a fat-soluble vitamin, plays key roles in cell growth and differentiation by activating nuclear receptors, RARs (α, β and γ), which are ligand dependent regulators of transcription. The past years highlighted several novelties in the field that increased the complexity of RA effects. Indeed, in addition to its classical genomic effects, RA also has extranuclear and non-transcriptional effects. RA induces the rapid and transient activation of kinase cascades, which are integrated in the nucleus via the phosphorylation of RARs at a conserved serine residue located in the N-terminal domain and their coregulators. In order to investigate the relevance of RARs' phosphorylation in cell differentiation, mouse embryonic stem (mES) cells were used as a model. When treated with RA, these pluripotent cells give rise to neuronal cells. Cells invalidated for each RAR were generated as well as stable rescue lines expressing RARs mutated in phosphor acceptor sites. Such a strategy revealed that RA-induced neuronal differentiation involves the RARγ2 subtype and requires RARγ2 phosphorylation. Moreover, in gene expression profiling experiments, the phosphorylated form of RARγ2 was found to regulate a small subset of genes through binding a novel RA response element consisting of two direct repeats with a 7 base pair spacer. These new findings suggest an important role for RAR phosphorylation during cell differentiation, and pave the way for further investigations with other cell types and during embryonic development. This article is part of a Special Issue entitled Linking transcription to physiology in lipodomics. © 2014 Elsevier B.V. All rights reserved.

Kern N.,University of Strasbourg | Blanc A.,University of Strasbourg | Weibel J.-M.,University of Strasbourg | Pale P.,University of Strasbourg
Chemical Communications | Year: 2011

Alkynylaziridines carrying an aryl group could be efficiently converted to spiro[isochroman-4,2′-pyrrolines] with gold salts as catalysts. This new rearrangement involved a Friedel-Crafts type intramolecular reaction followed by cyclization of the aminoallene intermediate, both initiated by the dual σ and π Lewis acidities of gold. © 2011 The Royal Society of Chemistry.

Candini A.,CNR Institute of Neuroscience | Candini A.,CNRS Neel Institute | Klyatskaya S.,Karlsruhe Institute of Technology | Ruben M.,Karlsruhe Institute of Technology | And 4 more authors.
Nano Letters | Year: 2011

The possibility to graft nano-objects directly on its surface makes graphene particularly appealing for device and sensing applications. Here we report the design and the realization of a novel device made by a graphene nanoconstriction decorated with TbPc2 magnetic molecules (Pc = phthalocyananine), to electrically detect the magnetization reversal of the molecules in proximity with graphene. A magnetoconductivity signal as high as 20% is found for the spin reversal, revealing the uniaxial magnetic anisotropy of the TbPc2 quantum magnets. These results depict the behavior of multiple-field-effect nanotransistors with sensitivity at the single-molecule level. © 2011 American Chemical Society.

Mauro M.,University of Strasbourg | Aliprandi A.,University of Strasbourg | Septiadi D.,University of Strasbourg | Kehr N.S.,University of Strasbourg | De Cola L.,University of Strasbourg
Chemical Society Reviews | Year: 2014

Luminescent platinum complexes have attractive chemical and photophysical properties such as high stability, emission in the visible region, high emission quantum yields and long excited state lifetimes. However the absorption spectrum of the compounds in the UV region, preventing their excitation in the harmless visible/red region, as well as the strong quenching of the luminescent triplet state, caused by dioxygen in water and biological fluids, reduces their possible applications for imaging. Therefore a possible solution to these drawbacks is to take advantage of the high tendency of such square planar compounds to self-assemble in supramolecular structures. The assemblies can be considered new chemical species with enhanced and tunable properties. Furthermore the assembly and disassembly process can be explored as a tool to obtain dynamic labels that can be applied in biomedicine. The change in color, the turn on and off of luminescence but also of the reactivity, the protection from quenching and environmental degradation are some of the attractive properties connected to the aggregation of the complexes. This journal is © the Partner Organisations 2014.

Ruff Y.,University of Strasbourg | Garavini V.,University of Strasbourg | Giuseppone N.,University of Strasbourg
Journal of the American Chemical Society | Year: 2014

The broad interest of using reversible covalent bonds in chemistry, in particular at its interfaces with biology and materials science, has been recently established through numerous examples in the literature. However, the challenging exchange of peptide fragments using a dynamic covalent peptide bond has not yet been achieved without enzymatic catalysis because of its high thermodynamic stability. Here we show that peptide fragments can be exchanged by a chemoselective and reversible native chemical ligation (NCL) which can take place at N-(methyl)-cysteine residues. This very mild reaction is efficient in aqueous solution, is buffered at physiological pH in the presence of dithiothreitol (DTT), and shows typical half-times of equilibration in the 10 h range. © 2014 American Chemical Society.

Kellenberger E.,University of Strasbourg | Hofmann A.,Griffith University | Quinn R.J.,Griffith University
Natural Product Reports | Year: 2011

Natural products are made by nature through interaction with biosynthetic enzymes. Natural products also exert their effect as drugs by interaction with proteins. Does the recognition of the natural product by biosynthetic enzymes translate to recognition of the therapeutic target? Molecular modelling of flavonoid biosynthetic enzymes and kinases with a series of natural product kinase inhibitors led to the development of the concept of Protein Fold Topology (PFT). PFT describes cavity recognition points unrelated to protein fold similarity. The topology or spatial properties are preserved even though there is deformation of the protein elements that participate in the protein-ligand interactions. We observe helices or β-strands as equivalent in providing the invariant topology for protein-ligand interaction. In this Highlight, we explore the question: Will PFT aid drug discovery or is it the reason natural products have drug properties? © 2011 The Royal Society of Chemistry.

Dang-Nguyen T.Q.,University of Strasbourg | Torres-Padilla M.-E.,University of Strasbourg
Current Opinion in Cell Biology | Year: 2015

Totipotent and pluripotent cells display different degrees of cellular plasticity. After fertilization, embryonic cells transit naturally from a totipotent to a pluripotent state. Major changes in nuclear architecture, chromatin mobility and gene expression occur during this transition. In particular, nuclear architecture has recently emerged as a potential regulator of heterochromatin formation in the early embryo. Future research should address whether a causal, functional link between nuclear organization and gene regulation is a general theme during reprogramming and the formation of pluripotent cells. © 2015 Elsevier Ltd.

Stein B.,University of Strasbourg | Laluet J.-Y.,University of Strasbourg | Devaux E.,University of Strasbourg | Genet C.,University of Strasbourg | Ebbesen T.W.,University of Strasbourg
Physical Review Letters | Year: 2010

The propagation of surface plasmon beams through singly and doubly periodic metallic gratings is analyzed both in real and Fourier spaces. Large beam steering effects are experimentally revealed by probing the isofrequency surfaces (IFS) related to propagating plasmonic Bloch waves inside the gratings. In particular, negative refraction is demonstrated close to the Bragg condition. We analyze how the local structure of the IFS can amplify the sensitivity of surface plasmon-based sensors. © 2010 The American Physical Society.

Gualberto J.M.,University of Strasbourg | Kuhn K.,Humboldt University of Berlin
Mitochondrion | Year: 2014

The structural complexity of plant mitochondrial genomes correlates with the variety of single-strand DNA-binding proteins found in plant mitochondria. Most of these are plant-specific and have roles in homologous recombination and genome maintenance. Mitochondrial nucleoids thus differ fundamentally between plants and yeast or animals, where the principal nucleoid protein is a DNA-packaging protein that binds double-stranded DNA. Major transcriptional cofactors identified in mitochondria of non-plant species are also seemingly absent from plants. This article reviews current knowledge on plant mitochondrial DNA-binding proteins and discusses that those may affect the accessibility and conformation of transcription start sites, thus functioning as transcriptional modulators without being dedicated transcription factors. © 2014 Elsevier B.V.

Niess F.,University of Strasbourg | Duplan V.,University of Strasbourg | Sauvage J.-P.,University of Strasbourg
Chemistry Letters | Year: 2014

The field of "molecular machines" based on interlocking ring compounds started about twenty years ago with the deliberate synthesis of molecules or molecular assemblies which could be set in motion using various types of signals (mostly photonic, electrochemical, or chemical). The complexity of the systems gradually increased and, twelve years ago, rotaxane dimmers whose length could be controlled were proposed. At that time, they were among the most sophisticated machines. In the present review article, we present a survey of the most significant systems published since the beginning of nanosize molecular muscles. The doubly threaded nature of rotaxane dimers consisting of two "ring-and-string" fragments with the ring of one fragment being threaded by the thread of the other fragment, and vice versa, is certainly very well adapted to contraction and elongation motions. The various muscle-like species discussed are based on significantly different principles: coordination chemistry, the transition metals used playing a central role, hydrophobic forces combined with photoisomerization processes or solvent effects when the threaded rings were cyclodextrins, hydrogen bonding and acceptordonor interactions, the movement being driven by a pH change in this latter case. Particularly promising extensions of the field have been reported in recent years. In a very significant example, contraction and extension of surface-bound "molecular muscles" was shown to induce the bending of a beam that is five orders of magnitude larger in size than the molecular species itself. In the most recent contribution, preparation of a polymer from an elemental nanosize molecular muscle was achieved, leading to a long molecular fragment able to undergo contraction and elongation under well-controlled conditions. The corresponding material, formed by the association of thousands of molecular muscles, was shown to behave as a contractile and extensible system at the macroscopic level. © 2014 The Chemical Society of Japan.

Schwenzer H.,University of Strasbourg
Topics in current chemistry | Year: 2014

Mitochondria are considered as the powerhouse of eukaryotic cells. They host several central metabolic processes fueling the oxidative phosphorylation pathway (OXPHOS) that produces ATP from its precursors ADP and inorganic phosphate Pi (PPi). The respiratory chain complexes responsible for the OXPHOS pathway are formed from complementary sets of protein subunits encoded by the nuclear genome and the mitochondrial genome, respectively. The expression of the mitochondrial genome requires a specific and fully active translation machinery from which aminoacyl-tRNA synthetases (aaRSs) are key actors. Whilst the macromolecules involved in mammalian mitochondrial translation have been under investigation for many years, there has been an explosion of interest in human mitochondrial aaRSs (mt-aaRSs) since the discovery of a large (and growing) number of mutations in these genes that are linked to a variety of neurodegenerative disorders. Herein we will review the present knowledge on mt-aaRSs in terms of their biogenesis, their connection to mitochondrial respiration, i.e., the respiratory chain (RC) complexes, and to the mitochondrial translation machinery. The pathology-related mutations detected so far are described, with special attention given to their impact on mt-aaRSs biogenesis, functioning, and/or subsequent activities. The collected data to date shed light on the diverse routes that are linking primary molecular possible impact of a mutation to its phenotypic expression. It is envisioned that a variety of mechanisms, inside and outside the translation machinery, would play a role on the heterogeneous manifestations of mitochondrial disorders.

Ciesielski A.,University of Strasbourg | Samori P.,University of Strasbourg
Chemical Society Reviews | Year: 2014

Graphene, the 2D form of carbon based material existing as a single layer of atoms arranged in a honeycomb lattice, has set the science and technology sectors alight with interest in the last decade in view of its astounding electrical and thermal properties, combined with its mechanical stiffness, strength and elasticity. Two distinct strategies have been undertaken for graphene production, i.e. the bottom-up and the top-down. The former relies on the generation of graphene from suitably designed molecular building blocks undergoing chemical reaction to form covalently linked 2D networks. The latter occurs via exfoliation of graphite into graphene. Bottom-up techniques, based on the organic syntheses starting from small molecular modules, when performed in liquid media, are both size limited, because macromolecules become more and more insoluble with increasing size, and suffer from the occurrence of side reactions with increasing molecular weight. Because of these reasons such a synthesis has been performed more and more on a solid (ideally catalytically active) surface. Substrate-based growth of single layers can be done also by chemical vapor deposition (CVD) or via reduction of silicon carbide, which unfortunately relies on the ability to follow a narrow thermodynamic path. Top-down approaches can be accomplished under different environmental conditions. Alongside the mechanical cleavage based on the scotch tape approach, liquid-phase exfoliation (LPE) methods are becoming more and more interesting because they are extremely versatile, potentially up-scalable, and can be used to deposit graphene in a variety of environments and on different substrates not available using mechanical cleavage or growth methods. Interestingly, LPE can be applied to produce different layered systems exhibiting different compositions such as BN, MoS2, WS2, NbSe2, and TaS2, thereby enabling the tuning of numerous physico-chemical properties of the material. Furthermore, LPE can be employed to produce graphene-based composites or films, which are key components for many applications, such as thin-film transistors, conductive transparent electrodes for indium tin oxide replacement, e.g. in light-emitting diodes, or photovoltaics. In this review, we highlight the recent progress that has led to successful production of high quality graphene by means of LPE of graphite. In particular, we discuss the mechanisms of exfoliation and methods that are employed for graphene characterization. We then describe a variety of successful liquid-phase exfoliation methods by categorizing them into two major classes, i.e. surfactant-free and surfactant-assisted LPE. Furthermore, exfoliation in aqueous and organic solutions is presented and discussed separately. © 2014 The Royal Society of Chemistry.

