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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.

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.

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.

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.

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.

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.

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.

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.

Bara G.I.,University of Strasbourg
Proceedings of the 2010 American Control Conference, ACC 2010 | Year: 2010

This paper addresses the robust admissibility/H2 performance analysis for continuous-time uncertain parameter-dependent descriptor systems. In order to achieve less conservative results, the proposed approach uses parameter-dependent Lyapunov functions and slack variables. Our main contribution consists in proposing new necessary and sufficient conditions for the admissibility and H2 performance analysis of time-invariant singular systems. These conditions are formulated as a strict linear matrix inequality (LMI) solvability problem and represent a generalization to singular systems of some dilated LMI analysis results developed in the literature for state-space systems. Also, we have extended our results to the analysis of descriptor systems with time-varying parametric uncertainties. A numerical example shows the applicability of our approach. © 2010 AACC.

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.

Lipsker D.,University of Strasbourg
Orphanet Journal of Rare Diseases | Year: 2010

The Schnitzler syndrome is a rare and underdiagnosed entity which is considered today as being a paradigm of an acquired/late onset auto-inflammatory disease. It associates a chronic urticarial skin rash, corresponding from the clinico-pathological viewpoint to a neutrophilic urticarial dermatosis, a monoclonal IgM component and at least 2 of the following signs: fever, joint and/or bone pain, enlarged lymph nodes, spleen and/or liver, increased ESR, increased neutrophil count, abnormal bone imaging findings. It is a chronic disease with only one known case of spontaneous remission. Except of the severe alteration of quality of life related mainly to the rash, fever and pain, complications include severe inflammatory anemia and AA amyloidosis. About 20% of patients will develop a lymphoproliferative disorder, mainly Waldenström disease and lymphoma, a percentage close to other patients with IgM MGUS. It was exceedingly difficult to treat patients with this syndrome until the IL-1 receptor antagonist anakinra became available. Anakinra allows a complete control of all signs within hours after the first injection, but patients need continuous treatment with daily injections. In many aspects, the Schnitzler syndrome resembles the genetically determined auto-inflammatory syndromes involving activating mutations of the NLRP3 inflammasome. This latter point and its consequences will be addressed. © 2010 Lipsker; licensee BioMed Central Ltd.

Petri J.,University of Strasbourg
Monthly Notices of the Royal Astronomical Society | Year: 2014

Pulsars are believed to lose their rotational kinetic energy primarily by a large-amplitude low-frequency electromagnetic wave which is eventually converted into particle creation, acceleration and followed by a broad-band radiation spectrum. To date, there exist no detailed calculation of the exact spin-down luminosity with respect to the neutron star magnetic moment and spin frequency, including general-relativistic effects. Estimates are usually given according to the flat space-time magnetodipole formula. This paper pursues our effort to look for accurate solutions of the general-relativistic electromagnetic field around a slowly rotating magnetized neutron star. In a previous work, we already found approximate stationary solutions to this problem. Here, we address again this problem but using a more general approach. We indeed solve the full set of time-dependent Maxwell equations in a curved vacuum space-time following the 3+1 formalism. The numerical code is based on our pseudo-spectral method exposed in a previous paper for flat space-time. We adapted it to an arbitrary fixed background metric. Stationary solutions are readily obtained and compared to semi-analytical calculations. © 2014 The Author Published by Oxford University Press on behalf of the Royal Astronomical Society.

Barrot M.,CNRS Pascal Institute | Barrot M.,University of Strasbourg
Trends in Neurosciences | Year: 2015

Recently, Kaufling and Aston-Jones showed that, under protracted opiate withdrawal, control of dopamine activity by the tail of the ventral tegmental area shifts from a bidirectional influence towards one-way inhibition. Beyond dysphoric states accompanying withdrawal, these results may also impact research on depression and individual differences in coping and affect. © 2015 Elsevier Ltd.

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.

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.

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.

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.

Mazet V.,University of Strasbourg
IEEE Signal Processing Letters | Year: 2011

This letter addresses the problem of decomposing a sequence of spectroscopic signals: data are a series of (energy or electromagnetic) spectra and we aim to estimate the peak parameters (centers, amplitudes, and widths). The key idea is to perform the decomposition of the whole sequence and to impose the parameters to evolve smoothly through the sequence. The problem is set within a Bayesian framework whose posterior distribution is sampled using a Markov chain Monte Carlo simulated annealing algorithm. Simulations conducted on synthetic data illustrate the performance of the method. © 2011 IEEE.

Meyer E.H.,University of Strasbourg
Frontiers in Plant Science | Year: 2012

Complex I is present in almost all aerobic species. Being the largest complex of the respiratory chain, it has a central role in energizing biological membranes and is essential for many organisms. Bacterial complex I is composed of 14 subunits that are sufficient to achieve the respiratory functions. Eukaryotic enzymes contain orthologs of the 14 bacterial subunits and around 30 additional subunits. This complexity suggests either that complex I requires more stabilizing subunits in mitochondria or that it fulfills additional functions. In many organisms recent work on complex I concentrated on the determination of its exact composition. This review summarizes the work done to elucidate complex I composition in the model plant Arabidopsis and proposes a model for the organization of its 44 confirmed subunits. The comparison of the different studies investigating the composition of complex I across species identifies sample preparation for the proteomic analysis as critical to differentiate between true subunits, assembly factors, or proteins associated with complex I. Coupling comparative proteomics with biochemical or genetic studies is thus required to define a subunit and its function within the complex. © 2012 Meyer.

Amstutz S.,University of Strasbourg
Structural and Multidisciplinary Optimization | Year: 2011

Material interpolation schemes, like SIMP, are very popular in topology optimization. They convert the difficult 0-1 problem into a nonlinear programming problem defined over a convex set by involving an interpolation (or penalization) function, usually constructed in rather empirical ways. This paper gives an insight into such methods with the help of the notion of topological sensitivity, and in particular provides some arguments for the choice of the penalization function. A simple algorithm based on these concepts is proposed and illustrated by numerical experiments. © 2010 Springer-Verlag.

Bara G.I.,University of Strasbourg
Systems and Control Letters | Year: 2011

In this paper, we address the robust admissibility analysis and control of descriptor systems with parameter-dependent, possibly time-varying, uncertainties. First, we propose a new necessary and sufficient condition for the admissibility of linear time-invariant (LTI) descriptor systems. This condition uses a strict linear matrix inequality (LMI) formulation and involves two additional matrix variables usually called slack variables. Then, we present an extension of this condition to robust admissibility of time-varying parameter-dependent descriptor systems. Using parameter-dependent Lyapunov functions and employing two slack variables, this extension states robust admissibility LMI conditions that are less restrictive, as supported by our numerical examples, than the existing ones. Our robust admissibility analysis result, which can be directly used for state estimation, cannot be so for state-feedback control design. This is due to the absence of duality between state estimation and state-feedback control in the case of parameter-dependent systems with uncertain parameters as recently reported in the literature. In order to overcome this problem, we also present in this paper a new robust admissibility analysis result, involving only one slack variable, which we apply to state-feedback control design. © 2011 Elsevier B.V. All rights reserved.

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.

Nelson D.,University of Tennessee Health Science Center | Werck-Reichhart D.,University of Strasbourg
Plant Journal | Year: 2011

Being by far the largest family of enzymes to support plant metabolism, the cytochrome P450s (CYPs) constitute an excellent reporter of metabolism architecture and evolution. The huge superfamily of CYPs found in angiosperms is built on the successful evolution of 11 ancestral genes, with very different fates and progenies. Essential functions in the production of structural components (membrane sterols), light harvesting (carotenoids) or hormone biosynthesis kept some of them under purifying selection, limiting duplication and sub/neofunctionalization. One group (the CYP71 clan) after an early trigger to diversification, has kept growing, producing bursts of gene duplications at an accelerated rate. The CYP71 clan now represents more than half of all CYPs in higher plants. Such bursts of gene duplication are likely to contribute to adaptation to specific niches and to speciation. They also occur, although with lower frequency, in gene families under purifying selection. The CYP complement (CYPomes) of rice and the model grass weed Brachypodium distachyon have been compared to view evolution in a narrower time window. The results show that evolution of new functions in plant metabolism is a very long-term process. Comparative analysis of the plant CYPomes provides information on the successive steps required for the evolution of land plants, and points to several cases of convergent evolution in plant metabolism. It constitutes a very useful tool for spotting essential functions in plant metabolism and to guide investigations on gene function. © The Plant Journal © 2011 Blackwell Publishing Ltd.

Bara G.I.,University of Strasbourg
International Journal of Control | Year: 2011

This article addresses the admissibility analysis and state-feedback control synthesis problems of discrete-time polytopic descriptor systems with possibly time-varying parameters. First, we present a new necessary and sufficient strict linear matrix inequality (LMI) condition for the admissibility analysis of linear time-invariant (LTI) descriptor systems. Then, based on the concept of poly-quadratic admissibility, introduced in this article, we extend this result to the admissibility analysis of possibly time-varying parameter-dependent descriptor systems. This extension, which applies to both uncertain and measurable parameters, uses parameter-dependent Lyapunov functions and employs two slack variables. The extended conditions are also expressed as strict LMI conditions which are easily tractable numerically compared to the non-strict ones often encountered when dealing with descriptor systems. Note that we have proposed two separate admissibility analysis conditions: one directly exploitable for state estimation and the other for state-feedback control. The need for different admissibility analysis conditions for each synthesis problem is motivated by the fact that the duality between state estimation and state-feedback control, which hold in the case of measurable parameters, does not hold when dealing with uncertain ones. In our approach, we overcome the absence of such duality by considering a dilation only on the dynamical part of the descriptor system. The application of our analysis result to both robust state-feedback control and polytopic state-feedback control are also presented in this article. Our analysis results extend to descriptor systems, some existing results developed for regular systems. © 2011 Taylor & Francis.

Marsault C.,University of Strasbourg
Movement and Sports Sciences - Science et Motricite | Year: 2015

This review shows that the link between health and physical education in schools (PE) is build differently. In accordance with epistemological point of view, there is three different ways. Indeed, some work consider them as separate entities which are necessary articulate to produce effects. Other sees the health, by observing a diversity of individual practices. Actually, the relationship between health and PE becomes a pretext to question the systems of community values. How the link is built in objects of study gives health as PE, specific roles: policy instrument, place of observation or test of value. This transformation impacts scientific, but also political and educational views. © ACAPS, EDP Sciences, 2014.

Gabriel E.,University of Strasbourg | Rowlingson B.,Lancaster University | Diggle P.J.,Lancaster University
Journal of Statistical Software | Year: 2013

stpp is an R package for analyzing, simulating and displaying space-time point patterns. It covers many of the models encountered in applications of point process methods to the study of spatio-temporal phenomena. The package also includes estimators of the space-time inhomogeneous K-function and pair correlation function. stpp is the first dedicated unified computational environment in the area of spatio-temporal point processes. In this paper we describe space-time point processes and introduce the package stpp to new users.

Georgel P.,University of Strasbourg
Human Immunology | Year: 2016

The discovery of Pattern Recognition Receptors (PRRs) followed by that of their role in the early detection of pathogens and the ignition of the innate immune response has been a formidable progress for immunological research in the past 15. years. This has massively fueled investigations aiming at developing better strategies to fight off infectious diseases and/or to prevent their occurrence. However, infected individuals are for most part outliers in a given population and therefore, the primary function of these receptors should be considered in pathogen-free conditions. Our current understanding indicates that an important physiological function of PRRs resides in their capacity to maintain epithelial homeostasis in response to colonizing commensals. In addition, endogenous host-derived ligands, expressed under stressed, albeit sterile, conditions (called DAMPs for Danger-Associated Molecular Patterns) are also able to trigger PRR signaling. Solid organ transplantation represents a unique situation where both contributions of PRRs signaling can be studied. Indeed, dysbiosis (either caused by antibiotherapy preceding organ transplantation or simply due to the microbiota differences between the transplanted organ and the recipient host) is a characteristic feature of this situation, which is also marked by a massive synthesis and liberation of DAMPs as a result of hypoxia/reperfusion injury. Therefore, in the transplanted organ, at least two compartments (epithelial and that composed of immune cells) participate in graft rejection/acceptance depending on the activation status of expressed PRRs. © 2016 American Society for Histocompatibility and Immunogenetics.

Schlur L.,CNRS Institute of Genetics and of Molecular and Cellular Biology | Carton A.,CNRS Institute of Genetics and of Molecular and Cellular Biology | Leveque P.,University of Strasbourg | Guillon D.,CNRS Institute of Genetics and of Molecular and Cellular Biology | Pourroy G.,CNRS Institute of Genetics and of Molecular and Cellular Biology
Journal of Physical Chemistry C | Year: 2013

We report on the growth control of zinc oxide nanorods to point out the effect of the ZnO nanorods quality on the power conversion efficiency (PCE) of transparent conductive oxide (TCO)/ZnO nanorods/dye/spiro-OMeTAD/metal electrode photovoltaic devices. A promising PCE of 0.61% was measured for the best nanorods growth conditions. A careful control of all the growth parameters during the seeds layer deposition and the hydrothermal synthesis was necessary to reach such a high PCE for this kind of device. A regular nanorod layer with a flat upper surface was obtained for ethylenediamine to zinc acetate dihydrate molar ratio equal to 1.74 and a pH of 8.2. The growth was performed at 65 C for 2 h to avoid zinc oxide brushes deposition on the surface, arising from zinc hydroxyacetate decomposition during the hydrothermal treatment. The effect of ZnO nanorods length (ranging from 1 to 3 μm) on solar cell efficiency was tested. Although the UV-vis absorption increases when the nanorods length increases, the best photovoltaic parameters were measured for the shortest nanorods length studied (1 μm). © 2013 American Chemical Society.

Wong T.-F.,State University of New York at Stony Brook | Baud P.,University of Strasbourg
Journal of Structural Geology | Year: 2012

Many of the earliest laboratory studies of the brittle-ductile transition were on porous rocks, with a focus on the evolution of failure mode from brittle faulting to cataclastic flow with increasing pressure. Recent advances in this area are reviewed. Porosity has been demonstrated to exert critical control on the brittle-ductile transition, and its phenomenology has two common attributes. Under low confinement, brittle faulting develops as a dilatant failure mode. Under high confinement, delocalized cataclasis is accompanied by shear-enhanced compaction and strain hardening. Plasticity models such as the cap and critical state models have been developed to describe such constitutive behaviors, and many aspects of the laboratory data on porous rock have been shown to be in basic agreement. Bifurcation analysis can be used in conjunction with a constitutive model to predict the onset of strain localization, which is in qualitative agreement with the laboratory data. However, recent studies have also underscored certain complexities in the inelastic behavior and failure mode. In some porous sandstones, compaction bands would develop as a localized failure mode intermediate between the end members of brittle faulting and cataclastic flow. In limestones (and selected sandstones) under relatively high confinement, cataclastic flow is accompanied first by shear-enhanced compaction which then evolves to dilatancy. Various techniques have been employed to characterize the microstructure and damage, which have elucidated the deformation mechanisms associated with the brittle-ductile transition. These observations have revealed a diversity of micromechanical processes, and fundamental differences were observed especially between sandstone and limestone with regard to inelastic compaction. Micromechanical models that have been formulated to describe these processes include the pore-emanated and sliding wing crack models in the brittle faulting regime, and the Hertzian fracture and cataclastic pore collapse models in the cataclastic flow regime. Numerical techniques based on the discrete element method have also been employed to simulate these processes. Comparison of the model predictions with laboratory and microstructural observations has provided useful insights into the mechanics of brittle-ductile transition in porous rock. © 2012 Elsevier Ltd.

Ball V.,French Institute of Health and Medical Research | Ball V.,University of Strasbourg
Materials | Year: 2012

Polyelectrolyte multilayer films are a versatile functionalization method of surfaces and rely on the alternated adsorption of oppositely charged species. Among such species, charged dyes can also be alternated with oppositely charged polymers, which is challenging from a fundamental point of view, because polyelectrolytes require a minimal number of charges, whereas even monovalent dyes can be incorporated during the alternated adsorption process. We will not only focus on organic dyes but also on their inorganic counterparts and on metal complexes. Such films offer plenty of possible applications in dye sensitized solar cells. In addition, dyes are massively used in the textile industry and in histology to stain textile fibers or tissues. However, the excess of non bound dyes poses serious environmental problems. It is hence of the highest interest to design materials able to adsorb such dyes in an almost irreversible manner. Polyelectrolyte multilayer films, owing to their ion exchange behavior can be useful for such a task allowing for impressive overconcentration of dyes with respect to the dye in solution. The actual state of knowledge of the interactions between charged dyes and adsorbed polyelectrolytes is the focus of this review article. © 2012 by the authors.

Drosophila melanogaster is a robust model to investigate many biological problems. It is however prone to some infections, which may endanger fly stocks if left unchecked for. One such infection is caused by an obligate fungal intracellular parasite, Tubulinosema ratisbonensis, which can be found in laboratory stocks. Here, we identify and briefly characterize a T. ratisbonensis strain that was infesting our Drosophila cultures and that required intensive measures to contain and eradicate the infection. We describe the phenotypes of infested stocks. We also report PCR-based techniques that allow the detection of infested stocks with a high sensitivity. We have developed a high-throughput qPCR assay that allows the efficient parallel screening of a large number of potentially-infested stocks. We also have investigated several prophylactic measures to prevent the further contamination of stocks, namely UV-exposure, ethanol treatment, bleaching, and desiccation. Bleaching was found to kill all spores. Other treatments were less effective but were found to be sufficient to prevent further contamination of noninfested stocks. Two treatments were efficacious in curing infested stocks (1) bleaching of eggs and subsequent raising of the larvae in clean vials; (2) fumagillin treatment. These cures only work on stocks that have not become too weak to withstand the procedures.

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.

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.

