Paris, France
Paris, France

Paris Diderot University - Paris 7, also known as Université Paris Diderot - Paris 7, is a leading French University located in Paris, France. It is one of the heirs of the Faculty of science of the University of Paris , which, founded in the mid-12th century, was one of the earliest universities established in Europe. It adopted its current name in 1994.Featuring two Nobel Prize laureates, a Fields Medal winner and two former French Ministers of Education among its faculty or former faculty, the University is famous for its teaching in science, especially in mathematics. Indeed many fundamental results of the theory of Probability have been discovered at one of its research centers, the Laboratoire de Probabilités et Modèles Aléatoires . The university is also known for its teaching in psychology, which adopts a specific approach drawing from both the domains of psychopathology and psychoanalysis.But the University also hosts many others disciplines: currently, there are 2300 educators and researchers, 1100 administrative personnel and 26,000 students studying humanities, science, and medicine.Paris Diderot University is a founding member of the higher education and research alliance Sorbonne Paris Cité which is a Public Institution for Scientific Cooperation bringing together four renowned Parisian universities and four higher education and research institutes.Formerly based at the Jussieu Campus in the 5th arrondissement, the University moved to a new campus in the 13th arrondissement, in the Paris Rive Gauche neighborhood. The first buildings were brought into use in 2006. The university has many facilities in Paris, and two in other parts of the general area. In 2012, the University completed its move in its new ultra-modern campus. Wikipedia.


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Patent
French Institute of Health, Medical Research and University Paris Diderot | Date: 2015-04-09

The present invention relates to a method for preventing Gram-negative bacterial colonization of an oropharyngeal material, the said method comprising bringing into contact a composition comprising a cranberry-derived proanthocyanidin extract on at least a part of the surface area of the said material.


Patent
French National Center for Scientific Research and University Paris Diderot | Date: 2015-05-04

The present invention relates to porphyrins of formula (I): wherein R^(1 )to R^(6), R^(1) to R^(6), X, X Y and Y are as described in claim 1. The invention also relates to complexes of said porphyrins with transition metals, in particular iron, preferably as Fe(III) or Fe(0) complex, and salts thereof, use thereof as catalysts for the selective electrochemical reduction of CO_(2 )into CO, electrochemical cells comprising said complexes, and a method for selectively reducing electrochemically CO_(2 )into CO using said complexes.


Patent
French Institute of Health, Medical Research, University Paris Diderot, University of Paris 13 and Assistance Publique Hopitaux De Paris | Date: 2016-11-22

The present invention relates to various soluble forms of CD31, including a novel form which is shed by activated platelets and released into the circulation. Methods for detecting said soluble forms of CD31 are disclosed, as are methods of specifically 1 detecting said platelet-derived shed CD31 and the use of such methods as a diagnostic tool.


Flutre T.,French National Institute for Agricultural Research | Duprat E.,University Paris Diderot | Feuillet C.,French National Institute for Agricultural Research | Quesneville H.,French National Institute for Agricultural Research
PLoS ONE | Year: 2011

Transposable elements (TEs) are mobile, repetitive DNA sequences that are almost ubiquitous in prokaryotic and eukaryotic genomes. They have a large impact on genome structure, function and evolution. With the recent development of highthroughput sequencing methods, many genome sequences have become available, making possible comparative studies of TE dynamics at an unprecedented scale. Several methods have been proposed for the de novo identification of TEs in sequenced genomes. Most begin with the detection of genomic repeats, but the subsequent steps for defining TE families differ. High-quality TE annotations are available for the Drosophila melanogaster and Arabidopsis thaliana genome sequences, providing a solid basis for the benchmarking of such methods. We compared the performance of specific algorithms for the clustering of interspersed repeats and found that only a particular combination of algorithms detected TE families with good recovery of the reference sequences. We then applied a new procedure for reconciling the different clustering results and classifying TE sequences. The whole approach was implemented in a pipeline using the REPET package. Finally, we show that our combined approach highlights the dynamics of well defined TE families by making it possible to identify structural variations among their copies. This approach makes it possible to annotate TE families and to study their diversification in a single analysis, improving our understanding of TE dynamics at the whole-genome scale and for diverse species. © 2011 Flutre et al.


De Sousa R.,University of Victoria | Allen M.,University of Victoria | Cazayous M.,University Paris Diderot
Physical Review Letters | Year: 2013

We present a microscopic theory that shows the importance of spin-orbit coupling in perovskite compounds with heavy ions. In BiFeO3 (BFO) the spin-orbit coupling at the bismuth ion sites results in a special kind of magnetic anisotropy that is linear in the applied E field. This interaction can convert the cycloid ground state into a homogeneous antiferromagnet, with a weak ferromagnetic moment whose orientation can be controlled by the E-field direction. Remarkably, the E-field control of magnetism occurs without poling the ferroelectric moment, providing a pathway for reduced energy dissipation in spin-based devices made of insulators. © 2013 American Physical Society.


Yan M.,Peking University | Dryer D.,Hazen and Sawyer | Korshin G.V.,University of Washington | Benedetti M.F.,University Paris Diderot
Water Research | Year: 2013

This study examined the binding of copper(II) by Suwannee River fulvic acid (SRFA) using the method of differential absorbance that was used at environmentally-relevant concentrations of copper and SRFA. The pH- and metal-differential spectra were processed via numeric deconvolution to establish commonalities seen in the changes of absorbance caused by deprotonation of SRFA and its interactions with copper(II) ions. Six Gaussian bands were determined to be present in both the pH- and Cu-differential spectra. Their maxima were located, in the order of increasing wavelengths at 208 nm, 242 nm, 276 nm, 314 nm, 378 nm and 551 nm. The bands with these maxima were denoted as A0, A1, A2, A3, A4 and A5, respectively. Properties of these bands were compared with those existing in the spectra of model compounds such as sulfosalicylic acid (SSA), tannic acid (TA), and polystyrenesulfonic acid-co-maleic acid (PSMA). While none of the features observed in differential spectra of the model compound were identical to those present in the case of SRFA, Gaussian bands A1, A3 and possibly A2 were concluded to be largely attributable to a combination of responses of salicylic- and polyhydroxyphenolic groups. In contrast, bands A4 and A5 were detected in the differential spectra of SRFA only. Their nature remains to be elucidated. To examine correlations between the amount of copper(II) bound by SRFA and changes of its absorbance, differential absorbances measured at indicative wavelengths 250 nm and 400 nm were compared with the total amount of SRFA-bound copper estimated based on Visual MINTEQ calculations. This examination showed that the differential absorbances of SRFA in a wide range of pH values and copper concentrations were strongly correlated with the concentration of SRFA-bound copper. The approach presented in this study can be used to generate in situ information concerning the nature of functional groups in humic substances engaged in interactions with metals ions. This information can be useful for further elaboration and development of detailed theoretic models that describe the complexation of metals in the environment. © 2012 Elsevier Ltd.


Yan M.,Peking University | Wang D.,CAS Research Center for Eco Environmental Sciences | Korshin G.V.,University of Washington | Benedetti M.F.,University Paris Diderot
Water Research | Year: 2013

This study introduces the concept of consistent examination of changes of log-transformed absorbance spectra of dissolved organic matter (DOM) at incrementally increasing concentrations of heavy metal cations such as copper, cadmium, and aluminum at environmentally relevant concentrations. The approach is designed to highlight contributions of low-intensity absorbance features that appear to be especially sensitive to DOM reactions. In accord with this approach, log-transformed absorbance spectra of fractions of DOM from the Suwannee River were acquired at varying pHs and concentrations of copper, cadmium, and aluminum. These log-transformed spectra were processed using the differential approach and used to examine the nature of the observed changes of DOM absorbance and correlate them with the extent of Me-DOM complexation. Two alternative parameters, namely the change of the spectral slope in the range of wavelengths 325-375 nm (DSlope325-375) and differential logarithm of DOM absorbance at 350 nm (DLnA350) were introduced to quantify Cu(II), Cd(II), and Al(III) binding onto DOMs. DLnA350 and DSlope325-375 datasets were compared with the amount of DOM-bound Cu(II), Cd(II), and Al(III) estimated based on NICA-Donnan model calculations. This examination showed that the DLnA350 and DSlope325-375 acquired at various pH values, metal ions concentrations, and DOM types were strongly and unambiguously correlated with the concentration of DOM-bound metal ions. The obtained experimental results and their interpretation indicate that the introduced DSlope325-375 and DLnA35 parameters are predictive of and can be used to quantify in situ metal ions interactions with DOMs. The presented approach can be used to gain more information about DOM-metal interactions and for further optimization of existing formal models of metal-DOM complexation. © 2013 Elsevier Ltd.


Lee T.,National University of Singapore | Magniez F.,University Paris Diderot | Santha M.,National University of Singapore | Santha M.,University Paris Diderot
Proceedings of the Annual ACM-SIAM Symposium on Discrete Algorithms | Year: 2013

We show that the quantum query complexity of detecting if an n-vertex graph contains a triangle is O(n9/7). This improves the previous best algorithm of Belovs [2] making O(n35/27) queries. For the problem of determining if an operation o:S x S → S is associative, we give an algorithm making O(|S|10/7) queries, the first improvement to the trivial O(|5|3/2) application of Grover search. Our algorithms are designed using the learning graph framework of Belovs. We give a family of algorithms for detecting constant-sized subgraphs, which can possibly be directed and colored. These algorithms are designed in a simple high-level language; our main theorem shows how this high-level language can be compiled as a learning graph and gives the resulting complexity. The key idea to our improvements is to allow more freedom in the parameters of the database kept by the algorithm. As in our previous work [9], the edge slots maintained in the database are specified by a graph whose edges are the union of regular bipartite graphs, the overall structure of which mimics that of the graph of the certificate. By allowing these bipartite graphs to be unbalanced and of variable degree we obtain better algorithms. Copyright © SIAM.


Amon A.,Rennes Institute of Physics | Nguyen V.B.,University Paris Diderot | Bruand A.,ISTO | Crassous J.,Rennes Institute of Physics | Clement E.,University Paris Diderot
Physical Review Letters | Year: 2012

We study experimentally the dynamical heterogeneities occurring at slow shear, in a model amorphous glassy material, i.e., a 3D granular packing. The deformation field is resolved spatially by using a diffusive wave spectroscopy technique. The heterogeneities show up as localized regions of strong deformations spanning a mesoscopic size of about 10 grains and called the "hot spots." The spatial clustering of hot spots is linked to the subsequent emergence of shear bands. Quantitatively, their appearance is associated with the macroscopic plastic deformation, and their rate of occurrence gives a physical meaning to the concept of "fluidity," recently used to describe the local and nonlocal rheology of soft glassy materials. © 2012 American Physical Society.


Fihey A.,University of Nantes | Perrier A.,University Paris Diderot | Perrier A.,University Pierre and Marie Curie | Browne W.R.,University of Groningen | And 2 more authors.
Chemical Society Reviews | Year: 2015

Molecular systems encompassing more than one photochromic entity can be used to build highly functional materials, thanks to their potential multi-addressability and/or multi-response properties. Over the last decade, the synthesis and spectroscopic and kinetic characterisation as well as the modeling of a wide range of multiphotochromes have been achieved in a field that is emerging as a distinct branch of photochemistry. In this review, we provide an overview of the available multiphotochromic compounds which use a variety of photoactive building blocks, e.g., diarylethene, azobenzene, spiropyran, naphthopyran or fulgimide derivatives. Their efficiency in terms of multi-responsiveness is discussed and several strategies to circumvent the most common limitation (i.e., the loss of photochromism of one part) are described. © The Royal Society of Chemistry 2015.


Ladoux B.,University Paris Diderot | Ladoux B.,National University of Singapore | Nicolas A.,Joseph Fourier University
Reports on Progress in Physics | Year: 2012

The minimal structural unit that defines living organisms is a single cell. By proliferating and mechanically interacting with each other, cells can build complex organization such as tissues that ultimately organize into even more complex multicellular living organisms, such as mammals, composed of billions of single cells interacting with each other. As opposed to passive materials, living cells actively respond to the mechanical perturbations occurring in their environment. Tissue cell adhesion to its surrounding extracellular matrix or to neighbors is an example of a biological process that adapts to physical cues. The adhesion of tissue cells to their surrounding medium induces the generation of intracellular contraction forces whose amplitude adapts to the mechanical properties of the environment. In turn, solicitation of adhering cells with physical forces, such as blood flow shearing the layer of endothelial cells in the lumen of arteries, reinforces cell adhesion and impacts cell contractility. In biological terms, the sensing of physical signals is transduced into biochemical signaling events that guide cellular responses such as cell differentiation, cell growth and cell death. Regarding the biological and developmental consequences of cell adaptation to mechanical perturbations, understanding mechanotransduction in tissue cell adhesion appears as an important step in numerous fields of biology, such as cancer, regenerative medicine or tissue bioengineering for instance. Physicists were first tempted to view cell adhesion as the wetting transition of a soft bag having a complex, adhesive interaction with the surface. But surprising responses of tissue cell adhesion to mechanical cues challenged this view. This, however, did not exclude that cell adhesion could be understood in physical terms. It meant that new models and descriptions had to be created specifically for these biological issues, and could not straightforwardly be adapted from dead matter. In this review, we present physical concepts of tissue cell adhesion and the unexpected cellular responses to mechanical cues such as external forces and stiffness sensing. We show how biophysical approaches, both experimentally and theoretically, have contributed to our understanding of the regulation of cellular functions through physical force sensing mechanisms. Finally, we discuss the different physical models that could explain how tissue cell adhesion and force sensing can be coupled to internal mechanosensitive processes within the cell body. © 2012 IOP Publishing Ltd.


Deruelle N.,University Paris Diderot | Rua J.,Brazilian Center for Research in Physics (CBPF)
Journal of Cosmology and Astroparticle Physics | Year: 2014

In this Note we show that Einstein's equations for gravity are generically invariant under "disformations". We also show that the particular subclass when this is not true yields the equations of motion of "Mimetic Gravity". Finally we give the "mimetic" generalization of the Schwarzschild solution. © 2014 IOP Publishing Ltd and Sissa Medialab srl.


Bergeron H.,University Paris - Sud | Gazeau J.P.,Brazilian Center for Research in Physics (CBPF) | Gazeau J.P.,University Paris Diderot
Annals of Physics | Year: 2014

The paper concerns integral quantization, a procedure based on operator-valued measure and resolution of the identity. We insist on covariance properties in the important case where group representation theory is involved. We also insist on the inherent probabilistic aspects of this classical-quantum map. The approach includes and generalizes coherent state quantization. Two applications based on group representation are carried out. The first one concerns the Weyl-Heisenberg group and the euclidean plane viewed as the corresponding phase space. We show that a world of quantizations exist, which yield the canonical commutation rule and the usual quantum spectrum of the harmonic oscillator. The second one concerns the affine group of the real line and gives rise to an interesting regularization of the dilation origin in the half-plane viewed as the corresponding phase space. © 2014 Elsevier Inc.


Kraljic K.,University Paris Diderot | Bournaud F.,University Paris Diderot | Martig M.,Swinburne University of Technology
Astrophysical Journal | Year: 2012

We study the evolution of galactic bars and the link with disk and spheroid formation in a sample of zoom-in cosmological simulations. Our simulation sample focuses on galaxies with present-day stellar masses in the 10 10-1011 M⊙ range, in field and loose group environments, with a broad variety of mass growth histories. In our models, bars are almost absent from the progenitors of present-day spirals at z > 1.5, and they remain rare and generally too weak to be observable down to z ≈ 1. After this characteristic epoch, the fractions of observable and strong bars rise rapidly, bars being present in 80% of spiral galaxies and easily observable in two thirds of these at z ≤ 0.5. This is quantitatively consistent with the redshift evolution of the observed bar fraction, although the latter is presently known up to z ≈ 0.8 because of band-shifting and resolution effects. Our models hence predict that the decrease in the bar fraction with increasing redshift should continue with a fraction of observable bars not larger than 10%-15% in disk galaxies at z > 1. Our models also predict later bar formation in lower-mass galaxies, in agreement with existing data. We find that the characteristic epoch of bar formation, namely redshift z ≈ 0.8-1 in the studied mass range, corresponds to the epoch at which today's spirals acquire their disk-dominated morphology. At higher redshift, disks tend to be rapidly destroyed by mergers and gravitational instabilities and rarely develop significant bars. We hence suggest that the bar formation epoch corresponds to the transition between an early "violent" phase of spiral galaxy formation at z ≥ 1 and a late "secular" phase at z ≤ 0.8. In the secular phase, the presence of bars substantially contributes to the growth of the (pseudo-)bulge, but the bulge mass budget remains statistically dominated by the contribution of mergers, interactions, and disk instabilities at high redshift. Early bars at z > 1 are often short-lived, while most of the bars formed at z ≤ 1 persist down to z = 0, late cosmological gas infall being necessary to maintain some of them. © 2012. The American Astronomical Society. All rights reserved.


Dahech S.,University of Sfax | Beltrando G.,University Paris Diderot
Climatic Change | Year: 2012

This paper studies temperature evolution in the city of Sfax (Middle Eastern Tunisia, with more than 600 000 people) from 1950 to 2007. Daily maximum and minimum temperatures recorded at Sfax observatory from 1950 to 2007 are analysed by studying their homogeneity, possible trends and their statistical significance. Linear regression, Student and Mann-Kendall trend test were applied to annual mean minimum and maximum temperature data to determine the existence and significance of trends. Using a number of statistical tests, it is found that the data measured at the surface station represent a non homogenous time-series. Furthermore, mean annual and monthly temperatures are evaluated and a statistically significant trend starting from year 1950 was found. Important increase of the surface temperature in the City of Sfax was found after 1984. The increase in the surface temperature in the city of Sfax is further associated with global, regional (e. g. Mediterranean area) and meso-scale temperature increase. In addition, the spatial pattern of surface temperature in the city of Sfax from 1982 to 2007 shows that the overall land surface temperature increased with the expansion of Urban Heat Island (UHI) from urban areas to suburban districts. © 2012 Springer Science+Business Media B.V.


Philippot P.,University Paris Diderot | Van Zuilen M.,University Paris Diderot
Nature Geoscience | Year: 2012

Volcanism on early Earth should have had an impact on atmospheric chemistry, but that impact can be challenging to reconstruct. The isotopic composition of sulphur contained in rocks deposited more than 2.45 billion years (Gyr) ago shows both mass-dependent (as denoted by δ 34 S) and mass-independent (δ 33 S) isotopic fractionation. This sulphur is predominantly in the form of suphides. These sulphides show a positive correlation between δ 34 S and δ 33 S between 4.0 and 2.45Gyr ago. Sulphates deposited episodically between about 3.5 and 3.2Gyr ago indicate a more homogeneous sulphur reservoir and show no correlation to the sulphide trend. Here we report sulphur isotope values of sulphide from volcanic ash layers in the 3.2-Gyr-old Mapepe Formation of South Africa. We find a δ 34 δ 33 S relationship that deviates from previous sulphide isotope records and instead overlaps with the range of values reported for sulphates. Coexisting sulphates and sulphides of a similar age found in Australia and India show a similar array of δ 34 δ 33 S values. We suggest that the occurrence of this δ 34 δ 33 S array reflects widespread, ultraviolet-light-triggered photodissociation of sulphur dioxide that was released into the atmosphere by short-lived but intense bursts of subaerial volcanic activity. © 2012 Macmillan Publishers Limited. All rights reserved.


Besbes I.,University of Sfax | Vilar M.R.,University Paris Diderot | Boufi S.,University of Sfax
Carbohydrate Polymers | Year: 2011

Cellulose fibres from Alfa (Alfa tenassissima), Eucalyptus and Pine pulp were fibrillated into nanosized fibrils using the homogenization process. To facilitate the fibrillation process, fibres were previously oxidised under neutral conditions to bring the carboxyl content up to 500 μmol/g. Comparison of light transmission and viscosity measurements of the ensuing gels showed that Eucalyptus and Pine fibres were more easily-fibrillated, with a yield in nanosized fibrils exceeding 90% after several passes at 600 bar, than Alfa fibres, which exhibit higher resistance to the fibrillation process. This difference in behaviour was ascribed to the higher crystallinity degree of the Alfa fibres. The morphology of the nanofibrillated cellulose (NFC) from the different fibres using FE-SEM observation revealed nanosized fibrils with widths from 5 to 20 nm, roughly the same for the three types. The reinforcing potential of the ensuing three nanofibrillated cellulose was investigated using dynamic mechanical analysis (DMA) from measurements carried out on nanocomposite films prepared by casting a mixture of NFC suspension and a commercial latex of poly(styrene-co-butyl acrylate). © 2011 Elsevier Ltd. All rights reserved.


Lund E.,University of Oslo | Oldenburg A.R.,University of Oslo | Delbarre E.,University of Oslo | Freberg C.T.,University of Oslo | And 5 more authors.
Genome Research | Year: 2013

The nuclear lamina is implicated in the organization of the eukaryotic nucleus. Association of nuclear lamins with the genome occurs through large chromatin domains including mostly, but not exclusively, repressed genes. How lamin interactions with regulatory elements modulate gene expression in different cellular contexts is unknown. We show here that in human adipose tissue stem cells, lamin A/C interacts with distinct spatially restricted subpromoter regions, both within and outside peripheral and intra-nuclear lamin-rich domains. These localized interactions are associated with distinct transcriptional outcomes in a manner dependent on local chromatin modifications. Down-regulation of lamin A/C leads to dissociation of lamin A/C from promoters and remodels repressive and permissive histone modifications by enhancing transcriptional permissiveness, but is not sufficient to elicit gene activation. Adipogenic differentiation resets a large number of lamin-genome associations globally and at subpromoter levels and redefines associated transcription outputs. We propose that lamin A/C acts as a modulator of local gene expression outcome through interaction with adjustable sites on promoters, and that these position-dependent transcriptional readouts may be reset upon differentiation. © 2013, Published by Cold Spring Harbor Laboratory Press.


Hirsch A.K.H.,CNRS Institute of Science and Supramolecular Engineering | Hirsch A.K.H.,University of Groningen | Buhler E.,University Paris Diderot | Lehn J.-M.,CNRS Institute of Science and Supramolecular Engineering
Journal of the American Chemical Society | Year: 2012

Polypeptide-type dynamic biopolymers (biodynamers) have been generated by polycondensation via acylhydrazone and imine formation of amino-acid-derived components that polymerize driven by self-organization. They have been characterized as globular particles, reminiscent of folded proteins, by cryo-TEM, LS, DOSY NMR, and SANS studies. The reversible polymers obtained show remarkably low dispersity and feature double covalent dynamics allowing for fine-tuning of both exchange and incorporation processes through pH control. In the course of build-up, they perform a selection of the most suitable building block, as indicated by the preferential incorporation of the more hydrophobic amino-acid component with increased rate and higher molecular weight of the polymer formed. The system described displays nucleation-elongation behavior driven by hydrophobic effects and represents a model for the operation of adaptation processes in the evolution of complex matter. © 2012 American Chemical Society.