Bellemin-Laponnaz S.,CNRS Institute of Genetics and of Molecular and Cellular Biology | Bellemin-Laponnaz S.,University of Strasbourg | Dagorne S.,CNRS Strasbourg Institute of Chemistry
Chemical Reviews | Year: 2014

Early transition metal N-Heterocyclic carbenes (NHC) complexes in catalysis remain a field to be explored and developed taking advantage of the robustness/stability imparted to the resulting metal-based catalytically active components. Recent and promising reports on the use of early transition metal NHC complexes in homogeneous catalysis include, most notably, their ability to effectively mediate ketone hydrosilylation, olefin/cyclic esters polymerization, and olefin hydroamination reactions. Recent developments in carbene lithium compounds includevthe isolation and structural characterization of Li+ adductsvbearing abnormal NHCs. In related studies on anionic NHCs, Lavallo and co-workers visolated and characterized a number of Li salts of carborane-containing NHC anions starting from a formally monoanionic carborane N-functionalized imidazolium salt as the protio ligand. Other examples of lithium and potassium NHC compounds have been reported and typically include polydentate ligands incorporating a carbene ligand with an anionic functional group and variously functionalized monodentate NHC ligands.

Donner C.D.,University of Melbourne | Casana M.I.,University of Strasbourg
Tetrahedron Letters | Year: 2012

The thiol-catalysed cyclization of acyl radicals generated directly from benzaldehyde precursors has been investigated. Hindered β- benzyloxyacrylates cyclize efficiently providing a tin-free radical cyclization approach to the serine/threonine kinase AKT inhibitor frenolicin B, whilst γ-aryloxy crotonates give good yields of benzopyran-4-ones. This method is applied to the synthesis of a novel tetracyclic analogue of the pyranonaphthoquinone antibiotics. © 2011 Elsevier Ltd. All rights reserved.

Behr J.-P.,University of Strasbourg | Behr J.-P.,Polyplus-transfection
Accounts of Chemical Research | Year: 2012

The discovery of RNA interference has given a new lease on life to both the chemistry of oligonucleotides and chemical approaches for the intracellular delivery of nucleic acids. In particular, delivery of siRNA, whether in vitro for screening and target validation purposes or in humans as a new class of drugs, may revolutionize our approach to therapy. Their impact could equal that of the bioproduction and various uses of monoclonal antibodies today. Unfortunately, global pharmaceutical companies again seem to be waiting to buy the next Genentech or Genzyme of gene silencing rather than investing research and development into this promising area of research.Gene silencing encounters barriers similar to gene addition and hence may benefit from the extra decade of experience brought by gene therapy. "Chemical" transfection of cells in culture has become routine, and this Account discusses some of the reasons this success has not extended to nonviral gene therapy trials, most of which do not progress beyond the phase 2 stage. The author also discusses a (much debated) mechanism of nucleic acid cell entry and subsequent release of the polycationic particles into the cytoplasm. Both topics should be useful to those interested in delivery of siRNA.The move from gene therapy toward siRNA as an oligonucleotide-based therapy strategy provides a much wider range of druggable targets. Even though these molecules are a hundredfold smaller than a gene, they are delivered via similar cellular mechanisms. Their complexes with cationic polymers are less stable than those with a higher number of phosphate groups, which may be compensated by siRNA concatemerization or by chemical conjugation with the cationic carrier. Thus chemistry is again desperately needed. © 2012 American Chemical Society.

Cribier B.,University of Strasbourg
Annales de Dermatologie et de Venereologie | Year: 2011

The physiopathology of rosacea involves a large number of factors that are at times difficult to correlate. There is not a single physiopathological model. Nevertheless, today it seems to have been established that two essential factors are involved: vascular and inflammatory. The disease occurs in individuals with a predisposition, mainly a light phototype subjected to substantial variations in climate. On a background of primary vascular anomaly, external factors (climate, exposure to ultraviolet rays, cutaneous flora, etc.) contribute to the development of abnormal superficial blood vessels, with a low permeability. The edema that results undoubtedly favors the colonization and multiplication of Demodex folliculorum. This parasite creates inflammation, directly and indirectly, which is seen in the papules and pustules as well as granulomas. Inflammation from rosacea is also characterized by innate immune system anomalies, with an increase in the expression of epidermal proteases and production of pro-inflammatory cathelicidin peptides. In addition, facial hypersensitivity exists, even though the cutaneous barrier is not altered. Finally, rhinophyma remains poorly explained; the vascular abnormalities induce local production of transforming growth factor β 1 (TGF-β1) capable of creating fibrosis and therefore cutaneous thickening. © 2011 Elsevier Masson SAS. All rights reserved.

Caillaux V.,University Paris Diderot | Gaucher D.,University of Strasbourg | Gualino V.,University Paris Diderot | Massin P.,University Paris Diderot | And 2 more authors.
American Journal of Ophthalmology | Year: 2013

Purpose To analyze dome-shaped maculas topographic features and related serous retinal detachment (SRD) in eyes with myopic staphyloma. Design Retrospective, observational case series. Methods We reviewed the records of 48 eyes in 33 patients with dome-shaped maculas who were referred because of decreased vision. Ophthalmologic examination included axial length measurement, spectral domain optical coherence tomography (OCT), and fluorescein and indocyanine green angiography. The height of the macular bulge was measured, and the choroidal thickness was mapped. Results Patient mean age was 55.0 ± 13.6 years. Mean axial length was 27.49 ± 2.53 mm. Mean best-corrected visual acuity (BCVA) was 0.50 ± 0.33 logMAR. Three dome-shaped macula patterns were observed: round dome in 10/48 (20.8%) eyes; horizontal oval-shaped dome in 30/48 (62.5%) eyes; and vertical oval-shaped dome in 8/48 (16.7%) eyes. The mean macular bulge height was 407.7 ± 215.1 μm (120-1130) and was significantly greater in vertical oval-shaped domes. The mean central choroidal thickness (CCT) was 146.5 ± 56.0 μm, significantly greater than at 3 mm nasal and temporal to the fovea (P < 0.0001). The CCT was positively correlated to macular bulge height but not to BCVA. Foveal SRD was present in 25/48 eyes and significantly increased for macular bulge height greater than 350 μm (P = 0.0047). BCVA was significantly lower when SRD was present (P = 0.043). Conclusions Most dome-shaped maculas did not display a round but a horizontal or vertical oval-shaped dome and could be missed on a single OCT scan. Chronic foveal SRD was associated with decreased vision and was more common when the macular bulge was highly elevated. © 2013 BY ELSEVIER INC. ALL RIGHTS RESERVED.

Keller N.,University of Strasbourg | Rebmann G.,University of Strasbourg | Keller V.,University of Strasbourg
Journal of Molecular Catalysis A: Chemical | Year: 2010

This review reports on the synthesis of dimethylcarbonate (DMC) and deals with the catalysts, the mechanisms as well as the industrial processes and the reactions for producing DMC, within the policy of developing clean and eco-friendly processes. DMC is considered as an environmentally benign chemical due to a negligible ecotoxicity, a low bioaccumulation and a low persistence, so that the production and chemical use of DMC have attracted much attention in the view of the so-called 'sustainable society' and 'green chemistry', mainly for replacing dimethylsulfate and methylhalides in methylation reactions and for replacing the harmful phosgene in polycarbonate and isocyanate syntheses. Special focus is made on the vapour phase oxycarbonylation of methanol by carbon monoxide in substitution to the old phosgenation process abandoned with years, and as an alternative process to both liquid phase methanol oxycarbonylation and methylnitrite carbonylation processes. The catalytic materials consist in high surface area active carbon supported copper chloride-based catalysts and chloride-free zeolite catalysts, both investigated in terms of catalyst preparation, active phase nature, performances and catalytic mechanisms. © 2009 Elsevier B.V. All rights reserved.

Harashima H.,University of Strasbourg | Schnittger A.,University of Strasbourg
Current Opinion in Plant Biology | Year: 2010

The development of a multicellular organism such as a flowering plant relies on the patterned control of cell proliferation, differentiation, and growth. Research in the recent years has revealed that the control of cell-cycle progression and growth in plants is distinct from the regulation found in yeast or metazoans. Understanding these plant-specific regulators and networks, in which they act, is key for the understanding of plant development and is of current global importance as a basis for breeding of energy crops as well as the breeding of plants adapted for changing environmental conditions. However, the production of cells and their specification and differentiation overlap in time and space and build an intricate interrelationship of dependencies and feedback loops. In this network, the developmental context and the generation of specific cell types and tissues are often decisive. © 2009 Elsevier Ltd. All rights reserved.

Zuryn S.,University of Strasbourg | Ahier A.,University of Strasbourg | Portoso M.,French Institute of Health and Medical Research | White E.R.,University of Strasbourg | And 4 more authors.
Science | Year: 2014

Natural interconversions between distinct somatic cell types have been reported in species as diverse as jellyfish and mice. The efficiency and reproducibility of some reprogramming events represent unexploited avenues in which to probe mechanisms that ensure robust cell conversion. We report that a conserved H3K27me3/me2 demethylase, JMJD-3.1, and the H3K4 methyltransferase Set1 complex cooperate to ensure invariant transdifferentiation (Td) of postmitotic Caenorhabditis elegans hindgut cells into motor neurons. At single-cell resolution, robust conversion requires stepwise histone-modifying activities, functionally partitioned into discrete phases of Td through nuclear degradation of JMJD-3.1 and phase-specific interactions with transcription factors that have conserved roles in cell plasticity and terminal fate selection. Our results draw parallels between epigenetic mechanisms underlying robust Td in nature and efficient cell reprogramming in vitro.

For ten years, the incidence of preterm birth does not decrease in developed countries despite the promotion of public health programs. Many risk factors have been identified including ethnicity, age, tobacco, and infection. However, almost 50% of preterm birth causes remain unknown. The periodontal diseases are highly prevalent inflammatory and infectious diseases of tooth supporting tissues leading to an oral disability. They influence negatively general health worsening cardiovascular diseases and diabetes. Periodontal diseases have been also suspected to increase the rate of preterm birth, but data remain contradictory. The objective of this review is to present the principal results of epidemiological, biological, and interventional studies on the link between periodontal diseases and preterm birth. The conclusions of this work underline the importance for the physician/obstetrician to identify women at risk for preterm birth and to address these patients to dentist for periodontal examination and treatment in order to limit adverse pregnancy outcomes.

Dekhili S.,University of Strasbourg | Achabou M.A.,France Business School
Business Strategy and the Environment | Year: 2013

This study investigates the extent to which prices of ecological products are fair. In particular, it explores the gap that can exist between the pricing policies adopted by enterprises and the consumers' price expectations in terms of fairness. The existing academic literature on sustainable consumption neglects this question. Findings from a qualitative investigation combining a consumer study and enterprise case studies show that managers' behaviors vary. While some enterprises take into account consumers' expectations and purchasing power to propose a fair price based on the value of the green product, others continue to adopt a pricing policy that is exclusively based on profitability and competition. The authors draw some business and academic implications. © 2012 John Wiley & Sons, Ltd and ERP Environment.

Challet E.,University of Strasbourg
Journal of Comparative Physiology B: Biochemical, Systemic, and Environmental Physiology | Year: 2010

Daily variations in behaviour and physiology are controlled by a circadian timing system consisting of a network of oscillatory structures. In mammals, a master clock, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, adjusts timing of other self-sustained oscillators in the brain and peripheral organs. Synchronisation to external cues is mainly achieved by ambient light, which resets the SCN clock. Other environmental factors, in particular food availability and time of feeding, also influence internal timing. Timed feeding can reset the phase of the peripheral oscillators whilst having almost no effect in shifting the phase of the SCN clockwork when animals are exposed (synchronised) to a light-dark cycle. Food deprivation and calorie restriction lead not only to loss of body mass (>15%) and increased motor activity, but also affect the timing of daily activity, nocturnal animals becoming partially diurnal (i.e. they are active during their usual sleep period). This change in behavioural timing is due in part to the fact that metabolic cues associated with calorie restriction affect the SCN clock and its synchronisation to light. © 2010 Springer-Verlag.

Lehn J.-M.,University of Strasbourg
Australian Journal of Chemistry | Year: 2010

Dynamers are defined as constitutional dynamic polymers, i.e. polymeric entities whose monomeric components are linked through reversible connections and have therefore the capacity to modify their constitution by exchange and reshuffling of their components. They may be either of supramolecular or molecular nature depending on whether the connections are non-covalent interactions or reversible covalent bonds. They are formed respectively either by polyassociation with interactional recognition or by polycondensation with functional recognition between the connecting subunits. Both types are illustrated by specific examples implementing hydrogen bonding on one hand and formation of imine-type bonds on the other. The dynamic properties confer to dynamers the ability to undergo adaptation and driven evolution under the effect of external chemical or physical triggers. Dynamers thus are constitutional dynamic materials resulting from the application of the principles of constitutional dynamic chemistry to polymer science. © CSIRO 2010.