Rivera C.,University of Bordeaux 1 | Falcoz P.-E.,University of Strasbourg | Bernard A.,University of Burgundy | Thomas P.A.,Aix - Marseille University | Dahan M.,Toulouse 1 University Capitole
Chest | Year: 2011

Background: The number of oncogeriatric patients with non-small cell lung cancer (NSCLC) is expected to increase in the next decades. Methods: We used the French Society of Thoracic and Cardiovascular Surgery database Epithor that includes information on > 140,000 procedures from 98 institutions. We prospectively collected data from January 2004 to December 2008 on 1,969 patients aged ≥ 70 years with NSCLC stage I or II and matched them with 1,969 control subjects aged < 70 years for sex, American Society of Anesthesia score, performance status, and FEV 1. Surgical treatment and postoperative outcomes were compared between the two age groups. Results: The absence of radical lymphadenectomy was more frequent in the older patients (14%, n = 269) than in the younger patients (9%, n = 170) (P < .0001). There was no significant difference in type of resection between older and younger patients, respectively (pneumonectomy, 8% [n = 164] vs 11% [n = 216]; lobectomy, 79% [n = 1,559] vs 77% [n = 1,521]; bilobectomy, 4% [n = 88] vs 5% [n = 97]; sublobar resection, 7% [n = 143] vs 6% [n = 118]; P = .08). Differences in number (P = .07) and severity (P = .69) of complications were not significant. Postoperative mortality was higher in elderly patients at every end point (30-day mortality, 3.6% [n = 70] vs 2.2% [n = 43] [P = .01]; 60-day mortality, 4.1% [n = 80] vs 2.4% [n = 47] [P = .003]; 90-day mortality, 4.7% [n = 93] vs 2.5% [n = 50] [P = .0002]). Conclusions: Elderly patients with NSCLC should not be denied pulmonary resection on the basis of chronologic age alone. Among patients aged ≥ 70 years, 90-day mortality compared acceptably with mortality among younger matched patients. Additionally, the data show that for older patients, a 90-day mortality better represents their real mortality risk than 30- or 60-day figures. Our contemporary, multiinstitutional data importantly reveal that elderly patients, compared with their younger counterparts, do not have increased morbidity, incidence, or severity after pulmonary resection. © 2011 American College of Chest Physicians.

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.

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.

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.

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.

Dufour M.,University of Strasbourg | Descouvemont P.,Free University of Colombia
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2011

We investigate the 16B spectrum within a microscopic 15B + n model, involving several channels. The wave functions are defined in the Generator Coordinate Method, associated with the microscopic R-matrix formalism. We suggest that the narrow peak observed in recent experiments above the 15B + n threshold can be assigned to a 0- resonance which decays by d-wave neutron emission. The GCM calculation shows that this state cannot be reproduced in a single-channel B15(3/2-)+n model, and that excited configurations are necessary. Other 1- and 2- s-wave resonances are found at low excitation energies. In particular, we find a 1- state which represents a possible candidate for the 16B ground state. In general, our results show the importance of a multichannel framework. Comparisons with shell-model calculations are briefly discussed. © 2010 Elsevier B.V.

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.

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.

Stipska P.,University of Strasbourg | Powell R.,University of Melbourne | White R.W.,University of Mainz | Baldwin J.A.,University of Montana
Journal of Metamorphic Geology | Year: 2010

Corona textures around kyanite, involving for example zoned plagioclase separating kyanite from the matrix, reflect the instability of kyanite with the matrix on changing P-T conditions, commonly related to decompression. The chemical potential gradients set up between the kyanite and the matrix as a consequence of slow Al diffusion drive corona development, with the zoning of the plagioclase reflecting the gradients. Calculated mineral equilibria are used to account for corona textures involving plagioclase ± garnet around kyanite, and replacement of kyanite by plagioclase + spinel symplectite, in quartz + plagioclase + K-feldspar + garnet + kyanite granulite facies gneiss from the Blanský les massif in the Bohemian massif, Czech Republic. In the garnet-bearing coronas, a commonly discontinuous garnet layer lies between the kyanite and the continuous plagioclase layer in the corona, with both the garnet and the plagioclase appearing mainly to replace matrix rather than kyanite. The garnet layer commonly extends around kyanite from original matrix garnet adjacent to the kyanite. Where garnet is missing in the corona, the kyanite itself may be replaced by a spinel. -plagioclase corona. In a local equilibrium model, the mineral and mineral compositional spatial relationships are shown to correspond to paths in μ(Na2O)-μ(CaO)-μ(K2O)-μ(FeO)-μ(MgO)-μ(SiO2) in the model chemical system, Na2O-CaO-K2O-FeO-MgO-Al2O3-SiO2 (NCKFMAS). The discontinuous nature of the garnet layer in coronas is accounted for by the effect of the adjacent original garnet on the chemical potential relationships. The replacement of kyanite by spinel + plagioclase appears to be metastable with respect to replacement by corundum + plagioclase, possibly reflecting the difficulty of nucleating corundum. © 2009 Blackwell Publishing Ltd.

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.

Capa R.L.,University of Liege | 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.

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

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).

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.

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.

Otsu Y.,French Institute of Health and Medical Research | Otsu Y.,University of Paris Descartes | Couchman K.,French Institute of Health and Medical Research | Couchman K.,University of Paris Descartes | And 11 more authors.
Nature Neuroscience | Year: 2015

Enhanced neuronal activity in the brain triggers a local increase in blood flow, termed functional hyperemia, via several mechanisms, including calcium (Ca 2+) signaling in astrocytes. However, recent in vivo studies have questioned the role of astrocytes in functional hyperemia because of the slow and sparse dynamics of their somatic Ca 2+ signals and the absence of glutamate metabotropic receptor 5 in adults. Here, we reexamined their role in neurovascular coupling by selectively expressing a genetically encoded Ca 2+ sensor in astrocytes of the olfactory bulb. We show that in anesthetized mice, the physiological activation of olfactory sensory neuron (OSN) terminals reliably triggers Ca 2+ increases in astrocyte processes but not in somata. These Ca 2+ increases systematically precede the onset of functional hyperemia by 1-2 s, reestablishing astrocytes as potential regulators of neurovascular coupling. © 2015 Nature America, Inc. All rights reserved.

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.

Walsh I.,University of Strasbourg | Kefi H.,University of Paris Descartes | Baskerville R.,Georgia State University
Journal of Strategic Information Systems | Year: 2010

This article describes a framework of IT user culture that has implications for organizational IT strategy. The research was conducted in multiple settings with a grounded theory approach. The resulting framework is anchored to nine archetypal IT user profiles and encompasses their inter-group dynamics. By adopting a cultural perspective on IT usage, the framework can inform IT adoption and usage strategy with possible cultural antecedents and determinants of usage constructs common in IS research. The proposed framework suggests how management can influence the migration of IT user culture (culture creep). This framework can also enrich other acceptance models in order to more fully consider the human factor during IT implementation and adoption. The results underscore the importance of culture-customizing organizational IT socialization, training and evolution programs. © 2010 Elsevier B.V. All rights reserved.

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.

During the period 1995-1996, 200 specimens of Collembola have been collected in the Bou Hedma National Park, in southern Tunisia, with the aim of studying the influence of mammalian herbivores plant overgrazing on the development of soil mesofauna. They belong to four diff erent species, all of the genus Seira Lubbock, 1869: S. uwei n. sp., S. deserti Jacquemart, 1974, S. dagamae Dallai, 1973 and S. ferrarii Parona, 1888. Seira deserti is a Tunisian species, described from a single specimen. The new description completes the characteristics given in the original description. This species is closely related to S. jacquemarti Barra, 2004 from the mainland Yemen. Seira dagamae, from the Eolic Islands (Italy), is here recorded for the first time outside its region of origin. The Tunisian specimens of Seira ferrarii present the same characteristics as specimens from Italy; the pigmentation corresponds to the pale form. Seira uwei n. sp. is a species of large size and variable pigmentation. The species shows clear sexual dimorphism, the males having developed pointed setae on the femorae and tibiotarsi of the front legs. This character has also been observed on S. polysperes Barra, 2004 from Yemen. © Publications Scientifi ques du Muséum national d'Histoire naturelle, Paris.

The predatory katydids of Mauritius, Rodrigues, and Réunion islands are examined. One new Hexacentrinae genus and species, and three new Phisidini species (Meconematinae) are described from Mauritius: Nepheliphila raptor n. g. n. sp., Brachyphisis nattecantor n. sp., Paradecolya expectata n. sp. and Paradecolya briseferi n. sp. The only Phisidini from Rodrigues Brachyphisis spinifera (Butler, 1876) is transferred to Rodriguesiophisis n. gen., n. comb. and the male is described for the first time. Descriptions of the two Phisidini from La Réunion Brachyphisis viettei Chopard, 1957 and Paradecolya inexpectata (Chopard, 1957) are given. The male of B. viettei is described for the first time. The song of all these species but P. briseferi n. sp. is described for the first time. In addition to these endemic species, the widespread Xiphidiopsis lita Hebard, 1922 occurs on all three Mascarene islands. Copyright © 2010 Magnolia Press.

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.

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.

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.

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.

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.

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.

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.

Ostrosi E.,University of Technology of Belfort - Montbeliard | 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.

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.

In 1996, the Wickens and the Kuhl labs developed the yeast three-hybrid system independently. By expressing two chimeric proteins and one chimeric RNA molecule in Saccharomyces cerevisiae, this method allows in vivo monitoring of RNA-protein interactions by measuring the expression levels of HIS3 and LacZ reporter genes. Specific RNA targets have been used to characterize unknown RNA binding proteins. Previously described RNA binding proteins have also been used as bait to select new RNA targets. Finally, this method has been widely used to investigate or confirm previously suspected RNA-protein interactions. However, this method falls short in some aspects, such as RNA display and selection of false positive molecules. This review will summarize the results obtained with this method from the past 15. years, as well as on recent efforts to improve its specificity. © 2012 Elsevier Inc.

Mathauer I.,World Health Organization | Nicolle E.,University of Strasbourg
Health Policy | Year: 2011

Objectives: Administrative costs are an important spending category in total health insurance expenditure. Yet, they have rarely been a topic outside the US and there is no cross-country comparison available. This paper provides a global overview and analysis of administrative costs for social security schemes (SSS) and private health insurance schemes (PHI). Methods: The analysis is based on data of the World Health Organization (WHO) National Health Accounts (NHA) and the Organisation for Economic Cooperation and Development (OECD) System of Health Accounts (SHA). These are the only worldwide databases on health expenditure data. Further data was retrieved from a literature search. Administrative costs are presented as a share of total health insurance costs. Results: Data is available for 58 countries. In high-income OECD countries, the average SSS administrative costs are 4.2%. Average PHI administrative costs are about three times higher. The shares are much higher for low- and middle-income countries. However, considerable variations across and within countries over time are revealed. Discussion and conclusion: Seven explanatory factors are explored to explain the variations: health financing system aspects, administrative activities undertaken, insurance design aspects, context factors, reporting format, accounting methods, and management and administrative efficiency measures. More detailed reporting of administrative costs would enhance comparability and provide benchmarks. Improved administrative efficiency could free resources to expand coverage. © 2011 Elsevier Ireland 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.

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.

Petri J.,University of Strasbourg
Monthly Notices of the Royal Astronomical Society | Year: 2016

Pulsar magnetospheres are shaped by ultrarelativistic electron/positron plasmas flowing in a strong magnetic field and subject to strong gravitational fields. The former induces magnetospheric currents and space charges responsible for the distortion of the electromagnetic field based on pure electrodynamics. The latter induces other perturbations in these fields based on space-time curvature. The force-free approximation describes the response of this magnetosphere to the presence of currents and charges and has been investigated by many authors. In this context, general relativity has been less discussed to quantify its influence on the neutron star electrodynamics. It is the purpose of this paper to compute general-relativistic force-free pulsar magnetospheres for realistic magnetic field configurations such as the inclined dipole. We performed time-dependent simulations of Maxwell equations in the 3+1 formalism of a stationary background metric in the slow-rotation approximation. We computed the resulting Poynting flux depending on the ratio R/rL and on frame-dragging through the spin parameter as, R is the neutron star radius and rL the light-cylinder radius. Both effects act together to increase the total Poynting flux seen by a distant observer by a factor up to 2 depending on the rotation rate. Moreover we retrieve the sin 2χ dependence of this luminosity, χ being the obliquity of the pulsar, as well as a braking index close to n = 3. We also show that the angular dependence of the Poynting flux scales like sin 2θ for the aligned rotator but like sin 4θ for the orthogonal rotator, θ being the colatitude. © 2015 The Authors.

Rao F.,University of Strasbourg
Journal of Physical Chemistry Letters | Year: 2010

The relationship between local atomic fluctuations and global protein rearrangements is elusive. Here, molecular dynamics simulations of a peptide concerted with complex network analysis show that local transition gradients provide a quantitative description of the free-energy landscape in terms of its valleys. The latter, compared with established methods, are found with the correct populations. Moreover, the iterative analysis of the fastest intervalley relaxations provides an intuitive tree-like representation of the system dynamics. These results indicate that knowledge of the fast local relaxations is sufficient to identify the general properties of free-energy surfaces in terms of basins of attraction and the hierarchy of transitions. © 2010 American Chemical Society.

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.

The tail behavior of a survival function is controlled by the extreme value index. The aim of this paper is to propose a general procedure for the estimation of this parameter in the case where the observations are not necessarily distributed from the same distribution. The idea is to estimate in a consistent way the survival function and to apply a general functional to obtain a consistent estimator for the extreme value index. This procedure permits to deal with a large set of models such as conditional extremes and heteroscedastic extremes. The consistency of the obtained estimator is established under general conditions. A simulation study and a concrete application on financial data are proposed to illustrate the finite sample behavior of the proposed procedure. © 2015, Springer Science+Business Media New York.

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.

Zhu Y.,Fudan University | Dong A.,Fudan University | Shen W.-H.,University of Strasbourg
Biochimica et Biophysica Acta - Gene Regulatory Mechanisms | Year: 2012

Genome organization into nucleosomes and higher-order chromatin structures has profound implications for the regulation of gene expression, DNA replication and repair. The structure of chromatin can be remodeled by several mechanisms; among others, nucleosome assembly/disassembly and replacement of canonical histones with histone variants constitute important ones. In this review, we provide a brief description on the current knowledge about histone chaperones involved in nucleosome assembly/disassembly and histone variants in Arabidopsis thaliana. We discuss recent advances in revealing crucial functions of histone chaperones, nucleosome assembly/disassembly and histone variants in plant response to abiotic stresses. It appears that chromatin structure remodeling may provide a flexible, global and stable means for the regulation of gene transcription to help plants more effectively cope with environmental stresses. This article is part of a Special Issue entitled: Histone chaperones and chromatin assembly. © 2011 Elsevier B.V.

Belostotsky R.,Shaare Zedek Medical Center | Frishberg Y.,Shaare Zedek Medical Center | Frishberg Y.,Hebrew University of Jerusalem | Entelis N.,University of Strasbourg
RNA Biology | Year: 2012

Mutations in human mitochondrial tRNA genes are associated with a number of multisystemic disorders. These single nucleotide substitutions in various domains of tRNA molecules may affect different steps of tRNA biogenesis. Often, the prominent decrease of aminoacylation and/or steady-state levels of affected mitochondrial tRNA have been demonstrated in patients' tissues and in cultured cells. Similar effect has been observed for pathogenic mutations in nuclear genes encoding mitochondrial aminoacyl-tRNA-synthetases, while over-expression of mitochondrial aminoacyl-tRNA synthetases or elongation factor EF-Tu rescued mutated tRNAs from degradation. In this review we summarize experimental data concerning the possible regulatory mechanisms governing mitochondrial tRNA steady-state levels, and propose a hypothesis based on the tRNA channelling principle. According to this hypothesis, interaction of mitochondrial tRNA with proteins ensures not only tRNA synthesis, maturation and function, but also protection from degradation. Mutations perturbing this interaction lead to decreased tRNA stability. © 2012 Landes Bioscience.

Ovchinnikov V.,Harvard University | Karplus M.,Harvard University | Karplus M.,University of Strasbourg
Journal of Physical Chemistry B | Year: 2012

The popular targeted molecular dynamics (TMD) method for generating transition paths in complex biomolecular systems is revisited. In a typical TMD transition path, the large-scale changes occur early and the small-scale changes tend to occur later. As a result, the order of events in the computed paths depends on the direction in which the simulations are performed. To identify the origin of this bias, and to propose a method in which the bias is absent, variants of TMD in the restraint formulation are introduced and applied to the complex open ↔ closed transition in the protein calmodulin. Due to the global best-fit rotation that is typically part of the TMD method, the simulated system is guided implicitly along the lowest-frequency normal modes, until the large spatial scales associated with these modes are near the target conformation. The remaining portion of the transition is described progressively by higher-frequency modes, which correspond to smaller-scale rearrangements. A straightforward modification of TMD that avoids the global best-fit rotation is the locally restrained TMD (LRTMD) method, in which the biasing potential is constructed from a number of TMD potentials, each acting on a small connected portion of the protein sequence. With a uniform distribution of these elements, transition paths that lack the length-scale bias are obtained. Trajectories generated by steered MD in dihedral angle space (DSMD), a method that avoids best-fit rotations altogether, also lack the length-scale bias. To examine the importance of the paths generated by TMD, LRTMD, and DSMD in the actual transition, we use the finite-temperature string method to compute the free energy profile associated with a transition tube around a path generated by each algorithm. The free energy barriers associated with the paths are comparable, suggesting that transitions can occur along each route with similar probabilities. This result indicates that a broad ensemble of paths needs to be calculated to obtain a full description of conformational changes in biomolecules. The breadth of the contributing ensemble suggests that energetic barriers for conformational transitions in proteins are offset by entropic contributions that arise from a large number of possible paths. © 2012 American Chemical Society.

Grandadam D.,HEC Montreal | Cohendet P.,University of Strasbourg | Simon L.,HEC Montreal
Regional Studies | Year: 2013

Places, spaces and the dynamics of creativity: the video game industry in Montreal, Regional Studies. The aim of this paper is to understand better the dynamics of situated creativity by reconsidering the formation of externalities in cities. What is suggested is that these externalities are not due to the proximity between institutions of the 'upperground' or between individuals of the 'underground', but rather they emerge from the articulation between places and spaces, which both contribute to fertilize a so-called 'middleground'. The case of the video game cluster in Montreal in Quebec, Canada, is analysed in order to illustrate this view. © 2013 Regional Studies Association.