Tartire-Kesri L.,Hopital Lon Berard | Tartire J.-M.,Hopital Font Pre | Tartire J.-M.,French Institute of Health and Medical Research | Logeart D.,French Institute of Health and Medical Research | And 3 more authors.
Journal of the American College of Cardiology | Year: 2012

Objectives: This study sought to demonstrate that arterial stiffness is probably underestimated in patients with heart failure with preserved ejection fraction (HFpEF) at rest and may be revealed with moderate exercise. Background: HFpEF is associated with ventriculoarterial stiffening. Methods: We compared 23 patients with stable chronic HFpEF, left ventricular ejection fraction >45%, and impaired relaxation with 15 controls without cardiac disease. Patients were compared at rest and during a 30-W exercise. The following variables were measured or calculated by Doppler echocardiography and tonometry: left ventricular volumes and end-systolic elastance (Ees), peripheral resistance, arterial elastance (Ea), arterial compliance, aortic pulse wave velocity, and carotid Peterson modulus (Ep). Results: Patients with HFpEF were comparable to controls in age, sex ratio, blood pressure, and heart rate. Ventriculoarterial coupling, assessed by Ees/Ea and Ees/Ep ratios, was moderately impaired at rest in patients compared with controls (both p < 0.01). HFpEF was associated during exercise with a major increase in Ep (+155 ± 193% vs. -5 ± 28%), pulse wave velocity (+20 ± 30% vs. -7 ± 24%), and Ea (+12 ± 15% vs. -5 ± 10%), and a lower decrease in peripheral resistance (-17 ± 12% vs. -26 ± 12%) (p < 0.05 for all). In addition, HFpEF patients showed a lower increase in stroke volume (+10 ± 16% vs. +21 ± 12%) despite a greater increase in Ees (+20 ± 18% vs. +3 ± 12%) (p < 0.05 for all). Also during exercise, adaptation of proximal ventriculoarterial coupling was impaired in HFpEF patients (Ees/Ep: -26 ± 47% vs. +20 ± 47% for controls) (p < 0.01), with no difference in Ees/Ea. Conclusions: In HFpEF patients, moderate exercise leads to a steep increase in proximal afterload that is underestimated at rest and is associated with unfavorable ventriculoarterial coupling and exercise intolerance. © 2012 American College of Cardiology Foundation.


Schmidtke P.,University of Barcelona | Le Guilloux V.,CNRS Institute of Organic and Analytical Chemistry | Maupetit J.,University Paris Diderot | Tuffery P.,University Paris Diderot
Nucleic Acids Research | Year: 2010

Computational small-molecule binding site detection has several important applications in the biomedical field. Notable interests are the identification of cavities for structure-based drug discovery or functional annotation of structures. fpocket is a small-molecule pocket detection program, relying on the geometric α-sphere theory. The fpocket web server allows: (i) candidate pocket detection-fpocket; (ii) pocket tracking during molecular dynamics, in order to provide insights into pocket dynamics-mdpocket; and (iii) a transposition of mdpocket to the combined analysis of homologous structures-hpocket. These complementary online tools allow to tackle various questions related to the identification and annotation of functional and allosteric sites, transient pockets and pocket preservation within evolution of structural families. The server and documentation are freely available at http://bioserv.rpbs.univ-paris-diderot.fr/fpocket. © The Author(s) 2010. Published by Oxford University Press.


Renaud F.,University Paris Diderot | Gieles M.,University of Cambridge | Gieles M.,University of Surrey
Monthly Notices of the Royal Astronomical Society: Letters | Year: 2013

Interacting galaxies favour the formation of star clusters but are also suspected to affect their evolution through an intense and rapidly varying tidal field. Treating this complex behaviour remains out-of-reach of (semi-)analytical studies. By computing the tidal field from galactic models and including it into star-by-star N-body simulations of star clusters, we monitor the structure and mass evolution of a population of clusters in a galaxy major merger, taking the Antennae galaxies (NGC 4038/39) as a prototype. On the long time-scale (~109 yr), the merger only indirectly affects the evolution of clusters by modifying their orbits in or around the galaxies: the mass-loss of clusters in the merger remnant is faster, while clusters ejected in the tidal debris survive much longer, compared to in an isolated galaxy. The tidal perturbations of the galactic collisions themselves are too short lived and not strong enough to significantly influence the structure and dissolution of realistically dense/massive star clusters. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.


Reffay M.,CNRS Chemistry Laboratory | Reffay M.,University Paris Diderot | Parrini M.C.,French Institute of Health and Medical Research | Cochet-Escartin O.,CNRS Chemistry Laboratory | And 7 more authors.
Nature Cell Biology | Year: 2014

The leading front of a collectively migrating epithelium often destabilizes into multicellular migration fingers where a cell initially similar to the others becomes a leader cell while its neighbours do not alter. The determinants of these leader cells include mechanical and biochemical cues, often under the control of small GTPases. However, an accurate dynamic cartography of both mechanical and biochemical activities remains to be established. Here, by mapping the mechanical traction forces exerted on the surface by MDCK migration fingers, we show that these structures are mechanical global entities with the leader cells exerting a large traction force. Moreover, the spatial distribution of RhoA differential activity at the basal plane strikingly mirrors this force cartography. We propose that RhoA controls the development of these fingers through mechanical cues: the leader cell drags the structure and the peripheral pluricellular acto-myosin cable prevents the initiation of new leader cells. © 2014 Macmillan Publishers Limited. All rights reserved.


Braybrook S.A.,University of Bern | Braybrook S.A.,University of Cambridge | Peaucelle A.,University Paris Diderot | Peaucelle A.,French National Institute for Agricultural Research
PLoS ONE | Year: 2013

How instructive signals are translated into robust and predictable changes in growth is a central question in developmental biology. Recently, much interest has centered on the feedback between chemical instructions and mechanical changes for pattern formation in development. In plants, the patterned arrangement of aerial organs, or phyllotaxis, is instructed by the phytohormone auxin; however, it still remains to be seen how auxin is linked, at the apex, to the biochemical and mechanical changes of the cell wall required for organ outgrowth. Here, using Atomic Force Microscopy, we demonstrate that auxin reduces tissue rigidity prior to organ outgrowth in the shoot apex of Arabidopsis thaliana, and that the de-methyl-esterification of pectin is necessary for this reduction. We further show that development of functional organs produced by pectin-mediated ectopic wall softening requires auxin signaling. Lastly, we demonstrate that coordinated localization of the auxin transport protein, PIN1, is disrupted in a naked-apex produced by increasing cell wall rigidity. Our data indicates that a feedback loop between the instructive chemical auxin and cell wall mechanics may play a crucial role in phyllotactic patterning. © 2013 Braybrook, Peaucelle.


Derganc J.,University of Ljubljana | Antonny B.,University of Nice Sophia Antipolis | Copic A.,University Paris Diderot
Trends in Biochemical Sciences | Year: 2013

Many cellular processes require membrane deformation, which is driven by specialized protein machinery and can often be recapitulated using pure lipid bilayers. However, biological membranes contain a large amount of embedded proteins. Recent research suggests that membrane-bound proteins with asymmetric distribution of mass across the bilayer can influence membrane bending in a nonspecific manner due to molecular crowding. This mechanism is physical in nature and arises from collisions between such 'mushroom-shaped' proteins. It can either facilitate or impede the action of protein coats, for example COPII, during vesicle budding. We describe the physics of how molecular crowding can influence membrane bending and discuss the implications for other cellular processes, such as sorting of glycosylphosphatidylinositol-anchored proteins (GPI-APs) and production of intraluminal vesicles. © 2013 Elsevier Ltd.


Cowie M.R.,Imperial College London | Woehrle H.,ResMed | Woehrle H.,Sleep and Ventilation Center Blaubeuren | Wegscheider K.,University of Hamburg | And 8 more authors.
New England Journal of Medicine | Year: 2015

BACKGROUND Central sleep apnea is associated with poor prognosis and death in patients with heart failure. Adaptive servo-ventilation is a therapy that uses a noninvasive ventilator to treat central sleep apnea by delivering servo-controlled inspiratory pressure support on top of expiratory positive airway pressure. We investigated the effects of adaptive servo-ventilation in patients who had heart failure with reduced ejection fraction and predominantly central sleep apnea. METHODS We randomly assigned 1325 patients with a left ventricular ejection fraction of 45% or less, an apnea-hypopnea index (AHI) of 15 or more events (occurrences of apnea or hypopnea) per hour, and a predominance of central events to receive guideline-based medical treatment with adaptive servo-ventilation or guidelinebased medical treatment alone (control). The primary end point in the time-toevent analysis was the first event of death from any cause, lifesaving cardiovascular intervention (cardiac transplantation, implantation of a ventricular assist device, resuscitation after sudden cardiac arrest, or appropriate lifesaving shock), or unplanned hospitalization for worsening heart failure. RESULTS In the adaptive servo-ventilation group, the mean AHI at 12 months was 6.6 events per hour. The incidence of the primary end point did not differ significantly between the adaptive servo-ventilation group and the control group (54.1% and 50.8%, respectively; hazard ratio, 1.13; 95% confidence interval [CI], 0.97 to 1.31; P = 0.10). All-cause mortality and cardiovascular mortality were significantly higher in the adaptive servo-ventilation group than in the control group (hazard ratio for death from any cause, 1.28; 95% CI, 1.06 to 1.55; P = 0.01; and hazard ratio for cardiovascular death, 1.34; 95% CI, 1.09 to 1.65; P = 0.006). CONCLUSIONS Adaptive servo-ventilation had no significant effect on the primary end point in patients who had heart failure with reduced ejection fraction and predominantly central sleep apnea, but all-cause and cardiovascular mortality were both increased with this therapy. (Funded by ResMed and others; SERVE-HF ClinicalTrials.gov number, NCT00733343.). © 2015 Massachusetts Medical Society. All rights reserved.


Ganem N.J.,Harvard University | Ganem N.J.,Boston University | Cornils H.,Harvard University | Chiu S.-Y.,Harvard University | And 7 more authors.
Cell | Year: 2014

Genetically unstable tetraploid cells can promote tumorigenesis. Recent estimates suggest that ∼37% of human tumors have undergone a genome-doubling event during their development. This potentially oncogenic effect of tetraploidy is countered by a p53-dependent barrier to proliferation. However, the cellular defects and corresponding signaling pathways that trigger growth suppression in tetraploid cells are not known. Here, we combine RNAi screening and in vitro evolution approaches to demonstrate that cytokinesis failure activates the Hippo tumor suppressor pathway in cultured cells, as well as in naturally occurring tetraploid cells in vivo. Induction of the Hippo pathway is triggered in part by extra centrosomes, which alter small G protein signaling and activate LATS2 kinase. LATS2 in turn stabilizes p53 and inhibits the transcriptional regulators YAP and TAZ. These findings define an important tumor suppression mechanism and uncover adaptive mechanisms potentially available to nascent tumor cells that bypass this inhibitory regulation. © 2014 Elsevier Inc.


Cohen A.T.,King's College | Spiro T.E.,Bayer AG | Haskell L.,Janssen Research and Development | Hu D.,Peking University | And 5 more authors.
New England Journal of Medicine | Year: 2013

BACKGROUND: The clinically appropriate duration of thromboprophylaxis in hospitalized patients with acute medical illnesses is unknown. In this multicenter, randomized, double-blind trial, we evaluated the efficacy and safety of oral rivaroxaban administered for an extended period, as compared with subcutaneous enoxaparin administered for a standard period, followed by placebo. METHODS: We randomly assigned patients 40 years of age or older who were hospitalized for an acute medical illness to receive subcutaneous enoxaparin, 40 mg once daily, for 10±4 days and oral placebo for 35±4 days or to receive subcutaneous placebo for 10±4 days and oral rivaroxaban, 10 mg once daily, for 35±4 days. The primary efficacy outcomes were the composite of asymptomatic proximal or symptomatic venous thromboembolism up to day 10 (noninferiority test) and up to day 35 (superiority test). The principal safety outcome was the composite of major or clinically relevant nonmajor bleeding. RESULTS: A total of 8101 patients underwent randomization. A primary efficacy outcome event occurred in 78 of 2938 patients (2.7%) receiving rivaroxaban and 82 of 2993 patients (2.7%) receiving enoxaparin at day 10 (relative risk with rivaroxaban, 0.97; 95% confidence interval [CI], 0.71 to 1.31; P = 0.003 for noninferiority) and in 131 of 2967 patients (4.4%) who received rivaroxaban and 175 of 3057 patients (5.7%) who received enoxaparin followed by placebo at day 35 (relative risk, 0.77; 95% CI, 0.62 to 0.96; P = 0.02). A principal safety outcome event occurred in 111 of 3997 patients (2.8%) in the rivaroxaban group and 49 of 4001 patients (1.2%) in the enoxaparin group at day 10 (P<0.001) and in 164 patients (4.1%) and 67 patients (1.7%) in the respective groups at day 35 (P<0.001). CONCLUSIONS: In acutely ill medical patients, rivaroxaban was noninferior to enoxaparin for standard-duration thromboprophylaxis. Extended-duration rivaroxaban reduced the risk of venous thromboembolism. Rivaroxaban was associated with an increased risk of bleeding. (Funded by Bayer HealthCare Pharmaceuticals and Janssen Research and Development; MAGELLAN ClinicalTrials.gov number, NCT00571649.) Copyright © 2013 Massachusetts Medical Society.


Durand S.,University Paris Diderot | Gilet L.,University Paris Diderot | Bessieres P.,French National Institute for Agricultural Research | Nicolas P.,French National Institute for Agricultural Research | Condon C.,University Paris Diderot
PLoS Genetics | Year: 2012

Bacillus subtilis possesses three essential enzymes thought to be involved in mRNA decay to varying degrees, namely RNase Y, RNase J1, and RNase III. Using recently developed high-resolution tiling arrays, we examined the effect of depletion of each of these enzymes on RNA abundance over the whole genome. The data are consistent with a model in which the degradation of a significant number of transcripts is dependent on endonucleolytic cleavage by RNase Y, followed by degradation of the downstream fragment by the 5′-3′ exoribonuclease RNase J1. However, many full-size transcripts also accumulate under conditions of RNase J1 insufficiency, compatible with a model whereby RNase J1 degrades transcripts either directly from the 5′ end or very close to it. Although the abundance of a large number of transcripts was altered by depletion of RNase III, this appears to result primarily from indirect transcriptional effects. Lastly, RNase depletion led to the stabilization of many low-abundance potential regulatory RNAs, both in intergenic regions and in the antisense orientation to known transcripts. © 2012 Durand et al.


Yan M.,Peking University | Benedetti M.F.,University Paris Diderot | Korshin G.V.,University of Washington
Water Research | Year: 2013

This study examined the evolution of absorbance and fluorescence spectra of standard Suwannee River fulvic acid (SRFA) induced by its interactions with iron and aluminum. The results show that changes of SRFA absorbance are associated with a consistent response of the carboxylic and phenolic functional groups to iron and aluminum forming bonds with these groups, and their deprotonation induced by such binding. The observed changes of SRFA absorbance were quantified via the use of DSlope325-375 parameter that determines the behavior of the slope of logarithms of SRFA absorbance in the range of wavelengths 325-375nm in the presence of varying concentrations of iron or aluminum. DSlope325-375 values were correlated linearly with the concentration of SRFA-bound iron and aluminum determined using either NICA-Donnan or Stockholm Humic Model (SHM) but the correlation was stronger for the former model (R2>0.98). The slopes of these correlations were similar for both iron and aluminum concentrations <10.0μM and at a wide pH range. Fluorescence of SRFA was responsive to metal binding but it changed less consistently in the presence of the examined metals, especially in the case of aluminum. The combination of these techniques can help explore in more detail manifestations of DOM site specificity at realistically low concentrations of DOM and metal ions. © 2013 Elsevier Ltd.


Grant
Agency: Cordis | Branch: FP7 | Program: CSA-SA | Phase: SiS.2013.2.1.1-1 | Award Amount: 3.77M | Year: 2014

TRIGGER aims at promoting systemic interventions designed to have deep, long lasting and widespread impacts at all the different levels in 5 research organisations. The project, coordinated and co-funded by the Italian Government, assisted by an institute specialised in gender and science, involves as co-funders five universities from different EU countries (Czech Republic, France, Italy, UK, Spain). Building on the results of earlier projects, integrated actions will be implemented at each university addressing different sides of gender inequality in science, i.e.: 1) Working environment, formal/informal culture and explicit/tacit rules (awareness-raising; collection of gender-sensitive data; support in the early stages of scientific careers; promotion of work-life balance, etc.). 2) Content and methods of scientific research, to acknowledge its gender dimension and impact (updating of teaching curricula; gendering the design of research and technological innovation; allocation of funds for gendered research; contrasting stereotypes about women in science, etc.). 3) Scientific leadership at different levels (selection procedures and criteria for the evaluation of scientific merit; introduction of equality targets in decision making bodies; enhancement of women researchers visibility, etc.). Each of the 5 involved partners have designed and will carry out a tailored action plan including measures related to all 3 sides, whose relative weight depends on their specific characteristics, situations and needs. TRIGGER will be characterised by integration, customisation, systematic nature, concreteness. Public debate and awareness will be generated on these issues Europe-wide. Added value will be yielded both on the strategic level, by the strong focus on gendering research, and on the operational level, through fostering mutual learning among partners and among the different European structural change projects, giving birth to an Integrated Model.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2010-ITN | Award Amount: 3.76M | Year: 2011

Protein aggregation is a hallmark of many late onset neurodegenerative disorders including Parkinsons Disease (PD), Alzheimers Disease (AD), amyotrophic lateral sclerosis (ALS), prion diseases as well as the group of polyglutamine diseases (polyQ). The aim of this proposal is to create a network of European partners bridging important basic mechanisms involved in proteinopathies, research of model diseases and treatment approaches. The TreatPolyQ network will focus on two main representatives of the polyQ diseases: Huntingtons disease as the most common polyQ disease as well as spinocerebellar ataxia type 3 (SCA3) as the most frequent autosomal-dominantly inherited ataxia. Patients suffer from a multitude of neurological symptoms including movement abnormalities with late onset and in a progressive manner. Up to now, no treatment or cure is available. The network will be consisting of a rare combination of experts from basic and translational research, including a Nobel prize laureate, four industrial partners (two medium, and two small companies, all incorporated as full participants) and academic leaders of the field. The network not only focuses on one special aspect of a disease but spans several important disease-associated mechanism as well as promising treatment strategies for HD and SCA3 (protein transport, protein folding, protein degradation via both the ubiquitin-proteasome system and autophagy), likely to be important across a range of neurodegenerative diseases. In order to implement these research projects, extensive collaborations and temporarily personnel secondments of the involved researchers will take place, enhancing interdisciplinary transfer of knowledge. Beyond the personalized local training plan for each employed researcher within the Network, there will be 4 structured courses covering aspects ranging from structural biology to protein degradation to model organisms and drug development, including soft skill training.


Grant
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 3.30M | Year: 2015

Electroactive polymers (EAP) consist of materials capable of changing dimensions and/or shape in response to electrical stimuli. Most EAPs are also capable of generating electrical energy in response to applied mechanical forces. These polymeric materials exhibit properties well beyond what conventional metal or plastic-based actuators can offer, including very high mechanical flexibility (can be stretched to twice their initial size), low density, a high grade of processability, scalability, microfabrication readiness and, in most cases, low cost. Micro-EAPs enable a new broad range of applications for which large strains and forces are desirable, and for which built-in intelligence is necessary. The main objective of the project will be the improvement of the career perspectives (in academia and in industry) of young researchers by training them at the forefront of research in the field of smart soft systems made of EAP microactuators for advanced miniaturized devices. The overall objective for the scientific programme is research and development of EAP materials and their integration for industrial applications. Special attention will be devoted to the development of microactuators. The field of smart materials is growing extremely fast. Materials whose stiffness and shape can be controlled, and that are capable of sensing their shape allow new classes of compliant complex systems. Through the MICACT programme, we hope to ensure that European researchers keep their leading role in this blossoming field, and to help them transition to industrial positions.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: NMP-11-2015 | Award Amount: 7.11M | Year: 2016

During the last four years the Multifun Consortium (FP7 project N. 262943) has developed and validated distinct nanoformulations as therapeutic approach against pancreatic and breast cancer. These nanoformulations are based on magnetic iron oxide nanoparticles (MNP) multifuntionalised with a target peptide and an anticancer chemical drug, allowing for a synergistic therapeutic effect produced by the combination of intracellular drug delivery and magnetic hyperthermia. In particular, some of the designed formulations (patent filed PCT/EP2015/056631) have proven their efficacy, safety and non-toxicicty, in in vitro and in vivo studies, against the mentioned cancers, thus making them promising candidates to produce a novel nanomedicine therapy for cancer. NoCanTher aims at translating one of these nanoformulations to early clinical development for pancreatic cancer. To successfully reach this objective, we will concentrate our efforts in two main group of activities: Nanomedicine up-scaling under GMP conditions: NoCanTher will scale up the manufacturing of the proposed nanoformulation from milligram-scale laboratory synthesis up to multigram-scale production to generate sufficient material for clinical and regulatory assays. To this aim, a GMP production line will be optimised and the relevant quality control will be conducted at the different stages of the up-scaling process. Clinical trial: NoCanTher will include late preclinical parameter testing to raise a clinical treatment protocol, regulatory assays, as well as the design of the clinical trial and the preparation of the Investigational Medicinal Product Dossier (IMPD). This strategy will allow us to apply for Clinical Trial Authorisation (CTA) then, we will carry out a Phase I clinical trial. NoCanTher involves the participation of institutions from three different sectors (academia, industry, clinical) and from five different countries (Ireland, France, Germany, Spain and the UK).