Mariette C.,University Hospital Claude Huriez | Pessaux P.,University of Strasbourg
Surgical Endoscopy and Other Interventional Techniques | Year: 2011

Background Ambulatory laparoscopic fundoplication for gastroesophageal reflux disease (GERD) has been developed in order to increase patients' satisfaction and to save bed costs. The aim of this systematic review was to assess the advantages and disadvantages of ambulatory surgery in patients undergoing elective fundoplication for GERD. Methods Two reviewers independently searched and identified 15 prospective or retrospective nonrandomized studies dealing with ambulatory laparoscopic fundoplication for GERD in the Medline, Cancerlit, and Embase databases between January 1990 and July 2010. Outcomes were postoperative mortality, morbidity, conversion and reoperation rates, mean operative time, hospital admission or readmission, unexpected consultation, and patient satisfaction. Because only one comparative study was identified, data compilation and relative risk evaluation through meta-analysis were not possible. Results A total of 1459 adult patients underwent an ambulatory laparoscopic fundoplication for GERD, 876 in a day-case setting and 583 in an outpatient setting. The procedure appears feasible for selected patients and expert surgeons, and it has a very low mortality rate and conversion, reoperation, and overall morbidity rates of 3.6, 0.6, and 11.1%, respectively. Hospital admission, nonprogrammed consultation, and hospital readmission rates were as high as 20, 11, and 12%, respectively. No study looked at comparative long-term functional results between ambulatory and inpatient procedures. Patient satisfaction rates based on self-evaluation were high. Conclusion The data available to date in the literature, mostly of level 4 evidence, suggest that laparoscopic fundoplication for GERD appears to be safe and feasible in a day-surgery setting, subject to careful patient selection and surgeon expertise. Randomized control trials are urgently needed to better evaluate this promising care management. © 2011 Springer Science+Business Media, LLC.

Torres-Padilla M.-E.,University of Strasbourg | Chambers I.,University of Edinburgh
Development (Cambridge) | Year: 2014

When pluripotent cells are exposed to a uniform culture environment they routinely display heterogeneous gene expression. Aspects of this heterogeneity, such as Nanog expression, are linked to differences in the propensity of individual cells to either self-renew or commit towards differentiation. Recent findings have provided new insight into the underlying causes of this heterogeneity, which we summarise here using Nanog, a key regulator of pluripotency, as a model gene. We discuss the role of transcription factor heterogeneity in facilitating the intrinsically dynamic and stochastic nature of the pluripotency network, which in turn provides a potential benefit to a population of cells that needs to balance cell fate decisions. © 2014. Published by The Company of Biologists Ltd.

Lipsker D.,University of Strasbourg
Journal of the European Academy of Dermatology and Venereology | Year: 2016

Some dermatologic entities are strongly associated with the presence of a monoclonal gammopathy. They should be referred to as monoclonal gammopathy of cutaneous significance (MGCS). A short review of the main entities that fit into the spectrum of MGCS is provided. Amyloidosis, macroglobulinoderma and follicular hyperkeratotic spicules result from extravascular immunoglobulin or immunoglobulin-related protein deposition. Skin findings include papules and plaques, follicular spicules, purpura, haemorrhagic bullae, macroglossia and nail changes. The skin findings in cryoglobulinemia (CG) result from vascular immunoglobulin deposition, either as immune complexes within the vessel walls in mixed CG or within the lumina of small vessels in monoclonal CG. Mixed CG manifests as palpable purpura of leukocytoclastic vasculitis, and monoclonal CG as stellar and/or retiform purpura that can evolve into extensive skin necrosis. In some rare instances, immunoglobulins have a specific biological activity. This is, for example, the case when they bind lipoproteins that precipitate and induce hypocomplementemic xanthomas. Xanthoderma related to antiflavin activity of the monoclonal component or acquired angioedema related to anti-C1INH activity is other example. Abnormal cytokine secretion is the hallmark of some entities. High vascular endothelial growth factor levels correlate with some of the skin manifestations of the Polyneuropathy organomegaly endocrinopathy monoclonal component skin changes syndrome, such as hypertrichosis or the adenopathy and extensive skin patch overlying plasmacytoma syndrome. All the clinical manifestations of the Schnitzler syndrome are IL-1 mediated. In other MGCS, such as scleromyxedema, Clarkson syndrome, TEMPI syndrome, cutis laxa and the neutrophilic dermatoses, the link between the monoclocal component and the entity is clearly established, but not understood so far. © 2016 European Academy of Dermatology and Venereology.

Mohn G.,University of Strasbourg | Manatschal G.,University of Strasbourg | Beltrando M.,CNR Institute of Geosciences and Earth Resources | Masini E.,University of Strasbourg | Kusznir N.,University of Liverpool
Tectonics | Year: 2012

Studies conducted in present-day magma-poor rifted margins reveal that the transition from weakly thinned continental crust (∼30 km) in proximal margins to hyper-extended crust (≤10 km) in distal margins occurs within a narrow zone, referred to as the necking zone. We have identified relics of a necking zone and of the adjacent distal margin in the Campo, Grosina and Bernina units of the fossil Alpine Tethys margins and investigated the deformation and sedimentary processes associated with extreme crustal thinning during rifting. Within the basement rocks of the necking zone, we show that: (1) Grosina basement represents pre-rift upper/middle crust, while the underlying Campo unit consists of pre-rift middle/lower crust that was exhumed and cooled below ∼300°C by ca. 180 Ma, when rifting started to localize within the future distal margin; (2) the juxtaposition of the Campo and Grosina units was accommodated by the Eita shear zone, which is interpreted as a decollement/decoupling horizon active at mid-crustal depth at 180-205 Ma; (3) the Grosina unit hosts a large-scale brittle detachment fault. Our observations suggest that crustal thinning, accommodated through the necking zone, is the result of the interplay between detachment faulting in the brittle layers and decoupling and thinning in ductile quartzo-feldspatic middle crustal levels along localized ductile decollements. The excision of ductile mid-crustal layers and the progressive embrittlement of the crust enables major detachment faults to cut into the underlying mantle, exhuming it to the seafloor. This structural evolution can explain the first-order crustal architecture of many present-day rifted margins. Copyright 2012 by the American Geophysical Union.

Teyssier L.,University of Strasbourg
Nonlinearity | Year: 2015

We study the complex Dulac map for a holomorphic foliation of the complex plane, near a non-degenerate singularity (both eigenvalues of the linearization are nonzero) with two separatrices. Following the well-known results of Il'yashenko we provide a geometric approach allowing to study the whole maximal domain of (geometric) definition of the Dulac map. In particular its topology and the regularity of its boundary are completely described. We also study the order of magnitude of the first non-trivial term of its asymptotic expansion and show how to compute it using path integrals supported in the leaves of the linearized foliation. Explicit bounds on the remainder are given. We perform similarly the study of the Dulac time spent around the singularity. All results are formulated in a unified framework taking no heed to the usual dynamical discrimination (i.e. no matter whether the singularity is formally orbitally linearizable or not and regardless of the arithmetic of the eigenvalues ratio). © 2015 IOP Publishing Ltd & London Mathematical Society.

Bourgin P.,University of Strasbourg | Hubbard J.,University of Lausanne
PLoS Biology | Year: 2016

In mammals, light exerts pervasive effects on physiology and behavior in two ways: indirectly through clock synchronization and the phase adjustment of circadian rhythms, and directly through the promotion of alertness and sleep, respectively, in diurnal and nocturnal species. A recent report by Pilorz and colleagues describes an even more complex role for the acute effects of light. In mice, blue light acutely causes behavioral arousal, whereas green wavelengths promote sleep. These opposing effects are mediated by melanopsin-based phototransduction through different neural pathways. These findings reconcile nocturnal and diurnal species through a common alerting response to blue light. One can hypothesize that the opposite responses to natural polychromatic light in night- or day-active animals may reflect higher sensitivity of nocturnal species to green, and diurnals to blue wavelengths, resulting in hypnogenic and alerting effects, respectively. Additional questions remain to be clarified. How do different light wavelengths affect other behaviors such as mood and cognition? How do those results apply to humans? How does light pose either a risk or benefit, depending on whether one needs to be asleep or alert? Indeed, in addition to timing, luminance levels, and light exposure duration, these findings stress the need to understand how best to adapt the color spectrum of light to our needs and to take this into account for the design of daily lighting concepts—a key challenge for today’s society, especially with the emergence of LED light technology. © 2016 Bourgin, Hubbard.

Lemoine M.,University Pierre and Marie Curie | Kotera K.,University Pierre and Marie Curie | Petri J.,University of Strasbourg
Journal of Cosmology and Astroparticle Physics | Year: 2015

Pulsar wind nebulae (PWNe) are outstanding accelerators in Nature, in the sense that they accelerate electrons up to the radiation reaction limit. Motivated by this observation, this paper examines the possibility that young pulsar wind nebulae can accelerate ions to ultra-high energies at the termination shock of the pulsar wind. We consider here powerful PWNe, fed by pulsars born with ∼ millisecond periods. Assuming that such pulsars exist, at least during a few years after the birth of the neutron star, and that they inject ions into the wind, we find that protons could be accelerated up to energies of the order of the Greisen-Zatsepin-Kuzmin cut-off, for a fiducial rotation period P ∼ 1 msec and a pulsar magnetic field B ∼ 1013 G, implying a fiducial wind luminosity Lp ∼ 1045 erg/s and a spin-down time tsd ∼ 3× 107 s. The main limiting factor is set by synchrotron losses in the nebula and by the size of the termination shock; ions with Z 1 may therefore be accelerated to even higher energies. We derive an associated neutrino flux produced by interactions in the source region. For a proton-dominated composition, our maximum flux lies slightly below the 5-year sensitivity of IceCube-86 and above the 3-year sensitivity of the projected Askaryan Radio Array. It might thus become detectable in the next decade, depending on the exact level of contribution of these millisecond pulsar wind nebulae to the ultra-high energy cosmic ray flux. © 2015 IOP Publishing Ltd and Sissa Medialab srl .

Pauli G.,University of Strasbourg | Malling H.-J.,Copenhagen University
Current Topics in Microbiology and Immunology | Year: 2011

Subcutaneous immunotherapy is a well-documented treatment of allergic rhinitis and asthma. The major limitation is the risk of anaphylactic side effects. The documentation of clinical efficacy is based on crude allergenic extracts sometimes containing varying amounts of individual allergens including allergens to which the patient may not be sensitized. The introduction of recombinant allergens offer a possibility to use well-defined molecules with consistent pharmaceutical quality defined in mass units. The proof-of-concept of the clinical efficacy of recombinant allergens is based on two studies published as full articles. One study applied a mixture of five Phleum pratense major allergens in a maximum dose of 40 μg protein. The clinical efficacy showed a significant efficacy with about 40% reduction in disease severity. The second study compared a commercial birch extract with both recombinant Bet v 1 and purified Bet v 1 in dosages of 15 μg allergen. The clinical effect was around 60% additional efficacy. Systemic side effects occurred more frequently with grass allergens. A third study used hypoallergenic fragments and a trimer of Bet v 1. The study did not show efficacy and a rather high frequency of systemic side effects. The advantages of using recombinant allergens for immunotherapy are obvious but more large-scale clinical studies are needed before the overall value in terms of efficacy and safety can be determined. © 2011 Springer-Verlag Berlin Heidelberg.

Sockett G.,University of Strasbourg | Toffoli D.,University of Strasbourg
ReCALL | Year: 2012

This article discusses the informal learning of English by non-native speakers with particular reference to the role of virtual communities. The concept of informal learning is presented and related to current areas of interest in the literature such as incidental learning, and dynamic systems theory. Our research investigates how non-specialist language learners use the Internet in their spare time to read and listen to English, and also communicate in English, notably in online communities through social networking websites. The study looks particularly at the dynamics of these phenomena by studying a small number of non-native users of English over a period of two months. The results of this research will be used to question the relevance of the learner autonomy paradigm, which has been a cornerstone of language learning policy in Europe for the past thirty years. © 2012 European Association for Computer Assisted Language Learning.

Valot G.,University of Strasbourg | Garcia J.,University of Strasbourg | Duplan V.,University of Strasbourg | Serba C.,University of Strasbourg | And 2 more authors.
Angewandte Chemie - International Edition | Year: 2012

Natural selection: An acyclic chain containing an ene-yne-ene motif, in analogy to farnesyl diphosphate, was cyclized to obtain six distinct scaffolds using different transition-metal catalysts (see scheme). Notably, the guaianolide framework was accessed through enynene metathesis enabling the synthesis of three natural products. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pastor V.,University of Buenos Aires | Host L.,University of Strasbourg | Zwiller J.,University of Strasbourg | Bernabeu R.,University of Buenos Aires
Journal of Neurochemistry | Year: 2011

Epigenetic mechanisms have recently been shown to be involved in the long-term effects of drugs of abuse. A well described epigenetic mechanism modulating transcriptional activity consists in the binding to DNA of methyl-CpG binding proteins, such as MeCP2, recruiting histone deacetylases (HDACs). Nicotine causes long-term changes in the brain, but little is known concerning the mechanisms involved in nicotine-preference. Using a nicotine-conditioned place preference protocol, we demonstrate here that the histone deacetylase inhibitor phenylbutyrate was able to dramatically reduce the preference for nicotine, without altering the aversive properties of the drug. We measured immunohistochemically the acetylation of lysine-9 of histone H3, and the expression of phosphorylated cAMP-response element-binding protein, HDAC2 and methyl-CpG-binding protein 2 in the striatum and prefrontal cortex of rats displaying nicotine-preference or aversion and treated with phenylbutyrate. We show that, at the dose administered, the inhibitor was effective in inhibiting HDAC activity. The data suggest that phosphorylated cAMP-response element-binding protein participates in the establishment of conditioned place preference, but not in the reduction of nicotine-preference in response to phenylbutyrate. Moreover, striatal expression of HDAC2 in response to phenylbutyrate mirrored the behavioral effects of the inhibitor, suggesting that HDAC2 is involved in promoting synaptic plasticity underlying the preference for nicotine. © 2011 International Society for Neurochemistry.