Barnig C.,University of Strasbourg | Levy B.D.,Harvard University
European Respiratory Review | Year: 2015

The resolution of inflammation is an integral and natural part of the physiological response to tissue injury, infection and allergens or other noxious stimuli. Resolution is now recognised as an active process with highly regulated cellular and biochemical events. Recent discoveries have highlighted that innate inflammatory cells have bimodal effector functions during the inflammatory response, including active roles during the resolution process. Several mediators displaying potent pro-resolving actions have recently been uncovered. Lipoxin A4, the lead member of this new class of pro-resolving mediators, has anti-inflammatory actions on type 2 innate lymphoid cells and pro-resolving actions through natural killer cells in asthma immunobiology. Eosinophils are also able to control crucial aspects of resolution through the generation of pro-resolving mediators. Uncontrolled asthma has been associated with a defect in the generation of specialised pro-resolving mediators, including lipoxin A4 and protectin D1. Thus, bioactive stable analogue mimetics of these mediators that can harness endogenous resolution mechanisms for inflammation may offer new therapeutic strategies for asthma and airway inflammation associated diseases. ©ERS 2015.

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.

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.

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.

Hahn J.S.,750 Welch Road | Hanauer A.,University of Strasbourg
European Journal of Medical Genetics | Year: 2012

The Coffin-Lowry syndrome (CLS) is a rare but well-defined X-linked semidominant syndrome characterized by psychomotor and growth retardation, and progressive skeletal changes. CLS is caused by loss of function mutations in the Rps6ka3 gene encoding the ribosomal S6 kinase 2 (RSK2) protein. A distinctive paroxysmal disorder has been described in some CLS patients, characterized by episodes of sudden falling, without apparent alteration of consciousness, usually induced by unexpected tactile or auditory stimuli. Duration of episodes is very short, usually lasting a few seconds. The appellation " Stimulus-induced drop episodes" (SIDEs) was proposed for these non-epileptic events in CLS patients. SIDEs are clinically heterogeneous; with some patients exhibiting cataplexy-like events characterized by sudden hypotonia and collapse, and others hyperekplexia-like episodes with a startle response. The pathophysiology of SIDEs is not well understood. © 2012 Elsevier Masson SAS.

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.

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.

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.

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.

Ingenbleek Y.,University of Strasbourg
Open Clinical Chemistry Journal | Year: 2011

Vegetarian subjects consuming subnormal amounts of methionine (Met) are characterized by subclinical protein malnutrition causing reduction in size of their lean body mass (LBM) best identified by the serial measurement of plasma transthyretin (TTR). As a result, the transsulfuration pathway is depressed at cystathionine-β-synthase (CβS) level triggering the upstream sequestration of homocysteine (Hcy) in biological fluids and promoting its conversion to Met. Maintenance of beneficial Met homeostasis is counterpoised by the drop of cysteine (Cys) and glutathione (GSH) values downstream to CβS causing in turn declining generation of hydrogen sulfide (H2S) from enzymatic sources. The biogenesis of H2S via non-enzymatic reduction is further inhibited in areas where earth's crust is depleted in elemental sulfur (S8) and sulfate oxyanions. Combination of subclinical malnutrition and S8-deficiency thus maximizes the defective production of Cys, GSH and H2S reductants, explaining persistence of unabated oxidative burden. The clinical entity increases the risk of developing cardiovascular diseases (CVD) and stroke in underprivileged plant-eating populations regardless of Framingham criteria and vitamin-B status. Although unrecognized up to now, the nutritional disorder is one of the commonest worldwide, reaching top prevalence in populated regions of Southeastern Asia. Increased risk of hyperhomocysteinemia and oxidative stress may also affect individuals suffering from intestinal malabsorption or westernized communities having adopted vegan dietary lifestyles. © Yves Ingenbleek.

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.

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.

Dantzer F.,University of Strasbourg | Santoro R.,University of Zurich
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.

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.

Mendoza-Temis J.,National Autonomous University of Mexico | Hirsch J.G.,National Autonomous University of Mexico | Zuker A.P.,University of Strasbourg
Nuclear Physics A | Year: 2010

The simplest version of the Duflo-Zuker mass model (due entirely to the late Jean Duflo) is described by following step by step the published computer code. The model contains six macroscopic monopole terms leading asymptotically to a Liquid Drop form, three microscopic terms supposed to mock configuration mixing (multipole) corrections to the monopole shell effects, and one term in charge of detecting deformed nuclei and calculating their masses. A careful analysis of the model suggests a program of future developments that includes a complementary approach to masses based on an independently determined monopole Hamiltonian, a better description of deformations and specific suggestions for the treatment of three body forces. © 2010 Elsevier B.V.

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.

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 .

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.

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.

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.

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

Herlenius E.,Karolinska Institutet | Kuhn P.,Karolinska Institutet | Kuhn P.,University of Strasbourg
Translational Stroke Research | Year: 2013

This study aimed to review available published reports concerning sudden unexpected postnatal collapse (SUPC) of apparently healthy infants within the first days of postnatal life, establish a structured presentation and delineate recommendations for preventive measures. All published reports of SUPC cases were retrospectively analyzed, and three not previously published SUPC cases at Karolinska University Hospital were detailed to exemplify the varying presentations and outcomes of SUPC. We found 398 published cases of SUPC occurring during first postnatal week. Estimated incidence of the SUPC of a presumably healthy infant after birth differs widely, ranging from 2. 6 cases to 133 cases/100,000. However, definition, inclusion, and exclusion criteria vary substantially between reports. Our summary indicates that reported SUPC occurs more frequently than expected from recent surveys. About half of the infants die, and of the remaining survivors, half have neurological sequela. Of the 233 cases of sudden unexpected death described, no etiology was found in 153 cases. When a defined time for the SUPC event is described, approximately one third of reported events occur during the first 2 h, between 2 and 24 h and between 1 and 7 days after birth, respectively. Adequate education of caregivers and appropriate surveillance during the first days of newborns should enable us to save hundreds of lives. © 2013 The Author(s).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Albiges L.,Institute Gustave Roussy | Chamming's F.,Hopital Europeen Georges Pompidou | Duclos B.,University of Strasbourg | Motzer R.J.,Sloan Kettering Cancer Center | And 2 more authors.
Annals of Oncology | Year: 2012

The administration of mammalian target of rapamycin (mTOR) inhibitors can give rise to a potentially life-threatening adverse event, often referred to as 'non-infectious pneumonitis' (NIP), which is characterized by non-infectious, non-malignant, and non-specific inflammatory infiltrates. Patients usually present with cough and/or dyspnoea. We provide a brief description of the mechanism of action of mTOR inhibitors and their overall safety in patients with metastatic renal cell carcinoma (mRCC) and review the literature on mTOR inhibitor-associated NIP in patients with solid tumours. The review was used to derive questions on the diagnosis, management, and monitoring of mRCC patients with NIP, and to develop a decision tree for use in routine clinical practise. A key recommendation was the subdivision of grade 2 NIP into grades 2a and 2b, where grade 2a is closer to grade 1 and grade 2b to grade 3. This subdivision is important because it takes into account the nature and severity of clinical symptoms potentially related to NIP, either the onset of new symptoms or the worsening of existing symptoms, and thus determines the type and frequency of follow-up. It also helps to identify a subgroup of patients in whom treatment, if effective, may be continued without dose adjustment. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Li G.,Howard Hughes Medical Institute | Li G.,New York University | Margueron R.,New York University | Ku M.,Howard Hughes Medical Institute | And 8 more authors.
Genes and Development | Year: 2010

The Polycomb group proteins foster gene repression profiles required for proper development and unimpaired adulthood, and comprise the components of the Polycomb-Repressive Complex 2 (PRC2) including the histone H3 Lys 27 (H3K27) methyltransferase Ezh2. How mammalian PRC2 accesses chromatin is unclear. We found that Jarid2 associates with PRC2 and stimulates its enzymatic activity in vitro. Jarid2 contains a Jumonji C domain, but is devoid of detectable histone demethylase activity. Instead, its artificial recruitment to a promoter in vivo resulted in corecruitment of PRC2 with resultant increased levels of di- and trimethylation of H3K27 (H3K27me2/3). Jarid2 colocalizes with Ezh2 and MTF2, a homolog of Drosophila Pcl, at endogenous genes in embryonic stem (ES) cells. Jarid2 can bind DNA and its recruitment in ES cells is interdependent with that of PRC2, as Jarid2 knockdown reduced PRC2 at its target promoters, and ES cells devoid of the PRC2 component EED are deficient in Jarid2 promoter access. In addition to the well-documented defects in embryonic viability upon down-regulation of Jarid2, ES cell differentiation is impaired, as is Oct4 silencing. © 2010 by Cold Spring Harbor Laboratory.

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.

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.

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.

Nguyen-Van P.,University of Strasbourg
Energy Economics | Year: 2010

This paper proposes a semiparametric analysis for the study of the relationship between energy consumption per capita and income per capita for an international panel dataset. It shows little evidence for the existence of an environmental Kuznets curve for energy consumption. Energy consumption increases with income for a majority of countries and then stabilizes for very high income countries. Neither changes in energy structure nor macroeconomic cycle/technological change have significant effect on energy consumption. © 2009 Elsevier B.V.

Janicic P.,University of Belgrade | Narboux J.,University of Strasbourg | Quaresma P.,University of Coimbra
Journal of Automated Reasoning | Year: 2012

The area method for Euclidean constructive geometry was proposed by Chou, Gao and Zhang in the early 1990's. The method can efficiently prove many non-trivial geometry theorems and is one of the most interesting and most successful methods for automated theorem proving in geometry. The method produces proofs that are often very concise and human-readable. In this paper, we provide a first complete presentation of the method. We provide both algorithmic and implementation details that were omitted in the original presentations. We also give a variant of Chou, Gao and Zhang's axiom system. Based on this axiom system, we proved formally all the lemmas needed by the method and its soundness using the Coq proof assistant. To our knowledge, apart from the original implementation by the authors who first proposed the method, there are only three implementations more. Although the basic idea of the method is simple, implementing it is a very challenging task because of a number of details that has to be dealt with. With the description of the method given in this paper, implementing the method should be still complex, but a straightforward task. In the paper we describe all these implementations and also some of their applications. © Springer Science+Business Media B.V. 2010.

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.

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.

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.

Cribier B.,University of Strasbourg
Annales de Dermatologie et de Venereologie | Year: 2012

Several studies dealing with adherence of treatments for psoriasis have been published, using various methods, including questionnaires for self-reporting, interviews, counting/ weighting of unused medication and electronic measuring systems that record every cap unscrewing. Adherence to treatments is limited first by prescriptions not redeemed and then by under dosing in up to 95% of patients. The mean measured compliance is close to 50/60% and is lower than the self reported compliance in all studies. Adherence to topical treatment of psoriasis is limited by difficult self-application, greasy vehicle, number of applications, side effects or fear of side effects. Adherence decreases with time, although an increase in frequency of application is recorded before control visits. A better compliance increases the therapeutic effect. The motivation of dermatologists, the type and quality of the prescribed medicine and clear explanations are simple factors that contribute to increase adherence. © 2012 Elsevier Masson SAS. Tous droits réservés.

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.

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.

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.

Ziessel R.,University of Strasbourg | Harriman A.,Northumbria University
Chemical Communications | Year: 2011

Electronic energy transfer (EET) plays a critical role in many biological processes and is used by nature to direct energy to a site where chemical reactions need to be initiated. Such EET can occur over large distances and can involve many individual molecules of identical, similar or disparate chemical identity. Advances in spectroscopy and data processing have allowed the rates of EET to be measured on extremely fast timescales such that improved mechanistic insight becomes feasible. At the same time, highly sophisticated synthetic operations have been devised that facilitate the isolation and purification of elaborate multi-component molecular arrays. A key feature of these arrays concerns the logical positioning of individual units in a way that favours directed EET along the molecular axis or along some other preferred pathway. The availability of these novel molecular materials allows close examination of popular theoretical models and paves the way for the development of advanced molecular sensors, artificial light harvesters, fluorescent labels and sensitizers. Of particular interest is the spectacular growth in the application of boron dipyrromethene dyes as basic reagents in such artificial photon collectors and these compounds have dominated the market in recent years because of their synthetic versatility and valuable photophysical properties. In this article, recent developments in the field are highlighted in terms of synthesis and subsequent spectroscopic exploration. © The Royal Society of Chemistry 2011.

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.

Jacob A.,Walton Center for Neurology and Neurosurgery | McKeon A.,Rochester College | Nakashima I.,Tohoku University | Sato D.K.,Tohoku University | And 3 more authors.
Journal of Neurology, Neurosurgery and Psychiatry | Year: 2013

Neuromyelitis optica (NMO) has been described as a disease clinically characterised by severe optic neuritis (ON) and transverse myelitis (TM). Other features of NMO include female preponderance, longitudinally extensive spinal cord lesions (>3 vertebral segments), and absence of oligoclonal IgG bands . In spite of these differences from multiple sclerosis (MS), the relationship between NMO and MS has long been controversial. However, since the discovery of NMO-IgG or aquaporin-4 (AQP4) antibody (AQP4-antibody), an NMO-specific autoantibody to AQP4, the dominant water channel in the central nervous system densely expressed on end-feet of astrocytes, unique clinical features, MRI and other laboratory findings in NMO have been clarified further. AQP4-antibody is now the most important laboratory finding for the diagnosis of NMO. Apart from NMO, some patients with recurrent ON or recurrent longitudinally extensive myelitis alone are also often positive for AQP4-antibody. Moreover, studies of AQP4-antibody-positive patients have revealed that brain lesions are not uncommon in NMO, and some patterns appear to be unique to NMO. Thus, the spectrum of NMO is wider than mere ON and TM. Pathological analyses of autopsied cases strongly suggest that unlike MS, astrocytic damage is the primary pathology in NMO, and experimental studies confirm the pathogenicity of AQP4-antibody. Importantly, therapeutic outcomes of some immunological treatments are different between NMO and MS, making early differential diagnosis of these two disorders crucial. We provide an overview of the epidemiology, clinical and neuroimaging features, immunopathology and therapy of NMO and NMO spectrum disorders.

The authors compared the intraoperative navigated measurements of the location of the tibial and femoral tunnels during arthroscopic-assisted anterior cruciate ligament reconstruction to the postoperative measurements performed on standard plain radiographs in 56 patients. The position of the center of the tibial and femoral tunnels was measured intraoperatively with the OrthoPilot (B. Braun Aesculap, Tuttlingen, Germany) and postoperatively on plain anteroposterior and lateral radiographs. The center of the tibial tunnel was located at 43% of the mediolateral tibial dimension intraoperatively and at 41% of the mediolateral tibial dimension postoperatively (P=.14). The center of the tibial tunnel tibial was located at 40% of the anteroposterior tibial dimension intraoperatively and at 35% of the anteroposterior tibial dimension postoperatively (P=.01). The center of the femoral tunnel was located at 85% of the anteroposterior femoral dimension intraoperatively and at 76% of the anteroposterior femoral dimension postoperatively (P<.001). A significant correlation was found between intraoperative navigated and postoperative radiographic measurements only at the femur. Good agreement existed between all navigated and radiographic measurements. The OrthoPilot navigation system allows an accurate measurement of the location of the tibial and femoral tunnels during anterior cruciate ligament reconstruction. Copyright 2012, SLACK Incorporated.

Cirera B.,TU Munich | Zhang Y.-Q.,TU Munich | Bjork J.,Linkoping University | Klyatskaya S.,Karlsruhe Institute of Technology | And 5 more authors.
Nano Letters | Year: 2014

Surface-assisted covalent synthesis currently evolves into an important approach for the fabrication of functional nanostructures at interfaces. Here, we employ scanning tunneling microscopy to investigate the homocoupling reaction of linear, terminal alkyne-functionalized polyphenylene building-blocks on noble metal surfaces under ultrahigh vacuum. On the flat Ag(111) surface, thermal activation triggers a variety of side-reactions resulting in irregularly branched polymeric networks. Upon alignment along the step-edges of the Ag(877) vicinal surface drastically improves the chemoselectivity of the linking process permitting the controlled synthesis of extended-graphdiyne wires with lengths reaching 30 nm. The ideal hydrocarbon scaffold is characterized by density functional theory as a 1D, direct band gap semiconductor material with both HOMO and LUMO-derived bands promisingly isolated within the electronic structure. The templating approach should be applicable to related organic precursors and different reaction schemes thus bears general promise for the engineering of novel low-dimensional carbon-based materials. © 2014 American Chemical Society.

Bernier F.,University of Strasbourg
Cellular and Molecular Life Sciences | Year: 2013

DING proteins, named after their conserved N-terminus, form an overlooked protein family whose members were generally discovered through serendipity. It is characterized by an unusually high sequence conservation, even between distantly related species, and by an outstanding diversity of activities and ligands. They all share a demonstrated capacity to bind phosphate with high affinity or at least a predicted phosphate-binding site. However, DING protein genes are conspicuously absent from databases. The many novel family members identified in recent years have confirmed that DING proteins are ubiquitous not only in animals and plants but probably also in prokaryotes. At the functional level, there is increasing evidence that they participate in many health-related processes such as cancers as well as bacterial (Pseudomonas) and viral (HIV) infections, by mechanisms that are now beginning to be understood. They thus represent potent targets for the development of novel therapeutic approaches, especially against HIV. The few genomic sequences that are now available are starting to give some clues on why DING protein genes and mRNAs are well conserved and difficult to clone. This could open a new era of research, of both fundamental and applied importance. © 2013 Springer Basel.