Patent
Occlugel, French National Center for Scientific Research, University Paris Diderot, Assistance Publique Hopitaux De Paris and University Paris - Sud | Date: 2010-09-09

The present invention relates to a polymer obtained from the polymerization of: (i) at least one monomer of formula (I) (CH_(2)CR_(1))COK (I) wherein: K represents 0-Z or NHZ, Z representing (CR_(2)R_(3))_(m)CH_(3), (CH_(2)CH_(2)O)_(m)H, (CH_(2)CH_(2)O)_(m)CH_(3), (CH_(2))_(m)NR_(4)R_(5 )with m representing an integer from 1 to 30; R_(1), R_(2), R_(3), R_(4 )and R_(5 )independently represent H or a C1-C6 alkyl; and (ii) at least one bio-resorbable block copolymer cross-linker.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: FETPROACT-01-2016 | Award Amount: 7.15M | Year: 2016

Viral infections diagnosis demands novel, cheaper and rapid technologies to overcome present constraints. Current gold standard for diagnosis of viral infections is based on pathogen-targeted nucleic acid identification; thus, it cannot discern infectious stages from latent ones and it demands time consuming adjustments when mutations occur or new emerging viruses are to be included in the diagnostic protocols. Lately, optomechanics has served to fundamental advancements in physics, from gravitational wave detection to the study of mechanical quantum ground states but it has not yet delivered its full applicability potential. VIRUSCAN aims to apply frontier advancements in optomechanics to the biosensing and diagnostic fields and to create a new interdisciplinary research community with the goal to advance optomechanics, nanoelectromechanics, native mass spectrometry and biophysics towards clinical applications. VIRUSCAN will provide a novel technology capable to identify viral particles and asses their infective potential through the characterization of two physical parameters: mass and stiffness. Stiffness of viral particles has been recently known to act as a regulator of their infectivity at different stages of the virus life cycle. In parallel, advancements in nanoelectromechanical systems have recently demonstrated that stiffness and mass information from nanoscale adsorbates can be disentangled. Targeting intrinsic physical properties of viral particles will allow developing an open platform that will tackle any virus and their mutations. VIRUSCAN will have impact at all levels by: providing a personalized treatment to the patients, reducing the use of not effective antibiotics, increasing safety in blood transfusions, allowing a quick and trustworthy response to emergency situations (e.g. recent EBOLA in West Africa and the ZIKA in Brazil), reducing the spread of viral infections, reducing costs per analysis and screening of a wide range of pathogens.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: REFLECTIVE-2-2015 | Award Amount: 2.52M | Year: 2016

SIGN-HUB aims to provide the first comprehensive response to the societal and scientific challenge resulting from generalized neglect of the cultural and linguistic identity of signing Deaf communities in Europe. It will provide an innovative and inclusive resource hub for the linguistic, historical and cultural documentation of the Deaf communities heritage and for sign language assessment in clinical intervention and school settings. To this end, it will create an open state-of-the-art digital platform with customized accessible interfaces. The project will initially feed that platform with core content in the following domains, expandable in the future to other sign languages: (i) digital grammars of 6 sign languages, produced with a new online grammar writing tool; (ii) an interactive digital atlas of linguistic structures of the worlds sign languages; (iii) online sign language assessment instruments for education and clinical intervention, and (iv) the first digital archive of life narratives by elderly signers, subtitled and partially annotated for linguistic properties. These components, made available for the first time through a centralized platform to specialists and to the general public, will (a) help explore and value the identity and the cultural, historical and linguistic assets of Deaf signing communities, (b) advance linguistic knowledge on the natural languages of the Deaf and (c) impact on the diagnosis of language deficits within these minorities. SIGN-HUB will thus contribute to the dissemination and reuse of those assets in broader contexts, as part of European identity. The project is a critical attempt to rescue, showcase and boost that largely unknown part of our common heritage, as well as to ultimately enhance the full participation of Deaf citizens in all spheres of public life on an equal footing with hearing citizens.


Patent
French Institute of Health, Medical Research, French National Institute for Agricultural Research and University Paris Diderot | Date: 2014-09-18

The present invention relates to the general field of therapy of Inflammatory Bowel Disease (IBD) and/or Irritable Bowel Syndrome (IBS). Thus, the invention relates to a molecule selected from the trappin-2 protein or an active fraction thereof, a member of the WAP family proteins or an active fraction thereof or a member of the Serpin family proteins or an active fraction thereof for the treatment of Irritable Bowel Syndrome (IBS). The invention also relates to a recombinant food-grade bacterium comprising a gene selected from a gene coding for the trappin-2 protein or an active fraction thereof, a gene coding for a member of the WAP family proteins or an active fraction thereof, or a gene coding for a member of the Serpin family proteins or an active fraction thereof.


Patent
French Institute of Health, Medical Research, University Paris Diderot and French National Institute for Agricultural Research | Date: 2013-05-21

The present invention relates to the general field of therapy of Inflammatory Bowel Disease (IBD) and/or Irritable Bowel Syndrome (IBS). Thus, the invention relates to a molecule selected from the trappin-2 protein or an active fraction thereof, a member of the WAP family proteins or an active fraction thereof or a member of the Serpin family proteins or an active fraction thereof for the treatment of Irritable Bowel Syndrome (IBS). The invention also relates to a recombinant food-grade bacterium comprising a gene selected from a gene coding for the trappin-2 protein or an active fraction thereof, a gene coding for a member of the WAP family proteins or an active fraction thereof, or a gene coding for a member of the Serpin family proteins or an active fraction thereof.


Patent
Occlugel, University Paris Diderot, Assistance Publique Hopitaux De Paris and French National Center for Scientific Research | Date: 2012-03-09

The present invention relates to a polymer obtained from the polymerization of: (i) at least one monomer of formula (I) (CH_(2)CR_(1))COK (1) wherein: K represents OZ or NHZ, Z representing (CR_(2)R_(3))m-CH_(3), (CH_(2)CH_(2)O)m-H, (CH_(2)CH_(2)O)m-CH_(3), (CH_(2))m-NR_(4)R_(5 )with m representing an integer from 1 to 30; R_(1), R_(2), R_(3), R_(4 )and R_(5 )independently represent H or a C1-C6 alkyl; (ii) at least between 0.1 and 50% mol, advantageously between 1 and 30% mol, more advantageously between 1 and 20 mol % of a cyclic monomer having a exomethylene group of formula (II) wherein: R6, R7, R8 and R9 represent independently H or a C5-C7 aryl group or R6 and R9 are absent and R7 and R8 form together with the carbon atom on which they are bonded a C5-C7 aryl group; i and j represent independently an integer chosen between 0 and 2; X represents either O or X is not present and in this latter case, CR6R7 and CR8R9 are linked via a single bond CC and (iii) at least one bio-resorbable block copolymer cross-linker.


Patent
Occlugel, University Paris Diderot, Assistance Publique Hopitaux De Paris and French National Center for Scientific Research | Date: 2012-03-09

The present invention relates to a macromolecule-loaded bioresorbable crosslinked polymer wherein the polymer is obtainable from the polymerization of: (i) at least one monomer of formula (I) (CH_(2)CR_(1))COK wherein: K represents O-Z or NH-Z, Z representing (CR_(2)R_(3))_(m)CH_(3), (CH_(2)CH_(2)O)_(m)H, (CH_(2)CH_(2)O)_(m)CH_(3), (CH_(2))_(m)NR_(4)R_(5 )with m representing an integer from 1 to 30; R_(1), R_(2), R_(3), R_(4 )and R_(5 )independently represent H or a C1-C6 alkyl; and (ii) at least one bio-resorbable block copolymer cross-linker, and wherein the macromolecule is chosen in the group consisting of proteins and nucleic acids.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2011.2.3.1-3 | Award Amount: 15.65M | Year: 2011

Antibiotics are a mainstay of public health, but their use has increased exponentially leading to the emergence of antibiotic resistance. The R-GNOSIS (Resistance in Gram-Negative Organisms: Studying Intervention Strategies) project combines 5 international clinical studies, all supported by highly innovative microbiology, mathematical modelling and data-management, to determine - in the most relevant patient populations - the efficacy and effectiveness of cutting-edge interventions to reduce carriage, infection and spread of Multi-Drug Resistant Gram-negative Bacteria (MDR-GNB). All work-packages will progress science beyond the state-of-the-art in generating new and translational clinically relevant knowledge, through hypothesis-driven studies focussed on patient-centred outcomes. The 5 clinical studies will investigate the following interventions: A Point-Of-Care-Testing guided management strategy to improve appropriate antibiotic prescription for uncomplicated UTI in primary care. Gut decolonization in outpatients with intestinal carriage of MDR-GNB. A test and prescribe strategy, based on rapid diagnostic testing of faeces for MDR-GNB to optimize antibiotic prophylaxis in colo-rectal surgery. Contact Isolation of patients with ESBL-producing Enterobacteriaceae in general hospital wards. Three Decolonization strategies in ICUs. Seven laboratories across Europe will perform microbiological analyses, as well as unique quantitative experiments. All information will be integrated by 3 groups of mathematical modellers into highly innovative models to better understand and predict future trends and effects of interventions. The studies and analyses proposed in R-GNOSIS will generate a step-change in identifying evidence-based preventive measures and clinical guidance for primary care and hospital-based physicians and health-care authorities, to combat the spread and impact of infections caused by MDR-GNB in Europe.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2012.2.1.1-1-C | Award Amount: 17.68M | Year: 2012

Despite examples of excellent practice, rare disease (RD) research is still mainly fragmented by data and disease types. Individual efforts have little interoperability and almost no systematic connection between detailed clinical and genetic information, biomaterial availability or research/trial datasets. By developing robust mechanisms and standards for linking and exploiting these data, RD-Connect will develop a critical mass for harmonisation and provide a strong impetus for a global trial-ready infrastructure ready to support the IRDiRC goals for diagnostics and therapies for RD in close collaboration with the successful A/B projects. It will build on and transform the current state-of-the-art across databases, registries, biobanks, bioinformatics, and ethical considerations to develop a quality-assured and comprehensive integrated hub/platform in which complete clinical profiles are combined with -omics data and sample availability for RD research. The integrated, user-friendly RD-Connect platform, built on efficient informatics concepts already implemented in international research infrastructures for large-scale data management, will provide access to federated databases/registries, biobank catalogues, harmonised -omics profiles, and cutting-edge bioinformatics tools for data analysis. All patient data types will be linked via the generation of a unique identifier (RD-ID) developed jointly with the US NIH. The RD-Connect platform will be one of the primary enablers of progress in IRDiRC-funded research and will facilitate gene discovery, diagnosis and therapy development. RD-Connect has the RD field at its heart and brings together partners with a strong track record in RD research (gene discovery and development of innovative treatments), as well as committed IRDiRC funding partners and representatives of all major international RD initiatives (EU/US/AU/JP) spanning patient organisations, research and public health, to maximise impact to RD patients


Grant
Agency: GTR | Branch: EPSRC | Program: | Phase: Training Grant | Award Amount: 5.00M | Year: 2014

Quantum technologies promise a transformation of measurement, communication and computation by using ideas originating from quantum physics. The UK was the birthplace of many of the seminal ideas and techniques; the technologies are now ready to translate from the laboratory into industrial applications. Since international companies are already moving in this area, there is a critical need across the UK for highly-skilled researchers who will be the future leaders in quantum technology. Our proposal is driven by the need to train this new generation of leaders. They will need to be equipped to function in a complex research and engineering landscape where quantum physics meets cryptography, complexity and information theory, devices, materials, software and hardware engineering. We propose to train a cohort of leaders to meet these challenges within the highly interdisciplinary research environment provided by UCL, its commercial and governmental laboratory partners. In their first year the students will obtain a background in devices, information and computational sciences through three concentrated modules organized around current research issues. They will complete a team project and a longer individual research project, preparing them for their choice of main research doctoral topic at the end of the year. Cross-cohort training in communication skills, technology transfer, enterprise, teamwork and career planning will continue throughout the four years. Peer to peer learning will be continually facilitated not only by organized cross-cohort activities, but also by the day to day social interaction among the members of the cohort thanks to their co-location at UCL.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2011.2.3.1-2 | Award Amount: 16.04M | Year: 2011

Antibiotics are essential therapeutics in the treatment of bacterial infections. However, the indiscriminate use of antibiotics has led to the emergence of antibiotic resistant bacteria that pose a major threat to human health as options for treating infections by these bacteria have become limited. The evolution, emergence and spread of antibiotic resistance genes are still only poorly understood and expanding our knowledge on these aspects will provide novel leads to combat the emergence of antibiotic resistance. The EvoTAR consortium gathers a multi-disciplinary group of leading European researchers in the fields of antibiotic resistance, microbial genomics and mathematical modelling. In addition, three research-intensive SMEs participate in EvoTAR, two of which are involved in the development of novel approaches to minimize the emergence and spread of antibiotic resistance. The purpose of EvoTAR is to increase the understanding of the evolution and spread of antibiotic resistance in human pathogens. EvoTAR will characterise the human reservoir of antibiotic resistance genes (the resistome) by investigating the dynamics and evolution of the interaction between resistant and non-resistant bacteria from the human microbiome and the interrelations of the human resistome with non-human reservoirs of resistance genes. Novel methods will be used to quantify resistance transfer under controlled conditions in gene exchange communities. Mathematical modelling will be applied to predict gene flow between different reservoirs and to predict future resistance trends. Novel in vitro and in vivo models will allow the study of the efficacy of novel therapeutics aimed at reducing selection and spread of antibiotic resistance. The EvoTAR project will generate novel insights into the evolution and spread of antibiotic resistance genes and thereby create opportunities for the development of novel interventions to curb the rising tide of antibiotic resistance in human pathogens.


El belrhiti H.,European Commission - Joint Research Center Ispra | Douady S.,University Paris Diderot
Geomorphology | Year: 2011

Barchans are crescentic dunes which occur in mainly mono-directional winds. Shape, aspect ratios and velocities of these dunes have been studied as if they were in equilibrium. However, following a study of the shape and migration of 11 barchans of different sizes for 18. months in the field on Moroccan Atlantic Sahara, we show that they only appear to be in a stationary state if studied over a long timeframe (at the scale of the year or several years), but are never in equilibrium at the scale of weeks or months. Rather, they are always 'trying' to reach a possible equilibrium state but never have enough time to accomplish this. This may be the main reason for the large variation observed in previous measurements, and justifies some caution in what can be deduced from them. © 2010 Elsevier B.V.


Kim H.,University of California at San Francisco | Al-Shahi Salman R.,University of Edinburgh | McCulloch C.E.,University of California at San Francisco | Stapf C.,University Paris Diderot
Neurology | Year: 2014

Objective: To identify risk factors for intracranial hemorrhage in the natural history course of brain arteriovenous malformations (AVMs) using individual patient data meta-analysis of 4 existing cohorts. Methods: We harmonized data from Kaiser Permanente of Northern California (n 5 856), University of California San Francisco (n 5 787), Columbia University (n 5 672), and the Scottish Intracranial Vascular Malformation Study (n 5 210). We censored patients at first treatment, death, last visit, or 10-year follow-up, and performed stratified Cox regression analysis of timeto-hemorrhage after evaluating hemorrhagic presentation, sex, age at diagnosis, deep venous drainage, and AVM size as predictors. Multiple imputation was performed to assess impact of missing data. Results: A total of 141 hemorrhage events occurred during 6,074 patient-years of follow-up (annual rate of 2.3%, 95% confidence interval [CI] 2.0%-2.7%), higher for ruptured (4.8%, 3.9%-5.9%) than unruptured (1.3%, 1.0%-1.7%) AVMs at presentation. Hemorrhagic presentation (hazard ratio 3.86, 95% CI 2.42-6.14) and increasing age (1.34 per decade, 1.17-1.53) independently predicted hemorrhage and remained significant predictors in the imputed dataset. Female sex (1.49, 95% CI 0.96-2.30) and exclusively deep venous drainage (1.60, 0.95-2.68, p 5 0.02 in imputed dataset) may be additional predictors. AVM size was not associated with intracerebral hemorrhage in multivariable models (p>0.5). Conclusion: This large, individual patient data meta-analysis identified hemorrhagic presentation and increasing age as independent predictors of hemorrhage during follow-up. Additional AVM cohort data may further improve precision of estimates, identify new risk factors, and allow validation of prediction models. © 2014 American Academy of Neurology.


Langlois D.,University Paris Diderot | Van Tent B.,University Paris - Sud
Classical and Quantum Gravity | Year: 2011

We investigate new shapes (in multipole space) of local primordial non-Gaussianities in the cosmic microwave background. Allowing for a primordial isocurvature mode along with the main adiabatic one, the angular bispectrum is in general a superposition of six distinct shapes: the usual adiabatic term, a purely isocurvature component and four additional components that arise from correlations between the adiabatic and the isocurvature modes. We present a class of early Universe models in which various hierarchies between these six components can be obtained, while satisfying the present upper bound on the isocurvature fraction in the power spectrum. Remarkably, even with this constraint, detectable non-Gaussianity could be produced by isocurvature modes. We finally discuss the prospects of detecting these new shapes with the Planck data, including polarization. © 2011 IOP Publishing Ltd.


Sacre K.,San Francisco General Hospital | Sacre K.,University Paris Diderot | Criswell L.A.,University of California at San Francisco | McCune J.M.,San Francisco General Hospital
Arthritis Research and Therapy | Year: 2012

Introduction: Plasmacytoid dendritic cells (pDCs) constitutively express two members of the Toll-like receptor (TLR) family, TLR-9 and TLR-7, through which they can be stimulated to produce high levels of interferon (IFN)-α, a key mediator of the pathogenesis of systemic lupus erythematosus (SLE). Given the known efficacy of hydroxychloroquine (HCQ) in the treatment of SLE, we examined its ability to inhibit such pDC function in vivo.Methods: Peripheral blood mononuclear cells (PBMCs) from SLE subjects treated or not with HCQ and from healthy controls were stimulated with the TLR-9 agonist, CpG oligodeoxynucleotides (CpG-A ODN)-2216, and the TLR-7 agonist, imiquimod. The proportion of monocytes, B cells, myeloid dendritic cells, pDCs, and natural killer (NK) cells producing IFN-α and tumor necrosis factor alpha (TNF-α) was then analyzed by multiparameter flow cytometry.Results: After TLR-9/7 stimulation in both SLE and healthy subjects, significant production of IFN-α and TNF-α was only observed in pDCs. TLR-7 and TLR-9 induced IFN-α and TNF-α production by pDCs from subjects with SLE was decreased relative to that found in controls (TLR-9/IFN-α, P < 0.0001; TLR-9/TNF-α P < 0.0001; TLR-7/TNF-α P = 0.01). TLR-9 and TLR-7 induced IFN-α and TNF-α production by pDCs was severely impaired in 36% (TLR-9) and 33% (TLR-7) of SLE subjects. In almost all cases, these subjects were being treated with HCQ (HCQ vs. no HCQ: impaired TLR-9/IFN-α, P = 0.0003; impaired TLR-7/IFN-α, P = 0.07; impaired TLR-9/TNF-α, P < 0.009; impaired TLR-7/TNF-α, P < 0.01).Conclusions: Treatment with HCQ is associated with impaired ability of pDCs from subjects with SLE to produce IFN-α and TNF-α upon stimulation with TLR-9 and TLR-7 agonists. © 2012 Sacre et al.; licensee BioMed Central Ltd.


Du G.,Charles Sadron Institute | Moulin E.,Charles Sadron Institute | Jouault N.,University Paris Diderot | Jouault N.,Columbia University | And 2 more authors.
Angewandte Chemie - International Edition | Year: 2012

Pumping iron: Double-threaded rotaxanes can be linked to coordination units and polymerized in the presence of iron or zinc ions. pH modulation triggers cooperative contractions (or extensions) of the individual rotaxanes, thus resulting in an amplified motion of the muscle-like supramolecular chains with changes of their contour lengths of several micrometers (see picture). Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Xu G.,University of Burgundy | Garnier J.,University Paris Diderot | Picozzi A.,University of Burgundy
Optics Letters | Year: 2014

We study the interaction of temporal incoherent solitons sustained by a highly noninstantaneous (Raman-like) nonlinear response. The incoherent solitons exhibit a nonmutual interaction, which can be either attractive or repulsive depending on their relative initial distance. The analysis reveals that incoherent solitons exhibit a long-range interaction in frequency space, which is in contrast with the expected spectral short-range interaction described by the usual approach based on the Raman-like spectral gain curve. Both phenomena of anomalous interaction and spectral long-range behavior of incoherent solitons are described in detail by a long-range Vlasov equation. © 2014 Optical Society of America.


Bretes H.,University Paris Diderot | Bretes H.,University Paris - Sud
Nucleic acids research | Year: 2014

Assembly of messenger ribonucleoparticles (mRNPs) is a pivotal step in gene expression, but only a few molecular mechanisms contributing to its regulation have been described. Here, through a comprehensive proteomic survey of mRNP assembly, we demonstrate that the SUMO pathway specifically controls the association of the THO complex with mRNPs. We further show that the THO complex, a key player in the interplay between gene expression, mRNA export and genetic stability, is sumoylated on its Hpr1 subunit and that this modification regulates its association with mRNPs. Altered recruitment of the THO complex onto mRNPs in sumoylation-defective mutants does not affect bulk mRNA export or genetic stability, but impairs the expression of acidic stress-induced genes and, consistently, compromises viability in acidic stress conditions. Importantly, inactivation of the nuclear exosome suppresses the phenotypes of the hpr1 non-sumoylatable mutant, showing that SUMO-dependent mRNP assembly is critical to allow a specific subset of mRNPs to escape degradation. This article thus provides the first example of a SUMO-dependent mRNP-assembly event allowing a refined tuning of gene expression, in particular under specific stress conditions.


Hajnsdorf E.,University Paris Diderot | Boni I.V.,RAS Shemyakin Ovchinnikov Institute of Bioorganic Chemistry
Biochimie | Year: 2012

In all organisms, RNA-binding proteins participate in modulating all the steps in the life cycle of RNA, including transcription, folding, translation and turnover. In bacteria, RNA-binding proteins may be specific for a few RNA targets (e.g., several ribosomal proteins that recognize both rRNA during ribosome assembly and their own mRNAs when acting as highly specific autogenous repressors) or function as global regulators implicated in numerous regulatory networks. Some RNA-binding proteins combine all these features, and this particularly concerns the ribosomal protein S1 and the Sm-like protein Hfq. S1 is a key mRNA-binding protein in gram-negative bacteria; it recognizes mRNA leaders and provides binding of diverse mRNAs to the ribosome at the initiation step of translation. Moreover, S1 is a highly specific autogenous repressor that is able to distinguish its own mRNA from all the others. Hfq is recognized as a global regulator that facilitates small RNA-mRNA interactions in bacteria; it thereby controls the expression of many mRNAs either positively or negatively. In addition, these two proteins were reported to affect transcription, RNA degradation and other processes. Although they have no sequence specificity, Hfq and S1 preferentially bind A/U-rich single-stranded RNA regions; despite this, they nevertheless carry out very different tasks in the cell. This review is focused on the diversity of functions that can be performed by these abundant RNA-binding bacterial proteins. © 2011 Elsevier Masson SAS. All rights reserved.