Oubel E.,University of Strasbourg
Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention | Year: 2010

In this paper we present a method for reconstructing D-MRI data on regular grids from sparse data without assuming specific diffusion models. This is particularly important when studying the fetal brain in utero, since registration methods applied for movement and distortion correction produce scattered data in spatial and angular (gradient) domains. We propose the use of a groupwise registration method, and a dual spatio-angular interpolation by using radial basis functions (RBF). Experiments performed on adult data showed a high accuracy of the method when estimating diffusion images in unavailable directions. The application to fetal data showed an improvement in the quality of the sequences according to criteria based on fractional anisotropy (FA) maps, and differences in the tractography results.

Rousseau F.,University of Strasbourg
Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention | Year: 2010

Super-resolution techniques provide a route to studying fine scale anatomical detail using multiple lower resolution acquisitions. In particular, techniques that do not depend on regular sampling can be used in medical imaging situations where imaging time and resolution are limited by subject motion. We investigate in this work the use of a super-resolution technique for anisotropic fetal brain MR data reconstruction without modifying the data acquisition protocol. The approach, which consists of iterative motion correction and high resolution image estimation, is compared with a previously used scattered data interpolation-based reconstruction method. To optimize acquisition time, an evaluation of the influence of the number of input images and image noise is also performed. Evaluation on simulated MR images and real data show significant improvements in performance provided by the super-resolution approach.

Kauntz H.,University of Strasbourg | Bousserouel S.,University of Strasbourg | Gosse F.,University of Strasbourg | Raul F.,University of Strasbourg
Apoptosis | Year: 2011

Silibinin, a flavonolignan isolated from the milk thistle plant (Silybum marianum), possesses antineoplastic properties. In vitro and in vivo studies have recently shown that silibinin inhibits the growth of colorectal cancer (CRC). The present study investigates the mechanisms of silibinin-induced cell death using an in vitro model of human colon cancer progression, consisting of primary tumor cells (SW480) and their derived metastatic cells (SW620) isolated from a metastasis of the same patient. Silibinin induced apoptotic cell death evidenced by DNA fragmentation and activation of caspase-3 in both cell lines. Silibinin enhanced the expression (protein and mRNA) of TNF-related apoptosis-inducing ligand (TRAIL) death receptors (DR4/DR5) at the cell surface in SW480 cells, and induced their expression in TRAILresistant SW620 cells normally not expressing DR4/DR5. Caspase-8 and -10 were activated demonstrating the involvement of the extrinsic apoptotic pathway in silibinintreated SW480 and SW620 cells. The protein Bid was cleaved in SW480 cells indicating a cross-talk between extrinsic and intrinsic apoptotic pathway. We demonstrated that silibinin activated also the intrinsic apoptotic pathway in both cell lines, including the perturbation of the mitochondrial membrane potential, the release of cytochrome c into the cytosol and the activation of caspase-9. Simultaneously to apoptosis, silibinin triggered an autophagic response. The inhibition of autophagy with a specific inhibitor enhanced cell death, suggesting a cytoprotective function for autophagy in silibinin-treated cells. Taken together, our data show that silibinin initiated in SW480 and SW620 cells an autophagic-mediated survival response overwhelmed by the activation of both the extrinsic and intrinsic apoptotic pathways. © 2011 Springer Science+Business Media, LLC.

Dufour M.,University of Strasbourg | Descouvemont P.,Free University of Colombia
Nuclear Physics A | Year: 2014

The 16O nucleus is investigated within a C12+α four α multicluster model. The generator coordinate method combined with the microscopic R-matrix method is used to determine bound and resonant states. The 12C nucleus is described by 3 α clusters located at the apexes of isosceles triangles. We optimize the generator coordinates to get a reasonable description of the 02+-01+ energy gap, where the 02+ is the so-called Hoyle state, considered as a 3 α state. Our calculations mainly focus on resonances located near the C12(02+)+α threshold. We emphasize the difficulty to interpret broad resonant states and we show that bound state approximation methods are not well adapted in the context of our study. An R-matrix analysis suggests the existence of 0 +, 2 + and 4 + molecular states which present a significant C12(02+)+α structure, and which may form a rotational band. © 2014 Elsevier B.V.

Polonyi J.,University of Strasbourg
Annals of Physics | Year: 2014

The effective Lagrangian of a point charge is derived by eliminating the electromagnetic field within the framework of the classical closed time path formalism. The short distance singularity of the electromagnetic field is regulated by an UV cutoff. The Abraham-Lorentz force is recovered and its similarity to quantum anomalies is underlined. The full cutoff-dependent linearized equation of motion is obtained, no runaway trajectories are found but the effective dynamics shows acausality if the cutoff is beyond the classical charge radius. The strength of the radiation reaction force displays a pole in its cutoff-dependence in a manner reminiscent of the Landau-pole of perturbative QED. Similarity between the dynamical breakdown of the time reversal invariance and dynamical symmetry breaking is pointed out. © 2014 Elsevier Inc.

Drouot N.,University of Strasbourg
European Journal of Human Genetics | Year: 2015

Ataxia is a symptom that is often associated with syndromic inherited diseases. We previously reported the linkage of a novel syndrome, ataxia with blindness and deafness (SCAR3/SCABD, OMIM# 271250), to chromosome 6p21–p23 by linkage mapping of an Arab Israeli consanguineous family. We have now identified by whole-exome sequencing a homozygous missense mutation in the Arab Israeli family in the SLC52A2 gene located in 8qter, therefore excluding linkage of this family to 6p. We confirmed the involvement of SLC52A2 by the identification of a second mutation in an independent family with an identical syndromic presentation, which we suggest to name SCABD2. SCABD2 is therefore allelic to Brown–Vialleto–Van Laere syndrome type 2 defined by prominent motoneuronopathy and deafness, and also caused by SLC52A2 mutations. In the course of this project, we identified a clinically similar family with a homozygous missense mutation in PEX6, which is located in 6p21. Therefore, despite false linkage in the initial family, SCABD1/SCAR3 is located in 6p21 and is caused by PEX6 mutations. Both SLC52A2 and PEX6 should be included in screening panels for the diagnosis of syndromic inherited ataxias, particularly as patients with mutations in SLC52A2 can be ameliorated by riboflavin supplementation.European Journal of Human Genetics advance online publication, 16 December 2015; doi:10.1038/ejhg.2015.259. © 2015 Macmillan Publishers Limited

Gachet C.,University of Strasbourg
Purinergic Signalling | Year: 2012

The P2Y12 receptor is a Gi-coupled ADP receptor first described in blood platelets where it plays a central role in the complex processes of activation and aggregation. Platelet granules store important amounts of ADP which are released upon stimulation by interaction of platelets with the damaged vessel wall. Therefore, the P2Y12 receptor is a key player in primary hemostasis and in arterial thrombosis and is an established target of antithrombotic drugs like the thienopyridine compounds ticlopidine, clopidogrel, and prasugrel or the direct, reversible antagonists ticagrelor and cangrelor. Beyond the platelet physiology and pharmacology, recent studies have revealed the expression of the P2Y12 receptor in other hematopoietic cells including leukocyte subtypes and microglia in the central nervous system as well as in vascular smooth muscle cells. These studies indicate putative roles of the P2Y12 receptor in inflammatory states and diseases of the brain, lung, and blood vessels. The selective role of P2Y12 among other P2 receptors as well as the possible impact of P2Y12 targeting drugs in these processes remain to be evaluated. © 2012 Springer Science+Business Media B.V.

Harashima H.,University of Strasbourg | Schnittger A.,University of Strasbourg
Plant Methods | Year: 2012

Background: Cell proliferation is an important determinant of plant growth and development. In addition, modulation of cell-division rate is an important mechanism of plant plasticity and is key in adapting of plants to environmental conditions. One of the greatest challenges in understanding the cell cycle of flowering plants is the large families of CDKs and cyclins that have the potential to form many different complexes. However, it is largely unclear which complexes are active. In addition, there are many CDK- and cyclin-related proteins whose biological role is still unclear, i.e. whether they have indeed enzymatic activity. Thus, a biochemical characterization of these proteins is of key importance for the understanding of their function.Results: Here we present a straightforward system to systematically express and purify active CDK-cyclin complexes from E. coli extracts. Our method relies on the concomitant production of a CDK activating kinase, which catalyzes the T-loop phosphorylation necessary for kinase activity. Taking the examples of the G1-phase cyclin CYCLIN D3;1 (CYCD3;1), the mitotic cyclin CYCLIN B1;2 (CYCB1;2) and the atypical meiotic cyclin SOLO DANCERS (SDS) in conjunction with A-, B1- and B2-type CDKs, we show that different CDKs can interact with various cyclins in vitro but only a few specific complexes have high levels of kinase activity.Conclusions: Our work shows that both the cyclin as well as the CDK partner contribute to substrate specificity in plants. These findings refine the interaction networks in cell-cycle control and pinpoint to particular complexes for modulating cell proliferation activity in breeding. © 2012 Harashima and Schnittger; licensee BioMed Central Ltd.

Dembele D.,University of Strasbourg | Kastner P.,University of Strasbourg
BMC Bioinformatics | Year: 2014

Background: Different methods have been proposed for analyzing differentially expressed (DE) genes in microarray data. Methods based on statistical tests that incorporate expression level variability are used more commonly than those based on fold change (FC). However, FC based results are more reproducible and biologically relevant.Results: We propose a new method based on fold change rank ordering statistics (FCROS). We exploit the variation in calculated FC levels using combinatorial pairs of biological conditions in the datasets. A statistic is associated with the ranks of the FC values for each gene, and the resulting probability is used to identify the DE genes within an error level. The FCROS method is deterministic, requires a low computational runtime and also solves the problem of multiple tests which usually arises with microarray datasets.Conclusion: We compared the performance of FCROS with those of other methods using synthetic and real microarray datasets. We found that FCROS is well suited for DE gene identification from noisy datasets when compared with existing FC based methods. © 2014 Dembélé and Kastner; licensee BioMed Central Ltd.

Klencklen G.,University of Strasbourg | Despres O.,University of Strasbourg | Dufour A.,University of Strasbourg
Ageing Research Reviews | Year: 2012

In order to cope with normal cognitive aging we must understand the patterns and neurofunctional underpinnings of cognitive and behavioral changes throughout adulthood. In this review, we summarize recent advances in our understanding of age-related behavioral differences and changes in brain structure throughout the spatial domain. Although spatial cognition is critically important to everyday life, few studies have examined the relationship between this cognitive function and neural changes in the aged brain. Thus, spatial cognition is considered a key area in which the cognitive neuroscience of aging may expand in the near future. The first section of this review examines the methodologies and studies used to assess differences in spatial cognition during normal cognitive aging in animals and humans. We then relate how each domain of spatial cognition (e.g., visuospatial perception, mental imagery, memory and navigation) is affected by the aging process, and discuss possible links with changes in neural mechanisms. Lastly, we address putative links among the age-related deterioration patterns of the various spatial domains and make suggestions for future research. © 2011 Elsevier B.V.

A formalism based on the complex-scaling method is used to solve a four-nucleon scattering problem above the breakup threshold using the realistic nuclear Hamiltonians. This method allows to solve diverse scattering problems based on very trivial boundary conditions and is compatible with the techniques used to solve bound state problems. © 2015, Springer-Verlag Wien.

Lazauskas R.,University of Strasbourg
Physical Review C - Nuclear Physics | Year: 2015

Background: Description of the collision process, which includes breakup, is one of the most challenging problems of the quantum mechanics. Recently I have developed a formalism based on the complex-scaling method, which describes accurately nuclear collisions in three- and four-body systems. Purpose: To provide accurate calculations for n-H3 scattering above the three- and four-nucleon breakup thresholds. Method: A four-nucleon system is described in configuration space employing Faddeev-Yakubovsky equations. The complex-scaling method is applied to overcome the difficulties related with the complicated boundary conditions. Results: Elastic observables as well as total breakup cross sections are calculated for neutron scattering on tritium at 14.1, 18, and 22.1 MeV using realistic NN interactions. Excellent agreement is found with the pioneering calculations of this process reported by A. Deltuva et al. [Phys. Rev. C 86, 011001 (2012)PRVCAN0556-281310.1103/PhysRevC.86.011001]. Strong correlation of the calculated cross sections is established with model-predicted trinucleon binding energy. The forementioned observables reveal little sensitivity to the short-range details of NN interaction. Conclusion: Reliable and accurate methods are now available to study four-nucleon scattering including the breakup. © 2015 American Physical Society.