Ronse C.,University of Strasbourg
Order | Year: 2011

Image segmentation algorithms can be modelled as image-guided operators (maps) on the complete lattice of partitions of space, or on the one of partial partitions (i. e., partitions of subsets of the space). In particular region-splitting segmentation algorithms correspond to block splitting operators on the lattice of partial partitions, in other words anti-extensive operators that act by splitting each block independently. This first paper studies in detail block splitting operators and their lattice-theoretical and monoid properties; in particular we consider their idempotence (a requirement in image segmentation). We characterize block splitting openings (kernel operators) as operators splitting each block into its connected components according to a partial connection; furthermore, block splitting openings constitute a complete sublattice of the complete lattice of all openings on partial partitions. Our results underlie the connective approach to image segmentation introduced by Serra. The second paper will study two classes of non-isotone idempotent block splitting operators, that are also relevant to image segmentation. © 2010 Springer Science+Business Media B.V.

Niederberger V.,Medical University of Vienna | Eckl-Dorna J.,Medical University of Vienna | Pauli G.,University of Strasbourg
Methods | Year: 2014

Over the last 25. years, recombinant allergens from all important allergen sources have been cloned and are now available as recombinant proteins. These molecules can be produced in practically unlimited amounts without biological or batch-to-batch variability. It has been shown in provocation tests that recombinant allergens have similar clinical effects as their natural counterparts. With the help of these tools it is possible to reveal the precise reactivity profiles of patients and to uncover and differentiate cross-reactivity from genuine sensitization to an allergen source. Although it has been shown some time ago that it would be possible to replace crude allergen extracts with recombinant allergens for skin prick testing, and even though the use of allergen components can improve routine diagnosis, these tools are still not available for clinical routine applications. The use of provocation tests is a crucial step in the development of new, hypoallergenic vaccines for therapy of allergic disease. Here we describe important provocation methods (skin prick test, intradermal test, atopy patch test, nasal provocation, colonoscopic provocation test) and give an overview of the clinical provocation studies which have been performed with recombinant allergens so far. © 2013 The Authors.

Jung I.,Brown University | Guevorkian K.,University of Strasbourg | Valles J.M.,Brown University
Physical Review Letters | Year: 2014

Models suggest that mechanical interactions alone can trap swimming microorganisms at surfaces. Testing them requires a method for varying the mechanical interactions. We tuned contact forces between Paramecia and surfaces in situ by varying their buoyancy with nonuniform magnetic fields. Remarkably, increasing their buoyancy can lead to ∼100% trapping at lower surfaces. A model of Paramecia in surface contact passively responding to external torques quantitatively accounts for the data implying that interactions with a planar surface do not engage their mechanosensing network and illuminating how their trapping differs from other smaller microorganisms. © 2014 American Physical Society.

Coccia M.,CNR Institute for Economic Research on Firms and Growth | Coccia M.,Georgia Institute of Technology | Coccia M.,University of Strasbourg
Breast Cancer Research and Treatment | Year: 2013

The aim of this study is to analyze the relationship between the incidence of breast cancer and income per capita across countries. Data on breast cancer incidence in 52 countries were obtained from GLOBOCAN, along with economic indicators of gross domestic product per capita from the World Bank. Number of computed tomography scanners and magnetic resonance imaging (from World Health Organization) were used as a surrogate for technology and access to screening for cancer diagnosis. Statistical analyses for correlation and regression were performed, along with an analysis of variance (ANOVA). A strong positive association between breast cancer incidence and gross domestic product per capita, Pearson's r = 65.4 %, controlling latitude, density of computed tomography scanners and magnetic resonance imaging was found in countries of temperate zones. The estimated relationship suggests that 1 % higher gross domestic product per capita, within the temperate zones (latitudes), increases the expected age-standardized breast cancer incidence by about 35.6 % (p < 0.001). ANOVA confirms these vital results. While some have argued that latitude and seasonality may affect breast cancer incidence, these findings suggest that wealthier nations may have a higher incidence of breast cancer independent of geographic location and screening technology. © 2013 Springer Science+Business Media New York.

Carpenter D.,Harvard University | Carpenter D.,University of Strasbourg | Chattopadhyay J.,Harvard University | Moffitt S.,Brown University | Nall C.,Stanford University
American Journal of Political Science | Year: 2012

Public agencies have discretion on the time domain, and politicians deploy numerous policy instruments to constrain it. Yet little is known about how administrative procedures that affect timing also affect the quality of agency decisions. We examine whether administrative deadlines shape decision timing and the observed quality of decisions. Using a unique and rich dataset of FDA drug approvals that allows us to examine decision timing and quality, we find that this administrative tool induces a piling of decisions before deadlines, and that these "just-before-deadline" approvals are linked with higher rates of postmarket safety problems (market withdrawals, severe safety warnings, safety alerts). Examination of data from FDA advisory committees suggests that the deadlines may impede quality by impairing late-stage deliberation and agency risk communication. Our results both support and challenge reigning theories about administrative procedures, suggesting they embody expected control-expertise trade-offs, but may also create unanticipated constituency losses. © 2011, Midwest Political Science Association.

Polonyi J.,University of Strasbourg
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2015

The effective Lagrangian of a test particle, interacting within an ideal gas, is calculated within the closed-time-path formalism in the one-loop approximation and in the leading order of the particle trajectory. The expansion in the time derivative, available for slow enough motion, uncovers diffusive forces and decoherence in the particle coordinate basis. The master equation, generated by the effective Lagrangian, is derived and its consistency is verified for a finite-temperature gas. © 2015 American Physical Society.

Gottenberg J.-E.,University of Strasbourg | Mariette X.,University Paris - Sud
Current Pharmaceutical Biotechnology | Year: 2012

Many important clinical questions concerning primary Sjögren's syndrome (pSS) remain, that can only be adequately addressed by prospective cohorts. Thus, a better knowledge of the clinical outcome, the course of disease activity and the risk factors of lymphoma requires the setting up of cohorts with biobanks. The homogeneous collection of clinical data, disease activity, patient-related outcome, and biological samples, including DNA, RNA and serum, is definitively mandatory to determine new biological prognostic factors and identify disease activity markers. Three large prospective cohorts have already started to enroll patients with pSS. This will be highly invaluable for scientists and clinicians to gain a better insight into the pathogenesis of pSS, as well as to identify prognostic markers and new therapeutic targets. © 2012 Bentham Science Publishers.

Grozdanov S.,University of Oxford | Grozdanov S.,Leiden University | Polonyi J.,University of Strasbourg
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

We study the equation of motion for the Noether current in an electron gas within the framework of the Schwinger-Keldysh closed-time-path formalism. The equation is shown to be highly nonlinear and irreversible even for a noninteracting, ideal gas of electrons at nonzero density. We truncate the linearized equation of motion, written as the Laurent series in Fourier space, so that the resulting expressions are local in time, both at zero and at small finite temperatures. Furthermore, we show that the one-loop Coulomb interactions only alter the physical picture quantitatively, while preserving the characteristics of the dynamics that the electric current exhibits in the absence of interactions. As a result of the composite nature of the Noether current, composite sound waves are found to be the dominant IR collective excitations at length scales between the inverse Fermi momentum and the mean free path that would exist in an interacting electron gas. We also discuss the difference and the transition between the hydrodynamical regime of an ideal gas, defined in this work, and the hydrodynamical regime in phenomenological hydrodynamics, which is normally used for the description of interacting gases. © 2015 American Physical Society.

Jenkins D.G.,University of York | Jenkins D.G.,University of Strasbourg
Nature Physics | Year: 2014

Nuclear physics is advancing rapidly at the precision frontier, where measurements of nuclear observables are challenging state-of-the-art nuclear models. A major contribution is associated with the increasing availability of accelerated beams of radioactive ions produced using the isotope separation on-line technique. These advances have come hand in hand with significant progress in the development of high-efficiency detector systems and improved target technologies which are invaluable in exploiting these beams to their full advantage. This article reviews some of the recent highlights in the field of nuclear structure profiting from these technological advances. © 2014 Macmillan Publishers Limited. All rights reserved.

Heap M.J.,University of Strasbourg | Xu T.,Northeastern University China | Chen C.-F.,Northeastern University China
Bulletin of Volcanology | Year: 2014

Volcanic rocks and magma display a wide range of porosity and vesicle size, a result of their complex genesis. While the role of porosity is known to exert a fundamental control on strength in the brittle field, less is known as to the influence of vesicle size. To help resolve this issue, here, we lean on a combination of micromechanical (Sammis and Ashby's pore-emanating crack model) and stochastic (rock failure and process analysis code) modelling. The models show, for a homogenous vesicle size, that an increase in porosity (in the form of circular vesicles, from 0 to 40 %) and/or vesicle diameter (from 0.1 to 2.0 mm) results in a dramatic reduction in strength. For example, uniaxial compressive strength can be reduced by about a factor of 5 as porosity is increased from 0 to 40 %. The presence of vesicles locally amplifies the stress within the groundmass and promotes the nucleation of vesicle-emanating microcracks that grow in the direction of the applied macroscopic stress. As strain increases, these microcracks continue to grow and eventually coalesce leading to macroscopic failure. Vesicle clustering, which promotes the overlap and interaction of the tensile stress lobes at the north and south poles of neighbouring vesicles, and the increased ease of microcrack interaction, is encouraged at higher porosity and reduces sample strength. Once a microcrack nucleates at the vesicle wall, larger vesicles impart higher stress intensities at the crack tips, allowing microcracks to propagate at a lower applied macroscopic stress. Larger vesicles also permit a shorter route through the groundmass for the macroscopic shear fracture. This explains the reduction in strength at higher vesicle diameters (at a constant porosity). The modelling highlights that the reduction in strength as porosity or vesicle size increases is nonlinear; the largest reductions are observed at low porosity and small vesicle diameters. In detail, we find that vesicle diameter can play an important role in dictating strength at low porosity but is largely inconsequential above 15 % porosity. Vesicle clustering and stress lobe interaction are implicit at high porosity, regardless of the vesicle diameter. In the case of an inhomogeneous vesicle size, the microcracks grow from the largest vesicles, and brittle strength is closer to that of the largest vesicle end-member. The results of this study highlight the important role of vesicle size, and the complex interplay between porosity and vesicle size, in controlling the brittle strength of volcanic rocks and magma. © 2014 Springer-Verlag Berlin Heidelberg.

Varnek A.,University of Strasbourg
Methods in molecular biology (Clifton, N.J.) | Year: 2011

This chapter reviews the application of fragment descriptors at different stages of virtual screening: filtering, similarity search, and direct activity assessment using QSAR/QSPR models. Several case studies are considered. It is demonstrated that the power of fragment descriptors stems from their universality, very high computational efficiency, simplicity of interpretation, and versatility.

Cribier B.,University of Strasbourg
Journal of the American Academy of Dermatology | Year: 2013

Throughout the 1800s, clinical illustrations helped to formalize what was then the recently developed field of dermatology. Knowledge of skin diseases was given new dimension as artists and clinicians alike strove to accurately document the physical characteristics of numerous dermatoses. Introduction of novel processes and refined techniques advanced the clinical use of disease images. The increasingly superior quality of these images aided in the early distinction between rosacea and acne. This article highlights these illustrative contributions in dermatology, and includes key images that serve as a road map to early clinical understanding of skin diseases. © 2013 by the American Academy of Dermatology, Inc.

Wicker N.,University of Strasbourg
Pattern Recognition Letters | Year: 2011

An important issue in clustering is the automatic determination of a number of clusters close to the true one. The aim of this paper is to revisit a method called density of points clustering (DPC) that tackles this problem by comparing the density inside a cluster and between two potential sub-clusters. Light is shed on the geometric probability aspect of this method by giving a closed-form formula on the probability distribution of the points generated by picking two points inside a p-dimensional ball (ball segment picking) and taking the middle of them. This sampling procedure is indeed at the heart of DPC. The result shows that such sampled points tend to be more concentrated towards the ball center than the uniform sampled points. The contribution of this study is to explain why DPC can produce good results.© 2010 Elsevier B.V. All rights reserved.

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.

Kastendeuch P.P.,University of Strasbourg
International Journal of Climatology | Year: 2013

Sky view factor (SVF) is a commonly used parameter in atmospheric sciences. A method how to obtain an approximate value of SVF from digital elevation models (DEM) is described. The method takes into account slopes and transmittance of objects and is able to compute SVF for complex geometries (e.g. urban environments, natural landscapes, etc.). It is based on the concept of view factor, sometimes called 'form factor' or 'shape factor' in the literature. The view factors are computed between the calculation point and numeric sky dome to obtain an estimate of the final SVF value. A special procedure is applied to take limitation of sky visibility by obstacles into account. Accuracy of the method is checked by comparison with theoretical SVF values and tested on examples of complex geometries. © 2012 Royal Meteorological Society.

Tilsner J.,University of Edinburgh | Amari K.,University of Strasbourg | Torrance L.,Scottish Crop Research Institute
Protoplasma | Year: 2011

A significant amount of work has been expended to identify the elusive components of plasmodesmata (PD) to help understand their structure, as well as how proteins are targeted to them. This review focuses on the role that lipid membranes may play in defining PD both structurally and as subcellular targeting addresses. Parallels are drawn to findings in other areas of research which focus on the lateral segregation of membrane domains and the generation of three-dimensional organellar shapes from flat lipid bilayers. We conclude that consideration of the protein-lipid interactions in cell biological studies of PD components and PD-targeted proteins may yield new insights into some of the many open questions regarding these unique structures. © 2010 Springer-Verlag.

Theoleyre F.,University of Strasbourg
Computer Networks | Year: 2011

The MAC layer for multihop wireless networks has drawn considerable research attention in the last few years. We focus here on the wireless multihop networks with a convergecast traffic pattern: the whole traffic is destined to a sink/gateway. We propose first to select a k-tree core, i.e. a sub-tree of the shortest paths to the sink containing exactly k-leaves. In particular, these k-tree core nodes are chosen among the nodes that must forward most traffic. We design c-mac, an optimized MAC layer for this kind of topology. c-mac is derived from the CSMA-CA like approaches and consists in giving a larger priority to the k-tree core nodes. Moreover, a proper coordination among the k-tree core nodes permits to limit collisions among them. Simulation results show that organizing the transmissions in c-mac permits to achieve a much larger throughput than the original ieee 802.11 - like protocol it is based on. This simple solution can be adapted to most CSMA-CA like protocols, and is particularly relevant for WSN or WMN in which traffic is mostly destined to the sink/gateway. © 2010 Elsevier B.V. All rights reserved.

Auffinger P.,University of Strasbourg
Metal ions in life sciences | Year: 2011

RNA crystal structures have provided a wealth of information on localized metal ions that are bound to specific sites, such as the RNA deep groove, the Hoogsteen face of guanine nucleotides and anionic phosphate oxygens. With a number of crystal structures being solved with heavy metal derivatives and other "reporter" ions, sufficient information is available to estimate global similarities and differences in ion binding properties and to begin determining the influence of RNA and ions on each other. Here we will discuss the ions that are observed bound to RNA, their coordination properties, and the roles they play in RNA structural studies. Analysis of the crystallographic data reinforces the fact that ion interactions with nucleic acids are not easily interchanged between similarly charged ions. The physiological relevance of RNA-ion interactions, mainly involving K+ and Mg2+ cations, needs to be analyzed with care as different structures are solved under very diverse ionic conditions. The analysis is complicated by the fact that the assignment is not always accurate, often done under sub-optimal conditions, which further limits the generalization about the types of interactions these ions can establish.

Lehn J.-M.,University of Strasbourg
Advances in Polymer Science | Year: 2013

Dynamers may be defined as constitutional dynamic polymers of either supramolecular or molecular nature, i.e., polymeric entities whose monomeric components are linked through reversible connections, which can be either non-covalent interactions or reversible covalent bonds. They may for example implement hydrogen bonding, resulting in supramolecular hydrogen-bonded polymers. Alternatively, covalent dynamic polymers may be derived from the formation of imine-type bonds. Dynamers thus present the capacity to modify their constitution by exchange and reshuffling of their components. These constitutional dynamic features confer on dynamers the ability to modulate their properties in response to external chemical or physical triggers such as heat, light, medium, chemical additives, etc. They thus give access to higher levels of behavior such as self- healing and adaptation. The exchange of monomeric components defines constitutional dynamic networks of interconverting polymeric entities of different constitutions, presenting agonistic and antagonistic relationships between their constituents, and responding to chemical or physical stimulations by upregulating or downregulating specific linked entities. Such arrays represent adaptive constitutional networks that may be implemented for the development of tunable adaptive materials and technologies, towards the advent of a systems polymer/materials science in line with the emergence of systems chemistry. © Springer-Verlag Berlin Heidelberg 2013.

Dracos M.,University of Strasbourg
Nuclear and Particle Physics Proceedings | Year: 2016

In addition to the world's most intense pulsed spallation neutron source, the European Spallation Source linac with 5 MW proton power has the potential to become the proton driver of the world's most intense neutrino beam. The physics performance of that neutrino Super Beam in conjunction with a megaton Water Cherenkov neutrino detector installed 1000 m down in a mine at a distance of about 500 km from ESS has been evaluated. In particular, the superior potential of such a neutrino experiment placed at the 2nd oscillation maximum to discover the lepton CP violation in order to explain the matter-antimatter asymmetry in Universe is presented. In addition, the choice of such detector will extent the physics program to proton-decay, atmospheric neutrinos and astrophysics searches. The ESS proton linac upgrades, the accumulator ring needed for proton pulse compression, the target station optimization and the physics potential are described. The ESS neutron installations will be fully ready by 2023 at which moment the upgrades for the neutrino facility could start. In this scenario data taking for neutrino physics could start around 2030. © 2015 Elsevier B.V.

Basso L.,University of Strasbourg | Basso L.,CNRS Hubert Curien Multi-disciplinary Institute | Basso L.,Aix - Marseille University
Journal of High Energy Physics | Year: 2016

Abstract: In recent years, the production of a SM particle with large missing transverse momentum, dubbed mono-X searches, have gained increasing attention. After the discovery of the Higgs boson in 2012, the run-II of the LHC will now scrutinise its properties, looking for BSM physics. In particular, one could search for mono-Higgs signals, that are typically studied in models addressing dark matter. However, this signal can appear also in models addressing the neutrino masses, if additional heavier neutrinos with masses at the electroweak scale are present. The latter will couple to the SM neutrinos and the Higgs boson, yielding a type of mono-Higgs signal not considered for dark matter: the resonant production of a Higgs boson and missing energy. In this paper, we address the LHC exclusion power of the latter with dedicated detector simulations, and reinterpret it in a benchmark scenario for neutrino mass generation. © 2016, The Author(s).