Mazur A.K.,University Paris Diderot | Maaloum M.,Charles Sadron Institute
Physical Review Letters | Year: 2014

Unusually high bending flexibility has been recently reported for DNA on short length scales. We use atomic force microscopy (AFM) in solution to obtain a direct estimate of DNA bending statistics for scales down to one helical turn. It appears that DNA behaves as a Gaussian chain and is well described by the wormlike chain model at length scales beyond 3 helical turns (10.5 nm). Below this threshold, the AFM data exhibit growing noise because of experimental limitations. This noise may hide small deviations from the Gaussian behavior, but they can hardly be significant. © 2014 American Physical Society.


Tuckerman L.S.,University Paris Diderot | Barkley D.,University of Warwick
Physics of Fluids | Year: 2011

Near transition, plane Couette flow takes the form of large-scale, oblique, and statistically steady alternating bands of turbulent and laminar flow. Properties of these flows are investigated using direct numerical simulation in a tilted computational domain. Four regimes-uniform, intermittent, periodic, and localized-are characterized. The Fourier spectrum along the direction of variation of the pattern is presented, and the component corresponding to the pattern wavenumber is investigated as an order parameter. The mean flow of a periodic pattern is characterized and shown to lead to a relation between the Reynolds number and the wavelength and angle of a pattern. © 2011 American Institute of Physics.


Garnier J.,University Paris Diderot | Xu G.,University of Burgundy | Trillo S.,University of Ferrara | Picozzi A.,University of Burgundy
Physical Review Letters | Year: 2013

We predict theoretically and numerically the existence of incoherent dispersive shock waves. They manifest themselves as an unstable singular behavior of the spectrum of incoherent waves that evolve in a noninstantaneous nonlinear environment. This phenomenon of "spectral wave breaking" develops in the weakly nonlinear regime of the random wave. We elaborate a general theoretical formulation of these incoherent objects on the basis of a weakly nonlinear statistical approach: a family of singular integro-differential kinetic equations is derived, which provides a detailed deterministic description of the incoherent dispersive shock wave phenomenon. © 2013 American Physical Society.


Chou J.,University of California at San Francisco | Lin J.H.,University of California at San Francisco | Brenot A.,University of California at San Francisco | Kim J.-W.,University of California at San Francisco | And 4 more authors.
Nature Cell Biology | Year: 2013

Despite advances in our understanding of breast cancer, patients with metastatic disease have poor prognoses. GATA3 is a transcription factor that specifies and maintains mammary luminal epithelial cell fate, and its expression is lost in breast cancer, correlating with a worse prognosis in human patients. Here, we show that GATA3 promotes differentiation, suppresses metastasis and alters the tumour microenvironment in breast cancer by inducing microRNA-29b (miR-29b) expression. Accordingly, miR-29b is enriched in luminal breast cancers and loss of miR-29b, even in GATA3-expressing cells, increases metastasis and promotes a mesenchymal phenotype. Mechanistically, miR-29b inhibits metastasis by targeting a network of pro-metastatic regulators involved in angiogenesis, collagen remodelling and proteolysis, including VEGFA, ANGPTL4, PDGF, LOX and MMP9, and targeting ITGA6, ITGB1 and TGFB, thereby indirectly affecting differentiation and epithelial plasticity. The discovery that a GATA3-miR-29b axis regulates the tumour microenvironment and inhibits metastasis opens up possibilities for therapeutic intervention in breast cancer. © 2013 Macmillan Publishers Limited. All rights reserved.


Vallot C.,University Paris Diderot | Vallot C.,French National Center for Scientific Research | Huret C.,University Paris Diderot | Huret C.,French National Center for Scientific Research | And 7 more authors.
Nature Genetics | Year: 2013

X-chromosome inactivation (XCI) in mammals relies on XIST, a long noncoding transcript that coats and silences the X chromosome in cis. Here we report the discovery of a long noncoding RNA, XACT, that is expressed from and coats the active X chromosome specifically in human pluripotent cells. In the absence of XIST, XACT is expressed from both X chromosomes in humans but not in mice, suggesting a unique role for XACT in the control of human XCI initiation. © 2013 Nature America, Inc. All rights reserved.


Gleyzes J.,CEA Saclay Nuclear Research Center | Gleyzes J.,French National Center for Scientific Research | Langlois D.,University Paris - Sud | Piazza F.,University Paris - Sud | And 4 more authors.
Physical Review Letters | Year: 2015

We introduce a new class of scalar-tensor theories of gravity that extend Horndeski, or "generalized Galileon," models. Despite possessing equations of motion of higher order in derivatives, we show that the true propagating degrees of freedom obey well-behaved second-order equations and are thus free from Ostrogradski instabilities, in contrast to standard lore. Remarkably, the covariant versions of the original Galileon Lagrangians - obtained by direct replacement of derivatives with covariant derivatives - belong to this class of theories. These extensions of Horndeski theories exhibit an uncommon, interesting phenomenology: The scalar degree of freedom affects the speed of sound of matter, even when the latter is minimally coupled to gravity. © 2015 American Physical Society.


Mazur A.K.,University Paris Diderot | Maaloum M.,Charles Sadron Institute
Nucleic Acids Research | Year: 2014

The apparently anomalous flexibility of DNA on short length scales has attracted a lot of attention in recent years. We use atomic force microscopy (AFM) in solution to directly study the DNA bending statistics for small lengths down to one helical turn. The accuracy of experimental estimates could be improved due to a large data volume and a refined algorithm for image processing and measuring bend angles. It is found that, at length scales beyond two helical turns (7 nm), DNA is well described by the harmonic wormlike chain (WLC) model with the bending persistence length of 56 nm. Below this threshold, the AFM data are also described by the WLC model assuming that the accuracy of measured bend angles is limited by the physical width of the double helix. We conclude that the double helical DNA behaves as a uniform elastic rod even at very short length scales. Strong bends due to kinks, melting bubbles and other deviations from the WLC model are statistically negligible. © The Author(s) 2014.


Chailloux A.,University Paris - Sud | Kerenidis I.,University Paris Diderot
Proceedings - Annual IEEE Symposium on Foundations of Computer Science, FOCS | Year: 2011

Bit commitment is a fundamental cryptographic primitive with numerous applications. Quantum information allows for bit commitment schemes in the information theoretic setting where no dishonest party can perfectly cheat. The previously best-known quantum protocol by Ambainis achieved a cheating probability of at most 3/4 [Amb01]. On the other hand, Kitaev showed that no quantum protocol can have cheating probability less than 1√2 [Kit03] (his lower bound on coin flipping can be easily extended to bit commitment). Closing this gap has since been an important open question. In this paper, we provide the optimal bound for quantum bit commitment. First, we show a lower bound of approximately 0.739, improving Kitaev's lower bound. For this, we present some generic cheating strategies for Alice and Bob and conclude by proving a new relation between the trace distance and fidelity of two quantum states. Second, we present an optimal quantum bit commitment protocol which has cheating probability arbitrarily close to 0.739. More precisely, we show how to use any weak coin flipping protocol with cheating probability 1/2 + ε in order to achieve a quantum bit commitment protocol with cheating probability 0.739 + O(ε). We then use the optimal quantum weak coin flipping protocol described by Mochon [Moc07]. Last, in order to stress the fact that our protocol uses quantum effects beyond the weak coin flip, we show that any classical bit commitment protocol with access to perfect weak (or strong) coin flipping has cheating probability at least 3/4. © 2011 IEEE.


De Vernejoul M.-C.,University Paris Diderot | Kornak U.,Max Planck Institute for Molecular Genetics
Annals of the New York Academy of Sciences | Year: 2010

Sclerosing bone disorders can be subdivided according to their clinical presentation, the primarily affected cell type, and the cellular pathways. Osteoclast-rich osteopetrosis and related disorders have been related in most cases to mutations in genes required for osteoclast function. More recently, osteoclast-poor forms of osteopetrosis have been described as being connected to factors that govern osteoclast differentiation. However, increased bone formation can also cause osteosclerosis. Camurati-Engelman disease and osteopoikilosis are both related transforming growth factor-β signaling. Rare recessive or dominant sclerosing disorders, such as endosteal hyperostosis, sclerosteosis, van Buchem disease, high bone-mass syndrome, and osteopathia striata, are caused by mutations in genes involved in the Wnt pathway, which regulates osteoblast differentiation. Finally, a third entity, including Ghosal syndrome and pachydermoperiostosis, is related to mutations in genes of the eicosanoid pathway. Clinical aspects and the consequences for our understanding of bone biology are discussed. © 2010 New York Academy of Sciences.


Jacquin H.,University Paris Diderot | Berthier L.,CNRS Charles Coulomb Laboratory | Zamponi F.,CNRS Physics Laboratory
Physical Review Letters | Year: 2011

Dense particle packings acquire rigidity through a nonequilibrium jamming transition commonly observed in materials from emulsions to sandpiles. We describe athermal packings and their observed geometric phase transitions by using equilibrium statistical mechanics and develop a fully microscopic, mean-field theory of the jamming transition for soft repulsive spherical particles. We derive analytically some of the scaling laws and exponents characterizing the transition and obtain new predictions for microscopic correlation functions of jammed states that are amenable to experimental verifications and whose accuracy we confirm by using computer simulations. © 2011 American Physical Society.


Picozzi A.,University of Burgundy | Garnier J.,University Paris Diderot | Garnier J.,Ecole Normale Superieure de Paris
Physical Review Letters | Year: 2011

The long-term behavior of a modulationally unstable nonintegrable system is known to be characterized by the soliton turbulence self-organization process: It is thermodynamically advantageous for the system to generate a large-scale coherent soliton in order to reach the ("most disordered") equilibrium state. We show that this universal process of self-organization breaks down in the presence of a highly nonlocal nonlinear response. A wave turbulence approach based on a Vlasov-like kinetic equation reveals the existence of an incoherent soliton turbulence process: It is advantageous for the system to self-organize into a large-scale, spatially localized, incoherent soliton structure. © 2011 American Physical Society.


Piram M.,University Paris - Sud | Mahr A.,University Paris Diderot
Current Opinion in Rheumatology | Year: 2013

PURPOSE OF REVIEW: To review the current knowledge of epidemiological features of immunoglobulin (Ig) A vasculitis (Henoch-Schönlein) and disease etiology. RECENT FINDINGS: The annual incidence of IgA vasculitis in the population is an estimated 3-26.7/100 000 for children and infants and 0.8-1.8/100 000 for adults. These may be conservative approximations of the true frequency because of skewed case-finding strategies. In children, the marked autumn-winter peak in incidence rates, the frequent occurrence after an upper respiratory tract infection and the short interval between disease onset in index cases and in other family members collectively point to a transmissible infectious process. A subset of adult IgA vasculitis could be related to preceding or concurrent malignancies. Despite several lines of evidence supporting the critical role of an exogenous factor in IgA vasculitis, recent progress has been made in understanding the genetic susceptibility to IgA vasculitis. Recent findings also lessened the suggestion that IgA vasculitis might be triggered by vaccination. SUMMARY: IgA vasculitis is two to 33 times more common in children than adults and appears to have a strong environmental component, with possibly different risk factors in childhood and adulthood. Support is strengthening for a role of genetics in IgA vasculitis. © 2013 Wolters Kluwer Health | Lippincott Williams &Wilkins.


De The H.,University Paris Diderot | De The H.,Shanghai JiaoTong University | Chen Z.,Shanghai JiaoTong University
Nature Reviews Cancer | Year: 2010

The fusion oncogene, promyelocytic leukaemia (PML) ĝ€"retinoic acid receptor-Î ± (RARA), initiates acute promyelocytic leukaemia (APL) through both a block to differentiation and increased self-renewal of leukaemic progenitor cells. The current standard of care is retinoic acid (RA) and chemotherapy, but arsenic trioxide also cures many patients with APL, and an RA plus arsenic trioxide combination cures most patients. This Review discusses the recent evidence that reveals surprising new insights into how RA and arsenic trioxide cure this leukaemia, by targeting PMLg-RARα ± for degradation. Drug-triggered oncoprotein degradation may be a strategy that is applicable to many cancers. © 2010 Macmillan Publishers Limited. All rights reserved.


Kauffmann F.,French Institute of Health and Medical Research | Kauffmann F.,University Paris - Sud | Demenais F.,French Institute of Health and Medical Research | Demenais F.,University Paris Diderot
Journal of Allergy and Clinical Immunology | Year: 2012

The concept of gene-environment (GxE) interactions has dramatically evolved in the last century and has now become a central theme in studies that assess the causes of human disease. Despite the numerous efforts to discover genes associated in asthma and allergy through various approaches, including the recent genome-wide association studies, investigation of GxE interactions has been mainly limited to candidate genes, candidate environmental exposures, or both. This review discusses the various strategies from hypothesis-driven strategies to the full agnostic search of GxE interactions with an illustration from recently published articles. Challenges raised by each piece of the puzzle (ie, phenotype, environment, gene, and analysis of GxE interaction) are put forward, and tentative solutions are proposed. New perspectives to integrate various types of data generated by new sequencing technologies and to progress toward a systems biology approach of disease are outlined. The future of a molecular network-based approach of disease to which GxE interactions are related requires space for innovative and multidisciplinary research. Assembling the various parts of a puzzle in a complex system could well occur in a way that might not necessarily follow the rules of logic. © 2012 American Academy of Allergy, Asthma & Immunology.


Madhusudan P.,University of Illinois at Urbana - Champaign | Parlato G.,University Paris Diderot
ACM SIGPLAN Notices | Year: 2011

We propose a generalization of results on the decidability of emptiness for several restricted classes of sequential and distributed automata with auxiliary storage (stacks, queues) that have recently been proved. Our generalization relies on reducing emptiness of these automata to finite-state graph automata (without storage) restricted to monadic second-order (MSO) definable graphs of bounded tree-width, where the graph structure encodes the mechanism provided by the auxiliary storage. Our results outline a uniform mechanism to derive emptiness algorithms for automata, explaining and simplifying several existing results, as well as proving new decidability results. Copyright © 2011 ACM.


Ariel F.,University Paris Diderot | Jegu T.,University Paris - Sud | Latrasse D.,University Paris - Sud | Romero-Barrios N.,University Paris Diderot | And 4 more authors.
Molecular Cell | Year: 2014

The eukaryotic epigenome is shaped by the genome topology in three-dimensional space. Dynamic reversible variations in this epigenome structure directly influence the transcriptional responses to developmental cues. Here, we show that the Arabidopsis long intergenic noncoding RNA (lincRNA) APOLO is transcribed by RNA polymerases II and V in response to auxin, a phytohormone controlling numerous facets of plant development. This dual APOLO transcription regulates the formation of a chromatin loop encompassing the promoter of its neighboring gene PID, a key regulator of polar auxin transport. Altering APOLO expression affects chromatin loop formation, whereas RNA-dependent DNA methylation, active DNA demethylation, and Polycomb complexes control loop dynamics. This dynamic chromatin topology determines PID expression patterns. Hence, the dual transcription of a lincRNA influences local chromatin topology and directs dynamic auxin-controlled developmental outputs on neighboring genes. This mechanism likely underscores the adaptive success of plants in diverse environments and may be widespread in eukaryotes. © 2014 Elsevier Inc.


Berthier L.,CNRS Charles Coulomb Laboratory | Jacquin H.,University Paris Diderot | Zamponi F.,Ecole Normale Superieure de Paris
Physical Review E - Statistical, Nonlinear, and Soft Matter Physics | Year: 2011

We develop a microscopic theory to analyze the phase behavior and compute correlation functions of dense assemblies of soft repulsive particles both at finite temperature, as in colloidal materials, and at vanishing temperature, a situation relevant for granular materials and emulsions. We use a mean-field statistical mechanical approach which combines elements of liquid state theory to replica calculations to obtain quantitative predictions for the location of phase boundaries, macroscopic thermodynamic properties, and microstructure of the system. We focus, in particular, on the derivation of scaling properties emerging in the vicinity of the jamming transition occurring at large density and zero temperature. The new predictions we obtain for pair correlation functions near contact are tested using computer simulations. Our work also clarifies the conceptual nature of the jamming transition and its relation to the phenomenon of the glass transition observed in atomic liquids. © 2011 American Physical Society.


Auregan J.-C.,University Paris - Sud | Auregan J.-C.,University Paris Diderot | Begue T.,University Paris - Sud
International Orthopaedics | Year: 2014

Purpose: The purpose of this study was to review experimental and clinical experiences about the use of an induced membrane to address critical bone size defect of the limbs. Methods: From a review of published experimental and clinical data and from our clinical experience, we present the key data about the use of an induced membrane to address critical bone size defect of the limbs. Results: After reviewing the concept of critical sized bone defect, we present the different indications of an induced membrane, the key points of the surgical technique and the strategy of bone grafting given the indication, localization and importance of the critical sized bone defect. Finally, we discuss the perspective of the use of an induced membrane with various bone substitutes. Conclusions: The use of an induced membrane to treat critical sized bone defects of the limbs is a simple, reliable and reproducible technique. Certain technical steps should be pointed out and observed with great caution in order to avoid any pitfalls. This technique will probably be a key step for facilitating bone inclusion of new bone substitutes proposed by recent bioengineering. © 2014 SICOT aisbl.


Roy A.,Tata Institute of Fundamental Research | Gonzalez-Gomez M.,University of La Laguna | Pierani A.,University Paris Diderot | Meyer G.,University of La Laguna | Tole S.,Tata Institute of Fundamental Research
Cerebral Cortex | Year: 2014

Early brain development is regulated by the coordinated actions of multiple signaling centers at key boundaries between compartments. Three telencephalic midline structures are in a position to play such roles in forebrain patterning: The cortical hem, the septum, and the thalamic eminence at the diencephalic-telencephalic boundary. These structures express unique complements of signaling molecules, and they also produce distinct populations of Cajal-Retzius cells, which are thought to act as "mobile patterning units," migrating tangentially to cover the telencephalic surface. We show that these 3 structures require the transcription factor Lhx2 to delimit their extent. In the absence of Lhx2 function, all 3 structures are greatly expanded, and the Cajal-Retzius cell population is dramatically increased. We propose that the hem, septum, and thalamic eminence together form a "forebrain hem system" that defines and regulates the formation of the telencephalic midline. Disruptions in the forebrain hem system may be implicated in severe brain malformations such as holoprosencephaly. Lhx2 functions as a central regulator of this system's development. Since all components of the forebrain hem system have been identified across several vertebrate species, the mechanisms that regulate them may have played a fundamental role in driving key aspects of forebrain evolution. © 2013 The Author.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-IRSES | Phase: FP7-PEOPLE-2011-IRSES | Award Amount: 374.30K | Year: 2012

THz band remains the last region of electromagnetic spectrum which does not have wide application in modern technology due to lack of solid state source of THz radiation: compact, reliable and scalable. Fundamental objection preventing creation of such source is small rate of spontaneous emission of the THz photons: according to the Fermi Golden rule this rate is about tens of inverse milliseconds, while lifetime of the charge carrier in the solid typically lies in picoseconds range due to the efficient interaction with phonons. The rate of spontaneous emission of THz photons can be increased by application Purcell effect, but even in this case cryogenic temperature is required for the operation of solid state THz devices. Further increase of emission rate can be achieved via bosonic stimulation, when THz radiative transition occurs into the quantum state, in which condensate of bosons is formed. Such situation can be realized for transition between upper and lower polariton state in semiconductor microcavity in polariton lasing regime, in the case when parity excitonic parts of upper and lower polariton states is made different. In this case emission of THz radiation characterized by substantial quantum efficiency can be achieved even at room temperature. Further, pronounced non-linear properties of polaritonic systems lead to various non-linear effects in coupled system of polaritons and THz photons, what open the way for development of novel class of solid state devices, like compact THz short pulse generators, THz switch, and THz detectors.


Patent
French Institute of Health, Medical Research, Cea, University Paris - Sud and University Paris Diderot | Date: 2013-07-31

The present invention relates to the prevention or treatment of inflammatory diseases. The present invention also relates to a method for screening a compound capable of promoting or restoring the resolution of inflammation and which may be useful for preventing or treating inflammatory disorders.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-IRSES | Phase: FP7-PEOPLE-2009-IRSES | Award Amount: 362.70K | Year: 2010

Remote sensing can provide systematic global estimations of vegetation structure and biochemistry imparting data such as leaf area index (LAI), water content or fractional light interception by green vegetation (fPAR). However a global network of standardize validation sites is required to reduce the uncertainty of these products. As part of that effort, SpecNet (Spectral Network), an independent international collaborative research iniciative, promotes the acquisition of field optical remote sensing and vegetation properties. These sites are also generally part of the flux tower network (FLUXNET) to better understand carbon and water vapor fluxes. The proposed Staff Exchanges will promote SpecNet by linking joint research activities that will work to develop methodologies to estimate vegetation biochemistry and structure from remote sensing, including the design, validation and assessment of new bi-dimensional and tri-dimensional radiative transfer models. We will emphasize the analysis and quantification of the uncertainty associated with the estimation of the vegetation parameters at different spatial scales, linking them to the flux tower measurements. A scaling-up methodology will be tested by comparing spectral information at leaf, canopy and ecosystem level using laboratory and field spectroscopy, airborne hyperspectral image, Lidar data and multispectral satellite data. We will adapt and distribute standard field protocols for different ecosystems and establish consensus on the metadata to include in the datasets. The results of these contributions will be made available to the academic community, and research conclusions drawn will be published in international journals. In these Staff Exchanges each participant will also seek to share their knowledge within their area of expertise by organizing training seminars for undergraduate and graduate students, also involving local, regional and/or national management agencies according to their needs or demands.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2013.2.1.1-1 | Award Amount: 16.16M | Year: 2013

Recently intense research identified around 4,000 single nucleotide polymorphisms (SNPs) associated with human age related diseases such as metabolic disorders. Despite their highly significant association to pathology, the functional role of these genetic variants is, in most cases, yet to be elucidated. The evolutionary distance of most animal models from humans represents a major limitation for the functional validation of these SNPs. To overcome these difficulties, HUMAN will generate mouse models carrying human hepatocytes or pancreatic cells from either primary cells (hepatocytes) or induced pluripotent stem cells (iPSCs). This innovative approach offers the unique possibility of studying function of genetic risk variants associated with metabolic diseases in an integrated living system (the mouse body), but within human-derived organs, i.e. liver and pancreas. iPSCs used to generate hepatocytes and cells will derive from extreme phenotypes, i.e. patients affected by severe metabolic diseases such as type 2 diabetes (T2D) or subjects selected for exceptional healthy longevity (subjects over 105 years and offspring of nonagenarian sibships) all fully clinically and metabolically characterised and genotyped; they will be selected according to the best combination of risk and protective alleles. We will test the effect of different nutritional regimes (e.g. high fat diet, caloric restriction), to disentangle the complex molecular mechanisms and circuitry across organs (e.g. hypothalamus-liver axis) which lead to pathology. HUMAN associates a core of outstanding basic research institutions to leading European biotech SMEs, and has the capability to produce at least 500 humanised mice. HUMAN will generate iPSCs biobanks and comprehensively manage all associated information. HUMAN is uniquely situated to drive innovation towards a better knowledge of the genetic basis of human metabolic diseases, thereby contributing to healthier aging of European citizens.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-IRSES | Phase: FP7-PEOPLE-2013-IRSES | Award Amount: 340.20K | Year: 2013

Most of transgenic plants are derived from crops of worldwide critical importance to food and feed producers: soybean, maize, rapeseed and cotton. Although the advantages presented by the genetically modified organisms (GMO), such as herbicide tolerance or resistance to insects, their cultivation has raised numerous concerns in the European Union (EU) and other parts of the world about food safety, environmental and economic impact. In spite of it, their production is steadily increasing mainly in the American countries, reaching a global area of 160 million hectares in 2011. To protect consumers, food and feed labelling legislation is in force in EU and other countries such as Brazil. The verification of its compliance demands reliable and accurate GMO detection methods, but also high throughput tools able to rapidly assess the actual prevalence of transgenic material in food and feed, which is unknown. The GMOsensor proposal intends to establish an innovative and well-organised scientific network aiming at advancing on nanobiosensor devices to assess the presence of GMO in food and feed products. The achievement of high throughput sensitive analysis requires novel approaches that combine different research areas. State-of-the-art methodologies and advanced techniques will be incorporated in this research for validation of the new tools and towards the efficient monitoring of transgenic soybean and maize derived products from diverse regions. The application of biosensors in food analysis is well suited due to their easy miniaturisation, simple instrumentation and cost-effective. The use of biosensors is promising since they answer to the demands of high sensitivity, specificity, and fast analysis. In this project, novel qualitative and quantitative bioanalytical methodologies (DNA- and protein-based) are proposed to answer the demands on multitarget analysis to screen and identify authorised and unauthorised GMO.