Michel C.J.,University of Strasbourg
Journal of Theoretical Biology | Year: 2015

In 1996, a set X of 20 trinucleotides is identified in genes of both prokaryotes and eukaryotes which has in average the highest occurrence in reading frame compared to the two shifted frames (Arquès and Michel, 1996). Furthermore, this set X has an interesting mathematical property as X is a maximal C3 self-complementary trinucleotide circular code (Arquès and Michel, 1996). In 2014, the number of trinucleotides in prokaryotic genes has been multiplied by a factor of 527. Furthermore, two new gene kingdoms of plasmids and viruses contain enough trinucleotide data to be analysed. The approach used in 1996 for identifying a preferential frame for a trinucleotide is quantified here with a new definition analysing the occurrence probability of a complementary/permutation (CP) trinucleotide set in a gene kingdom. Furthermore, in order to increase the statistical significance of results compared to those of 1996, the circular code X is studied on several gene taxonomic groups in a kingdom. Based on this new statistical approach, the circular code X is strengthened in genes of prokaryotes and eukaryotes, and now also identified in genes of plasmids. A subset of X with 18 or 16 trinucleotides is identified in genes of viruses. Furthermore, a simple probabilistic model based on the independent occurrence of trinucleotides in reading frame of genes explains the circular code frequencies and asymmetries observed in the shifted frames in all studied gene kingdoms. Finally, the developed approach allows to identify variant X codes in genes, i.e. trinucleotide codes which differ from X. In genes of bacteria, eukaryotes and plasmids, 14 among the 47 studied gene taxonomic groups (about 30%) have variant X codes. Seven variant X codes are identified with at least 16 trinucleotides of X. Two variant X codes XA in cyanobacteria and plasmids of cyanobacteria, and XD in birds are self-complementary, without permuted trinucleotides but non-circular. Five variant X codes XB in deinococcus, plasmids of chloroflexi and deinococcus, mammals and kinetoplasts, XC in elusimicrobia and apicomplexans, XE in fishes, XF in insects, and XG in basidiomycetes and plasmids of spirochaetes are C3 self-complementary circular. In genes of viruses, no variant X code is found. © 2015 Elsevier Ltd.

Lam Y.H.,University of Bordeaux 1 | Smirnova N.A.,University of Bordeaux 1 | Caurier E.,University of Strasbourg
Physical Review C - Nuclear Physics | Year: 2013

The question of isospin-symmetry breaking in nuclei of the sd shell is addressed. We propose a new global parametrization of the isospin-nonconserving shell-model Hamiltonian which accurately describes experimentally known isobaric mass splittings. The isospin-symmetry violating part of the Hamiltonian consists of the Coulomb interaction and effective charge-dependent forces of nuclear origin. Particular attention has been paid to the effect of the short-range correlations. The behavior of b and c coefficients of the isobaric-mass-multiplet equation (IMME) is explored in detail. In particular, a high-precision numerical description of the staggering effect is proposed and contribution of the charge-dependent forces to the nuclear pairing is discussed. The Hamiltonian is applied to the study of the IMME beyond a quadratic form in the A=32 quintet, as well as to calculation of nuclear structure corrections to superallowed 0+→0+ Fermi β decay and to amplitudes of Fermi transitions to nonanalog states in sd-shell nuclei. © 2013 American Physical Society.

Pevet P.,University of Strasbourg | Challet E.,University of Strasbourg
Journal of Physiology Paris | Year: 2011

Daily rhythms in physiological and behavioral processes are controlled by a network of circadian clocks, reset by inputs and delivering circadian signals to the brain and peripheral organs. In mammals, at the top of the network is a master clock located in the suprachiasmatic nuclei (SCN) of the hypothalamus, mainly reset by ambient light. The nocturnal synthesis and release of melatonin by the pineal gland are tightly controlled by the SCN clock and inhibited by light exposure. Several roles of melatonin in the circadian system have been identified. As a major hormonal output, melatonin distributes temporal cues generated by the SCN to the multitude of tissue targets expressing melatonin receptors. In some target structures, like the Pars tuberalis of the adenohypophysis, these melatonin signals can drive daily rhythmicity that would otherwise be lacking. In other target structures, melatonin signals are used for the synchronization (i.e., adjustment of the timing of existing oscillations) of peripheral oscillators, such as the fetal adrenal gland. Due to the expression of melatonin receptors in the SCN, endogenous melatonin is also able to feedback onto the master clock, although its physiological significance needs further characterization. Of note, pharmacological treatment with exogenous melatonin can synchronize the SCN clock. From a clinical point of view, provided that the subject is not exposed to light at night, the daily profile of circulating melatonin provides a reliable estimate of the timing of the human SCN. During the past decade, a number of melatonin agonists have been developed for treating circadian, psychiatric and sleep disorders. These drugs may target the SCN for improving circadian timing or act indirectly at some downstream level of the circadian network to restore proper internal synchronization. © 2011 Elsevier Ltd.

Daldrop P.,University of Dundee | Masquida B.,University of Strasbourg | Lilley D.M.J.,University of Dundee
RNA Biology | Year: 2013

Ribonuclease p RNA requires a sharply kinked RNA helix to make a loop-receptor interaction that creates the binding site for the substrate. In some forms of the ribozyme, this is accomplished by a k-turn, while others have a different element called the pk-turn. The structure of the pk-turn in RNase p of Thermotoga maritima is globally very similar to a k-turn, but lacks all the standard features of that structure, including long-range hydrogen bonds between the two helical arms. We show here that in an isolated RNA duplex, the pk-turn fails to adopt a tightly kinked structure, but rather is a flexible element. This suggests that the tertiary contacts of RNase p assist its folding into the required kinked structure. We find that we can replace the k-turn of the sAM-I riboswitch with the pk-turn, such that the resulting RNA retains its ability to bind sAM, although with lower affinity. We also find that we can replace the pk-turn of T. maritima RNase p with a standard k-turn (in either orientation) with retention of ribozyme activity. Thus, although the pk-turn cannot intrinsically fold into the kinked structure, it can be induced to fold correctly in context. And the pk-turn and k-turns can substitute functionally for one another. © 2013 Landes Bioscience.

Bihel F.,University of Strasbourg
Future Medicinal Chemistry | Year: 2016

Opioid analgesics continue to be the mainstay of pharmacologic treatment of moderate to severe pain. Many patients, particularly those suffering from chronic pain, require chronic high-dose analgesic therapy. Achieving clinical efficacy and tolerability of such treatment regimens is hampered by the appearance of opioid-induced side effects such as tolerance, hyperalgesia and withdrawal syndrome. Among the therapeutic options to improve the opioid effectiveness, this current review focuses on strategies combining opioids to other drugs that can modulate opioid-mediated effects. We will discuss about experimental evidences reported for several potential opioid adjuvants, including N-methyl-d-aspartate receptor antagonists, 5-HT7 agonists, sigma-1 antagonists, I2-R ligands, cholecystokinin antagonists, neuropeptide FF-R antagonists and toll-like receptor 4 antagonists. © 2016 Future Science Ltd.

Lupberger J.,University of Strasbourg | Felmlee D.J.,University of Strasbourg | Baumert T.F.,University of Strasbourg | Baumert T.F.,Hopitaux Universitaires Of Strasbourg
Hepatology | Year: 2013

Chronic infection with hepatitis C virus (HCV) is a common cause of liver cirrhosis and cancer. We performed RNA sequencing in primary human hepatocytes activated with synthetic double-stranded RNA to mimic HCV infection. Upstream of IFNL3 (IL28B) on chromosome 19q13.13, we discovered a new transiently induced region that harbors a dinucleotidevariant ss469415590 (TT or DG), which is in high linkage disequilibrium with rs12979860, a genetic marker strongly associated with HCV clearance. ss469415590[DG] is a frameshift variant that creates a novel gene, designated IFNL4, encoding the interferon-k4 protein (IFNL4), which is moderately similar to IFNL3. Compared to rs12979860, ss469415590 is more strongly associated with HCV clearance in individuals of African ancestry, although it provides comparable information in Europeans and Asians. Transient overexpression of IFNL4 in a hepatoma cell line induced STAT1 and STAT2 phosphorylation and the expression of interferon-stimulated genes. Our findings provide new insights into the genetic regulation of HCV clearance and its clinical management.

Pevet P.,University of Strasbourg
Revue Neurologique | Year: 2014

Daily rhythms in physiological and behavioural processes are controlled by a network of circadian clocks. In mammals, at the top of the network is a master clock located in the suprachiasmatic nuclei (SCN) of the hypothalamus. The nocturnal synthesis and release of melatonin by the pineal gland are tightly controlled by the SCN clock. Several roles of melatonin in the circadian system have been identified. As a major hormonal output, melatonin distributes temporal cues generated by the SCN to the multitude of tissues expressing melatonin receptors. In some target tissues, these melatonin signals can drive daily rhythmicity that would otherwise be lacking. In other target structures, melatonin signals are used for the synchronization (i.e., adjustment of the timing of existing oscilla-tions) of peripheral oscillators. Due to the expression of melatonin receptors in the SCN, endogenous melatonin is also able to feedback onto the master clock. Of note, pharmaco-logical treatment with exogenous melatonin can synchronize the SCN clock. From a clinical point of view, provided that the subject is not exposed to light at night, the daily profile of circulating melatonin provides a reliable estimate of the timing of the human SCN. During the past decade, a number of melatonin agonists have been developed. These drugs may target the SCN for improving circadian timing or act indirectly at some downstream level of the circadian network to restore proper internal synchronization. © 2014 Elsevier Masson SAS.

We show that some results presented by Meisami-Azad, Mohammadpour, and Grigoriadis [Meisami-Azad, M.; Mohammadpour, J. & Grigoriadis, K. M. (2009). Dissipative analysis and control of state-space symmetric systems. Automatica, 45, 15741579] are erroneous. First, we present a counterexample contradicting the necessary and sufficient condition of Lemma 5. Then, we point out that Lemma 4, which is a key instrumental lemma in the proof of Theorem 6, is also erroneous and we propose a new lemma that corrects and completes the proof of Theorem 6. Finally, we show that H∞ norm formulations claimed by Theorems 6, 7 and 8 are inaccurate which is also sustained by previously published results as well as numerical examples taken from the commented paper. © 2012 Elsevier Ltd. All rights reserved.

Tape C.,California Institute of Technology | Liu Q.,University of Toronto | Maggi A.,University of Strasbourg | Tromp J.,Princeton University
Geophysical Journal International | Year: 2010

We iteratively improve a 3-D tomographic model of the southern California crust using numerical simulations of seismic wave propagation based on a spectral-element method (SEM) in combination with an adjoint method. The initial 3-D model is provided by the Southern California Earthquake Center. The data set comprises three-component seismic waveforms (i.e. both body and surface waves), filtered over the period range 2-30 s, from 143 local earthquakes recorded by a network of 203 stations. Time windows for measurements are automatically selected by the FLEXWIN algorithm. The misfit function in the tomographic inversion is based on frequency-dependent multitaper traveltime differences. The gradient of the misfit function and related finite-frequency sensitivity kernels for each earthquake are computed using an adjoint technique. The kernels are combined using a source subspace projection method to compute a model update at each iteration of a gradient-based minimization algorithm. The inversion involved 16 iterations, which required 6800 wavefield simulations. The new crustal model, m16, is described in terms of independent shear (VS) and bulk-sound (VB) wave speed variations. It exhibits strong heterogeneity, including local changes of ±30 per cent with respect to the initial 3-D model. The model reveals several features that relate to geological observations, such as sedimentary basins, exhumed batholiths, and contrasting lithologies across faults. The quality of the new model is validated by quantifying waveform misfits of full-length seismograms from 91 earthquakes that were not used in the tomographic inversion. The new model provides more accurate synthetic seismograms that will benefit seismic hazard assessment. © 2009 The Authors Journal compilation © 2009 RAS.

Quoix E.,University of Strasbourg
Therapeutic Advances in Medical Oncology | Year: 2012

The increase in life expectancy, with its concomitant increase in the risk of cancer, has led to an increased incidence of lung cancer in older people. The median age at diagnosis of lung cancer is between 63 and 70 years. For a long time, there has been a pessimistic attitude by doctors, patients and their relatives and thus an undertreatment of older patients. Older patients have some specific differences compared with younger patients: more comorbidities with concomitant medications that may interfere with chemotherapy, geriatric syndromes, frailty and so on. The first trial devoted to older patients with advanced non-small cell lung cancer (NSCLC) was a comparison between vinorelbine and best supportive care. There was a significant benefit of survival in the chemotherapy arm. Doublet therapy with gemcitabine plus vinorelbine did not give better results than either of these drugs alone. Thus, the recommendations for the treatment of older patients with advanced NSCLC were to give monotherapy. In some clinical trials not dedicated to older patients it appeared that patients might benefit from platinum-based doublet therapy like their younger counterparts. A randomized trial conducted by the French intergroup, IFCT, in patients aged at least 70 years comparing vinorelbine or gemcitabine alone with monthly carboplatin combined with weekly paclitaxel demonstrated that there was a highly significant benefit of survival in the doublet arm. This study resulted in a modification of the recommendations on the treatment of older patients with advanced NSCLC. © The Author(s), 2012.

Denans N.,University of Strasbourg | Iimura T.,Stowers Institute for Medical Research | Pourquie O.,University of Strasbourg
eLife | Year: 2015

In vertebrates, the total number of vertebrae is precisely defined. Vertebrae derive from embryonic somites that are continuously produced posteriorly from the presomitic mesoderm (PSM) during body formation. We show that in the chicken embryo, activation of posterior Hox genes (paralogs 9-13) in the tail-bud correlates with the slowing down of axis elongation. Our data indicate that a subset of progressively more posterior Hox genes, which are collinearly activated in vertebral precursors, repress Wnt activity with increasing strength. This leads to a graded repression of the Brachyury/T transcription factor, reducing mesoderm ingression and slowing down the elongation process. Due to the continuation of somite formation, this mechanism leads to the progressive reduction of PSM size. This ultimately brings the retinoic acid (RA)-producing segmented region in close vicinity to the tail bud, potentially accounting for the termination of segmentation and axis elongation.