Significant advances have been made in our understanding of the host defense against microbial infections taking place at frontier epithelia of Drosophila flies. Immune deficiency (IMD), the major NF-κB immune response pathway induced in these epithelia, displays remarkable adaptations in its activation and regulation in the respiratory and digestive tract. The host defense against ingested pathogens is not limited to resistance, that is, the immune response. It also involves resilience, the capacity of the host to endure and repair damages inflicted by pathogens or the host's own immune response. For instance, enterocytes damaged by pathogens, the microbiota of aging flies, or host-derived reactive oxygen species (ROS), are replaced under the control of multiple pathways by the compensatory proliferation of intestinal stem cells (ISCs). © 2012 Elsevier Ltd.

Andres E.,University of Strasbourg | Andres E.,Hopitaux Universitaires Of Strasbourg
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2012

Cationic host-defence antimicrobial peptides are recognised as an important component of the innate immune response in most multicellular organisms. In humans, several antimicrobial peptides have recently been recognised as key factors in the pathology of diseases such as cystic fibrosis, septic shock, atopic dermatitis and morbus Kostmann. To date, several hundred cationic antimicrobial peptides have been characterised. They are amphipathic peptides, comprising 20 to 50 amino acids, and exhibiting large structural diversity. These peptides display a broad spectrum of activity against bacterial, fungal and viral pathogens. Their mode of action is best known for cecropins and magainins, which act upon the cytoplasmic membrane of microorganisms, causing its disruption by a detergent-like activity and pore formation. In the last few years, several of these peptides or analogues (derived from magainin, protegrin, indolicidin and histatin) were in advanced clinical development, especially for localised infections (oral and cutaneous infections, pneumonias etc.). Several other molecules (rBPI, heliomicin and thanatin) are currently under development for various systemic infections (Staphylococcus sp., Aspergillus sp., Candida sp. etc.) and may represent important additions to the anti-infectious therapeutic arsenal. © Springer-Verlag 2011.

Ball V.,University of Strasbourg | Ball V.,French Institute of Health and Medical Research
Macromolecular Chemistry and Physics | Year: 2015

The step-by-step deposition of poly(allylamine hydrochloride) (PAH) and sodium hexametaphosphate (PSP) leads to coatings displaying interesting intumescent properties and is a fascinating model system to understand the fundamental mechanism behind such a deposition process. In this investigation, the deposition kinetics of (PAH-PSP)n is followed in situ by means of a quartz crystal microbalance with dissipation monitoring, as a function of NaCl concentration. The evolution of the film deposition is analyzed in detail and the data are compared with previous data obtained by ellipsometry on dried films. These results are also compared with the expectations from the PAH/PSP phase diagram. The (PAH-PSP)n films are also able to incorporate hexacyanoferrate anions with an amount of an incorporated redox probe reflecting the film thickness as obtained in the presence of eletrolyte solutions of increasing ionic strength. The in situ measurements and the electrochemical probe experiments reveal details of the film deposition mechanism that are not accessible by dry-state characterization methods. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fournier N.,Institute of Geological & Nuclear Sciences | Chardot L.,Institute of Geological & Nuclear Sciences | Chardot L.,University of Strasbourg | Chardot L.,University of Canterbury
Journal of Geophysical Research: Solid Earth | Year: 2012

In this work we assess how volcano geodetic observations can be used to gain insights into hydrothermal system dynamics. We designed a range of numerical models of hydrothermal unrest and associated ground deformation caused by the thermo-poro-elastic response of the substratum. Throughout an episode of unrest, ground deformation is consistently first controlled by the poroelastic response of the substratum to pore pressure increase near the injection area. Later, thermal expansion may become the dominant process if the injection is sustained. We inverted these synthetic geodetic data using simple conventional pressure source models and compared the retrieved source characteristics with that of the synthetic hydrothermal systems. Simple pressure source models can reproduce well ground deformation caused by pore-pressure increase at depth. Most importantly, the pressure source's depth retrieved from the inversions corresponds to those of the area of injection of the hot magmatic fluids into the hydrothermal system. When the thermoelastic contribution to ground deformation becomes significant through time, simple point or spherical finite sources cannot reproduce the ground deformation signal. This allows one to determine whether observed ground deformation events due to hydrothermal unrest are distinct episodes of unrest and injection at depth, or whether one may correspond to the late, thermally-controlled phase of a previous event. Finally we applied this strategy to White Island volcano, New Zealand, to gain insights into the processes driving the last two episodes of ground uplift. © 2012. American Geophysical Union. All Rights Reserved.

Urzhumtseva L.,University of Strasbourg | Urzhumtsev A.,French Institute of Health and Medical Research | Urzhumtsev A.,University of Lorraine
Journal of Applied Crystallography | Year: 2011

Crystallographic Fourier maps may contain barely interpretable or non-interpretable regions if these maps are calculated with an incomplete set of diffraction data. Even a small percentage of missing data may be crucial if these data are distributed non-uniformly and form connected regions of reciprocal space. Significant time and effort can be lost trying to interpret poor maps, in improving them by phase refinement or in fighting against artefacts, whilst the problem could in fact be solved by completing the data set. To characterize the distribution of missing reflections, several types of diagrams have been suggested in addition to the usual plots of completeness in resolution shells and cumulative data completeness. A computer program, FOBSCOM, has been developed to analyze the spatial distribution of unmeasured diffraction data, to search for connected regions of unmeasured reflections and to obtain numeric characteristics of these regions. By performing this analysis, the program could help to save time during structure solution for a number of projects. It can also provide information about a possible overestimation of the map quality and model-biased features when calculated values are used to replace unmeasured data. © 2011 International Union of Crystallography Printed in Singapore-all rights reserved.

Chiantia S.,State University of New York at Stony Brook | Schwille P.,TU Dresden | Klymchenko A.S.,University of Strasbourg | London E.,State University of New York at Stony Brook
Biophysical Journal | Year: 2011

We report a simple method to obtain stable asymmetric giant unilamellar vesicles (GUVs). Fluorescence correlation spectroscopy was used to quantitatively characterize vesicle properties. After brain sphingomyelin (bSM) was exchanged into dioleoylphosphatidylcholine (DOPC) GUVs, lateral diffusion in the bSM-containing outer leaflet decreased, whereas that in the DOPC-containing inner leaflet was largely unchanged, confirming asymmetry and a lack of coupling between the physical states of the inner and outer leaflets. In contrast, after bSM was exchanged into brain phosphatidylcholine vesicles, lateral diffusion decreased in both leaflets. Thus, asymmetric GUVs should be useful for investigating the molecular mechanisms behind interleaflet coupling. © 2011 by the Biophysical Society.

Cribier B.,University of Strasbourg
Annales de Dermatologie et de Venereologie | Year: 2012

Apart from plaque-type psoriasis, there are multiple particular or rare clinical presentations, according to signs and symptoms, localization or distribution of lesions. Psoriasis can affect mucous membranes, especially the genital areas of male and female patients, causing pain or burning sensation and decreased quality of life. Geographic tongue is not specific of psoriasis, but is more frequent in this context. Other localizations like the lips and the eylids are rare, but should not be overlooked. Certain lesions have an unusual distribution, like psoriasis gyrata and blaschko linear forms. Pustules are frequently observed on the palms and soles. Acrodermatitis continua is a rare chronic pustular condition affecting the acral areas, mainly the fingers, which is associated with severe nail involvement. Nails can also be involved in the unusual pachydermo-periostitis, a clinical form of psoriasis without epidermal lesions, which has characteristic radiologic presentation. © 2012 Elsevier Masson SAS. All rights reserved.

Schulmann K.,University of Strasbourg | Jezek J.,Charles University
International Journal of Earth Sciences | Year: 2012

During the ascent, emplacement and post-emplacement deformation of igneous rocks, two or more phases of deformation that overprint each other are often depicted. These overprints, when magnetic minerals are present, are recorded in magnetic fabric. In this contribution, overprints are studied by means of numerical modeling, following several basic scenarios common to igneous rocks. Biotite and amphibole that occur often together in igneous rocks are considered as carriers of the anisotropy of magnetic susceptibility. Modeling shows that (1) a constrictional fabric with a low degree of anisotropy as commonly recorded in magmatic rocks may result from a deformation overprint and not necessarily from an extensional/transtensional regime, and (2) that the constrictional AMS fabrics originates from orthogonal superimposition of a deformation event on an AMS fabric inherited from earlier magma emplacement history. Therefore, the interpretation of a constrictional fabric must be performed with caution. Numerical modeling may provide a suitable help in strengthening the interpretation of real magnetic fabric data. © 2011 Springer-Verlag.

Yalcin I.,French National Center for Scientific Research | Barthas F.,French National Center for Scientific Research | Barthas F.,University of Strasbourg | Barrot M.,French National Center for Scientific Research
Neuroscience and Biobehavioral Reviews | Year: 2014

Mood disorders such as depression and anxiety are frequently observed in patients suffering from chronic pain, including neuropathic pain. While this comorbidity is clinically well established, the underlying mechanism(s) remained unclear. The recent development of animal models now allows addressing the consequences of neuropathic pain. In this review, we report the preclinical evidences from anatomical, neuroimaging, behavioral, pharmacological and biochemical studies that address the anxiodepressive consequences of neuropathic pain. We present an overview of rodent models of these consequences and we discuss the challenges and parameters to consider for generating these models. We then discuss the possible mechanism(s) underlying anxiodepressive consequences by describing morphological and functional changes. Information is provided concerning neuroanatomical changes and plasticity, including LTP and LTD, in the anterior cingulate cortex, the insula, the hippocampus, the amygdala and the mesolimbic system, neuroendocrine parameters concerning the hypothalamo-pituitary-adrenal axis, neuroimmune response including the role of glial cells and cytokines, monoamine systems and changes in locus coeruleus noradrenergic system, and neurotrophic factors such as BDNF. © 2014 Elsevier Ltd.

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.

Gachet C.,French Institute of Health and Medical Research | Gachet C.,University of Strasbourg
Journal of Thrombosis and Haemostasis | Year: 2015

The current standard care for acute coronary syndromes is dual antiplatelet therapy combining the COX1 inhibitor aspirin with a drug targeting the P2Y12 receptor, together with anticoagulation during and after early revascularization by percutaneous intervention. In very high-risk patients, glycoprotein (GP) IIb/IIIa antagonists may also be used. Secondary prevention of ischemic events requires dual antiplatelet therapy for several months followed by lifelong low-dose aspirin. The duration of treatment and the drugs to combine nevertheless remain matters of debate and the focus of ongoing research. Despite great progress, there is still room for improved efficacy and this could involve new targets for both antiplatelet drugs (like the thrombin receptor PAR1) and anticoagulants. However, improved efficacy is offset by an increased risk of bleeding. Stroke patients are still waiting for better treatment, their bleeding risk being particularly high. New targets including the collagen receptor, glycoprotein VI (GPVI), and the GPIb-von Willebrand factor axis, governing platelet interaction with the diseased vessel wall, should enable us to complete the armamentarium of antiplatelet drugs. © 2015 International Society on Thrombosis and Haemostasis.

Background:We aimed to evaluate whether EGFR mutations (mEGFR) and KRAS amino acid substitutions can predict first site of recurrence or metastasis after non-small-cell lung cancer (NSCLC) surgery.Methods:Data were reviewed from 481 patients who underwent thoracic surgery for NSCLC between 2007 and 2012.Results:Patients with KRAS G12C developed significantly more bone metastases compared with the remainder of the cohort (59% vs 16%, P<0.0001). This was confirmed in multivariate analysis (MA) (odds ratio (OR): 0.113 (95% confidence interval (CI): 0.055–0.231), P<0.0001). Significantly, more patients with mEGFR developed liver and brain metastases compared with the remainder of the cohort (30% vs 10%, P=0.006; 59% vs 1%, P<0.0001, respectively). These were confirmed in MA (OR: 0.333 (95% CI: 0.095–0.998), P=0.05; OR: 0.032 (95% CI: 0.008–0.135), P<0.0001, respectively). Patients with KRAS G12V developed significantly more pleuro-pericardial metastases compared with the remainder of the cohort (94% vs 12%, P<0.0001). This was confirmed in MA (OR: 0.007 (95% CI: 0.001–0.031), P<0.0001). Wild-type patients developed significantly more lung metastases (35% vs 10%, P<0.0001). This was confirmed in MA (OR: 0.383 (95% CI: 0.193–0.762), P=0.006).Conclusion:Epidermal growth factor receptor mutation and KRAS amino acid substitutions seem to predict site-specific recurrence and metastasis after NSCLC surgery.British Journal of Cancer advance online publication, 23 June 2016; doi:10.1038/bjc.2016.182 www.bjcancer.com. © 2016 Cancer Research UK

Carapito R.,University of Strasbourg
European Journal of Human Genetics | Year: 2016

Spondylocarpotarsal synostosis syndrome (SCT) is a rare Mendelian disorder (OMIM #272460) characterized by prenatal vertebral fusion, scoliosis, short stature and carpal and tarsal synostosis. SCT is typically known as an autosomal recessive disease caused by variants in the FLNB gene. The genetic basis of the rarer cases of vertical transmissions remains unknown. In two independent families with symptoms related to autosomal dominant SCT, we identified – by exome sequencing – two protein-altering variants in the embryonic myosin heavy chain 3 (MYH3) gene. As MYH3 variants are also associated with distal arthrogryposis (DA1, DA2A, DA2B) and autosomal dominant multiple pterygium syndromes (MPS), the present study expands the phenotypic spectrum of MYH3 variants to autosomal dominant SCT. Vertebral, carpal and tarsal fusions observed in both families further confirm that MYH3 plays a key role in skeletal development.European Journal of Human Genetics advance online publication, 6 July 2016; doi:10.1038/ejhg.2016.84. © 2016 Macmillan Publishers Limited

Ibata R.,University of Strasbourg | Nipoti C.,Viale Berti Pichat | Sollima A.,National institute for astrophysics | Bellazzini M.,National institute for astrophysics | And 2 more authors.
Monthly Notices of the Royal Astronomical Society | Year: 2013

We use recently published measurements of the kinematics, surface brightness and stellarmassto- light ratio of the globular cluster NGC 2419 to examine the possibility that this Galactic halo satellite is embedded in a low-mass darkmatter halo. NGC2419 is a promising target for such a study, since its extreme Galactocentric distance and large mass would have greatly facilitated the retention of dark matter. A Markov chain Monte Carlo approach is used to investigate composite dynamical models containing a stellar and a dark matter component. We find that it is unlikely that a significant amount of dark matter (≲6 per cent of the luminous mass inside the tidal limit of the cluster) can be present if the stars follow an anisotropic Michie model and the dark matter a double power-law model. However, we find that more general models, derived using a new technique we have developed to compute non-parametric solutions to the spherical Jeans equation, suggest the presence of a significant dark matter fraction (approximately twice the stellar mass). Thus, the presence of a dark matter halo around NGC 2419 cannot be fully ruled out at present, yet any dark matter within the 10 arcmin visible extent of the cluster must be highly concentrated and cannot exceed 1.1 × 106M⊙ (99 per cent confidence), in stark contrast to expectations for a plausible progenitor halo of this structure. © 2012 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.

Ingenbleek Y.,University of Strasbourg | McCully K.S.,Pathology and Laboratory Medicine Service | McCully K.S.,Harvard University
Nutrition | Year: 2012

Objective: To explain why vegetarian subjects develop morbidity and mortality from cardiovascular diseases unrelated to vitamin B status and Framingham criteria. Methods: A study of 24 rural male subjects 18 to 30 y old and 15 urban male controls was conducted in the Sahel region of Chad. Food consumption was determined from a dietary questionnaire, and overall health status was assessed by body weight, body mass index, serum albumin, plasma transthyretin, urinary nitrogen, and creatinine. Plasma lipids, vitamins B6, B9 and B12, homocysteine, and related sulfur amino acids were measured as selected cardiovascular disease risk factors. Results: Body weight, body mass index, blood, and urinary markers of protein status were significantly lower, with an estimated 10% decrease of lean body mass in the study group compared withurban controls. Neither lipid fractions nor plasma levels of vitamins B6, B9, and B12 were significantly different between the two groups. Although the mean consumption of sulfur amino acids(10.4 mg·kg -1·d -1) by rural subjects was significantly below the recommended dietary allowances (13 mg·kg -1·d -1), plasma methionine values were similar in the two groups. In contrast, homocysteine concentration was significantly increased (18.6 μmol/L, P < 0.001), and the levels of cysteine and glutathione were significantly decreased in the study group, demonstrating inhibition of the trans-sulfuration pathway. The strong negative correlation (r = -0.71) between transthyretin and homocysteine implicated lean body mass as a critical determinant of hyperhomocysteinemia. Conclusion: The low dietary intake of protein and sulfur amino acids by a plant-eating population leads to subclinical protein malnutrition, explaining the origin of hyperhomocysteinemia and the increased vulnerability of these vegetarian subjects to cardiovascular diseases. © 2012.

Rognan D.,University of Strasbourg
MedChemComm | Year: 2015

Protein-protein interactions are at the heart of most physiopathological processes. As such, they have attracted considerable attention for designing drugs of the future. Although initially considered as high-value but difficult to identify, low molecular weight compounds able to selectively and potently modulate protein-protein interactions have recently reached clinical trials. Along with high-throughput screening of compound libraries, combining structural and computational approaches has boosted this formerly minor area of research into a currently tremendously active field. This review highlights the very recent developments in the rational design of protein-protein interaction inhibitors. This journal is © The Royal Society of Chemistry.