Fanconi anemia (FA) is a rare inherited syndrome characterized by the early development of bone marrow failure and increasing predisposition to cancer with age. Allogeneic hematopoietic cell transplantation (alloHCT) is the only curative therapy for hematopoietic manifestations of FA, although associated with complications arising from myeloablation, graft versus host disease and increased incidence of squamous cell carcinoma. The genetic correction of autologous hematopoietic stem cells (HSC) with lentiviral vectors constitutes a recent and safe alternative for the treatment of different genetic diseases affecting mature cells from different tissues and/or committed progenitors of the hematopoietic system. One of the key features of FA that make it a unique disease for gene therapy approaches rely on the characteristic proliferation defect that is already evident in the very primitive HSCs. Thus, a marked survival advantage would be expected from corrected HSCs, potentially allowing normalization of hematopoiesis in the absence or after mild conditioning. Difficulties in the collection of sufficient numbers of HSC from FA patients and the use of sub-optimal transduction protocols with gammaretroviral vectors limited the success of FA gene therapy trials conducted 10 years ago in the USA. Our innovative approach to develop for the first time an efficient and safe gene therapy of FA is based on two recent innovations: 1) Discovery of potent HSC mobilizers, such as plerixafor, and 2) Development of a new lentiviral vector by members of this Consortium, designed as Orphan Drug by the EC in December 2010. The principal objective of this Project is, therefore, the development of a multicentric Phase I/II gene therapy trial for FA-A patients, based on the genetic correction of plerixafor\G-CSF mobilized HSCs with the novel lentiviral vector, accompanied by comprehensive and groundbreaking safety and efficacy patient monitoring studies.


Grant
Agency: GTR | Branch: EPSRC | Program: | Phase: Fellowship | Award Amount: 807.01K | Year: 2015

Complex fluid flows are ubiquitous in both the natural and man-made worlds. From the pulsatile flow of blood through our bodies, to the pumping of personal products such as shampoos or conditioners through complex piping networks as they are processed. For such complex fluids the underlying microstructure can give rise to flow instabilities which are often totally absent in simple Newtonian fluids such as water or air. For example, many wormlike micellar surfactant (soap/detergent) systems are known to exhibit shear-banding where the homogenous solution splits into two (or more) bands of fluid: such flows are often unstable to even infinitesimally small perturbations. At higher pump speeds the flows can develop chaotic motion caused by the elastic normal-stresses developed in flow. Such elastic turbulence can also develop for other flowing complex fluids, such as polymer solutions and melts, and give rise to new phenomena. Often such instabilities are unwelcome, for example in rheometric devices when the aim is to measure material properties or in simple pumping operations when they can give rise to unacceptably large pressure drops and prevent pumping. In other cases they can give rise to enhanced mixing of heat and mass which would otherwise be difficult to achieve (e.g. microfluidics applications).


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.88M | Year: 2013

The realization of efficient, cheap, reliable, scalable and portable terahertz (THz) radiation sources and detectors is one of the important objectives in modern applied physics. THz emitters and detectors have potential applications in biology, medicine, security and nondestructive in-depth imaging. However none of the existing THz devices satisfy the application requirements. The project consortium, which includes teams from the leading European universities: Durham, Vilnius, Paris-7, Exeter, St. Petersburg, Prague, Amiens, University of Iceland, Swiss Company Alpes laser and several industrial associated partners, proposes a broad range of new approaches aiming to bridge the terahertz gap: (i) Polariton-based THz emission using microcavities in the strong coupling regime, (ii) New types and concepts of semiconducting materials for short pulsed THz emission, (iii) Carbon nanotubes and graphene as THz emitters and detectors, (iv) Application of Ferroelectric and Multiferroic materials for THz devices. To achieve this objective, we are planning to educate and train a team of collaborating young physicists and device engineers able to conduct research and exploit its application in this new area.


Carvajal M.,University of Huelva | Kleiner I.,University Paris Diderot | Demaison J.,CNRS Atomic and Molecular Physics Laboratory
Astrophysical Journal, Supplement Series | Year: 2010

A compilation of the available spectroscopicmillimeter- and submillimeter-wave data of the ground and first excited states of 13C1-methyl formate (H13COOCH3) has been carried out. The exhaustive analysis of the available transition lines of H13COOCH3 has led to the assignment of 7457 spectral lines by means of a global fit of 45 parameters, using the Rho-Axis Method and the BELGI-Cs code, with a resulting unitless standard deviation of 0.57. Over 1600 lines are included for the first time in the fit. In addition, the line strengths of spectral lines are also calculated using the most recent experimental measurement of the electric dipole moment. In conclusion, the present study represents a notable improvement with respect to previous H 13COOCH3 spectral analyses. Therefore, the better accuracy of the present analysis may help the future identification of new H 13COOCH3 lines in the interstellar and circumstellar media, and may contribute to decrease some of the spectral confusion due to these species in astronomical surveys. © 2010. The American Astronomical Society. All rights reserved.


Garnier J.,University Paris Diderot | Picozzi A.,University of Burgundy
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2010

This article presents a unified kinetic formulation of partially coherent nonlinear optical waves propagating in a noninstantaneous response Kerr medium. We derive a kinetic equation that combines the weak Langmuir turbulence kinetic equation and a Vlasov-like equation within a general framework: It describes the evolution of the spectrum of a random field that exhibits a quasistationary statistics in the presence of a noninstantaneous nonlinear response. The kinetic equation sheds new light on the dynamics of partially coherent nonlinear waves and allows for a qualitative interpretation of the interplay between the noninstantaneous nonlinearity and the nonstationary statistics of the incoherent field. It is shown that the incoherent modulational instability of a random nonlinear wave can be suppressed by the noninstantaneous nonlinear response. Moreover, incoherent modulational instability can prevent the generation of spectral incoherent solitons. © 2010 The American Physical Society.


Patent
Assistance Publique Hopitaux De Paris Aphp, University of Paris Descartes, University Pierre, Marie Curie, University Paris Diderot, University Paris - Sud and Institute Gustave Roussy | Date: 2014-10-03

The present invention provides novel methods for the modulation of autophagy and the treatment of autophagy-related diseases, including cancer, neurodegenerative diseases, liver diseases, muscle diseases and pancreatitis.


Patent
French Institute of Health, Medical Research, French National Center for Scientific Research, University of Paris Descartes, Fondation Image, University Paris - Sud, Assistance Publique Hopitaux De Paris Aphp and University Paris Diderot | Date: 2013-08-02

The present disclosure relates to antagonists of transferrin receptor and compositions and methods of use of said antagonists for treating pathological disorders such as thalassemia disorders


Ruprecht V.,Institute of Science and Technology Austria | Wieser S.,Institute of Science and Technology Austria | Wieser S.,Innsbruck Medical University | Callan-Jones A.,University Paris Diderot | And 8 more authors.
Cell | Year: 2015

3D amoeboid cell migration is central to many developmental and disease-related processes such as cancer metastasis. Here, we identify a unique prototypic amoeboid cell migration mode in early zebrafish embryos, termed stable-bleb migration. Stable-bleb cells display an invariant polarized balloon-like shape with exceptional migration speed and persistence. Progenitor cells can be reversibly transformed into stable-bleb cells irrespective of their primary fate and motile characteristics by increasing myosin II activity through biochemical or mechanical stimuli. Using a combination of theory and experiments, we show that, in stable-bleb cells, cortical contractility fluctuations trigger a stochastic switch into amoeboid motility, and a positive feedback between cortical flows and gradients in contractility maintains stable-bleb cell polarization. We further show that rearward cortical flows drive stable-bleb cell migration in various adhesive and non-adhesive environments, unraveling a highly versatile amoeboid migration phenotype. © 2015 The Authors.


Serreau J.,University Paris Diderot | Parentani R.,CNRS Physics Laboratory
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

We study the O(N) scalar field theory with quartic self-coupling in de Sitter space. When the field is light in units of the expansion rate, perturbative methods break down at very low momenta due to large infrared logarithmic terms. Using the nonperturbative large-N limit, we compute the four-point vertex function in the deep infrared regime. The resummation of an infinite series of perturbative (bubble) diagrams leads to a modified power law which is analogous to the generation of an anomalous dimension in critical phenomena. We discuss in detail the role of high momentum (subhorizon) modes, including the issue of renormalization, and show that they influence the dynamics of infrared (superhorizon) modes only through a constant renormalization factor. This provides an explicit example of effective decoupling between high and low energy physics in an expanding space-time. © 2013 American Physical Society.


Perreau M.,University Paris Diderot | Tafforeau P.,European Synchrotron Radiation Facility
Systematic Entomology | Year: 2011

Fossils provide excellent opportunities for bringing to light evolutionary trends, and testing phylogenetic hypotheses. However, the difficulty in accessing internal structures limits the provision of accurate descriptions, and thus limits the comparison of fossil specimens with extant fauna. The virtual dissection of amber fossils by propagation phase-contrast X-ray synchrotron microtomography (PPC-SRμCT) allows incomparable possibilities for the visualization of genital structures, which are of prime importance in assessing the taxonomic status and phylogenetic relationships in many groups of insects. The method is illustrated on one new species of Coleoptera Leiodidae Anemadini in Baltic amber: Nemadus microtomographicus sp.n. © 2011 The Authors. Systematic Entomology © 2011 The Royal Entomological Society.


Etienne J.,University Grenoble Alpes | Etienne J.,French National Center for Scientific Research | Fouchard J.,University Paris Diderot | Mitrossilis D.,University Paris Diderot | And 3 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015

Living cells adapt and respond actively to the mechanical properties of their environment. In addition to biochemical mechanotransduction, evidence exists for a myosin-dependent purely mechanical sensitivity to the stiffness of the surroundings at the scale of the whole cell. Using a minimal model of the dynamics of actomyosin cortex, we show that the interplay of myosin power strokes with the rapidly remodeling actin network results in a regulation of force and cell shape that adapts to the stiffness of the environment. Instantaneous changes of the environment stiffness are found to trigger an intrinsic mechanical response of the actomyosin cortex. Cortical retrograde flow resulting from actin polymerization at the edges is shown to bemodulated by the stress resulting from myosin contractility, which in turn, regulates the cell length in a forcedependent manner. Themodel describes themaximum force that cells can exert and the maximum speed at which they can contract, which are measured experimentally. These limiting cases are found to be associated with energy dissipationphenomena, whichare of the samenature as those taking place during the contraction of a whole muscle. This similarity explains the fact that single nonmuscle cell and wholemuscle contraction both follow a Hill-like force-velocity relationship.


Fahraeus R.,University Paris Diderot | Olivares-Illana V.,Autonomous University of San Luis Potosi
Oncogene | Year: 2014

MDM2 is considered a hub protein due to its capacity to interact with a large number of different partners of which p53 is most well described. MDM2 is an E3 ubiquitin ligase, and many, but not all, of its interactions relate directly to this activity, such as substrates, adaptors or bridges, promoters, inhibitors or complementary factors. Some interactions serve regulatory functions that in response to cellular stresses control the localisation and functions of MDM2 including protein kinases, ribosomal proteins and proteases. Moreover, interactions with nucleotides serve other functions such as mRNA to regulate protein synthesis and DNA to control transcription. To perform such a pleiotropic panorama of different functions, MDM2 is subjected to a multitude of post-translational modifications and is expressed in different isoforms. The large and diverse interactome is made possible due to the plasticity of MDM2 and in this review we have listed the MDM2 interactions until now and we will discuss how this multifaceted protein can interact with such a variety of substrates to provide a key intermediary role in different signalling pathways.


Asnacios A.,University Paris Diderot | Hamant O.,University Claude Bernard Lyon 1 | Hamant O.,University of Lyon
Trends in Cell Biology | Year: 2012

The generation of cell polarity is one of the most intriguing symmetry-breaking events in biology. It is involved in almost all physiological and developmental processes and, despite the differences between plant and animal cell structures, cell polarity is generated by a similar core mechanism that comprises the extracellular matrix (ECM), Rho GTPase, the cytoskeleton, and the membranes. Several recent articles show that mechanical factors also contribute to the establishment and robustness of cell polarity, and the different molecular actors of cell polarity are now viewed as integrators of both biochemical and mechanical signals. Although cell polarity remains a complex process, some level of functional convergence between plants and animals is revealed. Following comparative presentation of cell polarity in plants and animals, we will discuss the theoretical background behind the role of mechanics in polarity and the relevant experimental tests, focusing on ECM anchorage, cytoskeleton behavior, and membrane tension. © 2012 Elsevier Ltd.


Solon A.P.,University Paris Diderot | Chate H.,CEA Saclay Nuclear Research Center | Chate H.,University Pierre and Marie Curie | Chate H.,Beijing Computational Science Research Center | Tailleur J.,University Paris Diderot
Physical Review Letters | Year: 2015

We show that the flocking transition in the Vicsek model is best understood as a liquid-gas transition, rather than an order-disorder one. The full phase separation observed in flocking models with Z2 rotational symmetry is, however, replaced by a microphase separation leading to a smectic arrangement of traveling ordered bands. Remarkably, continuous deterministic descriptions do not account for this difference, which is only recovered at the fluctuating hydrodynamics level. Scalar and vectorial order parameters indeed produce different types of number fluctuations, which we show to be essential in selecting the inhomogeneous patterns. This highlights an unexpected role of fluctuations in the selection of flock shapes. © 2015 American Physical Society.


Matt S.P.,University Paris Diderot | MacGregor K.B.,High Altitude Observatory | Pinsonneault M.H.,Ohio State University | Greene T.P.,NASA
Astrophysical Journal Letters | Year: 2012

We use two-dimensional axisymmetric magnetohydrodynamic simulations to compute steady-state solutions for solar-like stellar winds from rotating stars with dipolar magnetic fields. Our parameter study includes 50 simulations covering a wide range of relative magnetic field strengths and rotation rates, extending from the slow- and approaching the fast-magnetic-rotator regimes. Using the simulations to compute the angular momentum loss, we derive a semi-analytic formulation for the external torque on the star that fits all of the simulations to a precision of a few percent. This formula provides a simple method for computing the magnetic braking of Sun-like stars due to magnetized stellar winds, which properly includes the dependence on the strength of the magnetic field, mass loss rate, stellar radius, surface gravity, and spin rate, and which is valid for both slow and fast rotators. © 2012. The American Astronomical Society. All rights reserved..


Gallais Y.,University Paris Diderot | Paul I.,University Paris Diderot | Chauviere L.,University Paris Diderot | Schmalian J.,Karlsruhe Institute of Technology
Physical Review Letters | Year: 2016

In a fully gapped superconductor the electronic Raman response has a pair-breaking peak at twice the superconducting gap Δ, if the Bogoliubov excitations are uncorrelated. Motivated by the iron based superconductors, we study how this peak is modified if the superconducting phase hosts a nematic-structural quantum critical point. We show that, upon approaching this point by tuning, e.g., doping, the growth of nematic correlations between the quasiparticles transforms the pair-breaking peak into a nematic resonance. The mode energy is below 2Δ, and stays finite at the quantum critical point, where its spectral weight is sharply enhanced. The latter is consistent with recent experiments on electron-doped iron based superconductors and provides direct evidence of nematic correlations in their superconducting phases. © 2016 American Physical Society.


Divoux T.,CNRS Paul Pascal Research Center | Fardin M.A.,University Paris Diderot | Manneville S.,CNRS Physics Laboratory | Lerouge S.,University Paris Diderot
Annual Review of Fluid Mechanics | Year: 2016

Even in simple geometries, many complex fluids display nontrivial flow fields, with regions where shear is concentrated. The possibility for such shear banding has been known for several decades, but in recent years, we have seen an upsurge in studies offering an ever-more precise understanding of the phenomenon. The development of new techniques to probe the flow on multiple scales with increasing spatial and temporal resolution has opened the possibility for a synthesis of the many phenomena that could only have been thought of separately before. In this review, we bring together recent research on shear banding in polymeric and soft glassy materials and highlight their similarities and disparities. © Copyright 2016 by Annual Reviews. All rights reserved.


Weitzman M.D.,University of Pennsylvania | Weitzman M.D.,Children's Hospital of Philadelphia | Weitzman J.B.,University Paris Diderot
Cell Host and Microbe | Year: 2014

Maintaining genome integrity and transmission of intact genomes is critical for cellular, organismal, and species survival. Cells can detect damaged DNA, activate checkpoints, and either enable DNA repair or trigger apoptosis to eliminate the damaged cell. Aberrations in these mechanisms lead to somatic mutations and genetic instability, which are hallmarks of cancer. Considering the long history of host-microbe coevolution, an impact of microbial infection on host genome integrity is not unexpected, and emerging links between microbial infections and oncogenesis further reinforce this idea. In this review, we compare strategies employed by viruses, bacteria, and parasites to alter, subvert, or otherwise manipulate host DNA damage and repair pathways. We highlight how microbes contribute to tumorigenesis by directly inducing DNA damage, inactivating checkpoint controls, or manipulating repair processes. We also discuss indirect effects resulting from inflammatory responses, changes in cellular metabolism, nuclear architecture, and epigenome integrity, and the associated evolutionary tradeoffs. ©2014 Elsevier Inc.


Nelson N.J.,University of Colorado at Boulder | Brown B.P.,University of Wisconsin - Madison | Brun A.S.,University Paris Diderot | Miesch M.S.,High Altitude Observatory | Toomre J.,University of Colorado at Boulder
Astrophysical Journal | Year: 2013

Solar-type stars exhibit a rich variety of magnetic activity. Seeking to explore the convective origins of this activity, we have carried out a series of global three-dimensional magnetohydrodynamic simulations with the anelastic spherical harmonic code. Here we report on the dynamo mechanisms achieved as the effects of artificial diffusion are systematically decreased. The simulations are carried out at a nominal rotation rate of three times the solar value (3Ω), but similar dynamics may also apply to the Sun. Our previous simulations demonstrated that convective dynamos can build persistent toroidal flux structures (magnetic wreaths) in the midst of a turbulent convection zone and that high rotation rates promote the cyclic reversal of these wreaths. Here we demonstrate that magnetic cycles can also be achieved by reducing the diffusion, thus increasing the Reynolds and magnetic Reynolds numbers. In these more turbulent models, diffusive processes no longer play a significant role in the key dynamical balances that establish and maintain the differential rotation and magnetic wreaths. Magnetic reversals are attributed to an imbalance in the poloidal magnetic induction by convective motions that is stabilized at higher diffusion levels. Additionally, the enhanced levels of turbulence lead to greater intermittency in the toroidal magnetic wreaths, promoting the generation of buoyant magnetic loops that rise from the deep interior to the upper regions of our simulated domain. The implications of such turbulence-induced magnetic buoyancy for solar and stellar flux emergence are also discussed. © 2013. The American Astronomical Society. All rights reserved..


Hazra D.K.,Asia Pacific Center for Theoretical Physics | Shafieloo A.,Pohang University of Science and Technology | Smoot G.F.,University Paris Diderot | Smoot G.F.,University of California at Berkeley | Starobinsky A.A.,Russian Academy of Sciences
Physical Review Letters | Year: 2014

Motivated by the idea that inflation occurs at the grand unified theory symmetry breaking scale, in this Letter we construct a new class of large field inflaton potentials where the inflaton starts with a power law potential; after an initial period of relatively fast roll that lasts until after a few e folds inside the horizon it transits to the attractor of the slow roll part of the potential with a lower power. Because of the initial fast roll stages of inflation, we find a suppression in scalar primordial power at large scales and at the same time the choice of the potential can provide us a tensor primordial spectrum with a high amplitude. This suppression in scalar power with a large tensor-to-scalar ratio helps us to reconcile the Planck and BICEP2 data in a single framework. We find that a transition from a cubic to quadratic form of inflaton potential generates an appropriate suppression in the power of the scalar primordial spectrum that provides a significant improvement in fit compared to the power law model when compared with Planck and BICEP2 data together. We calculate the extent of non-Gaussianity, specifically, the bispectrum for the best fit potential, and show that it is consistent with Planck bispectrum constraints. © 2014 American Physical Society.


Espinosa-Medina I.,French Institute of Health and Medical Research | Outin E.,French Institute of Health and Medical Research | Picard C.A.,French Institute of Health and Medical Research | Chettouh Z.,French Institute of Health and Medical Research | And 5 more authors.
Science | Year: 2014

Neural crest cells migrate extensively and give rise to most of the peripheral nervous system, including sympathetic, parasympathetic, enteric, and dorsal root ganglia. We studied how parasympathetic ganglia form close to visceral organs and what their precursors are. We find that many cranial nerve-associated crest cells coexpress the pan-autonomic determinant Paired-like homeodomain 2b (Phox2b) together with markers of Schwann cell precursors. Some give rise to Schwann cells after down-regulation of PHOX2b. Others form parasympathetic ganglia after being guided to the site of ganglion formation by the nerves that carry preganglionic fibers, a parsimonious way of wiring the pathway. Thus, cranial Schwann cell precursors are the source of parasympathetic neurons during normal development.