Billard I.,University of Strasbourg | Ouadi A.,University of Strasbourg | Gaillard C.,IPN Lyon UMR 5822
Dalton Transactions | Year: 2013

A general chemical model describing the extraction mechanism of cations from an acidified aqueous phase toward an ionic liquid phase in which an extracting agent is dissolved is proposed. On this basis, fits are made which recover very satisfactorily the variation of the distribution ratio as a function of [HNO3] for several experimental data sets from the literature. This chemical model is discussed and compared to another model. © 2013 This journal is The Royal Society of Chemistry.

Danopoulos A.A.,CNRS Coordination Chemistry | Danopoulos A.A.,University of Strasbourg | Braunstein P.,University of Strasbourg
Dalton Transactions | Year: 2013

Aminolysis of [Co(NHC){N(SiMe3)2}Cl] with N-H acidic compounds such as substituted amidines and anilines leads to novel Co(ii) complexes with monodentate N-heterocyclic carbene ligation. Attempts to prepare Co(ii) dibenzyl complexes with bulky IPr coligands led to metal reduction to Co(i) and aromatic C-H activation and C-C coupling between the benzyl groups. © 2013 The Royal Society of Chemistry.

Freynet A.,Jean Minjoz University Hospital | Falcoz P.-E.,University of Strasbourg
Interactive Cardiovascular and Thoracic Surgery | Year: 2010

A best evidence topic was constructed according to a structured protocol. The question addressed was whether the use of transcutaneous electrical nerve stimulation (TENS) is effective in reducing post-thoracotomy pain. Of the 74 papers found with a report search, nine prospective randomized controlled trials (RCT), among which three were double-blind, presented the best evidence to answer the clinical question. All investigated the effect of TENS as an adjunct therapy for relieving acute post-thoracotomy pain in patients undergoing thoracic surgery. The authors, journal, date and country of publication, study type, group studied, relevant outcomes and results of these papers are given. We conclude that a vast majority - seven of the nine retrieved studies - were in favor of TENS as an adjuvant to narcotic analgesics for improving outcome after thoracic surgery. Indeed, the interest and benefit has been shown not only in the treatment of acute post-thoracotomy pain (pain scores and narcotic requirements were consistently lower in the TENS group as opposed to the Placebo-TENS group), but also when used together with narcotic analgesics to reduce the duration of recovery room stay and to increase chest physical tolerance (better coughing attempts during chest physiotherapy) with positive effects on pulmonary ventilator function wforced expiratory volume in 1 s (FEV1) andyor forced vital capacity (FVC)x. Specifically, the TENS treatment was shown to be ineffective when used alone in severe post-thoracotomy pain (i.e. posterolateral thoracotomy incision), but useful as an adjunct to other medications in moderate post-thoracotomy pain (i.e. muscle sparing thoracotomy incision) and very effective as the sole pain-control treatment in patients experiencing mild post-thoracotomy pain (i.e. video-assisted thoracoscopy incision). Hence, current evidence shows TENS associated with postoperative medications to be safe and effective in alleviating postoperative pain and in improving patient recovery, thus enhancing the choice of available medical care and bettering outcome after thoracic surgery.

Loison L.,University of Strasbourg
Comptes Rendus - Biologies | Year: 2015

The development of molecular biology placed in the foreground a mechanistic and deterministic conception of the functioning of macromolecules. In this article, I show that this conception was neither obvious, nor necessary. Taking Jacques Monod as a case study, I detail the way he gradually came loose from a statistical understanding of determinism to finally support a mechanistic understanding. The reasons of the choice made by Monod at the beginning of the 1950s can be understood only in the light of the general theoretical schema supported by the concept of mechanistic determinism. This schema articulates three fundamental notions for Monod, namely that of the rigidity of the sequence of the genetic program, that of the intrinsic stability of macromolecules (DNA and proteins), and that of the specificity of molecular interactions. © 2015 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

Lazauskas R.,University of Strasbourg
Few-Body Systems | Year: 2013

Formalism based on complex-scaling method is presented, which enables solution of the few-body scattering problem using trivial boundary conditions. Several applications are provided proving efficiency of the method in describing elastic and three-body breakup reactions for Hamiltonians which may combine short-range, Coulomb as well as optical potentials. © 2012 Springer-Verlag.

Dracos M.,University of Strasbourg
Nuclear Physics B - Proceedings Supplements | Year: 2013

The OPERA neutrino experiment has measured the neutrino velocity using the CERN CNGS beam over a baseline of 730 km. The measurement is based on data taken by OPERA in the years 2009, 2010, 2011. An arrival time of CNGS muon neutrinos with respect to the one computed assuming the speed of light in vacuum of (6.5±7.4(stat.)-8.0+8.3(sys.))ns was measured corresponding to a relative difference of the muon neutrino velocity with respect to the speed of light (v-c)/c=(2.7±3.1(stat.)-3.3+3.4(sys.))×10-6. During spring 2012 the CNGS provided during two weeks a short proton bunched beam dedicated to the neutrino velocity measurement. The OPERA neutrino experiment at the underground Gran Sasso Laboratory has measured the velocity of neutrinos with slightly modified setup compared to 2011 measurements. These modifications increased the timing accuracy and also fixed previous problems. The arrival time of CNGS muon neutrinos with respect to the one computed assuming the speed of light in vacuum has been found to be in agreement with the previous measurement. This result confirms the revised OPERA result and that indeed the neutrino anticipation announced in September 2011 was due to technical problems. © 2013 Elsevier B.V.

Michel C.J.,University of Strasbourg
Journal of Theoretical Biology | Year: 2015

The reading frame coding (RFC) of codes (sets) of trinucleotides is a genetic concept which has been largely ignored during the last 50 years. An extended definition of the statistical parameter PrRFC (Michel, 2014) is proposed here for analysing the probability (efficiency) of reading frame coding of usage of any trinucleotide code. It is applied to the analysis of the RFC efficiency of usage of the C3 self-complementary trinucleotide circular code X identified in prokaryotic and eukaryotic genes (Arquès and Michel, 1996). The usage of X is called usage XU. The highest RFC probabilities of usage XU are identified in bacterial plasmids and bacteria (about 49.0%). Then, by decreasing values, the RFC probabilities of usage XU are observed in archaea (47.5%), viruses (45.4%) and nuclear eukaryotes (42.8%). The lowest RFC probabilities of usage XU are found in mitochondria and chloroplasts (about 36.5%). Thus, genes contain information for reading frame coding. Such a genetic property which to our knowledge has never been identified, may bring new insights in the origin and evolution of the genetic code. © 2014 Elsevier Ltd.

Song Y.-H.,University of South Carolina | Lazauskas R.,University of Strasbourg | Gudkov V.,University of South Carolina
Physical Review C - Nuclear Physics | Year: 2013

Background: The existence of the electric dipole moment (EDM) of stable nuclei would be a direct evidence of the time reversal invariance violation (TRIV). Therefore, its measurement could be considered as a complement to the search for neutron and atomic EDMs. Purpose: To clarify theoretical issues related to calculations of EDMs in many-body systems we calculated the EDMs of the simplest nuclei. Method: For calculations of three-nucleon systems EDMs we used TRIV potentials based on the meson exchange theory, as well as the ones derived by using effective field theories (EFT) with and without explicit pions. Nuclear wave functions were obtained by solving Faddeev equations in configuration space for the complete Hamiltonians comprising both TRIV and realistic strong interactions. Results: The expressions for EDMs of 3He and 3H are given in terms of meson exchange couplings and low energy constants of EFT potentials. Conclusions: The obtained results are compared with the previous calculations of 3He EDM and with time reversal invariance violating effects in neutron-deuteron scattering. The model dependence on strong interactions is discussed. © 2013 American Physical Society.

Chrust M.,University of Strasbourg | Bouchet G.,Aix - Marseille University | Duek J.,University of Strasbourg
Physics of Fluids | Year: 2013

We present a comprehensive parametric study of the transition scenario of freely falling discs. The motion of the discs is investigated by a direct numerical simulation of the solid-fluid interaction. The discs are assumed to be homogeneous and infinitely thin. The problem is shown to depend on two independent parameters, the Galileo number expressing the ratio between effects of gravity and viscosity and the non-dimensionalized mass characterizing the inertia of the disc. The obtained results are in agreement with known experimental and numerical data and provide both detailed and comprehensive picture of the transition scenario in the two-parameter plane defined by the Galileo number and the non-dimensionalized mass. © 2013 American Institute of Physics.

Crossley D.,Saint Louis University | Hinderer J.,University of Strasbourg | Riccardi U.,University of Naples Federico II
Reports on Progress in Physics | Year: 2013

This review covers basic theory and techniques behind the use of ground-based gravimetry at the Earth's surface. The orientation is toward modern instrumentation, data processing and interpretation for observing surface, land-based, time-variable changes to the geopotential. The instrumentation side is covered in some detail, with specifications and performance of the most widely used models of the three main types: the absolute gravimeters (FG5, A10 from Micro-g LaCoste), superconducting gravimeters (OSG, iGrav from GWR instruments), and the new generation of spring instruments (Micro-g LaCoste gPhone, Scintrex CG5 and Burris ZLS). A wide range of applications is covered, with selected examples from tides and ocean loading, atmospheric effects on gravity, local and global hydrology, seismology and normal modes, long period and tectonics, volcanology, exploration gravimetry, and some examples of gravimetry connected to fundamental physics. We show that there are only a modest number of very large signals, i.e. hundreds of μGal (10-8 m s-2), that are easy to see with all gravimeters (e.g. tides, volcanic eruptions, large earthquakes, seasonal hydrology). The majority of signals of interest are in the range 0.1-5.0 μGal and occur at a wide range of time scales (minutes to years) and spatial extent (a few meters to global). Here the competing effects require a careful combination of different gravimeter types and measurement strategies to efficiently characterize and distinguish the signals. Gravimeters are sophisticated instruments, with substantial up-front costs, and they place demands on the operators to maximize the results. Nevertheless their performance characteristics such as drift and precision have improved dramatically in recent years, and their data recording ability and ruggedness have seen similar advances. Many subtle signals are now routinely connected with known geophysical effects such as coseismic earthquake displacements, post-glacial rebound, local hydrological mass balances, and detection of non-steric sea level changes. © 2013 IOP Publishing Ltd.

Ostrosi E.,University of Technology of Belfort - Montbéliard | Haxhiaj L.,University of Strasbourg | Fukuda S.,Stanford University
Research in Engineering Design | Year: 2012

Consensus can be used for working out an agreement during design conflict resolution. This paper introduces an approach for consensus modelling in collaborative and distributed design. Consensus is represented by a formal model based on the fuzzy set theory. Defining a design cluster as a fuzzy evaluation relationship between a group of functional requirements and a group of conjecture regions allows the concept of consensus as a problem of the overlapping of design clusters of different perspectives to be introduced. To measure consensus, two key concepts are suggested: The intraconsensus design coefficient and the interconsensus design coefficient. Using the concept of consensus and its properties, the actors can more easily move towards consensus improvement or towards ideal consensus. From our observation, the result of interactions during collaborative and distributed design shows that a solution is a set of consensual design clusters. The concept of consensus is used (1) to evaluate design solution, (2) to assist the collaborative designing of a group of conjecture regions according to consensual functional requirements and finally (3) to capitalize on and share the know-how of the different actors. © Springer-Verlag London Limited 2011.

Stein B.,University of Strasbourg | Devaux E.,University of Strasbourg | Genet C.,University of Strasbourg | Ebbesen T.W.,University of Strasbourg
Optics Letters | Year: 2012

We generate self-collimating surface plasmon beams in a doubly periodic plasmonic grating. The self-collimation effect is understood from the local anisotropy of the isofrequency surface of the grating in the vicinity of the bandgap. The properties of the beams are analyzed by leakage radiation microscopy and show to an unprecedented level significantly reduced diffraction as compared with plasmon beams propagating on a flat metal film. © 2012 Optical Society of America.

Zallat J.,University of Strasbourg | Torzynski M.,University of Strasbourg | Lallement A.,University of Strasbourg
Optics Letters | Year: 2012

We present a new method that allows efficient spectral calibration for a polarization state analyzer. The procedure does not require any additional polarization optical element other than the polarization state analyzer itself. It uses a double-pass technique that can be achieved up to a very good precision. The method is illustrated using real measurements done at several wavelengths with a rotating wave plate polarization state analyzer. Alignment of axis as well as true retardation at a specific wavelength are easily obtained by a standard function fitting. © 2012 Optical Society of America.

Przybilla F.,University of Strasbourg | Genet C.,University of Strasbourg | Ebbesen T.W.,University of Strasbourg
Optics Express | Year: 2012

We analyze the progressive introduction of disorder in periodic subwavelength hole arrays. Two models of disorder are discussed from their associated Fourier transforms and correlation functions. The optical transmission properties of the corresponding arrays are closely related with the evolutions of structure factors, as experimentally detailed. Remarkably, the optical properties of random arrays are not in general equal to those of the single hole as a result of short-range correlations corresponding to hole-to-hole interactions. These correlations are due to packing constraints that are controlled through the careful generation of random patterns. For high density pattern, short-range order can take over long-range order associated with the periodic array. © 2012 Optical Society of America.