Pourquie O.,University of Strasbourg
Cell | Year: 2011

One of the most striking features of the human vertebral column is its periodic organization along the anterior-posterior axis. This pattern is established when segments of vertebrates, called somites, bud off at a defined pace from the anterior tip of the embryo's presomitic mesoderm (PSM). To trigger this rhythmic production of somites, three major signaling pathways - Notch, Wnt/β-catenin, and fibroblast growth factor (FGF) - integrate into a molecular network that generates a traveling wave of gene expression along the embryonic axis, called the "segmentation clock." Recent systems approaches have begun identifying specific signaling circuits within the network that set the pace of the oscillations, synchronize gene expression cycles in neighboring cells, and contribute to the robustness and bilateral symmetry of somite formation. These findings establish a new model for vertebrate segmentation and provide a conceptual framework to explain human diseases of the spine, such as congenital scoliosis. © 2011 Elsevier Inc.

Andres E.,University of Strasbourg | Maloisel F.,Saint Anne Clinic | Zimmer J.,CRP Sante
British Journal of Haematology | Year: 2010

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.

Klaholz B.P.,CNRS Institute of Genetics and of Molecular and Cellular Biology | Klaholz B.P.,French Institute of Health and Medical Research | Klaholz B.P.,French National Center for Scientific Research | Klaholz B.P.,University of Strasbourg
Trends in Biochemical Sciences | Year: 2011

When the ribosome machinery reaches a stop codon in the mRNA, protein synthesis stops, and nascent polypeptide release is catalysed by class-I release factors (RFs); class-II RFs then promote the release of class-I RFs. Cryo electron microscopy structures of termination complexes and crystal structures of isolated factors have provided insights into key concepts such as bridging of active sites on the ribosome, and conformational changes that regulate the termination process. Recent crystal structures of the four possible functional ribosome complexes that contain the class-I RFs and the three stop codons have uncovered the molecular mechanisms by which RF1/RF2 (i) both recognise UAA, but discriminate specifically between UAG and UGA, and (ii) catalyse peptide release. Moreover, ongoing research also promises to reveal the structure-function relations of class-II RFs. © 2011.

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.

Jenkins D.,University of York | Jenkins D.,University of Strasbourg
Journal of Physics G: Nuclear and Particle Physics | Year: 2016

Shape coexistence, where different deformed minima compete within a small range of excitation energy, appears to be ubiquitous across the chart of nuclides. In many light alpha-conjugate nuclei, experimental data points to the coexistence of highly deformed nuclear configurations. It has long been suggested, with strong theoretical justification, that these deformed states are attributable to nuclear clustering based on building blocks of alpha particles. This short review will consider how well alpha clustering fits within the shape coexistence canon and point to future opportunities for experiments that can place the topic on a firmer footing. © 2016 IOP Publishing Ltd.

Jimenez-Lara A.M.,Institute Investigaciones Biomedicas Of Madrid Alberto Sols | Aranda A.,Institute Investigaciones Biomedicas Of Madrid Alberto Sols | Gronemeyer H.,University of Strasbourg
Molecular Cancer | Year: 2010

Background: Retinoids, through their cognate nuclear receptors, exert potent effects on cell growth, differentiation and apoptosis, and have significant promise for cancer therapy and chemoprevention. These ligands can determine the ultimate fate of target cells by stimulating or repressing gene expression directly, or indirectly through crosstalking with other signal transducers.Results: Using different breast cancer cell models, we show here that depending on the cellular context retinoids can signal either towards cell death or cell survival. Indeed, retinoids can induce the expression of pro-apoptotic (i.e. TRAIL, TNF-Related Apoptosis-Inducing Ligand, Apo2L/TNFSF10) and anti-apoptotic (i.e. cIAP2, inhibitor of apoptosis protein-2) genes. Promoter mapping, gel retardation and chromatin immunoprecipitation assays revealed that retinoids induce the expression of this gene mainly through crosstalk with NF-kappaB. Supporting this crosstalk, the activation of NF-kappaB by retinoids in T47D cells antagonizes the apoptosis triggered by the chemotherapeutic drugs etoposide, camptothecin or doxorubicin. Notably apoptosis induced by death ligands (i.e. TRAIL or antiFAS) is not antagonized by retinoids. That knockdown of cIAP2 expression by small interfering RNA does not alter the inhibition of etoposide-induced apoptosis by retinoids in T47D cells reveals that stimulation of cIAP2 expression is not the cause of their anti-apoptotic action. However, ectopic overexpression of a NF-kappaB repressor increases apoptosis by retinoids moderately and abrogates almost completely the retinoid-dependent inhibition of etoposide-induced apoptosis. Our data exclude cIAP2 and suggest that retinoids target other regulator(s) of the NF-kappaB signaling pathway to induce resistance to etoposide on certain breast cancer cells.Conclusions: This study shows an important role for the NF-kappaB pathway in retinoic acid signaling and retinoic acid-mediated resistance to cancer therapy-mediated apoptosis in breast cancer cells, independently of cIAP2. Our data support the use of NF-kappaB pathway activation as a marker for screening that will help to develop novel retinoids, or retinoid-based combination therapies with improved efficacy. © 2010 Jiménez-Lara et al; licensee BioMed Central Ltd.

Westhof E.,University of Strasbourg
Methods in molecular biology (Clifton, N.J.) | Year: 2012

It is now about 30 years since ribozymes, catalytically active RNA molecules, were discovered. Although the chemical versatility of RNA does not come close to that of proteins, the chemical properties of nucleic acid systems are nevertheless thoroughly exploited in biological systems, leading to diverse ways of accelerating chemical reactions. Ribozymes are truly fascinating biological molecules. After all, is catalytic RNA an accident of life or, instead, is life an accident of catalytic RNA?

Jung P.P.,University of Strasbourg
G3 (Bethesda, Md.) | Year: 2012

Mitochondria are organelles, which play a key role in some essential functions, including respiration, metabolite biosynthesis, ion homeostasis, and apoptosis. The vast numbers of mitochondrial DNA (mtDNA) sequences of various yeast species, which have recently been published, have also helped to elucidate the structural diversity of these genomes. Although a large corpus of data are now available on the diversity of yeast species, little is known so far about the mtDNA diversity in single yeast species. To study the genetic variations occurring in the mtDNA of wild yeast isolates, we performed a genome-wide polymorphism survey on the mtDNA of 18 Lachancea kluyveri (formerly Saccharomyces kluyveri) strains. We determined the complete mt genome sequences of strains isolated from various geographical locations (in North America, Asia, and Europe) and ecological niches (Drosophila, tree exudates, soil). The mt genome of the NCYC 543 reference strain is 51,525 bp long. It contains the same core of genes as Lachancea thermotolerans, the nearest relative to L. kluyveri. To explore the mt genome variations in a single yeast species, we compared the mtDNAs of the 18 isolates. The phylogeny and population structure of L. kluyveri provide clear-cut evidence for the existence of well-defined geographically isolated lineages. Although these genomes are completely syntenic, their size and the intron content were found to vary among the isolates studied. These genomes are highly polymorphic, showing an average diversity of 28.5 SNPs/kb and 6.6 indels/kb. Analysis of the SNP and indel patterns showed the existence of a particularly high overall level of polymorphism in the intergenic regions. The dN/dS ratios obtained are consistent with purifying selection in all these genes, with the noteworthy exception of the VAR1 gene, which gave a very high ratio. These data suggest that the intergenic regions have evolved very fast in yeast mitochondrial genomes.

Pinot F.,University of Strasbourg | Beisson F.,Aix - Marseille University
FEBS Journal | Year: 2011

In plants, fatty acids (FA) are subjected to various types of oxygenation reactions. Products include hydroxyacids, as well as hydroperoxides, epoxides, aldehydes, ketones and α,ω-diacids. Many of these reactions are catalysed by cytochrome P450s (P450s), which represent one of the largest superfamilies of proteins in plants. The existence of P450-type metabolizing FA enzymes in plants was established approximately four decades ago in studies on the biosynthesis of lipid polyesters. Biochemical investigations have highlighted two major characteristics of P450s acting on FAs: (a) they can be inhibited by FA analogues carrying an acetylenic function, and (b) they can be enhanced by biotic and abiotic stress at the transcriptional level. Based on these properties, P450s capable of producing oxidized FA have been identified and characterized from various plant species. Until recently, the vast majority of characterized P450s acting on FAs belonged to the CYP86 and CYP94 families. In the past five years, rapid progress in the characterization of mutants in the model plant Arabidopsis thaliana has allowed the identification of such enzymes in many other P450 families (i.e. CYP703, CYP704, CYP709, CYP77, CYP74). The presence in a single species of distinct enzymes characterized by their own regulation and catalytic properties raised the question of their physiological meaning. Functional studies in A. thaliana have demonstrated the involvement of FA hydroxylases in the synthesis of the protective biopolymers cutin, suberin and sporopollenin. In addition, several lines of evidence discussed in this minireview are consistent with P450s metabolizing FAs in many aspects of plant biology, such as defence against pathogens and herbivores, development, catabolism or reproduction. © 2010 FEBS.

Meunier H.,University of Strasbourg | Meunier H.,Aix - Marseille University | Vauclair J.,Aix - Marseille University | Fagard J.,University of Paris Descartes
PLoS ONE | Year: 2012

To test the role of gestures in the origin of language, we studied hand preferences for grasping or pointing to objects at several spatial positions in human infants and adult baboons. If the roots of language are indeed in gestural communication, we expect that human infants and baboons will present a comparable difference in their pattern of laterality according to task: both should be more right-hand/left-hemisphere specialized when communicating by pointing than when simply grasping objects. Our study is the first to test both human infants and baboons on the same communicative task. Our results show remarkable convergence in the distribution of the two species' hand biases on the two kinds of tasks: In both human infants and baboons, right-hand preference was significantly stronger for the communicative task than for grasping objects. Our findings support the hypothesis that left-lateralized language may be derived from a gestural communication system that was present in the common ancestor of baboons and humans. © 2012 Meunier et al.

Chronic drug exposure alters gene expression in the brain, which is believed to underlie compulsive drug seeking and drug taking behavior. Recent evidence shows that drug-induced long-term neuroadaptations in the brain are mediated in part by epigenetic mechanisms. By remodeling chromatin, this type of regulation contributes to drug-induced synaptic plasticity that translates into behavioral modifications. How drug-induced alterations in DNA methylation regulate gene expression is reviewed here, with a focus on MeCP2, a protein binding methylated DNA. The importance of histone modifications, especially acetylation is also discussed, with an emphasis on the effects of inhibitors of histone deacetylases on drug-induced behavioral changes. The precise identification of the epigenetic mechanisms that are under the control of drugs of abuse may help to uncover novel targets for the treatment of drug seeking and relapse. © 2015 médecine/sciences - Inserm.

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.

Li X.-H.,CAS Institute of Geology and Geophysics | Faure M.,CNRS Earth Sciences Institute of Orleans | Lin W.,CAS Institute of Geology and Geophysics | Manatschal G.,University of Strasbourg
Lithos | Year: 2013

The Chenaillet Ophiolite is one of the best-preserved remnants of the Piemont-Liguria oceanic basin, a branch of the Central Atlantic that opened during the separation of Adria/Africa from Europe. Despite numerous studies of structure, petrology, geochemistry and isotope geochronology, the timing and genesis of various magmatic rocks within the Chenaillet Ophiolite are still controversial. We provide in this study integrated in situ analyses of zircon U-Pb age and O-Hf isotopes for the troctolite and albitite within the Chenaillet Ophiolite. Our new results indicate that the troctolite and albitite crystallized synchronously at ~165Ma. Zircons from the troctolite have homogeneous Hf and O isotopic compositions, with εHf(T)=+13.5±1.0 (2SD) and δ18O=5.4±0.4% (2SD), indicating crystallization from magmas that were derived from a depleted, MORB-like mantle. The albitite zircons give consistent εHf(T) values (+13.0 to +13.5) within errors with those of troctolite zircons, but variable δ18O values. The altered zircon domains have relatively low δ18O values of 4.7±0.6% (2SD) due to subsolidus hydrothermal alteration, whilst the least-altered zircon domains give δ18Ozir values of 5.1±0.4% (2SD), indistinguishable within errors with the troctolite zircons and the igneous zircons from the Mid-Atlantic and Southwest Indian Ridges gabbros, norites, and plagiogranites of modern oceanic crust. In situ zircon O-Hf isotopic data suggest that the troctolites and albitites are most likely cogenetic, with the albitites being formed by extreme fractional crystallization from the basaltic magma. Based on our new age results and compilation of the reliable literature U-Pb age data, the ophiolitic gabbros from Eastern, Central and, Western Alps, Liguria and Corsica crystallized nearly synchronously at 158-166. Ma, suggesting a short life span of < 11 m.y. for the formation of the Piemont-Liguria oceanic domain, rather than a ~ 30 m.y. life span as previously thought. The Chenaillet ophiolite is likely a remnant of embryonic oceanic crust, rather than a piece of "mature" oceanic crust. Provided the spreading velocities of < 3 cm/yr full rate for magma-poor MOR sequences, the maximum width to the Piemont-Liguria oceanic floor would have been in the order of 300. km. © 2013 Elsevier B.V.

Poulain B.,University of Strasbourg
Revue Neurologique | Year: 2010

Botulinum toxin is a multi-molecular complex comprised of a neuro-active moiety (i.e. botulinum neurotoxin) and several associated non-toxic proteins. The toxin dissociates rapidly at plasmatic pH, thereby releasing neurotoxin. Nerve terminals only take up the neurotoxin. In the peripheral nerve system, the neurotoxin mainly blocks acetylcholine release. When acting at the neuromuscular junctions, this results in paralysis of the muscle fibers. The duration of the neurotoxin action is mainly determined by the life-time of neurotoxin molecules inside the nerve terminals. Inhibition of cholinergic transmission induces rapid atrophy of the muscle fibres, and, sometimes, sprouting from poisoned nerve terminals. These effects, as well as the acetylcholine release blockade are entirely reversible. When injected in the periphery, a direct action of botulinum neurotoxin in the central nervous system remains unlikely despite its retrograde ascent demonstrated in animal models. However, indirect effects are numerous. The constituting proteins of the toxin complex can lead to immunisation against the non-toxic associated proteins and neurotoxin. Only the antibodies directed against neurotoxin are potentially neutralizing. © 2009 Elsevier Masson SAS. All rights reserved.

Schradin C.,University of Strasbourg
Philosophical transactions of the Royal Society of London. Series B, Biological sciences | Year: 2013

Previously, it was widely believed that each species has a specific social organization, but we know now that many species show intraspecific variation in their social organization. Four different processes can lead to intraspecific variation in social organization: (i) genetic variation between individuals owing to local adaptation (between populations) or evolutionarily stable strategies within populations; (ii) developmental plasticity evolved in long-term (more than one generation) unpredictable and short-term (one generation) predictable environments, which is mediated by organizational physiological effects during early ontogeny; (iii) social flexibility evolved in highly unpredictable environments, which is mediated by activational physiological effects in adults; (iv) entirely extrinsic factors such as the death of a dominant breeder. Variation in social behaviour occurs between individuals in the case of genetic variation and developmental plasticity, but within individuals in the case of social flexibility. It is important to study intraspecific variation in social organization to understand the social systems of species because it reveals the mechanisms by which species can adapt to changing environments, offers a useful tool to study the ultimate and proximate causes of sociality, and is an interesting phenomenon by itself that needs scientific explanation.

Lamiable O.,French National Center for Scientific Research | Imler J.-L.,French National Center for Scientific Research | Imler J.-L.,University of Strasbourg
Current Opinion in Microbiology | Year: 2014

Immunity to viral infections in the model organism Drosophila melanogaster involves both RNA interference and additional induced responses. The latter include not only cellular mechanisms such as programmed cell death and autophagy, but also the induction of a large set of genes, some of which contribute to the control of viral replication and resistance to infection. This induced response to infection is complex and involves both virus-specific and cell-type specific mechanisms. We review here recent developments, from the sensing of viral infection to the induction of signaling pathways and production of antiviral effector molecules. Our current understanding, although still partial, validates the Drosophila model of antiviral induced immunity for insect pests and disease vectors, as well as for mammals. © 2014 Elsevier Ltd.

Petri J.,University of Strasbourg
Monthly Notices of the Royal Astronomical Society | Year: 2013

Pulsars are thought to be highly magnetized rotating neutron stars accelerating charged particles along magnetic field lines in their magnetosphere and visible as pulsed emission from the radio wavelength up to high-energy X-rays and gamma-rays. Being highly compact objects with compactness close to Ξ = Rs/R ≈ 0.5, where Rs = 2GM/c2 is the Schwarzschild radius and {M, R} the mass and radius of the neutron star, general-relativistic effects become important close to their surface. This is especially true for the polar caps where radio emission is supposed to emanate from, leading to well-defined signatures such as linear and circular polarization. In this paper, we derive a general formalism to extend to general relativity the Deutsch field solution valid in vacuum space. Thanks to a vector spherical harmonic expansion of the electromagnetic field, we are able to express the solution to any order in the spin parameter ω of the compact object. We hope this analysis to serve as a benchmark to test numerical codes used to compute black hole and neutron star magnetospheres. © 2013 The Author. Published by Oxford University Press on behalf of the Royal Astronomical Society.

Maenner S.,Ludwig Maximilians University of Munich | Muller M.,Ludwig Maximilians University of Munich | Frohlich J.,Ludwig Maximilians University of Munich | Langer D.,Ludwig Maximilians University of Munich | And 2 more authors.
Molecular Cell | Year: 2013

Dosage compensation in Drosophila involves a global activation of genes on the male X chromosome. The activating complex (MSL-DCC) consists of male-specific-lethal (MSL) proteins and two long, noncoding roX RNAs. The roX RNAs are essential for X-chromosomal targeting, but their contributions to MSL-DCC structure and function are enigmatic. Conceivably, the RNA helicase MLE, itself an MSL subunit, is actively involved in incorporating roX into functional DCC. We determined the secondary structure of roX2 and mapped specific interaction sites for MLE invitro. Upon addition of ATP, MLE disrupted a functionally important stem loop in roX2. This RNA remodeling enhanced specific ATP-dependent association of MSL2, the core subunit of the MSL-DCC, providing a link between roX and MSL subunits. Probing the conformation of roX invivo revealed a remodeled stem loop in chromatin-bound roX2. The active remodeling of a stable secondary structure by MLE may constitute a rate-limiting step for MSL-DCC assembly. © 2013 Elsevier Inc.