Kotloff R.M.,University of Pennsylvania | Thabut G.,University Paris Diderot
American Journal of Respiratory and Critical Care Medicine | Year: 2011

First performed in 1963, lung transplantation is approaching the half-century mark. With more than 32,000 procedures having been performed worldwide, lung transplantation has become the standard of care for select patients with advanced lung diseases of various nonmalignant etiologies. Indications for transplantation have broadened over the years, and selection criteria have become less restrictive.Arelatively scarce donor pool limits wider application of this therapy, but this is being addressed in part through relaxation of donor selection criteria, donor management protocols that preserve and optimize lung function, and development of ex vivo perfusion techniques to "recondition" suboptimal organs. Bilateral lung transplantation has become the procedure of choice for most indications, although its preferential use in patients with idiopathic pulmonary fibrosis remains controversial. Post-transplantation survival has steadily improved, but significant constraints on long-term survival persist as evidenced by a median survival rate that currently stands at 5.7 years. This has brought into focus the question of whether and for whom transplantation actually confers a survival advantage, a question that in the absence of randomized trials can only be answered with statistical modeling. Primary graft dysfunction, infection, and bronchiolitis obliterans syndrome are common complications encountered by the lung transplant recipient and are major impediments to long-term survival. This review provides an overview of the current status of lung transplantation, highlighting both the many advances that have taken place and the challenges that remain.


Brun A.S.,University Paris Diderot | Miesch M.S.,High Altitude Observatory | Toomre J.,University of Colorado at Boulder
Astrophysical Journal | Year: 2011

The global dynamics of a rotating star like the Sun involves the coupling of a highly turbulent convective envelope overlying a seemingly benign radiative interior. We use the anelastic spherical harmonic code to develop a new class of three-dimensional models that nonlinearly couple the convective envelope to a deep stable radiative interior. The numerical simulation assumes a realistic solar stratification from r = 0.07 up to 0.97R (with R the solar radius), thus encompassing part of the nuclear core up through most of the convection zone. We find that a tachocline naturally establishes itself between the differentially rotating convective envelope and the solid body rotation of the interior, with a slow spreading that is here diffusively controlled. The rapid angular momentum redistribution in the convective envelope leads to a fast equator and slow poles, with a conical differential rotation achieved at mid-latitudes, much as has been deduced by helioseismology. The convective motions are able to overshoot downward about 0.04R into the radiative interior. However, the convective meridional circulation there is confined to a smaller penetration depth and is directed mostly equatorward at the base of the convection zone. Thermal wind balance is established in the lower convection zone and tachocline but departures are evident in the upper convection zone. Internal gravity waves are excited by the convective overshooting, yielding a complex wave field throughout the radiative interior. © 2011. The American Astronomical Society. All rights reserved.


Gajjar M.,University Paris Diderot | Candeias M.M.,University Paris Diderot | Malbert-Colas L.,University Paris Diderot | Mazars A.,University Paris Diderot | And 4 more authors.
Cancer Cell | Year: 2012

The ATM kinase and p53 are key tumor suppressor factors that control the genotoxic stress response pathway. The ATM substrate Mdm2 controls p53 activity by either targeting p53 for degradation or promoting its synthesis by binding the p53 mRNA. The physiological role and regulation of Mdm2's dual function toward p53 is not known. Here we show that ATM-dependent phosphorylation of Mdm2 at Ser395 is required for the p53 mRNA-Mdm2 interaction. This event also promotes SUMO-conjugation of Mdm2 and its nucleoli accumulation. Interfering with the p53 mRNA-Mdm2 interaction prevents p53 stabilization and activation following DNA damage. These results demonstrate how ATM activity switches Mdm2 from a negative to a positive regulator of p53 via the p53 mRNA. © 2012 Elsevier Inc.


Jeanneret R.,University Paris Diderot | Bartolo D.,University Paris Diderot | Bartolo D.,CNRS Physics Laboratory
Nature Communications | Year: 2014

When periodically driven, a number of markedly different systems (colloids, droplets, grains, flux lines) have revealed a transition from a reversible to an irreversible dynamics that hardly depends on the very nature of the interacting objects. Yet, no clear structural signature has been found for this collective self-organization. Here, we demonstrate an archetypal Loschmidt-echo experiment involving thousands of droplets that interact in a reversible fashion via a viscous fluid. First, we show that periodically driven microfluidic emulsions self-organize and geometrically protect their macroscopic reversibility. Self-organization is not merely dynamical: it has a clear structural signature. Second, we show that, above a maximal shaking amplitude, structural order and reversibility are lost simultaneously through a first-order non-equilibrium phase transition. We account for this discontinuous transition in terms of a memory-loss process. Finally, we suggest potential applications of microfluidic echo as a robust tool to tailor colloidal self-assembly at large scales. © 2014 Macmillan Publishers Limited. All rights reserved.


Patent
French Institute of Health, Medical Research, French National Center for Scientific Research, University of Rennes 1, University Paris Diderot, University Pierre and Marie Curie | Date: 2011-04-04

A method for treating and/or ameliorating and/or preventing a disease or a disorder, the method comprising administering to an individual in need thereof at least one nitrogen heterocycle derivative of formula (I): The at least one nitrogen heterocycle derivative may also be used as a proteasome activity modulator in the manufacture of a pharmaceutical composition intended to prevent and/or treat a disease condition mediated by the proteasome activity.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2011.9.10 | Award Amount: 7.65M | Year: 2013

The aim of ASSISI_bf is to develop (1) a fundamental new class of distributed ICT systems, which are bio-hybrid collective adaptive systems (CASs) that consist of two sub-systems: One is a self-organising society of animals; the other one is a society of technical devices. These CASs will solve problems by distributed spatial computation; this heterogeneous system (animals, robots, nodes) will perform collective decision-making and maintain internal homeostasis. (2) We plan to develop a fundamental new method to design CASs by exploiting evolutionary computation on mathematical models that are used to drive the engineered part of the CAS. This way the collective of animals and robots will adapt to environmental changes and will maximize its efficiency and stability. (3) We will develop several novel benchmarks, using the level of acceptance of robots by the animal society as a hard-to-reach criterion. (4) Finally, we will derive a general model for heterogeneous CASs, which will be used to develop new algorithms for other heterogeneous robotic CASs. We address all 3 principles that should be researched for CASs, which are: design, operation and evolution. The project tackles several severe engineering challenges. It has a high potential of impact and foundational character on several communities. On the one hand it has the potential to establish a new field of science, which focuses on self-adapting engineered systems able to integrate themselves into an existing natural society. On the other hand, the proposed long-term impact reaches from establishing important new methods in agriculture, environmental sustainability policies, live stock management, environmental monitoring, bio-hybrid engineering and pharmaceutical industry, as our proposed technology allows fully automated (but non-invasive, non-harmful) experimentation with social animals. By deducting models and algorithms our project can also influence and promote general research of distributed ICT systems.


Grant
Agency: Cordis | Branch: H2020 | Program: MSCA-RISE | Phase: MSCA-RISE-2015 | Award Amount: 1.62M | Year: 2016

According to UNEP, the building sector is estimated to be worth 10% of the global GDP and employs 111 million people. In addition, buildings use about 40% of global energy, 40% of global resources and emit approximately 33% of global GHG emissions. Finally, the fact that people today spend, on average, more than 80% of their time indoors, enhances its social importance. All above indicate the necessity to optimize building design. Architects usually name optimal design the choice among a very limited set of design alternatives, dictated by their experience and intuition. However, modern design of structures requires one to account for a great number of criteria deriving from multiple disciplines, often of conflicting nature. The vast number of alternative choices enhances the possibility of arriving at an optimum with the incorporation of smart, automatic tools in the design process, further guiding designers intuition. The principal aim of the proposed Network is to create and test methodologies for the application of optimization techniques in different design phases of civil structures by developing strong synergies among a multi-disciplinary team of academic experts from Greece, France, Cyprus, Canada, Turkey, Egypt & Jordan and SMEs from France & Greece. A first goal of the project is to exploit the use of shape and topology optimization techniques in computer aided architectural design. Moreover, the Network wants to exchange ideas, propose formulations that correspond to real-life applications and develop solutions for optimal multi-disciplinary architectural design. Of particular interest is the combination of criteria deriving from structural mechanics, eco-design, bioclimatic design and acoustic performance. For each topic, joint workshops, seminars and long-term visits will be organized at the coordinating and partner institutions. The results will be published in scientific journals, professional magazines and presented in international conferences.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2007.2.2 | Award Amount: 3.89M | Year: 2009

The goal of the proposed study is to equip a highly biomimetic robot hand-arm system with the agility, robustness and versatility that are hallmarks of the human motor system by understanding and mimicking the variable stiffness paradigms that are so effectively employed by the human CNS. A key component of the study will be the anatomically accurate musculoskeletal modelling of the human arm and hand. The project will develop novel methodologies to comprehend how the human arm can adapt its impedance, e.g. by changing the co-contraction level or by adapting the reflex gains. The impedance of the arm and of the hand will be investigated using powerful robot manipulators capable of imposing force perturbations. The existing closed-loop system identification techniques will be extended with non-linear time-variant techniques which can identify the behaviour during reaching and grasping tasks. The grasp force modulation and hand muscle activity correlations will be learned for use on the robotic system. Finally, optimization techniques gleaned and validated on the detailed biophysical model will be transferred to the variable impedance actuation of the novel biomorphic robotic system The central question that this proposal focuses on for both the human and robotic arm is: how is stiffness used to enhance performance?; and this project represents one of the first attempts where targeted modelling studies will go the full circle by exploiting these results for optimal control of an embodied, high dimensional, variable impedance robotic system.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2009.2.1 | Award Amount: 2.17M | Year: 2009

The proposal objective is to investigate new approaches to the design and development of humanoid robots with advanced perception and action capabilities, showing robust, adaptive, predictive and effective behaviour in the real world. The proposed new approaches are strongly based on the concept of human sense of movement by Alain Berthoz, a key partner in this proposal. There are two main ideas related to this concept, which are relevant to robotics: 1) the vestibular unified reference frame, as set by the vestibular system in the centre of the head; 2) Expected Perception (EP), or the capability to make predictions of consequences of actions, which is at the basis of the human predictive control. The expected robot behaviour is the capability to follow a visual target by coordinating eye, head, and leg movements, with head stabilization, walking smoothly and effectively in an unstructured environment, with a robust reactive behaviour, improved by predictions. This behaviour is a fundamental, but quite novel, capability for humanoid robots, and it may result in a truly robust and effective behaviour in many helpful tasks in real-world scenarios. The proposed project will use the existing and fully operational biped humanoid robotic platform named Sabian, available at SSSA. It is a copy of the Wabian robot developed at WUT. The legs have functional hip and waiste DOF that allow to de-couple the leg and head movements. This unique feature guarantees a truly human-like walking behaviour with head stabilization. IST has developed and has in its lab the same head as the Sabian robot. It is strong belief of proposers that the service robotics markets needs a new generation of robotic systems with a better behaviour in real world, in terms of sensory-motor performance, adaptability, robustness, and that understanding the principles underlying the biological brain sense of movement can lead to the design of robots that represent one important step in this direction.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: NMP-2008-1.3-2 | Award Amount: 5.27M | Year: 2009

Engineered Nanoparticles (ENP) are increasingly produced for use in a wide range of industrial and consumer products. Yet it is known that exposure to some types of particles can cause severe health effects. Therefore it is essential to ascertain whether exposure to ENP can lead to possible health risks for workers and consumers. We have formed a consortium of well-known scientists from European Universities and Research Institutes, with over 100 publications in the field of Nanotoxicology. Our aim is to develop an approach for the Risk Assessment of ENP (ENPRA). Our objectives are: (i) to obtain a bank of commercial ENP with contrasting physico-chemical characteristics and measure them; (ii) to investigate the toxic effects of ENP on 5 (pulmonary, hepatic, renal, cardiovascular and developmental) target systems and 5 endpoints (oxidative stress, inflammation; immuno-toxicity; fibrogenecity; genotoxicity) using in vitro animal/human models; (iii) to validate the in vitro findings with a small set of carefully chosen in vivo animal experiments; (iv) to construct mathematical models to extrapolate the exposure-dose-response relationship from in vitro to in vivo and to humans; (v) to use QSAR like models to identify the key ENP characteristics driving the adverse effects; (vi) to implement a risk assessment of ENP using the Weight-of-Evidence approach; (vii) to disseminate our findings to potential stakeholders. To harmonise the research activities between our EU group and the US, we have established links with scientists from US Universities (Duke, Rochester) and Government Agencies (NIH/NIEHS, NIOSH and EPA) with on-going research in Nanotoxicology. Our objectives here are (vii) to share information and agree on experimental protocols; (viii) to avoid duplication of work; (ix) to further validate the findings of this proposed study.


Grant
Agency: Cordis | Branch: FP7 | Program: NOE | Phase: ICT-2007.3.2 | Award Amount: 3.76M | Year: 2008

The Network of Excellence (NoE) PolyNet aims to establish Europe in the area of organic and large area electronics as the world leader in science, technology development and subsequent commercial exploitation of printing and large area technologies for heterointegration of flexible electronics.\n\nFuture industrial Exploitation needs a research cooperation base and a service base to foster transfer from science to industry within EU. Therefore fragmentation of European research landscape has to be overcome.\n\nThe NoE PolyNet will support these aims with three core platforms:\n- a research cooperation platform\n- a service platform\n- a knowledge platform\n\nFor a long-term integration of European research landscape concepts for the continuation of research cooperation and service offers will be developed, validate and put into operation.\n\nImpact is expected not only on the research landscape of Organic and Large Area Electronics but also indirectly on European industry by long-term stimulation of innovative technologies and new companies.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2009.3.3 | Award Amount: 2.37M | Year: 2010

Electronic transduction can open new perspectives for point-of-care diagnosis and treatment monitoring. In this respect, label free, organic field-effect transistor (OFET) sensors have recently raised the interest of the organic-electronic community. The EGOFET biosensor aims at an electronic transduction of a bio-recognition event, eventually leading to an amplified response. The sensor combines the specificity of a defined bio-probe with the label-free and high sensitivity of the field-effect transduction principle. The recognition will be achieved through antigens, antibodies or membrane proteins placed on top of the organic semiconductor, right where the electrical transport occurs in this dielectrics/oxide-free structure. Supramolecular architectures will be used to immobilize the bio-probes into polymeric or phospholipid layers to maximise recognition capabilities and minimize non-specific binding and fouling. High sensitivity will be achieved by exploiting conformational changes and/or charge generation effects occurring upon the recognition process. To attain low-operating voltage and low-power consumption, the OFET will take advantage of the high capacitance offered by the electrolytic or protonic medium used to carry the analyte up to the semi-conductor surface. Implementation of the devices on paper and plastic substrates will be realized by low-cost printing-compatible technologies. The sensors figures of merit will be assessed by exploiting the highly specific biotin/avidin affinity reaction. A proof-of-principle for a point-of-care relevant application, using the immunoassay approach, will be pursued afterwards.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ENV.2013.6.1-2 | Award Amount: 11.51M | Year: 2013

Massive economic and population growth and urbanisation are expected to lead to a tripling of anthropogenic emissions in southern West Africa (SWA) between 2000 and 2030, the impacts of which on human health, ecosystems, food security and the regional climate are largely unknown. An assessment of these impacts is complicated by (a) a superposition with effects of global climate change, (b) the strong dependence of SWA on the sensitive West African monsoon, (c) incomplete scientific understanding of interactions between emissions, clouds, radiation, precipitation and regional circulations and (d) by a lack of observations to advance our understanding and improve predictions. The DACCIWA project will conduct extensive fieldwork in SWA to collect high-quality observations, spanning the entire process chain from surface-based natural and anthropogenic emissions to impacts on health, ecosystems and climate. Combining the resulting benchmark dataset with a wide range of modelling activities will allow (a) to assess all relevant physical and chemical processes, (b) to improve the monitoring of climate and compositional parameters from space and (c) to develop the next generation of weather and climate models capable of representing coupled cloud-aerosol interactions, which will ultimately lead to reduced uncertainties in climate predictions. SWA with its rich mix of emissions and diverse clouds is ideal for such a study and many findings and technical developments will be applicable to other monsoon regions. Using a targeted dissemination strategy, DACCIWA will deliver a comprehensive scientific assessment and actively guide sustainable future planning and policy-making for West Africa and beyond. The interdisciplinary and experienced DACCIWA team will build on the scientific and logistical foundations established by AMMA (EU FP6) and collaborate closely with operational centres, international programs (e.g. WCRP, IGBP), policy-makers and users to maximise impact.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: SSH-2007-4.3-01 | Award Amount: 2.01M | Year: 2009

Geographers are the most critical social scientists when it comes to the delimitation of borders of the so-called European continent. Continents as Huntingtons civilisation are ideological productions that are certainly not based on natural facts. But they are deeply enhanced in the mind of European citizens and policy makers because they were historically produced by Europeans as a tool of world power. It is therefore crucial to examine which divisions of the world are perceived by people located outside the European Union, in order to produce a non Eurocentric view. The project EuroBroadMap is based on a worldwide survey trying to catch both the perception of European Union global role and attraction power level and the definition of EU from a qualitative and spatial point of view as well as the relative attraction of countries, or even cities that compose it. The survey will be realized on a panel of license degree students in a relevant panel of external countries and in different academic fields. The questionnaire will combine different kinds of methods, like drawings on maps, open questions, ranking etc Variations in answer will be examined according to both geographical location and social status. The individual mental maps will be compared to collective representations: websites of organization, tourist guides, teaching books, international media, etc. Particular attention will be paid to (carto)graphic representations of Europe and other world divisions. Spiritual flows that are revealed by individual and collective mental maps will be then compared to four types of effective flows linking EU and the rest of the world (Trade, Aid, FDI, Migrations) in order to examine possible discrepancies. The diffusion of results in various formats (report, website, teaching material, ) will be organized in order to insure a growing awareness of the complexity of actual situation of Europe in the world, according to material and spiritual dimensions.


Salmon J.,University Paris Diderot | Dalalyan A.,University Paris Est Creteil
Journal of Machine Learning Research | Year: 2011

We consider the problem of combining a (possibly uncountably infinite) set of affine estimators in non-parametric regression model with heteroscedastic Gaussian noise. Focusing on the exponentially weighted aggregate, we prove a PAC-Bayesian type inequality that leads to sharp oracle inequalities in discrete but also in continuous settings. The framework is general enough to cover the combinations of various procedures such as least square regression, kernel ridge regression, shrinking estimators and many other estimators used in the literature on statistical inverse problems. As a consequence, we show that the proposed aggregate provides an adaptive estimator in the exact minimax sense without neither discretizing the range of tuning parameters nor splitting the set of observations. We also illustrate numerically the good performance achieved by the exponentially weighted aggregate. © 2011 J. Salmon & A. Dalalyan.


Artero V.,CNRS Chemistry and Biology of Metals Laboratory | Saveant J.-M.,University Paris Diderot
Energy and Environmental Science | Year: 2014

Molecular electrocatalysts for H2 evolution are usually studied under various conditions (solvent and proton sources) that prevent direct comparison of their performances. We provide here a rational method for such a benchmark based on (i) the recent analysis of the current-potential response for two-electron-two-step mechanisms and (ii) the derivation of catalytic Tafel plots reflecting the interdependency of turnover frequency and overpotential based on the intrinsic properties of the catalyst, independent of contingent factors such as cell characteristics. Such a methodology is exemplified on a series of molecular catalysts among the most efficient in the recent literature. © 2014 the Partner Organisations.


Belazzougui D.,University Paris Diderot | Navarro G.,University of Chile
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2011

Self-indexes can represent a text in asymptotically optimal space under the k-th order entropy model, give access to text substrings, and support indexed pattern searches. Their time complexities are not optimal, however: they always depend on the alphabet size. In this paper we achieve, for the first time, full alphabet-independence in the time complexities of self-indexes, while retaining space optimality. We obtain also some relevant byproducts on compressed suffix trees. © 2011 Springer-Verlag Berlin Heidelberg.


Koschorreck M.,ICFO - Institute of Photonic Sciences | Napolitano M.,ICFO - Institute of Photonic Sciences | Dubost B.,ICFO - Institute of Photonic Sciences | Dubost B.,University Paris Diderot | Mitchell M.W.,ICFO - Institute of Photonic Sciences
Physical Review Letters | Year: 2010

Quantum nondemolition (QND) measurement of collective variables by off-resonant optical probing has the ability to create entanglement and squeezing in atomic ensembles. Until now, this technique has been applied to real or effective spin one-half systems. We show theoretically that the buildup of Raman coherence prevents the naive application of this technique to larger spin atoms, but that dynamical decoupling can be used to recover the ideal QND behavior. We experimentally demonstrate dynamical decoupling by using a two-polarization probing technique. The decoupled QND measurement achieves a sensitivity 5.7(6)dB better than the spin projection noise. © 2010 The American Physical Society.


Koschorreck M.,ICFO - Institute of Photonic Sciences | Napolitano M.,ICFO - Institute of Photonic Sciences | Dubost B.,ICFO - Institute of Photonic Sciences | Dubost B.,University Paris Diderot | Mitchell M.W.,ICFO - Institute of Photonic Sciences
Physical Review Letters | Year: 2010

We demonstrate sub-projection-noise sensitivity of a broadband atomic magnetometer using quantum nondemolition spin measurements. A cold, dipole-trapped sample of rubidium atoms provides a long-lived spin system in a nonmagnetic environment, and is probed nondestructively by paramagnetic Faraday rotation. The calibration procedure employs as known reference state, the maximum-entropy or "thermal" spin state, and quantitative imaging-based atom counting to identify electronic, quantum, and technical noise in both the probe and spin system. The measurement achieves a sensitivity 1.6 dB (2.8 dB) better than projection-noise (thermal state quantum noise) and will enable squeezing-enhanced broadband magnetometry. © 2010 The American Physical Society.


Ulgherait M.,University of California at Los Angeles | Rana A.,University of California at Los Angeles | Rera M.,University of California at Los Angeles | Rera M.,University Paris Diderot | And 2 more authors.
Cell Reports | Year: 2014

AMPK exerts prolongevity effects in diverse species; however, the tissue-specific mechanisms involved are poorly understood. Here, we show that upregulation of AMPK in the adult Drosophila nervous system induces autophagy both in the brain and also in theintestinal epithelium. Induction of autophagy is linked to improved intestinal homeostasis during aging and extended lifespan. Neuronal upregulation of the autophagy-specific protein kinase Atg1 is both necessary and sufficient to induce these intertissue effects during aging and to prolong the lifespan. Furthermore, upregulation of AMPK in the adult intestine induces autophagy both cell autonomously and non-cell-autonomously in the brain, slows systemic aging, and prolongs the lifespan. We show that the organism-wide response to tissue-specific AMPK/Atg1 activation is linked to reduced insulin-like peptide levels in the brain and a systemic increase in 4E-BP expression. Together, these results reveal that localized activation of AMPK and/or Atg1 in key tissues can slow aging in a non-cell-autonomous manner. © 2014 The Authors.