Lange H.,University of Strasbourg | Sement F.M.,University of Strasbourg | Gagliardi D.,University of Strasbourg
Plant Journal | Year: 2011

The exosome is a conserved protein complex that is responsible for essential 3′→5′ RNA degradation in both the nucleus and the cytosol. It is composed of a nine-subunit core complex to which co-factors confer both RNA substrate recognition and ribonucleolytic activities. Very few exosome co-factors have been identified in plants. Here, we have characterized a putative RNA helicase, AtMTR4, that is involved in the degradation of several nucleolar exosome substrates in Arabidopsis thaliana. We show that AtMTR4, rather than its closely related protein HEN2, is required for proper rRNA biogenesis in Arabidopsis. AtMTR4 is mostly localized in the nucleolus, a subcellular compartmentalization that is shared with another exosome co-factor, RRP6L2. AtMTR4 and RRP6L2 cooperate in several steps of rRNA maturation and surveillance, such as processing the 5.8S rRNA and removal of rRNA maturation by-products. Interestingly, degradation of the Arabidopsis 5′ external transcribed spacer (5′ ETS) requires cooperation of both the 5′→3′ and 3′→5′ exoribonucleolytic pathways. Accumulating AtMTR4 targets give rise to illegitimate small RNAs; however, these do not affect rRNA metabolism or contribute to the phenotype of mtr4 mutants. Plants lacking AtMTR4 are viable but show several developmental defects, including aberrant vein patterning and pointed first leaves. The mtr4 phenotype resembles that of several ribosomal protein and nucleolin mutants, and may be explained by delayed ribosome biogenesis, as we observed a reduced rate of rRNA accumulation in mtr4 mutants. Taken together, these data link AtMTR4 with rRNA biogenesis and development in Arabidopsis. © 2011 Blackwell Publishing Ltd.

Organic nanomaterials are attracting a great deal of interest for use in flexible electronic applications such as logic circuits, displays and solar cells. These technologies have already demonstrated good performances, but flexible organic memories are yet to deliver on all their promise in terms of volatility, operational voltage, write/erase speed, as well as the number of distinct attainable levels. Here, we report a multilevel non-volatile flexible optical memory thin-film transistor based on a blend of a reference polymer semiconductor, namely poly(3-hexylthiophene), and a photochromic diarylethene, switched with ultraviolet and green light irradiation. A three-terminal device featuring over 256 (8 bit storage) distinct current levels was fabricated, the memory states of which could be switched with 3 ns laser pulses. We also report robustness over 70 write–erase cycles and non-volatility exceeding 500 days. The device was implemented on a flexible polyethylene terephthalate substrate, validating the concept for integration into wearable electronics and smart nanodevices. © 2016 Nature Publishing Group

Sieja K.,University of Strasbourg | Sieja K.,French National Center for Scientific Research | Nowacki F.,University of Strasbourg | Nowacki F.,French National Center for Scientific Research
Physical Review C - Nuclear Physics | Year: 2012

We present state-of-the-art shell-model calculations in a large model space (pf for protons, fpgd for neutrons), which allows us to study simultaneously excitations across the Z=28 and N=50 shell gaps. We explore the region in the vicinity of 78Ni, which is a subject of intense experimental investigations. Our calculations correctly account for the known low-lying excited states in this region, including those which may correspond to cross-shell excitations. We observe the minimum of the N=50 mass gap at Z=32 consistent with experimental data and its further increase toward Z=28, indicating a robustness of the N=50 gap in 78Ni. The evolution of the N=50 gap along the nickel chain is shown to bear similarities to what is known in oxygen and calcium chains, providing a new opportunity for the studies of three-body monopole effects in medium-mass nuclei. © 2012 American Physical Society.

Song Y.-H.,University of South Carolina | Lazauskas R.,University of Strasbourg | Gudkov V.,University of South Carolina
Physical Review C - Nuclear Physics | Year: 2012

Parity-violating (PV) effects in neutron-deuteron radiative capture are studied using Desplanques, Donoghue, and Holstein (DDH) and effective field theory weak potentials. The values of PV effects are calculated using wave functions, obtained by solving three-body Faddeev equations in configuration space for realistic strong potentials. The relations between physical observables and low-energy constants are presented, and dependencies of the calculated PV effects on strong and weak potentials are discussed. The presented analysis shows the possible reason for the existing discrepancy in PV nuclear data analysis using the DDH approach and reveals a new opportunity to study short-range interactions in nuclei. © 2012 American Physical Society.

Lazauskas R.,University of Strasbourg
Physical Review C - Nuclear Physics | Year: 2012

A formalism based on the complex-scaling method is developed and applied to solve the four-nucleon scattering problem above the break-up threshold. Converged calculations are presented for the isospin T=0 and T=1 channels in several energy regions above both the three- and the four-particle break-up thresholds. © 2012 American Physical Society.

Allegre V.,University of Strasbourg | Jouniaux L.,University of Strasbourg | Lehmann F.,CNRS Hydrology and Geochemistry Laboratory of Strasbourg | Sailhac P.,University of Strasbourg
Geophysical Journal International | Year: 2010

The electrokinetic potential results from the coupling between the water flow and the electrical current because of the presence of ions within water. The electrokinetic coefficient is well described in fluid-saturated media, however its behaviour under unsaturated flow conditions is still discussed. We propose here an experimental approach to investigate streaming potential variations in sand at unsaturated conditions. We present for the first time continuous records of the electrokinetic coefficient as a function of water content. Two drainage experiments have been performed within a column filled with a clean sand. Streaming potential measurements are combined with water pressure and water content measurements every 10 cm along the column. In order to model hydrodymanics during the experiments, we solve Richards equation coupled with an inverse problem to estimate the hydraulic parameters of the constitutive relations between hydraulic conductivity, water pressure and water content. The electrokinetic coefficient C shows a more complex behaviour for unsaturated conditions than it was previously reported and cannot be fitted by the existing models. The normalized electrokinetic coefficient increases first when water saturation decreases from 100 to about 65-80 per cent, and then decreases as the water saturation decreases, whereas all previous works described a monotone decrease of the normalized electrokinetic coupling as water saturation decreases. We delimited two water saturation domains, and deduced two different empirical laws describing the evolution of the electrokinetic coefficient for unsaturated conditions. Moreover, we introduce the concept of the electrokinetic residual saturation, Sr,ek w, which allows us to propose a new model derived from the approach of the relative permeability used in hydrodynamics. © 2010 The Authors Journal compilation © 2010 RAS.

Gutmann B.,University of Strasbourg | Gobert A.,University of Strasbourg | Giege P.,University of Strasbourg
Genes and Development | Year: 2012

RNase P is an essential enzyme that cleaves the 59 leader sequence of tRNA precursors. RNase Ps were believed until now to occur universally as ribonucleoproteins in organisms performing RNase P activity. Here we find that protein-only RNase P enzymes called PRORP (for proteinaceous RNase P) support RNase P activity in vivo in both organelles and the nucleus in Arabidopsis. Beyond tRNA, PRORP proteins are involved in the maturation of small nucleolar RNA (snoRNA) and mRNA. Finally, ribonucleoprotein RNase MRP is not involved in tRNA maturation in plants. Altogether, our results indicate that ribonucleoprotein enzymes have been entirely replaced by proteins for RNase P activity in plants. © 2012 by Cold Spring Harbor Laboratory Press.

Ngondo R.P.,University of Strasbourg | Carbon P.,University of Strasbourg
Nucleic Acids Research | Year: 2014

A transcriptional feedback loop is the simplest and most direct means for a transcription factor to provide an increased stability of gene expression. In this work performed in human cells, we reveal a new negative auto-regulatory mechanism involving an alternative transcription start site (TSS) usage. Using the activating transcription factor ZNF143 as a model, we show that the ZNF143 low-affinity binding sites, located downstream of its canonical TSS, play the role of protein sensors to induce the up-or down-regulation of ZNF143 gene expression. We uncovered that the TSS switch that mediates this regulation implies the differential expression of two transcripts with an opposite protein production ability due to their different 5′ untranslated regions. Moreover, our analysis of the ENCODE data suggests that this mechanism could be used by other transcription factors to rapidly respond to their own aberrant expression level. © 2013 The Author(s). Published by Oxford University Press.

Marsan D.,University of Savoy | Lengline O.,University of Savoy | Lengline O.,University of Strasbourg
Journal of Geophysical Research: Solid Earth | Year: 2010

We investigate how aftershocks are spatially distributed relative to the mainshock. Compared to previous studies, ours focuses on earthquakes causally related to the mainshock rather than on aftershocks of previous aftershocks. We show that this distinction can be made objectively but becomes uncertain at long time scales and large distances. Analyzing a regional earthquake data set, it is found that, at time t following a mainshock of magnitude m, the probability of finding an aftershock at distance r relative to the mainshock fault decays as r-γ, where γ is typically between 1.7 and 2.1 for 3 ≤ m < 6 and is independent of m, for r less than 10 to 20 km and t less than 1 day. Uncertainties on this probability at larger r and t do not allow for a correct estimation of this spatial decay. We further show that a static stress model coupled with a rate-and-state friction model predicts a similar decay, with an exponent γ= 2.2, in the same space and time intervals. This suggests that static stress changes could explain the repartition of aftershocks around the mainshock even at distances larger than 10 times the rupture length. © Copyright 2010 by the American Geophysical Union.

Mileshina D.,University of Strasbourg | Mileshina D.,Russian Academy of Sciences | Koulintchenko M.,Russian Academy of Sciences | Konstantinov Y.,Russian Academy of Sciences | Dietrich A.,University of Strasbourg
Nucleic Acids Research | Year: 2011

Investigation and manipulation of mitochondrial genetics in animal and plant cells remains restricted by the lack of an efficient in vivo transformation methodology. Mitochondrial transfection in whole cells and maintenance of the transfected DNA are main issues on this track. We showed earlier that isolated mitochondria from different organisms can import DNA. Exploiting this mechanism, we assessed the possibility to maintain exogenous DNA in plant organelles. Whereas homologous recombination is scarce in the higher plant nuclear compartment, recombination between large repeats generates the multipartite structure of the plant mitochondrial genome. These processes are under strict surveillance to avoid extensive genomic rearrangements. Nevertheless, following transfection of isolated organelles with constructs composed of a partial gfp gene flanked by fragments of mitochondrial DNA, we demonstrated in organello homologous recombination of the imported DNA with the resident DNA and integration of the reporter gene. Recombination yielded insertion of a continuous exogenous DNA fragment including the gfp sequence and at least 0.5kb of flanking sequence on each side. According to our observations, transfection constructs carrying multiple sequences homologous to the mitochondrial DNA should be suitable and targeting of most regions in the organelle genome should be feasible, making the approach of general interest. © 2011 The Author(s).

Cruz J.A.,University of Strasbourg | Westhof E.,University of Strasbourg
Nature Methods | Year: 2011

Structural RNA modules, sets of ordered non-Watson-Crick base pairs embedded between Watson-Crick pairs, have central roles as architectural organizers and sites of ligand binding in RNA molecules, and are recurrently observed in RNA families throughout the phylogeny. Here we describe a computational tool, RNA three-dimensional (3D) modules detection, or RMDetect, for identifying known 3D structural modules in single and multiple RNA sequences in the absence of any other information. Currently, four modules can be searched for: G-bulge loop, kink-turn, C-loop and tandem-GA loop. In control test sequences we found all of the known modules with a false discovery rate of 0.23. Scanning through 1,444 publicly available alignments, we identified 21 yet unreported modules and 141 known modules. RMDetect can be used to refine RNA 2D structure, assemble RNA 3D models, and search and annotate structured RNAs in genomic data. © 2011 Nature America, Inc. All rights reserved.

Mellitzer G.,University of Strasbourg | Gradwohl G.,University of Strasbourg
Current Opinion in Lipidology | Year: 2011

Purpose of Review: To examine recent papers linking enteroendocrine cells to lipid absorption. Recent Findings: Specific inactivation of the proendocrine transcription factor neurogenin 3 (Ngn3) in the intestine leads to a loss of enteroendocrine cells, growth retardation, impaired lipid absorption and a high mortality during the weaning period. Furthermore, gain and loss of function experiments using mouse, hamster and primary enterocytes demonstrate that apoB-48-containing chylomicron formation and secretion may be regulated by enteroendocrine hormones. This seems to involve the multilineage scavenger receptor CD36, glycosylation of which is indirectly stimulated by enteroendocrine hormones. Summary: Hormones and peptides secreted by enteroendocrine cells are well known for their effect on food intake and appetite, the regulation of glucose homeostasis, gut motility, and various other physiological functions. What can now be added to this list is that they also influence lipid absorption, which opens up new opportunities to develop treatments for people suffering from overweight and its associated metabolic disorders. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Smith T.,Phenomenome Discoveries Inc | Ghandour M.S.,University of Strasbourg | Wood P.L.,Phenomenome Discoveries Inc
Journal of Neurochemistry | Year: 2011

Despite the fact that N-acetyl methionine (NAM) supplementation has long been reported as a bioavailable source of methionine in humans, and known to reduce liver toxicity after acetaminophen overdose, its cellular endogenous presence has never been investigated. We demonstrate for the first time that NAM is present in both human and mouse tissues and cells in culture. A wide variety of cultured cells, including a number of brain derived cell types, as well as mouse and human brain tissue all have clearly detectable levels of NAM. Methionine is rapidly acetylated to form NAM in cultured human oligodendroglioma cells with an initial rate of 0.44 ± 0.064 atom percent excess per minute. The presence of measurable quantities of NAM in brain cells in combination with its rapid formation point to a potential physiological role for N-acetylated methionine in the brain. Aminoacylase 1 is responsible for metabolism of NAM to methionine and acetate. Deficiencies in aminoacylase 1 have been linked to a variety of neurological disorders; however, it is unclear whether and how the brain is affected by this defect. The reported presence of NAM in the human brain may provide an invaluable key to discovering the link between aminoacylase 1 mutations and neurological problems. © 2011 International Society for Neurochemistry.