Laugel V.,University of Strasbourg
Mechanisms of Ageing and Development | Year: 2013

Cockayne syndrome is a progressive multisystem disorder characterized by a specific cellular defect in transcription-coupled repair. Typical features include developmental delay, failure to thrive, microcephaly, cutaneous photosensitivity, dental anomalies, progressive hearing loss, pigmentary retinopathy, cataracts and enophthalmia. Various levels of severity have been described including the " classical" or moderate type I CS, the early-onset or severe type II and the mild or late-onset type III. Adult-onset cases with prolonged survival and normal initial development have also been identified. At the opposite end of the scale, the most severely affected patients, showing a prenatal onset of the symptoms, are overlapping with the cerebro-oculo-facio-skeletal (COFS) syndrome. These overlapping subtypes build a continuous spectrum without clear thresholds. Revised diagnostic criteria are proposed to improve the recognition of the disease. Two thirds of the patients are linked to mutations in the CSB (ERCC6) gene, one third to mutations in the CSA (ERCC8) gene. At least 78 different mutations are known in the CSB gene and 30 in the CSA gene to date, in more than 120 genetically confirmed patients. Large clinical and molecular databases are needed to unravel genotype-phenotype correlations and to gain more insight into the underlying molecular mechanisms. © 2013 Elsevier Ireland Ltd.

Nassif J.,University of Strasbourg
Surgical technology international | Year: 2010

Laparoscopy was considered marginal to surgical specialties before 1990. Rare innovations in instruments were done. With the realization of the first laparoscopic hysterectomy, this surgical route gained wide acceptance during the 1990s. Technical advances were made by instrument companies offering a wide variety of instruments to surgeons and by surgeons themselves to cope with problems during laparoscopic procedures. Manipulators are among the first instruments that surgeons suggested to ameliorate laparoscopic performance. Instruments that have multiple functions (i.e., grasping, cutting, coagulating) are more and more appreciated because surgeons can avoid changing instruments during surgery. Manipulators offer multifunctional assistance during gynecologic surgical procedures. They are useful for exposure purposes and also for reproductive surgery (and hysterectomy). This article explains the benefits and help that a manipulator can provide, especially in total laparoscopic hysterectomy. In the latter intervention, the manipulator will help to expose the pelvis by moving the uterus in any direction, to identify structures and find anatomical landmarks such as the vaginal fornices for culdotomy, and to avoid complications by pulling the ureter away from the operative field. Also, it is useful to avoid carbon dioxide leakage at the vaginal opening and to retrieve the surgical specimen. Each step is shown in a photograph with the specific hand movements corresponding to the manipulator's handling. We think that the use of manipulators during laparoscopic surgery is very useful and helps to reduce operative time.

Brunelli A.,St Jamess Hospital | Falcoz P.E.,University of Strasbourg
Journal of Thoracic Disease | Year: 2014

To improve standardization of general thoracic surgery (GTS) practice across Europe, the European Society of Thoracic Surgeons (ESTS) has implemented a program of Institutional Accreditation. We reviewed the methods and rules of engagement of this program. A composite performance score (CPS) including outcome and process indicators is used to measure institutional performance and assess eligibility for accreditation. Eligible units are invited to participate and accept a local audit performed by an external auditors team composed by data inspectors and thoracic surgeons. In addition to data quality, a series of structural, procedural and qualification characteristics are inspected. Once the visit is complete, the team will produce an audit report to be sent to the members of the database committee for deliberation on the institutional accreditation of that unit. The Database committee will send an executive report to the ESTS Executive Committee for their final decision on the accreditation. © Pioneer Bioscience Publishing Company.

Blanc M.,University of Strasbourg
Housing Studies | Year: 2010

In France, a Housing Act, called Solidarité et Renouvellement Urbain (Solidarity and Urban Renewal), came into force in 2000. Its main aim is to challenge segregation in housing and to strengthen solidarity among citizens. It promotes a tenure mix through legal requirements: in urban areas, every commune should reach a minimum of 20 per cent social housing in its housing stock before 2020. This paper attempts to explain why policy makers believe in the virtues of a tenure mix. The second aim is to assess the discrepancies between the rhetorical level of policy aims and the pragmatic level of policy outputs, raising methodological issues on the relevance of the communal scale for the measure of segregation and social mix. The conclusion raises paradoxical issues: social class segmentation resists social mixing more strongly than ethnic segmentation; the French social mix policy strengthens ghettos and hinders the right to decent housing for the very poor. © 2010 Taylor & Francis.

Mouallem R.,University of Strasbourg
IEEE Instrumentation and Measurement Magazine | Year: 2010

This series presents some procedural guidance for inventors and entrepreneurs who would otherwise either not pursue protection for their inventions or would file a patent application pro se without the input of a qualified patent practitioner. This series will focus exclusively on patents and will not cover other forms of intellectual property (IP) such as trademarks and copyrights. It will provide tips for such inventors in order to minimize the risk of devaluing an invention, jeopardizing chances of allowance of a patent during prosecution, having a patent application being deemed unpatentable or lacking enablement, or having a patent being deemed unenforceable against infringement. Having a professional patent practitioner draft and file a patent application can be beyond the budget of many inventors. The material presented here is meant to be informational and in no way serves as legal advice. Individuals who are interested in discussing their innovations in detail should consult a qualified patent practitioner. © 2006 IEEE.

Atzenhoffer J.-P.,University of Strasbourg
Environmental Economics and Policy Studies | Year: 2012

It is widely recognized that informal monitoring and sanctions foster cooperation in common resource dilemmas. Theoretical models usually assume that agents who punish are those who cooperate on efficient harvesting norms. However, observations from the field show that sanctions are also practiced by those who overexploit the resource. Emotional reasons such as revenge or spiteful motives are suggested to account for this behavior, but none of them insist on economic incentives. Using an evolutionary model, we provide an alternative explanation for the presence of punishing actions undertaken by overexploiters. By assuming that overexploiters have the opportunity to sanction other harvesters, we find that a dual state composed of both cooperators and punishing overexploiters can be stable. Despite the typically negative judgment about such behavior, punishments inflicted by overexploiters may increase cooperation on more efficient harvesting levels. We discuss the implication of this result for resource management. © 2011 Springer.

Sparrrow J.R.,Columbia University | Hicks D.,University of Strasbourg | Hamel C.P.,French Institute of Health and Medical Research
Current Molecular Medicine | Year: 2010

Retinal pigment epithelial cells (RPE) constitute a simple layer of cuboidal cells that are strategically situated behind the photoreceptor (PR) cells. The inconspicuousness of this monolayer contrasts sharply with its importance [1]. The relationship between the RPE and PR cells is crucial to sight; this is evident from basic and clinical studies demonstrating that primary dysfunctioning of the RPE can result in visual cell death and blindness. RPE cells carry out many functions including the conversion and storage of retinoid, the phagocytosis of shed PR outer segment membrane, the absorption of scattered light, ion and fluid transport and RPE-PR apposition. The magnitude of the demands imposed on this single layer of cells in order to execute these tasks, will become apparent to the reader of this review as will the number of clinical disorders that take origin from these cells. © 2010 Bentham Science Publishers Ltd.

Ganzhorn M.,CNRS Neel Institute | Klyatskaya S.,Karlsruhe Institute of Technology | Ruben M.,Karlsruhe Institute of Technology | Ruben M.,University of Strasbourg | Wernsdorfer W.,CNRS Neel Institute
ACS Nano | Year: 2013

Due to outstanding mechanical and electronic properties, carbon nanotube nanoelectromechanical systems (NEMS) were recently proposed as ultrasensitive magnetometers for single-molecule magnets (SMM). In this article, we describe a noninvasive grafting of a SMM on a carbon nanotube NEMS, which conserves both the mechanical properties of the carbon nanotube NEMS and the magnetic properties of the SMM. We will demonstrate that the nonlinearity of a carbon nanotube's mechanical motion can be used to probe the reversal of a molecular spin, associated with a bis(phthalocyaninato)terbium(III) single-molecule magnet, providing an experimental evidence for the detection of a single spin by a mechanical degree of freedom on a molecular level. © 2013 American Chemical Society.

Thuery P.,CEA Saclay Nuclear Research Center | Harrowfield J.,University of Strasbourg
CrystEngComm | Year: 2014

Four complexes were obtained from reaction of uranyl nitrate with (1R,3S)-(+)-camphoric acid under solvo-/hydrothermal conditions with either acetonitrile or N-methyl-2-pyrrolidone (NMP) as the organic component. All complexes crystallize in chiral space groups and are enantiopure species. Complexes [(UO2)4(L)3(OH)2(H 2O)4]·3H2O (1) and [(UO 2)8K8(L)12(H2O) 12]·H2O (2) were obtained in water-acetonitrile in the presence of LiOH or KOH in excess beyond or equal to that simply required to neutralize the acid, respectively. Whereas 1 is a 1D coordination polymer including hydroxide ions resulting from hydrolysis of the uranyl aqua-ion, 2 contains octanuclear uranyl camphorate cages analogous, but for their crystallographic symmetry, to those previously published; these cages are assembled into a 3D framework by bridging potassium ions. The two complexes obtained in water-NMP, [UO2(L)(NMP)] (3) and [(UO2) 2Cu(L)3(NMP)2] (4), are devoid both of water molecules and any solvent-derived anions, and they crystallize as 2D assemblies. The sheets in 4, with a thickness of ∼14 Å, display a central layer of copper(ii) ions surrounded by two layers of uranyl ions. These and previous results suggest that solvo-/hydrothermal conditions using NMP provide a new means of avoiding the formation of uranyl-containing oligomeric or 1D polymeric hydrolysis products which are frequent and often unpredictable outcomes in the synthesis of uranyl-organic assemblies under aqueous conditions, especially in the presence of cosolvents which in themselves are susceptible to hydrolysis. The emission spectrum of compound 3 under excitation at 350 nm displays the usual vibronic fine structure in the ∼460-600 nm range, while uranyl luminescence is quenched by Cu(ii) cations in complex 4. This journal is © the Partner Organisations 2014.

Thuery P.,CEA Saclay Nuclear Research Center | Harrowfield J.,University of Strasbourg
Crystal Growth and Design | Year: 2014

all-cis-1,3,5-Cyclohexanetricarboxylic acid (LH3) was reacted with uranyl nitrate under solvo-hydrothermal conditions, either alone or in the presence of additional metal cations (Na+, K+, Ni 2+, Cu2+, or Tb3+), resulting in the crystallization of a series of eight complexes which were characterized by their crystal structures and luminescence properties. The six complexes [UO 2(H2O)5][UO2(L)]2· 2H2O·3THF (1), [Ni(bipy)2(H2O) 2][UO2(L)]2·4H2O (2), [Ni(bipy)3][Ni(bipy)2(H2O)2][UO 2(L)]4·5H2O (3), [Ni(H 2O)6][UO2(L)]2·2H 2O (4), [Cu(H2O)6][UO2(L)] 2·2H2O (5), and [Tb(H2O) 8][UO2(L)]3·8H2O (6) all contain the same {UO2(L)-}∞ anionic motif, in which the uranyl ion is tris-chelated by three L3- anions to give a two-dimensional assembly with hexagonal {63} topology. The reaction of uranyl nitrate alone with LH3 in water/N-methyl-2- pyrrolidone (NMP) yields the complex [(UO2)3(L) 2(NMP)2] (7), which crystallizes as a three-dimensional framework. Finally, in the presence of Na+, K+, or even Kemp's triacid (cis,cis-1,3,5-trimethylcyclohexane-1,3,5-tricarboxylic acid), the complex [UO2(LH)] (8) is generated, the structure of which displays a well-resolved nanotubular species possibly associated with extremely disordered molecules or counterions of uncertain nature. These nanotubules have {63} topology and can be seen as resulting from the folding of the two-dimensional assembly present in the former complexes. Emission spectra measured in the solid state show the usual vibronic fine structure, with various degrees of resolution and quenching. © 2014 American Chemical Society.

Kossinova O.,Russian Academy of Sciences | Malygin A.,Russian Academy of Sciences | Krol A.,University of Strasbourg | Karpova G.,Russian Academy of Sciences
RNA | Year: 2013

The amino acid selenocysteine is encoded by UGA, usually a stop codon, thus requiring a specialized machinery to enable its incorporation into selenoproteins. The machinery comprises the tRNASec, a 3'-UTR mRNA stem-loop termed SElenoCysteine Insertion Sequence (SECIS), which is mandatory for recoding UGA as a Sec codon, the SECIS Binding Protein 2 (SBP2), and other proteins. Little is known about the molecular mechanism and, in particular, when, where, and how the SECIS and SBP2 contact the ribosome. Previous work by others used the isolated SECIS RNA to address this question. Here, we developed a novel approach using instead engineered minimal selenoprotein mRNAs containing SECIS elements derivatized with photoreactive groups. By cross-linking experiments in rabbit reticulocyte lysate, new information could be gained about the SBP2 and SECIS contacts with components of the translation machinery at various translation steps. In particular, we found that SBP2 was bound only to the SECIS in 48S pre-initiation and 80S pretranslocation complexes. In the complex where the Sec-tRNASec was accommodated to the A site but transpeptidation was blocked, SBP2 bound the ribosome and possibly the SECIS element as well, and the SECIS had flexible contacts with the 60S ribosomal subunit involving several ribosomal proteins. Altogether, our findings led to broadening our understanding about the unique mechanism of selenocysteine incorporation in mammals. © 2013; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Schlienger J.-L.,University of Strasbourg
Medecine des Maladies Metaboliques | Year: 2014

Botanic extracts have been widely used as medicinal agents to treat diabetes in traditional Chinese medicine, in ayurvedic medicine and in folk medicine and now in phytotherapy. Unfortunately there is a paucity of definitive clinical data concerning an improvement in carbohydrate metabolism in human despite exciting in vitro and in vivo experimental results. To date there is insufficient evidence to recommend the use of any herbal to treat hyperglycemia and their related risk factors or complications. However, clinical studies should be conducted with care, because the plants are filing many active molecules that can lead to new antidiabetic agents. © 2014 Elsevier Masson SAS.

Duputel Z.,California Institute of Technology | Rivera L.,University of Strasbourg | Kanamori H.,California Institute of Technology | Hayes G.,U.S. Geological Survey
Geophysical Journal International | Year: 2012

Rapid characterization of the earthquake source and of its effects is a growing field of interest. Until recently, it still took several hours to determine the first-order attributes of a great earthquake (e.g. M w≥ 7.5), even in a well-instrumented region. The main limiting factors were data saturation, the interference of different phases and the time duration and spatial extent of the source rupture. To accelerate centroid moment tensor (CMT) determinations, we have developed a source inversion algorithm based on modelling of the W phase, a very long period phase (100-1000s) arriving at the same time as the P wave. The purpose of this work is to finely tune and validate the algorithm for large-to-moderate-sized earthquakes using three components of W phase ground motion at teleseismic distances. To that end, the point source parameters of all M w≥ 6.5 earthquakes that occurred between 1990 and 2010 (815 events) are determined using Federation of Digital Seismograph Networks, Global Seismographic Network broad-band stations and STS1 global virtual networks of the Incorporated Research Institutions for Seismology Data Management Center. For each event, a preliminary magnitude obtained from W phase amplitudes is used to estimate the initial moment rate function half duration and to define the corner frequencies of the passband filter that will be applied to the waveforms. Starting from these initial parameters, the seismic moment tensor is calculated using a preliminary location as a first approximation of the centroid. A full CMT inversion is then conducted for centroid timing and location determination. Comparisons with Harvard and Global CMT solutions highlight the robustness of W phase CMT solutions at teleseismic distances. The differences in M w rarely exceed 0.2 and the source mechanisms are very similar to one another. Difficulties arise when a target earthquake is shortly (e.g. within 10 hr) preceded by another large earthquake, which disturbs the waveforms of the target event. To deal with such difficult situations, we remove the perturbation caused by earlier disturbing events by subtracting the corresponding synthetics from the data. The CMT parameters for the disturbed event can then be retrieved using the residual seismograms. We also explore the feasibility of obtaining source parameters of smaller earthquakes in the range 6.0 ≤M w < 6.5. Results suggest that the W phase inversion can be implemented reliably for the majority of earthquakes of M w= 6 or larger. © 2012 The Authors Geophysical Journal International © 2012 RAS.

Hill R.J.,CSIRO | Billas I.M.L.,University of Strasbourg | Bonneton F.,CNRS Lyon Institute of Functional Genomics | Graham L.D.,CSIRO | And 2 more authors.
Annual Review of Entomology | Year: 2013

In 1974, Ashburner and colleagues postulated a model to explain the control of the puffing sequence on Drosophila polytene chromosomes initiated by the molting hormone 20-hydroxyecdysone. This model inspired a generation of molecular biologists to clone and characterize elements of the model, thereby providing insights into the control of gene networks by steroids, diatomic gases, and other small molecules. It led to the first cloning of the EcR subunit of the heterodimeric EcR-USP ecdysone receptor. X-ray diffraction studies of the ligand-binding domain of the receptor are elucidating the specificity of receptor-ecdysteroid interactions, the selectivity of some environmentally friendly insecticides, the evolution of the EcR-USP heterodimer, and indeed Ashburner's classical biochemical evidence for the central role of the ecdysone receptor in his model. © 2013 by Annual Reviews. All rights reserved.