Groll A.H.,University of Munster | Castagnola E.,Instituto Giannina Gaslini | Cesaro S.,Pediatric Hematology Oncology | Dalle J.-H.,University Paris Diderot | And 6 more authors.
The Lancet Oncology | Year: 2014

Invasive opportunistic fungal diseases (IFDs) are important causes of morbidity and mortality in paediatric patients with cancer and those who have had an allogeneic haemopoietic stem-cell transplantation (HSCT). Apart from differences in underlying disorders and comorbidities relative to those of adults, IFDs in infants, children, and adolescents are unique with respect to their epidemiology, the usefulness of diagnostic methods, the pharmacology and dosing of antifungal agents, and the absence of interventional phase 3 clinical trials for guidance of evidence-based decisions. To better define the state of knowledge on IFDs in paediatric patients with cancer and allogeneic HSCT and to improve IFD diagnosis, prevention, and management, the Fourth European Conference on Infections in Leukaemia (ECIL-4) in 2011 convened a group that reviewed the scientific literature on IFDs and graded the available quality of evidence according to the Infectious Diseases Society of America grading system. The final considerations and recommendations of the group are summarised in this manuscript. © 2014 Elsevier Ltd.


Martin A.,Cornell University | Orgogozo V.,University Paris Diderot
Evolution | Year: 2013

What is the nature of the genetic changes underlying phenotypic evolution? We have catalogued 1008 alleles described in the literature that cause phenotypic differences among animals, plants, and yeasts. Surprisingly, evolution of similar traits in distinct lineages often involves mutations in the same gene ("gene reuse"). This compilation yields three important qualitative implications about repeated evolution. First, the apparent evolution of similar traits by gene reuse can be traced back to two alternatives, either several independent causative mutations or a single original mutational event followed by sorting processes. Second, hotspots of evolution-defined as the repeated occurrence of de novo mutations at orthologous loci and causing similar phenotypic variation-are omnipresent in the literature with more than 100 examples covering various levels of analysis, including numerous gain-of-function events. Finally, several alleles of large effect have been shown to result from the aggregation of multiple small-effect mutations at the same hotspot locus, thus reconciling micromutationist theories of adaptation with the empirical observation of large-effect variants. Although data heterogeneity and experimental biases prevented us from extracting quantitative trends, our synthesis highlights the existence of genetic paths of least resistance leading to viable evolutionary change. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.


Erlinger S.,University Paris Diderot | Arias I.M.,U.S. National Institutes of Health | Dhumeaux D.,University Paris Est Creteil
Gastroenterology | Year: 2014

Inherited disorders of bilirubin metabolism might reduce bilirubin uptake by hepatocytes, bilirubin conjugation, or secretion of bilirubin into bile. Reductions in uptake could increase levels of unconjugated or conjugated bilirubin (Rotor syndrome). Defects in bilirubin conjugation could increase levels of unconjugated bilirubin; the effects can be benign and frequent (Gilbert syndrome) or rare but severe, increasing the risk of bilirubin encephalopathy (Crigler-Najjar syndrome). Impairment of bilirubin secretion leads to accumulation of conjugated bilirubin (Dubin-Johnson syndrome). We review the genetic causes and pathophysiology of disorders of bilirubin transport and conjugation as well as clinical and therapeutic aspects. We also discuss the possible mechanisms by which hyperbilirubinemia protects against cardiovascular disease and the metabolic syndrome and the effects of specific genetic variants on drug metabolism and cancer development. © 2014 by the AGA Institute.


Rothwell P.M.,University of Oxford | Rothwell P.M.,John Radcliffe Hospital | Algra A.,University Utrecht | Amarenco P.,University Paris Diderot
The Lancet | Year: 2011

Stroke is a major cause of death and disability worldwide. Without improvements in prevention, the burden will increase during the next 20 years because of the ageing population, especially in developing countries. Major advances have occurred in secondary prevention during the past three decades, which demonstrate the broader potential to prevent stroke. We review the main medical treatments that should be considered for most patients with transient ischaemic attack or ischaemic stroke in the acute phase and the long term, and draw attention to recent developments. © 2011 Elsevier Ltd.


Ewing R.C.,Texas A&M University | Hayes A.G.,Cornell University | Lucas A.,University Paris Diderot
Nature Geoscience | Year: 2014

Linear sand dunes cover the equatorial latitudes of Saturn's moon Titan and are shaped by global wind patterns. These dunes are thought to reflect present-day diurnal, tidal and seasonal winds, but climate models have failed to reproduce observed dune morphologies with these wind patterns. Dunes diagnostic of a specific wind or formative timescale have remained elusive. Here we analyse radar imagery from NASA's Cassini spacecraft and identify barchan, star and reoriented dunes in sediment-limited regions of Titan's equatorial dune fields that diverge by 23° on average from the orientation of linear dunes. These morphologies imply shifts in wind direction and sediment availability. Using a numerical model, we estimate that the observed reorientation of dune crests to a change in wind direction would have taken around 3,000 Saturn years (1 Saturn year 29.4 Earth years) or longer-a timescale that exceeds diurnal, seasonal or tidal cycles. We propose that shifts in winds and sediment availability are the product of long-term climate cycles associated with variations in Saturn's orbit. Orbitally controlled landscape evolution-also proposed to explain the distribution of Titan's polar lakes-implies a dune-forming climate on equatorial Titan that is analogous to Earth. © 2014 Macmillan Publishers Limited. All rights reserved.


Costa D.,École Nationale Supérieure de Chimie de Paris | Garrain P.-A.,École Nationale Supérieure de Chimie de Paris | Baaden M.,University Paris Diderot
Journal of Biomedical Materials Research - Part A | Year: 2013

Interactions between biomolecules and inorganic surfaces play an important role in natural environments and in industry, including a wide variety of conditions: marine environment, ship hulls (fouling), water treatment, heat exchange, membrane separation, soils, mineral particles at the earth's surface, hospitals (hygiene), art and buildings (degradation and biocorrosion), paper industry (fouling) and more. To better control the first steps leading to adsorption of a biomolecule on an inorganic surface, it is mandatory to understand the adsorption mechanisms of biomolecules of several sizes at the atomic scale, that is, the nature of the chemical interaction between the biomolecule and the surface and the resulting biomolecule conformations once adsorbed at the surface. This remains a challenging and unsolved problem. Here, we review the state of art in experimental and theoretical approaches. We focus on metallic biomaterial surfaces such as TiO2 and stainless steel, mentioning some remarkable results on hydroxyapatite. Experimental techniques include atomic force microscopy, surface plasmon resonance, quartz crystal microbalance, X-ray photoelectron spectroscopy, fluorescence microscopy, polarization modulation infrared reflection absorption spectroscopy, sum frequency generation and time of flight secondary ion mass spectroscopy. Theoretical models range from detailed quantum mechanical representations to classical forcefieldbased approaches. © 2012 Wiley Periodicals, Inc.


Bahouri H.,University Paris Est Creteil | Gallagher I.,University Paris Diderot
Archive for Rational Mechanics and Analysis | Year: 2013

Let X be a suitable function space and let G ⊂ X be the set of divergence free vector fields generating a global, smooth solution to the incompressible, homogeneous three-dimensional Navier-Stokes equations. We prove that a sequence of divergence free vector fields converging in the sense of distributions to an element of G belongs to G if n is large enough, provided the convergence holds "anisotropically" in frequency space. Typically, this excludes self-similar type convergence. Anisotropy appears as an important qualitative feature in the analysis of the Navier-Stokes equations; it is also shown that initial data which do not belong to G (hence which produce a solution blowing up in finite time) cannot have a strong anisotropy in their frequency support. © 2013 Springer-Verlag Berlin Heidelberg.


Caballero I.,University Paris Diderot | Wilms J.,Center for Astroparticle Physics
Memorie della Societa Astronomica Italiana, Supplementi - Journal of the Italian Astronomical Society, Supplement | Year: 2012

Accreting X-ray pulsars are among the most luminous objects in the X-ray sky. In highly magnetized neutron stars (B ∼ 1012 G), the flow of matter is dominated by the strong magnetic field. The general properties of accreting X-ray binaries are presented, focusing on the spectral characteristics of the systems. The use of cyclotron lines as a tool to directly measure a neutron star's magnetic field and to test the theory of accretion are discussed.We conclude with the current and future prospects for accreting X-ray binary studies. © SAIt 2012.


Belazzougui D.,University Paris Diderot | Navarro G.,University of Chile
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2012

Sequence representations supporting queries access, select and rank are at the core of many data structures. There is a considerable gap between different upper bounds, and the few lower bounds, known for such representations, and how they interact with the space used. In this article we prove a strong lower bound for rank, which holds for rather permissive assumptions on the space used, and give matching upper bounds that require only a compressed representation of the sequence. Within this compressed space, operations access and select can be solved within almost-constant time. © 2012 Springer-Verlag.


Chevalier X.,University Paris Est Creteil | Eymard F.,University Paris Est Creteil | Richette P.,University Paris Diderot
Nature Reviews Rheumatology | Year: 2013

New treatment options are needed for osteoarthritis (OA) to slow down the structural progression of the disease; current therapies mostly target pain and function with minimal effectiveness. OA results from an imbalance between catabolic and anabolic factors, and biologic agents either target specific catabolic proinflammatory mediators, such as cytokines, nitric oxide synthesis, or affect anabolism more generally. Biologic agents have dramatic effects in other rheumatic inflammatory diseases such as rheumatoid arthritis; they were hoped to have similar effects in the treatment of OA. In this Review, we will discuss the three main types of cytokine blockers used in knee and hand OA, which target β-nerve growth factor (β-NGF), IL-1β or TNF. We will also discuss inhibitors of nitrogen oxide production and the use of growth factors to treat OA. Among the targeted agents, anti-β-NGF therapy has shown promising results, although cases of rapid destructive arthropathy caution against its widespread use. The future of therapies targeting cytokines, nitrogen oxide synthesis and growth factors in OA is questionable, as results from clinical trials have been repeatedly negative. Strategies in OA therapy need to be reconsidered. New molecules emerging from preclinical data should focus on treating the early phase of the disease where damage may be reversible, and treatment should be modified to fit each patient. © 2013 Macmillan Publishers Limited. All rights reserved.


Schwell M.,University Paris Diderot | Hochlaf M.,University Paris Est Creteil
Topics in Current Chemistry | Year: 2015

We review here the photoionization and photoelectron spectroscopy of the gas phase nucleic acid bases adenine, thymine, uracil, cytosine, and guanine, as well as the three base analogues 2-hydroxyisoquinoline, 2-pyridone, and δ-valerolactam in the vacuum ultraviolet (VUV) spectral regime. The chapter focuses on experimental work performed with VUV synchrotron radiation and related ab initio quantum chemical calculations of higher excited states beyond the ionization energy. After a general part, where experimental and theoretical techniques are described in detail, key results are presented by order of growing complexity in the spectra of the molecules. Here we concentrate on (1) the accurate determination of ionization energies of isolated gas phase NABs and investigation of the vibrational structure of involved ionic states, including their mutual vibronic couplings, (2) the treatment of tautomerism after photoionization, in competition with other intramolecular processes, (3) the study of fragmentation of these molecular systems at low and high internal energies, and (4) the study of the evolution of the covalent character of hydrogen bonding upon substitution, i.e., examination of electronic effects (acceptor, donor, etc.). © Springer-Verlag Berlin Heidelberg 2014.


Deffayet C.,University Paris Diderot | Randjbar-Daemi S.,Abdus Salam International Center For Theoretical Physics
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2011

The nonlinear aspects of a recently proposed model of massive spin-2 particles with propagating torsion are studied. We obtain a nonlinear equation which reduces at linear order to a generalized Fierz-Pauli equation in any background space-time with or without a vanishing torsion. We contrast those results with properties of a class of bigravity theories in an arbitrary background Einstein manifold. It is known that the nonperturbative spectrum of the bigravity model has 8 propagating physical degrees of freedom. This is identical to the physical propagating degrees of freedom of the massive spin-2 torsion model at the linearized order. The obtained nonlinear version of the Fierz-Pauli field equations, however, contains terms absent in the bigravity case which indicates that the curved space generalization of the unique flat space Fierz-Pauli equation is not unique. Moreover, in the torsion massive gravity model the Fierz-Pauli field appears as a derivative of fundamental fields. This, however, does not generate any unwanted pole once coupled to some external sources. © 2011 American Physical Society.


Bradshaw S.J.,Rice University | Aulanier G.,University Paris Diderot | Del Zanna G.,University of Cambridge
Astrophysical Journal | Year: 2011

We conduct numerical experiments to determine whether interchange reconnection at high altitude coronal null points can explain the outflows observed as blueshifts in coronal emission lines at the boundaries between open and closed magnetic field regions. In this scenario, a strong, post-reconnection pressure gradient forms in the field-aligned direction when dense and hot, active region core loops reconnect with neighboring tenuous and cool, open field lines. We find that the pressure gradient drives a supersonic outflow and a rarefaction wave develops in both the open and closed post-reconnection magnetic field regions. We forward-model the spectral line profiles for a selection of coronal emission lines to predict the spectral signatures of the rarefaction wave. We find that the properties of the rarefaction wave are consistent with the observed velocity versus temperature structure of the corona in the outflow regions, where the velocity increases with the formation temperature of the emission lines. In particular, we find excellent agreement between the predicted and observed Fe XII 195.119 spectral line profiles in terms of the blueshift (10 km s-1), full width at half-maximum (83 m) and symmetry. Finally, we find that Ti < Te in the open field region, which indicates that the interchange reconnection scenario may provide a viable mechanism and source region for the slow solar wind. © 2011. The American Astronomical Society. All rights reserved.


Fox K.,Imperial College London | Ford I.,University of Glasgow | Ford I.,French Institute of Health and Medical Research | Steg P.G.,Imperial College London | And 5 more authors.
New England Journal of Medicine | Year: 2014

Background An elevated heart rate is an established marker of cardiovascular risk. Previous analyses have suggested that ivabradine, a heart-rate-reducing agent, may improve outcomes in patients with stable coronary artery disease, left ventricular dysfunction, and a heart rate of 70 beats per minute or more.Methods We conducted a randomized, double-blind, placebo-controlled trial of ivabradine, added to standard background therapy, in 19,102 patients who had both stable coronary artery disease without clinical heart failure and a heart rate of 70 beats per minute or more (including 12,049 patients with activity-limiting angina [class ≥II on the Canadian Cardiovascular Society scale, which ranges from I to IV, with higher classes indicating greater limitations on physical activity owing to angina]). We randomly assigned patients to placebo or ivabradine, at a dose of up to 10 mg twice daily, with the dose adjusted to achieve a target heart rate of 55 to 60 beats per minute. The primary end point was a composite of death from cardiovascular causes or nonfatal myocardial infarction.Results At 3 months, the mean (±SD) heart rate of the patients was 60.7±9.0 beats per minute in the ivabradine group versus 70.6±10.1 beats per minute in the placebo group. After a median follow-up of 27.8 months, there was no significant difference between the ivabradine group and the placebo group in the incidence of the primary end point (6.8% and 6.4%, respectively; hazard ratio, 1.08; 95% confidence interval, 0.96 to 1.20; P = 0.20), nor were there significant differences in the incidences of death from cardiovascular causes and nonfatal myocardial infarction. Ivabradine was associated with an increase in the incidence of the primary end point among patients with activity-limiting angina but not among those without activity-limiting angina (P = 0.02 for interaction). The incidence of bradycardia was higher with ivabradine than with placebo (18.0% vs. 2.3%, P<0.001).Conclusions Among patients who had stable coronary artery disease without clinical heart failure, the addition of ivabradine to standard background therapy to reduce the heart rate did not improve outcomes. Copyright © 2014 Massachusetts Medical Society.


Stanghellini L.,National Optical Astronomy Observatory | Haywood M.,University Paris Diderot
Astrophysical Journal | Year: 2010

Planetary nebulae (PNe) derive from the evolution of 1-8 M · mass stars, corresponding to a wide range of progenitor ages, and thus are essential probes of the chemical evolution of galaxies, and indispensable to constrain the results from chemical models. We use an extended and homogeneous data set of Galactic PNe to study the metallicity gradients and the Galactic structure and evolution. The most up-to-date abundances, distances (calibrated with Magellanic Cloud PNe), and other parameters have been employed, together with a novel homogeneous morphological classification, to characterize the different PN populations. We confirm that morphological classes have a strong correlation with Peimbert's type PN, and also with their distribution on the Galactic landscape. We studied the α-element distribution within the Galactic disk, and found that the best selected disk population (i.e., excluding bulge and halo component), together with the most reliable PN distance scale yields to a radial oxygen gradient of Δlog(O/H)/ΔR G = -0.023±0.006dexkpc-1 for the whole disk sample, and of Δlog(O/H)/ΔR G = -0.035±0.024, -0.023±0.005, and -0.011 0.013dexkpc-1, respectively for TypeI, II, and III PNe, i.e., for high-, intermediate-, and low-mass progenitors. Neon gradients for the same PN types confirm the trend. Accurate statistical analysis shows moderately high uncertainties in the slopes, but also confirms the trend of steeper gradient for PNe with more massive progenitors, indicating a possible steepening with time of the Galactic disk metallicity gradient for what the α-elements are concerned. We found that the metallicity gradients are almost independent on the distance scale model used, as long as these scales are equally well calibrated with the Magellanic Clouds. The PN metallicity gradients presented here are consistent with the local metallicity distribution; furthermore, oxygen gradients determined with young and intermediate age PNe show good consistency with oxygen gradients derived respectively from other young (OB stars, H II regions) and intermediate (open cluster) Galactic populations. We also extend the Galactic metallicity gradient comparison by revisiting the open cluster [Fe/H] data from high resolution spectroscopy. The analysis suggests that they could be compliant with the same general picture of a steepening of gradient with time. © 2010. The American Astronomical Society. All rights reserved.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2009-2.4.4-1 | Award Amount: 9.25M | Year: 2010

Leukodystrophies (LDs) are inherited rare neurodegenerative diseases of the white matter and its main component, the myelin, that are affecting predominantly children. Severity of the disease is related to the axonal dysfunction due to myelin deficiency or destruction. Despite the achievement of remarkable advances made in the past decade, there is no current curative therapy. The development of therapeutic approaches for myelin repair and neuroprotection constitutes the main objective of the LeukoTreat project. Indeed LDs constitute prototypic pathologies to tackle myelin formation/destruction issues as well as glial cells dysfunctions in neurodegeneration. The global aim is to promote the development of therapeutic strategies for the largest number of LD affected patients and further applications to more common white matter disorders and finally neurodegenerative diseases. For this purpose, the project will combine the expertise of (i) recognized European research teams in the field of White Matter diseases (COST Myelinet), (ii) high-technology SMEs, (iii) experts in medical ethics and (iv) LD patients and families associations. To develop efficient therapies, the LeukoTreat project is based on 5 complementary approaches consisting in: (i) collecting information on the epidemiology, the natural history, the genotype/phenotype correlation of LDs for at least 500 patients; (ii) validating/identifying biomarkers for therapeutic decisions/follow up to isolate new therapeutic targets; (iii) developing pharmacological strategies with the ultimate objective to launch at least 4 pharmacological clinical trials during 5 years following the project; (iv) developing innovative gene and cell therapies with the ultimate objective to launch at least 3 clinical trials during the next 5 years; (v) tackling ethical impacts of the proposed therapeutic challenges by integrating the participation of patients driven by a well-experienced research team strongly skilled in ethics


Patent
French Institute of Health, Medical Research, University Paris Diderot and University Paris Est Creteil | Date: 2012-11-23

The present invention relates to methods and compositions for preventing or treating various immune diseases including graft-versus-host disease (GVHD) using populations or compositions of immunoregulatory T cells specific for an irrelevant antigen; such cells being activated in vivo by a simultaneous, separate or sequential administration of said antigen.


Patent
French Institute of Health, Medical Research, Assistance Publique Hopitaux De Paris, University Paris Est Creteil and University Paris Diderot | Date: 2014-05-28

The present invention relates to a ligand molecule that specifically binds to KTR3DL2 at the surface of KTR3DL2 expressing malignant T-cells for the treatment of lymphomas. It also relates to the in vitro use of a level of expression of KIR3DL2 is a biomarker useful for diagnosing and/or monitoring a lymphoma.


Patent
Institute Telecom Telecom Paris Technology, French National Center for Scientific Research and University Paris Diderot | Date: 2010-05-28

A method for quantifying the development of pathologies involving changes in volume of a body represented via an imaging technique, including normalizing gray levels by a midway technique for two images I_(1 )and I_(2 )representing the same scene, resulting in two normalized images I_(1 )and I_(2); calculating a map of signed differences between the two normalized images I_(1 )and I_(2); and performing one or more statistical tests based on the assumption of a Gaussian distribution of the gray levels for healthy tissues in the normalized images I_(1 )and I_(2 )and/or in the calculated difference map. Advantageously, results of two or more of the tests can be combined for a more specific characterization of the development.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-1.3-4 | Award Amount: 3.93M | Year: 2008

Nanoparticles (NP) have unique, potentially beneficial properties, but their possible impact on human health has not been adequately assessed. The main goal of this proposal is to develop alternative high-throughput testing strategies using in vitro and in silico methods to assess the toxicological profile of NP used in medical diagnostics. Our specific aims are to: 1. Define NP properties and fully characterize NP to be used 2. Study NP interactions with molecules, cells and organs and develop in vitro methods to study the toxicological potential of NP 3. Validate in vitro findings in short-term in vivo models and study particle effects in animals and (ex vivo) in humans to assess individual susceptibility to NP 4. Develop in silico models of NP interactions Experimental work is structured in 4 WPs to address NP characterisation and key elements in evaluation of NP uptake, exposure and toxicology. NANOTEST integrates the investigation of toxicological properties and effects of NP in several target systems by developing a battery of in vitro assays using cell cultures, organotypic cell culture and small organ fragments (ex vivo) derived from different biological systems; blood, vascular system, liver, lung, placenta, digestive and central nervous systems. As NP action is likely to involve oxidative stress we will focus on the cross-cutting areas of inflammation, cellular toxicity, immunotoxicity, genotoxicity and related endpoints. Following development of SOP and generation of a common database and in parallel with in silico assays (QSAR, PBPK modelling), NanoTest will evaluate toxic effects and interactions of NP used in nanomedicine. Results will be validated in an experimental ethically approved in vivo model. The most advanced and standardised techniques will be adapted for automation and prepared for validation by ECVAM. Separate WPs will be dedicated to dissemination and to effective administrative and scientific management.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-ITN-2008 | Award Amount: 4.33M | Year: 2009

Mathematical logic is a rapidly-developing subject with sophisticated techniques and many applications in algebra, geometry, number theory, analysis, and computer science. Even though the branches of logic share vital concepts and techniques, in recent years increased specialism has meant that most researchers are trained in just one branch of logic, and there is a need in Europe for researchers who have an overview of techniques from logic. To meet this need, this project will provide a broad training for early stage researchers across the main areas of mathematical logic and its many applications. 18 early-stage researchers (ESRs) will be trained for 36 months each, and a further 20 ESRs, undertaking doctoral studies elsewhere, will be appointed for 3--6 months each. Doctoral research projects for ESRs have been prepared in model theory, aspects of complexity theory (proof complexity, finite model theory), proof theory, computability theory, set theory, and real valued logics. Network-wide training will be provided through three 7-day training workshops, two 3-day and one 5-day research workshops, and a 5-day final conference. Some secondments of ESRs, and short ESR appointments, will be coordinated around a special semester in model theory in Lyon, and a later one in logical aspects of complexity theory in Prague. Complementary training is provided by the hosts, and through the training workshops. The network consists of 8 full partners, each a major logic group with strength in more than one branch of logic and experience in the training of early stage researchers, and each based in a major European university. The partners have been chosen to complement each other in strengths, and together to cover most branches of mathematical logic. In addition to the 8 full partners, training is provided by an academic Associated Partner (University of East Anglia) and two industrial Associated Partners (Onera and BT Group, each at Level 2).