Over the past decade, several technologies have emerged to access nucleic acid-tagged libraries and select the fittest compound within such libraries. This perspective focuses on recent development with PNA-tagged small molecules displayed on DNA templates for screening purposes and to probe the optimal geometry in multivalent interactions.

Van Paesschen W.,University Hospital Gasthuisberg | Hirsch E.,University of Strasbourg | Johnson M.,UCB Pharma | Falter U.,UCB Pharma | Von Rosenstiel P.,UCB Pharma
Epilepsia | Year: 2013

Purpose: To evaluate the efficacy and tolerability of adjunctive brivaracetam (BRV), a novel high-affinity synaptic vesicle protein 2A ligand that also displays inhibitory activity at neuronal voltage-dependent sodium channels, in adult epilepsy patients with uncontrolled partial-onset seizures. Methods: A phase IIb, double-blind, randomized, placebo-controlled, parallel-group, dose-ranging study (N01114; NCT00175929) was conducted in patients aged 16-65 years. To be included in the study, patients were required to have experienced four or more partial-onset seizures during a 4-week prospective baseline, despite treatment with 1-2 concomitant antiepileptic drugs. Patients were randomized in a ratio of 1:1:1 to receive BRV 50 mg/day (BRV50), 150 mg/day (BRV150), or placebo. A 3-week up-titration period was followed by a 7-week maintenance period (total treatment period of 10 weeks). Key Findings: A total of 157 patients were randomized (intent-to-treat [ITT] population; BRV50 n = 53, BRV150 n = 52, placebo n = 52) and overall 148 (94.3%) completed the study. The percent reduction in baseline-adjusted partial-onset seizure frequency/week over placebo during the 7-week maintenance period (primary efficacy outcome) did not reach statistical significance (14.7% for BRV50 [p = 0.093] and 13.6% for BRV150 [p = 0.124]). However, during the entire 10-week treatment period a statistically significant difference was observed for both BRV groups (17.7% for BRV50 [p = 0.026] and 16.3% for BRV150 [p = 0.043]). The median percent reduction from baseline in partial-onset seizure frequency/week during the maintenance period was 38.2% for BRV50 (p = 0.017) and 30.0% for BRV150 (p = 0.113) versus 18.9% in the placebo group. During the treatment period, this was 34.9% for BRV50 (p = 0.004) and 28.3% for BRV150 (p = 0.070) compared with 16.3% for placebo. Fifty percent responder rates during the maintenance period were 23.1% for placebo compared with 39.6% for BRV50 (odds ratio [OR] 2.17, p = 0.077) and 33.3% for BRV150 (OR 1.66, p = 0.261). During the treatment period, 50% responder rates were 17.3% for placebo compared with 35.8% for BRV50 (OR 2.69, p = 0.038) and 30.8% for BRV150 (OR 2.15, p = 0.114). Nine patients were free from partial-onset seizures during the 10-week treatment period (five patients [9.4%] in the BRV50 group and three [5.8%] in the BRV150 group compared with one patient [1.9%] in the placebo group). Treatment-emergent adverse events (TEAEs) reported during the treatment period were mostly mild-to-moderate with similar incidence across treatment groups (BRV50 36/53, 67.9%; BRV150 35/52, 67.3%; placebo 37/52, 71.2%). The most frequently reported TEAEs in BRV groups were headache, fatigue, nasopharyngitis, nausea, somnolence, and dizziness, although nausea had a higher incidence in the placebo group. Significance: In this double-blind, placebo-controlled, phase IIb study of adjunctive BRV (50 and 150 mg/day) in adults with uncontrolled partial-onset seizures, the primary efficacy analysis did not reach statistical significance; however, statistically significant differences compared with placebo were observed on several secondary efficacy outcomes. BRV was well tolerated. © 2012 International League Against Epilepsy.

Hugel S.,University of Strasbourg
Journal of Insect Conservation | Year: 2015

Threats to the endemic grasshopper fauna of the Mascarene Islands (Mauritius, Rodrigues, and La Réunion), in the South Western Indian ocean are examined. Most endemic species were previously only known from very old type specimens lacking locality data. All were found again, and their precise distribution and habitat are given for the first time. The species Pyrgacris relictus Descamps, 1968, only known from the holotype and believed to be extinct, is rediscovered in a 0.4 km2 locality, but is under serious threat as its only habitat has been strongly modified during the past months. All Mascarene endemic grasshoppers are critically endangered. The total area of occupancy per species ranges between a few hectares and 5 km2, most species occurring in five or less locations. Mascarene grasshoppers rank among the most threatened Caelifera of known status in the world. However, most of their localities are included in a protected area, leaving hope to preserve these species, providing suitable conservation schemes are conducted. © 2014, Springer International Publishing Switzerland.

Cuche A.,University of Strasbourg | Mahboub O.,University of Strasbourg | Devaux E.,University of Strasbourg | Genet C.,University of Strasbourg | Ebbesen T.W.,University of Strasbourg
Physical Review Letters | Year: 2012

We demonstrate that optical trapping can be driven by delocalized surface plasmon modes resonantly excited within a standing wave trap. Dynamical modifications are shown to be determined by the near-field symmetry of the plasmonic modes with negligible thermal effect. With low trapping powers and polarization control, remarkable stiffness enhancements are recorded, the larger the smaller the particle. The results can be simply modeled accounting for a coherent interaction between the plasmon field and the Gaussian standing wave of the trap. © 2012 American Physical Society.

Genaud S.,University of Strasbourg | Gossa J.,University of Strasbourg
Proceedings - 2011 IEEE 4th International Conference on Cloud Computing, CLOUD 2011 | Year: 2011

Recent Infrastructure-as-a-Service offers, such as Amazon's EC2 cloud, provide virtualized on-demand computing resources on a pay-per-use model. From the user point of view, the cloud provides an inexhaustible supply of resources, which can be dynamically claimed and released. This drastically changes the problem of resource provisioning and job scheduling. This article presents how billing models can be exploited by provisioning strategies to find a trade-off between fast/expensive computations and slow/cheap ones for indepedent sequential jobs. We study a dozen strategies based on classic heuristics for online scheduling and bin-packing problems, with the double objective of minimizing the wait time (and hence the completion time) of jobs and the monetary cost of the rented resources. We simulate these strategies on real grid workloads in two cases. First, we use the workloads as a whole, which is representative of a large community of users sharing some common resources. Second, we use the workloads extracted for each individual user. These lighter workloads correspond to users submitting work independently from others and paying for their own resources. Our findings show that on large workloads, a little budget increase allows to achieve optimal wait time, while trade-off heuristics may be largely beneficial for individual users with lighter workloads. © 2011 IEEE.

Lago-Penas C.,University of Vigo | Dellal A.,University of Strasbourg
Journal of Human Kinetics | Year: 2010

In soccer, the ability to retain possession of the ball for prolonged periods of time has been suggested to be linked to success. The accuracy of this assertion was investigated by examining 380 matches involving Spanish League First Division teams during the 2008-2009 season. Possession of the ball, according to the status of the match (winning, drawing and losing), was recorded during the different matches using a multiple-camera match analysis system (Gecasport®). The results suggest that the best classified teams maintained a higher percentage of ball possession and that their pattern of play was more stable. The coefficient of variation, with respect to ball possession per match, was smaller for the best placed teams. Indeed, first placed F.C. Barcelona had the smallest coefficient of variation for possession time (8.4%), while bottom placed Recreativo showed the highest values with 17.1%. Linear regression analysis showed that possession strategies were influenced by situation variables. Team possession was greater when losing than when winning (p<0.01) or drawing (p<0.01), home teams enjoyed greater possession than visiting teams (p<0.01), and playing against strong opposition was associated with a reduction in time spent in possession (p<0.01). The findings indicate that strategies in soccer are influenced by situational variables and that teams alter their playing style accordingly during the match. © Editorial Committee of Journal of Human Kinetics.

Sieber F.,University of Strasbourg | Duchene A.-M.,University of Strasbourg | Marechal-Drouard L.,University of Strasbourg
International Review of Cell and Molecular Biology | Year: 2011

Mitochondria, owing to their bacterial origin, still contain their own DNA. However, the majority of bacterial genes were lost or transferred to the nuclear genome and the biogenesis of the "present-day" mitochondria mainly depends on the expression of the nuclear genome. Thus, most mitochondrial proteins and a small number of mitochondrial RNAs (mostly tRNAs) expressed from nuclear genes need to be imported into the organelle. During evolution, macromolecule import systems were universally established. The processes of protein mitochondrial import are very well described in the literature. By contrast, deciphering the mitochondrial RNA import phenomenon is still a real challenge. The purpose of this review is to present a general survey of our present knowledge in this field in different model organisms, protozoa, plants, yeast, and mammals. Questions still under debate and major challenges are discussed. Mitochondria are involved in numerous human diseases. The targeting of macromolecule to mitochondria represents a promising way to fight mitochondrial disorders and recent developments in this area of research are presented. © 2011 Elsevier Inc.

Meyer L.,University of Strasbourg | Patte-Mensah C.,University of Strasbourg | Taleb O.,University of Strasbourg | Mensah-Nyagan A.G.,University of Strasbourg
Cellular and Molecular Life Sciences | Year: 2010

Painful neuropathy is a major side-effect limiting cancer chemotherapy. Therefore, novel strategies are required to suppress the neuropathic effects of anticancer drugs without altering their chemotherapeutic effectiveness. By combining biochemical, neuroanatomical/neurochemical, electrophysiological and behavioral methods, we demonstrated that progesterone-derived neurosteroids including 5α-dihydroprogesterone and 3α,5α- tetrahydroprogesterone suppressed neuropathic symptoms evoked in naive rats by vincristine. Neurosteroids counteracted vincristine-induced alterations in peripheral nerves including 2′,3′-cyclic nucleotide 3′-phosphodiesterase, neurofilament-200 kDa and intraepidermal nerve fiber repression, nerve conduction velocity, and pain transmission abnormalities (allodynia/hyperalgesia). In skin-tumor rats generated with carcinosarcoma- cells, vincristine, which suppressed the skin tumor and restored normal blood concentration of vascular endothelial growth factor (VEGF), reproduced neuropathic side-effects. Administered alone, neurosteroids did not affect the tumor and VEGF level. Combined with vincristine, neurosteroids preserved vincristine anti-tumor action but counteracted vincristine-induced neural side-effects. Together, these results provide valuable insight into the cellular and functional mechanisms underlying anticancer drug-induced neuropathy and suggest a neurosteroid-based strategy to eradicate painful neuropathy. © 2010 Springer Basel AG.

Capa R.L.,University of Liège | Bouquet C.A.,University of Poitiers | Dreher J.-C.,University of Lyon | Dufour A.,University of Strasbourg
Cortex | Year: 2013

Motivation is often thought to interact consciously with executive control, although recent studies have indicated that motivation can also be unconscious. To date, however, the effects of unconscious motivation on high-order executive control functions have not been explored. Only a few studies using subliminal stimuli (i.e., those not related to motivation, such as an arrow to prime a response) have reported short-lived effects on high-order executive control functions. Here, building on research on unconscious motivation, in which a behavior of perseverance is induced to attain a goal, we hypothesized that subliminal motivation can have long-lasting effects on executive control processes. We investigated the impact of unconscious/conscious monetary reward incentives on evoked potentials and neural activity dynamics during cued task-switching performance. Participants performed long runs of task-switching. At the beginning of each run, a reward (50cents or 1 cent) was displayed, either subliminally or supraliminally. Participants earned the reward contingent upon their correct responses to each trial of the run. A higher percentage of runs was achieved with higher (conscious and unconscious) than lower rewards, indicating that unconscious high rewards have long-lasting behavioral effects. Event-related potential (ERP) results indicated that unconscious and conscious rewards influenced preparatory effort in task preparation, as suggested by a greater fronto-central contingent negative variation (CNV) starting at cue-onset. However, a greater parietal P3 associated with better reaction times (RTs) was observed only under conditions of conscious high reward, suggesting a larger amount of working memory invested during task performance. Together, these results indicate that unconscious and conscious motivations are similar at early stages of task-switching preparation but differ during task performance. © 2012 Elsevier Ltd.

Freel K.C.,University of Strasbourg | Friedrich A.,University of Strasbourg | Hou J.,University of Strasbourg | Schacherer J.,University of Strasbourg
Genome biology and evolution | Year: 2014

The increasing availability of mitochondrial (mt) sequence data from various yeasts provides a tool to study genomic evolution within and between different species. While the genomes from a range of lineages are available, there is a lack of information concerning intraspecific mtDNA diversity. Here, we analyzed the mt genomes of 50 strains from Lachancea thermotolerans, a protoploid yeast species that has been isolated from several locations (Europe, Asia, Australia, South Africa, and North / South America) and ecological sources (fruit, tree exudate, plant material, and grape and agave fermentations). Protein-coding genes from the mtDNA were used to construct a phylogeny, which reflected a similar, yet less resolved topology than the phylogenetic tree of 50 nuclear genes. In comparison to its sister species Lachancea kluyveri, L. thermotolerans has a smaller mt genome. This is due to sh