Duputel Z.,California Institute of Technology | Rivera L.,University of Strasbourg | Fukahata Y.,Kyoto University | Kanamori H.,California Institute of Technology
Geophysical Journal International | Year: 2012

Source inversion is a widely used practice in seismology. Magnitudes, moment tensors, slip distributions are now routinely calculated and disseminated whenever an earthquake occurs. The accuracy of such models depends on many aspects like the event magnitude, the data coverage and the data quality (instrument response, isolation, timing, etc.). Here, like in any observational problem, the error estimation should be part of the solution. It is however very rare to find a source inversion algorithm which includes realistic error analyses, and the solutions are often given without any estimates of uncertainties. Our goal here is to stress the importance of such estimation and to explore different techniques aimed at achieving such analyses. In this perspective, we use the W phase source inversion algorithm recently developed to provide fast CMT estimations for large earthquakes. We focus in particular on the linear-inverse problem of estimating the moment tensor components at a given source location. We assume that the initial probability densities can be modelled by Gaussian distributions. Formally, we can separate two sources of error which generally contribute to the model parameter uncertainties. The first source of uncertainty is the error introduced by the more or less imperfect data. This is carried by the covariance matrix for the data (C d). The second source of uncertainty, often overlooked, is associated with modelling error or mismodelling. This is represented by the covariance matrix on the theory, C T. Among the different sources of mismodelling, we focus here on the modelling error associated with the mislocation of the centroid position. Both C d and C T describe probability densities in the data space and it is well known that it is in fact C D=C d+C T that should be included into the error propagation process. In source inversion problems, like in many other fields of geophysics, the data covariance (C D) is often considered as diagonal or even proportional to the identity matrix. In this work, we demonstrate the importance of using a more realistic form for C D. If we incorporate accurate covariance components during the inversion process, it refines the posterior error estimates but also improves the solution itself. We discuss these issues using several synthetic tests and by applying the W phase source inversion algorithm to several large earthquakes such as the recent 2011 Tohoku-oki earthquake. © 2012 The Authors Geophysical Journal International © 2012 RAS.

Wencel-Delord J.,University of Strasbourg | Glorius F.,University of Munster
Nature Chemistry | Year: 2013

The beginning of the twenty-first century has witnessed significant advances in the field of C-H bond activation, and this transformation is now an established piece in the synthetic chemists' toolbox. This methodology has the potential to be used in many different areas of chemistry, for example it provides a perfect opportunity for the late-stage diversification of various kinds of organic scaffolds, ranging from relatively small molecules like drug candidates, to complex polydisperse organic compounds such as polymers. In this way, C-H activation approaches enable relatively straightforward access to a plethora of analogues or can help to streamline the lead-optimization phase. Furthermore, synthetic pathways for the construction of complex organic materials can now be designed that are more atom- and step-economical than previous methods and, in some cases, can be based on synthetic disconnections that are just not possible without C-H activation. This Perspective highlights the potential of metal-catalysed C-H bond activation reactions, which now extend beyond the field of traditional synthetic organic chemistry. © 2013 Macmillan Publishers Limited.

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.

Cheung C.S.N.,State University of New York at Stony Brook | Baud P.,University of Strasbourg | Wong T.-F.,State University of New York at Stony Brook
Geophysical Research Letters | Year: 2012

Compaction bands are strain localization structures that are relatively impermeable and can act as barriers to fluid flow in reservoirs. Laboratory studies have shown that discrete compaction bands develop in several sandstones with porosities of 22-25%, at stress states in the transitional regime between brittle faulting and cataclastic flow. To identify the microstructural parameters that influence compaction band formation, we conducted a systematic study of mechanical deformation, failure mode and microstructural evolution in Bleurswiller and Boise sandstones, of similar porosity (∼25%) and mineralogy but different sorting. Discrete compaction bands were observed to develop over a wide range of pressure in the Bleurswiller sandstone that has a relatively uniform grain size distribution. In contrast, compaction localization was not observed in the poorly sorted Boise sandstone. Our results demonstrate that grain size distribution exerts important influence on compaction band development, in agreement with recently published data from Valley of Fire and Buckskin Gulch, as well as numerical studies. © 2012. American Geophysical Union. All Rights Reserved.

Thuery P.,CEA Saclay Nuclear Research Center | Harrowfield J.,University of Strasbourg
European Journal of Inorganic Chemistry | Year: 2014

As a heterofunctional pro-ligand with both hard and soft coordination sites, trans-3-(3-pyridyl)acrylic acid (LH) is of potential interest for the design of heterometallic complexes of f- and d-block cations, as previously shown in the case of lanthanides. The reaction of LH with uranyl nitrate in water/acetonitrile at 180 °C yields the complex [(UO2)3(L)(HL)(O)(OH)3]·2.5H2O·CH3CN (2), which is different from the previously reported complex [UO2(L)(OH)] (1). Complex 2 crystallizes as a ribbon-like 1D coordination polymer with a skeleton bridged by oxido and hydroxido ligands, in which the uranyl cation is bound to the bridging bidentate carboxylato groups, and the pyridyl groups (one of them protonated) are directed sideways. In the presence of copper nitrate, the reaction affords the heterometallic complex [(UO2)2Cu(L)3(O)(H2O)](NO3) (3), in which the harder uranium atom is bound to two μ3-oxido anions and to chelating and bridging carboxylato groups to generate a tetranuclear secondary building unit, whereas the softer copper cations are bound to three pyridyl groups and only one carboxylato donor. The copper atoms are further involved in cation-cation interactions with uranyl oxido groups, and the Cu-O(oxido) bond lengths of 2.162(13) and 2.248(16) Å are among the shortest measured to date. 3 crystallizes as a 3D assembly, which displays narrow channels, and it illustrates the ability of copper cations, in combination with a ditopic ligand, to assemble discrete uranyl-containing units into a framework structure. The emission spectra of complexes 1 and 2 in the solid state display the usual vibronic progression of the uranyl ion in the range 450-650 nm, and the width of the bands indicates that they may be the superposition of slightly different series, due to the inequivalent uranyl centres in the lattices. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

D'Ischia M.,University of Naples Federico II | Napolitano A.,University of Naples Federico II | Ball V.,University of Strasbourg | Ball V.,French National Institute for Agricultural Research | And 2 more authors.
Accounts of Chemical Research | Year: 2014

Polydopamine (PDA), a black insoluble biopolymer produced by autoxidation of the catecholamine neurotransmitter dopamine (DA), and synthetic eumelanin polymers modeled to the black functional pigments of human skin, hair, and eyes have burst into the scene of materials science as versatile bioinspired functional systems for a very broad range of applications. PDA is characterized by extraordinary adhesion properties providing efficient and universal surface coating for diverse settings that include drug delivery, micro fluidic systems, and water-treatment devices. Synthetic eumelanins from dopa or 5,6-dihydroxyindoles are the focus of increasing interest as UV-absorbing agents, antioxidants, free radical scavengers, and waterdependent hybrid electronic-ionic semiconductors. Because of their peculiar physicochemical properties, eumelanins and PDA hold considerable promise in nanomedicine and bioelectronics, as they are biocompatible, biodegradable, and exhibit suitable mechanical properties for integration with biological tissues. Despite considerable similarities, very few attempts have so far been made to provide an integrated unifying perspective of these two fields of technology-oriented chemical research, and progress toward application has been based more on empirical approaches than on a solid conceptual framework of structure-property relationships. The present Account is an attempt to fill this gap. Following a vis-à-vis of PDA and eumelanin chemistries, it provides an overall view of the various levels of chemical disorder in both systems and draws simple correlations with physicochemical properties based on experimental and computational approaches. The potential of large-scale simulations to capture the macroproperties of eumelanin-like materials and their hierarchical structures, to predict the physicochemical properties of new melanin-inspired materials, to understand the structure-property-function relationships of these materials from the bottom up, and to design and optimize materials to achieve desired properties is illustrated. The impact of synthetic conditions on melanin structure and physicochemical properties is systematically discussed for the first time. Rational tailoring strategies directed to critical control points of the synthetic pathways, such as dopaquinone, DAquinone, and dopachrome, are then proposed, with a view to translating basic chemical knowledge into practical guidelines for material manipulation and tailoring. This key concept is exemplified by the recent demonstration that varying DA concentration, or using Tris instead of phosphate as the buffer, results in PDA materials with quite different structural properties. Realizing that PDA and synthetic eumelanins belong to the same family of functional materials may foster unprecedented synergisms between research fields that have so far been apart in the pursuit of tailorable and marketable materials for energy, biomedical, and environmental applications. (Chemical Equation Presented). © 2014 American Chemical Society.

Li Z.,Fudan University | Li B.,Fudan University | Shen W.-H.,University of Strasbourg | Huang H.,CAS Institute of Plant Physiology and Ecology | Dong A.,Fudan University
Plant Journal | Year: 2012

Summary Leaf organogenesis occurs within the peripheral zone of the shoot apical meristem (SAM). The initiation and subsequent development of a leaf requires the stable repression of a highly conserved class of plant genes, namely class-I KNOTTED 1-like homeobox (KNOX) genes. In Arabidopsis, this class comprises four members: SHOOT MERISTEMLESS (STM); BREVIPEDICELLUS (BP); KNAT2 and KNAT6. Two transcription factors, ASYMMETRIC LEAVES 1 (AS1) and AS2, are known to form a protein complex to repress BP, KNAT2 and KNAT6. Here, we show that AS2 physically interacts with the microRNA319 (miR319)-regulated CINCINNATA-like TEOSINTE BRANCHED 1-CYCLOIDEA-PCF (TCP) transcription factors in vitro and in vivo. By chromatin immunoprecipitation, we demonstrated that AS2 and TCPs bind to similar regions of the BP and KNAT2 promoters. In addition, DNA-binding activities of the TCP proteins rely on the presence of AS2, as the activities were dramatically reduced in the as2 mutant. The jaw-D mutant, which overexpresses MIR319a to downregulate several target TCP genes, strongly enhanced the as2 phenotypes and caused more severe ectopic expression of BP, KNAT2 and KNAT6. Our results reveal that KNOX repression requires different types of transcription factors that function together to ensure normal leaf development. © 2012 Blackwell Publishing Ltd.

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.

Stricher F.,CNRS Immunopathology and Therapeutic Chemistry | Macri C.,CNRS Immunopathology and Therapeutic Chemistry | Ruff M.,University of Strasbourg | Muller S.,CNRS Immunopathology and Therapeutic Chemistry
Autophagy | Year: 2013

HSPA8/HSC70 protein is a fascinating chaperone protein. It represents a constitutively expressed, cognate protein of the HSP70 family, which is central in many cellular processes. In particular, its regulatory role in autophagy is decisive. We focused this review on HSC70 structure-function considerations and based on this, we put a particular emphasis on HSC70 targeting by small molecules and peptides in order to develop intervention strategies that deviate some of HSC70 properties for therapeutic purposes. Generating active biomolecules regulating autophagy via its effect on HSC70 can effectively be designed only if we understand the fine relationships between HSC70 structure and functions. © 2013 Landes Bioscience.

Nedelcu M.,University of Strasbourg | Cotirlet A.,Moinesti Emergency Hospital | Noel P.,Private Hospital La Casamance | Gagner M.,Sacre Coeur Hospital
Obesity Surgery | Year: 2015

Background: Leaks after laparoscopic sleeve gastrectomy (LSG) are estimated to be the most serious complication of this procedure due to difficult healing process using non-standardized endoscopic approaches. Initially, endoscopic management recommended the use of stents.Methods: A total of 19 patients received endoscopic treatment after LSG to manage leaks. The leak was classified depending on the primary orifice’s size (more or less than 10 mm) or on the presence of gastric stenosis. The primary aim was to develop a therapeutic algorithm in order to reduce the number of endoscopic procedures.Results: The average number of endoscopic procedures was 2.8 (range 2–5) in group A (leak size <10 mm) and 4 (range 3–7) in group B (leak size >10 mm). Two out of 13 patients had stent migration (15.4 %) and required an additional procedure, one in group A and another in group B.The average duration to achieve complete healing was 3.4 months (range 2–14 months), 2.8 months for group A and 3.9 months for group B.Conclusions: Limited data can be found in the literature on leaks after LSG. A new algorithm based on leak size permits standardization of endoscopic management and reduces procedures after LSG. © 2015, Springer Science+Business Media New York.

RUGRAFF E. Foreign direct investment (FDI) and supplier-oriented upgrading in the Czech motor vehicle industry, Regional Studies. The Czech Republic has succeeded in building a new comparative advantage in motor vehicle and motor component production. Yet, the Czech-owned companies only contribute weakly to the Czech upgrading. The Czech-owned companies are totally absent from first-tier suppliers and are only linked by casual technological relationships to foreign-owned multinational subsidiaries. This kind of relationship limits the vertical spillovers from foreign-owned multinational subsidiaries and is responsible for the existence of a weak link in the Czech automotive system that may foster the relocation of foreign-owned subsidiaries in foreign countries. © 2010 Regional Studies Association.

Mosbech H.,Copenhagen University | Deckelmann R.,Center for Clinical Trials | De Blay F.,University of Strasbourg | Pastorello E.A.,Ospedale Niguarda Ca Granda | And 3 more authors.
Journal of Allergy and Clinical Immunology | Year: 2014

Background Investigations meeting current standards are limited for the effect of house dust mite (HDM) allergy immunotherapy in asthmatic patients. Objective This trial investigated the efficacy and safety of a standardized quality (SQ; allergen standardization method proprietary to the trial sponsor) HDM SLIT-tablet (ALK, Hørsholm, Denmark) in adults and adolescents with HDM respiratory allergic disease. This publication reports the results of the endpoints related to asthma. Methods Six hundred four subjects 14 years or older with HDM allergic rhinitis and mild-to-moderate asthma were randomized 1:1:1:1 to double-blind daily treatment with one of 3 active doses (1, 3, or 6 SQ-HDM) or placebo. Their use of inhaled corticosteroid (ICS) was standardized and adjusted at baseline and the end of treatment to the lowest dose providing asthma control. The primary end point was a reduction in ICS dose from the individual subject's baseline dose after 1 year of treatment. Results The primary analysis revealed a mean difference between 6 SQ-HDM and placebo in the reduction in daily ICS dose of 81 μg (P =.004). Relative mean and median reductions were 42% and 50% for 6 SQ-HDM and 15% and 25% for placebo, respectively. No statistically significant differences were observed for the other assessed asthma parameters, reflecting the intended controlled status of the trial subjects. The most common adverse events were local reactions in the mouth. The rate and severity of adverse events were higher for 3 and 6 SQ-HDM than for 1 SQ-HDM and placebo. Conclusion Efficacy in mild-to-moderate asthma of 6 SQ-HDM relative to placebo was demonstrated by a moderate statistically significant reduction in the ICS dose required to maintain asthma control. All active doses were well tolerated. © 2014 The Authors. Published by Elsevier Inc.

Vincentelli R.,CNRS Architecture and Functions of Biological Macromolecules Lab | Romier C.,University of Strasbourg
Current Opinion in Structural Biology | Year: 2013

Escherichia coli is the major expression host for the production of homogeneous protein samples for structural studies. The introduction of high-throughput technologies in the last decade has further revitalized E. coli expression, with rapid assessment of different expression strategies and successful production of an ever-increasing number of proteins. In addition, miniaturization of biophysical characterizations should soon help choosing expression strategies based on quantitative and qualitative observations. Since many proteins form larger assemblies in vivo, dedicated co-expression systems for E. coli are now addressing the reconstitution of protein complexes. Yet, co-expression approaches show an increasing experimental combinatorial intricacy when considering larger complexes. The current combination of high-throughput and co-expression technologies paves the way, however, for tackling larger and more complex macromolecular assemblies. © 2013.

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.

Jouniaux L.,University of Strasbourg | Ishido T.,Japan National Institute of Advanced Industrial Science and Technology
International Journal of Geophysics | Year: 2012

We describe in this paper the theoretical background for the electrokinetics in rocks and in porous media, to be included in the special issue "Electrokinetics in Earth Sciences" of International Journal of Geophysics. We describe the methodology used for self-potential (SP) and for seismoelectromagnetic measurements, for both field and laboratory experiments and for modelling. We give a large bibliography on the studies performed in hydrology to detect at distance the water flow, to deduce the thickness of the aquifer and to predict the hydraulic conductivity. The observation of SP has also been proposed to detect fractures in boreholes, to follow the hydraulic fracturing, and to predict the earthquakes. Moreover, we detail the studies on geothermal applications. © 2012 L. Jouniaux and T. Ishido.

Tora L.,University of Strasbourg | Timmers H.,University Utrecht
Trends in Biochemical Sciences | Year: 2010

Early work established the TATA box as the predominant DNA element of core promoters which directed accurate transcription initiation by RNA polymerase II. This element is recognized by TATA-binding protein (TBP), the central DNA-binding subunit of TFIID. In vitro binding and structural experiments indicate that TBP has a strong preference for TATA and induces severe DNA bending. Recent in vivo studies in Saccharomyces cerevisiae indicate that TBP turnover is higher at TATA-containing than at TATA-less promoters; this turnover seems to be regulated by NC2 and Mot1p. We propose that bending of TATA by TBP acts in synergy with NC2 and Mot1p to release TBP more rapidly from TATA promoters in vivo, thus providing a rationale for the predominance of TATA boxes in highly regulated promoters versus constitutively active TATA-less promoters. © 2010 Elsevier Ltd.

Leveque D.,University of Strasbourg
Anticancer Research | Year: 2014

In recent years, much has been discussed on the development of oral anticancer treatment in terms of practical aspects and convenience for the patient. Less has been devoted to the potential of subcutaneous administration as a parenteral alternative. However, recent approvals (bortezomib, omacetaxine, trastuzumab) seem to show a renewed interest in this route of administration. All anticancer agents given subcutaneously display a very high bioavailability (>80%) and are rapidly absorbed (except the monoclonal antibodies trastuzumab and alemtuzumab). Subcutaneous delivery does not impact on the rate of elimination when compared to the intravenous route (azacitidine, cladribine, bortezomib, trastuzumab). Some formulations may be self-administered in educated patients (methotrexate, cladribine) but others require hospitalization (omacetaxine). When available, comparative studies with intravenous administration showed comparable clinical issues with an advantage for subcutaneous bortezomib with regard to the occurrence of peripheral neurotoxicity. Subcutaneous formulations of trastuzumab and, in the future rituximab, may allow for ambulatory treatment and self-administration. From an economic point of view, subcutaneous formulations of mono