Grant
Agency: Cordis | Branch: FP7 | Program: MC-IRSES | Phase: FP7-PEOPLE-2011-IRSES | Award Amount: 777.30K | Year: 2012

**The joint exchange programme Non-equilibrium dynamics of soft and active matter (SoftActive) aims at bringing closer communities of physicists working at the forefront of statistical/nonlinear physics of out-of-equilibrium systems. Although many aspects of this very wide topic will be covered, the project is centered on the dynamics and fluctuations in soft and active matter, a subject of crucial importance in quantitative biology/biophysics. **The three countries involved, France, Germany, and Japan, and indeed almost all the participants of SoftActive, have a long history of collaboration on these topics, which are well-developed in each country. But these past and present collaborations have remained, so far, mostly bilateral, and it has become clear that further integration is needed. In particular, the groups involved in this proposal are leaders of the emerging field of active matter which is so far particularly well represented in France, Germany, and Japan. It is now time to structure international ties, which will strengthen the quality of research and allow for a rapid and organized growth. **The SoftActive project mirrors the Dynamics of Nonequilibrium Soft and Active Matter project just approved recently within the Core-to-Core program of the Japanese Society for the Promotion of Science (JSPS). It is divided into four main scientific topics, in parallel to the JSPS-funded Core-to-Core project: -Nonlinear response and non-equilibrium dynamics of liquid crystals and related problems -Slow dynamics of colloids and related problems -Dynamics and fluctuations far from equilibrium -Dynamics of active soft matter **The scientific goals will be reached via the exchange of researchers, notably young ones for long-enough periods of time to insure efficient transfer of knowledge, plus a comprehensive calendar of project-wide events in the form of schools and workshops.


Vuong Q.L.,University of Mons | Berret J.-F.,University Paris Diderot | Fresnais J.,CNRS Analytical Sciences Lab | Gossuin Y.,University of Mons | Sandre O.,CNRS Organic Polymer Chemistry Laboratory
Advanced Healthcare Materials | Year: 2012

Magnetic particles are very efficient magnetic resonance imaging (MRI) contrast agents. In recent years, chemists have unleashed their imagination to design multi-functional nanoprobes for biomedical applications including MRI contrast enhancement. This study is focused on the direct relationship between the size and magnetization of the particles and their nuclear magnetic resonance relaxation properties, which condition their efficiency. Experimental relaxation results with maghemite particles exhibiting a wide range of sizes and magnetizations are compared to previously published data and to wellestablished relaxation theories with a good agreement. This allows deriving the experimental master curve of the transverse relaxivity versus particle size and to predict the MRI contrast efficiency of any type of magnetic nanoparticles. This prediction only requires the knowledge of the size of the particles impermeable to water protons and the saturation magnetization of the corresponding volume. To predict the T2 relaxation efficiency of magnetic single crystals, the crystal size and magnetization - obtained through a single Langevin fit of a magnetization curve - is the only information needed. For contrast agents made of several magnetic cores assembled into various geometries (dilute fractal aggregates, dense spherical clusters, core-shell micelles, hollow vesicles...), one needs to know a third parameter, namely the intra-aggregate volume fraction occupied by the magnetic materials relatively to the whole (hydrodynamic) sphere. Finally a calculation of the maximum achievable relaxation effect - and the size needed to reach this maximum - is performed for different cases: maghemite single crystals and dense clusters, core-shell particles (oxide layer around a metallic core) and zinc-manganese ferrite crystals. © 2012 WILEY-VCH Verlag GmbH & Co.KGaA, Weinheim.


Texier B.,University Paris Diderot | Zumbrun K.,Indiana University Bloomington
Communications in Mathematical Physics | Year: 2011

We show that transition to longitudinal instability of strong detonation solutions of reactive compressible Navier-Stokes equations is generically associated with Hopf bifurcation to nearby time-periodic "galloping", or "pulsating", solutions, in agreement with physical and numerical observation. In the process, we determine readily numerically verifiable stability and bifurcation conditions in terms of an associated Evans function, and obtain the first complete nonlinear stability result for strong detonations of the reacting Navier-Stokes equations, in the limit as amplitude (hence also heat release) goes to zero. The analysis is by pointwise semigroup techniques introduced by the authors and collaborators in previous works. © 2011 Springer-Verlag.


Masliah-Planchon J.,UF de Genetique Moleculaire | Darnige L.,Service dHematologie biologique | Bellucci S.,Service dHematologie biologique | Bellucci S.,University Paris Diderot
British Journal of Haematology | Year: 2013

Delta storage pool deficiency (δ-SPD) is a rare heterogeneous group of platelet disorders characterized by a reduction in the number or content of dense granules. δ-SPD causes a mild to moderate bleeding diathesis characterized mainly by mucocutaneous bleeding. Currently, no specific treatment is available and the therapeutic approach is based on prevention of excessive bleeding. However, during the last few years, important insights into the pathophysiology of δ-SPD have been achieved using mouse models and dense granule deficiency-associated congenital diseases, such as Hermansky-Pudlak syndrome and Chediak-Higashi syndrome. It thus appears that δ-SPD represents a genetically heterogeneous group of intracellular vesicle biogenesis and/or trafficking disorders. This review summarizes recent data regarding the molecular mechanisms together with clinical features of the different types of δ-SPD. Although the molecular basis of isolated inherited δ-SPD remains currently unknown, next-generation sequencing strategies should enable researchers to identify the causative genes. Identification of those genes should contribute to our understanding of the pathophysiology, represent useful tools for genetic diagnosis, and eventually lead to new specific therapeutic approaches. © 2012 Blackwell Publishing Ltd.


Henin J.,University Paris Diderot | Salari R.,Rutgers University | Murlidaran S.,Rutgers University | Brannigan G.,Rutgers University
Biophysical Journal | Year: 2014

Modulation of the GABA type A receptor (GABAAR) function by cholesterol and other steroids is documented at the functional level, yet its structural basis is largely unknown. Current data on structurally related modulators suggest that cholesterol binds to subunit interfaces between transmembrane domains of the GABAAR. We construct homology models of a human GABAAR based on the structure of the glutamate-gated chloride channel GluCl of Caenorhabditis elegans. The models show the possibility of previously unreported disulfide bridges linking the M1 and M3 transmembrane helices in the α and γ subunits. We discuss the biological relevance of such disulfide bridges. Using our models, we investigate cholesterol binding to intersubunit cavities of the GABAAR transmembrane domain. We find that very similar binding modes are predicted independently by three approaches: analogy with ivermectin in the GluCl crystal structure, automated docking by AutoDock, and spontaneous rebinding events in unbiased molecular dynamics simulations. Taken together, the models and atomistic simulations suggest a somewhat flexible binding mode, with several possible orientations. Finally, we explore the possibility that cholesterol promotes pore opening through a wedge mechanism. © 2014 The Authors.


Busigny V.,University Paris Diderot | Bebout G.E.,Lehigh University
Elements | Year: 2013

Nitrogen is the main constituent of Earth's atmosphere and a key component of the biosphere, but it is a trace element in the major silicate reservoirs. The relatively low concentrations (parts per million level) complicate efforts to constrain the nitrogen speciation and abundance in the mantle and crust. In most silicates, nitrogen occurs as NH4 + (substituting for K+), whereas its speciation in hydrous fl uids and silicate melts can vary widely depending in large part on redox conditions. Current knowledge of nitrogen isotope fractionation among relevant mineral and fl uid/melt phases is limited by the lack of experimental data to confi rm theoretical predictions of these fractionations. Modeling of modern and long-term nitrogen cycling on Earth will be advanced by better constraints on the sizes and isotopic compositions of the major crust and mantle nitrogen reservoirs. © OCTOBER 2013.


Rockwell T.K.,San Diego State University | Klinger Y.,University Paris Diderot
Bulletin of the Seismological Society of America | Year: 2013

We analyzed high-resolution aerial photography taken soon after the 1940 Imperial Valley earthquake to provide a higher resolution distribution of displacement with which to test variation in lateral slip, to compare the difference in making slip measurements parallel to local or regional fault strike, and to compare to the seismological properties of the 1940 earthquake. We performed 648 new measurements of displacement along the 15 km section of rupture for which imagery exists. Nearly 7 m of maximum displacement occurred within 2 km of the border, which was higher than previous estimates, with an average slip of about 5.5 m for this section. There is considerable variation along the strike, on the order of 1 m of variability across hundreds of meters of lateral distance in the section of high slip; areas of larger offset tend to have greater variations in displacement. From these observations, we conclude that lateral variability of displacement typically varies by as much as 30% along a rupture section. The difference in measured displacement at a specific point along the fault varied considerably when using local fault strikes versus that of regional or average fault. However, the overall average difference between measurements for different azimuths at a specific point is only -0.01 ± 0.19 m, indicating that this is not a major issue if one is consistent. Finally, abrupt changes in displacement along a strike are apparently related to segmentation and the rupture process, and mimic the subevents, as documented through seismological methods. The largest moment pulse corresponds to the section south of the border, whereas the greatest displacements occurred north of the border where the average moment release is inferred to be less. We explain this by inferring a strong, shallow asperity in the border region, consistent with 1979 rupture event beneath it.


Hoen B.,University of Franche Comte | Duval X.,Association Pour lEtude et la Prevention de lEndocardite Infectieuse | Duval X.,University Paris Diderot
New England Journal of Medicine | Year: 2013

A 55-year-old man with a history of mitral regurgitation seeks care after an episode of transient weakness in his right arm and speech difficulties. He underwent dental scaling 1 month earlier. He notes recent intermittent fevers and weight loss. On cardiac examination, his regurgitation murmur appears to be unchanged. A transthoracic echocardiogram shows a mobile, 12-mm mitral-valve vegetation and grade 2 (mild) regurgitation. Magnetic resonance imaging of the brain reveals recent ischemic lesions. How should the patient be further evaluated and treated? Copyright © 2013 Massachusetts Medical Society.


Braendle C.,University Paris Diderot | Braendle C.,University of Nice Sophia Antipolis | Baer C.F.,University of Florida | Felix M.-A.,University Paris Diderot
PLoS Genetics | Year: 2010

Genetic and developmental architecture may bias the mutationally available phenotypic spectrum. Although such asymmetries in the introduction of variation may influence possible evolutionary trajectories, we lack quantitative characterization of biases in mutationally inducible phenotypic variation, their genotype-dependence, and their underlying molecular and developmental causes. Here we quantify the mutationally accessible phenotypic spectrum of the vulval developmental system using mutation accumulation (MA) lines derived from four wild isolates of the nematodes Caenorhabditis elegans and C. briggsae. The results confirm that on average, spontaneous mutations degrade developmental precision, with MA lines showing a low, yet consistently increased, proportion of developmental defects and variants. This result indicates strong purifying selection acting to maintain an invariant vulval phenotype. Both developmental system and genotype significantly bias the spectrum of mutationally inducible phenotypic variants. First, irrespective of genotype, there is a developmental bias, such that certain phenotypic variants are commonly induced by MA, while others are very rarely or never induced. Second, we found that both the degree and spectrum of mutationally accessible phenotypic variation are genotype-dependent. Overall, C. briggsae MA lines exhibited a two-fold higher decline in precision than the C. elegans MA lines. Moreover, the propensity to generate specific developmental variants depended on the genetic background. We show that such genotype-specific developmental biases are likely due to cryptic quantitative variation in activities of underlying molecular cascades. This analysis allowed us to identify the mutationally most sensitive elements of the vulval developmental system, which may indicate axes of potential evolutionary variation. Consistent with this scenario, we found that evolutionary trends in the vulval system concern the phenotypic characters that are most easily affected by mutation. This study provides an empirical assessment of developmental bias and the evolution of mutationally accessible phenotypes and supports the notion that such bias may influence the directions of evolutionary change. © 2010 Braendle et al.


Woerther P.-L.,Institute Gustave Roussy | Burdet C.,University Paris Diderot | Chachaty E.,Institute Gustave Roussy | Andremont A.,University Paris Diderot
Clinical Microbiology Reviews | Year: 2013

In the last 10 years, extended-spectrum β-lactamase-producing enterobacteria (ESBL-E) have become one of the main challenges for antibiotic treatment of enterobacterial infections, largely because of the current CTX-M enzyme pandemic. However, most studies have focused on hospitalized patients, though today it appears that the community is strongly affected as well. We therefore decided to devote our investigation to trends in ESBL-E fecal carriage rates and comprehensively reviewed data from studies conducted on healthy populations in various parts of the world. We show that (i) community ESBL-E fecal carriage, which was unknown before the turn of the millennium, has since increased significantly everywhere, with developing countries being the most affected; (ii) intercontinental travel may have emphasized and globalized the issue; and (iii) CTX-M enzymes, especially CTX-M-15, are the dominant type of ESBL. Altogether, these results suggest that CTX-M carriage is evolving toward a global pandemic but is still insufficiently described. Only a better knowledge of its dynamics and biology will lead to further development of appropriate control measures. © 2013, American Society for Microbiology. All Rights Reserved.


Bayart E.,CNRS Laboratory of Biology and Applied Pharmacology | Cohen-Haguenauer O.,CNRS Laboratory of Biology and Applied Pharmacology | Cohen-Haguenauer O.,University Paris Diderot
Current Gene Therapy | Year: 2013

The unlimited proliferation capacity of embryonic stem cells (ESCs) combined with their pluripotent differentiation potential in various lineages raised great interest in both the scientific community and the public at large with hope for future prospects of regenerative medicine. However, since ESCs are derived from human embryos, their use is associated with significant ethical issues preventing broad studies and therapeutic applications. To get around this bottleneck, Takahashi and Yamanaka have recently achieved the conversion of adult somatic cells into ES-like cells via the forced expression of four transcription factors: Oct3/4, Sox2, Klf4 and c-Myc. This first demonstration attracted public attention and opened a new field of stem cells research with both cognitive - such as disease modeling - and therapeutic prospects. This pioneer work just received the 2012 Nobel Prize in Physiology or Medicine. Many methods have been reported since 2006, for the generation of induced pluripotent stem (iPS) cells. Most strategies currently under use are based on gene delivery via gamma-retroviral or lentiviral vectors; some experiments have also been successful using plasmids or transposons- based systems and few with adenovirus. However, most experiments involve integration in the host cell genome with an identified risk for insertional mutagenesis and oncogenic transformation. To circumvent such risks which are deemed incompatible with therapeutic prospects, significant progress has been made with transgene-free reprogramming methods based on e.g.: sendaï virus or direct mRNA or protein delivery to achieve conversion of adult cells into iPS. In this review we aim to cover current knowledge relating to both delivery systems and combinations of inducing factors including chemicals which are used to generate human iPS cells. Finally, genetic instability resulting from the reprogramming process is also being considered as a safety bottleneck for future clinical translation and stem cell-therapy prospects based on iPS. © 2013 Bentham Science Publishers.


Kett D.H.,University of Miami | Azoulay E.,University Paris Diderot | Echeverria P.M.,University of Miami | Vincent J.-L.,Erasme University Hospital
Critical Care Medicine | Year: 2011

Objectives: To provide a global, up-to-date picture of the prevalence, treatment, and outcomes of Candida bloodstream infections in intensive care unit patients and compare Candida with bacterial bloodstream infection. Design: A retrospective analysis of the Extended Prevalence of Infection in the ICU Study (EPIC II). Demographic, physiological, infection-related and therapeutic data were collected. Patients were grouped as having Candida, Gram-positive, Gram-negative, and combined Candida/bacterial bloodstream infection. Outcome data were assessed at intensive care unit and hospital discharge. Setting: EPIC II included 1265 intensive care units in 76 countries. Patients: Patients in participating intensive care units on study day. Interventions: None. MEASUREMENT AND MAIN RESULTS:: Of the 14,414 patients in EPIC II, 99 patients had Candida bloodstream infections for a prevalence of 6.9 per 1000 patients. Sixty-one patients had candidemia alone and 38 patients had combined bloodstream infections. Candida albicans (n = 70) was the predominant species. Primary therapy included monotherapy with fluconazole (n = 39), caspofungin (n = 16), and a polyene-based product (n = 12). Combination therapy was infrequently used (n = 10). Compared with patients with Gram-positive (n = 420) and Gram-negative (n = 264) bloodstream infections, patients with candidemia were more likely to have solid tumors (p < .05) and appeared to have been in an intensive care unit longer (14 days [range, 5-25 days], 8 days [range, 3-20 days], and 10 days [range, 2-23 days], respectively), but this difference was not statistically significant. Severity of illness and organ dysfunction scores were similar between groups. Patients with Candida bloodstream infections, compared with patients with Gram-positive and Gram-negative bloodstream infections, had the greatest crude intensive care unit mortality rates (42.6%, 25.3%, and 29.1%, respectively) and longer intensive care unit lengths of stay (median [interquartile range]) (33 days [18-44], 20 days [9-43], and 21 days [8-46], respectively); however, these differences were not statistically significant. Conclusion: Candidemia remains a significant problem in intensive care units patients. In the EPIC II population, Candida albicans was the most common organism and fluconazole remained the predominant antifungal agent used. Candida bloodstream infections are associated with high intensive care unit and hospital mortality rates and resource use. Copyright © 2011 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.


Vriz S.,The Interdisciplinary Center | Vriz S.,University Paris Diderot | Reiter S.,University of Geneva | Galliot B.,University of Geneva
Current Topics in Developmental Biology | Year: 2014

Recent studies in Drosophila, Hydra, planarians, zebrafish, mice, indicate that cell death can open paths to regeneration in adult animals. Indeed injury can induce cell death, itself triggering regeneration following an immediate instructive mechanism, whereby the dying cells release signals that induce cellular responses over short and/or long-range distances. Cell death can also provoke a sustained derepressing response through the elimination of cells that suppress regeneration in homeostatic conditions. Whether common properties support what we name "regenerative cell death," is currently unclear. As key parameters, we review here the injury proapoptotic signals, the signals released by the dying cells, the cellular responses, and their respective timing. ROS appears as a common signal triggering cell death through MAPK and/or JNK pathway activation. But the modes of ROS production vary, from a brief pulse upon wounding, to repeated waves as observed in the zebrafish fin where ROS supports two peaks of cell death. Indeed regenerative cell death can be restricted to the injury phase, as in Hydra, Drosophila, or biphasic, immediate, and delayed, as in planarians and zebrafish. The dying cells release in a caspase-dependent manner a variety of signaling molecules, cytokines, growth factors, but also prostaglandins or ATP as recorded in Drosophila, Hydra, mice, and zebrafish, respectively. Interestingly, the ROS-producing cells often resist to cell death, implying a complex paracrine mode of signaling to launch regeneration, involving ROS-producing cells, ROS-sensing cells that release signaling molecules upon caspase activation, and effector cells that respond to these signals by proliferating, migrating, and/or differentiating. © 2014 Elsevier Inc.


Noatynska A.,University of Geneva | Tavernier N.,University Paris Diderot | Gotta M.,University of Geneva | Pintard L.,University Paris Diderot
Open Biology | Year: 2013

Spatio-temporal coordination of events during cell division is crucial for animal development. In recent years, emerging data have strengthened the notion that tight coupling of cell cycle progression and cell polarity in dividing cells is crucial for asymmetric cell division and ultimately for metazoan development. Although it is acknowledged that such coupling exists, the molecular mechanisms linking the cell cycle and cell polarity machineries are still under investigation. Key cell cycle regulators control cell polarity, and thus influence cell fate determination and/or differentiation, whereas some factors involved in cell polarity regulate cell cycle timing and proliferation potential. The scope of this review is to discuss the data linking cell polarity and cell cycle progression, and the importance of such coupling for asymmetric cell division. Because studies in model organisms such as Caenorhabditis elegans and Drosophila melanogaster have started to reveal the molecular mechanisms of this coordination, we will concentrate on these two systems. We review examples of molecular mechanisms suggesting a coupling between cell polarity and cell cycle progression. © 2013 The Authors.


Patent
French Institute of Health, Medical Research, University of Paris Descartes, French National Center for Scientific Research, Assistance Publique Hopitaux De Paris, University Paris Diderot and Imagine | Date: 2015-09-03

The present invention relates to the treatment or prevention of skeletal disorders, in particular skeletal diseases, developed by patients that display abnormal increased activation of the fibroblast growth factor receptor 3 (FGFR3), in particular by expression of a constitutively activated mutant of FGFR3.


Patent
Assistance Publique Hopitaux De Paris, Volterra and University Paris Diderot | Date: 2010-03-12

Oral drug delivery formulations which specifically administer antibacterial agents to the ileum, caecum, and/or the colon, without significant administration elsewhere in the gastrointestinal tract, are disclosed. The formulations include, as actives, a combination of a macrolide or aminoglysoside, or quinolone antibacterial and an anti-Gram-negative lipopeptide (polymyxin) antibacterial agent or other peptide antibacterials effective against Gram-negative bacteria. The formulations can be used to treat infections or unwanted colonization in the colon, and to provide effective decontamination of the colonic flora from unwanted or potentially pathogenic bacteria.


Patent
Volterra, Assistance Publique Hopitaux De Paris and University Paris Diderot | Date: 2011-12-22

The present invention relates to a method for the controlled repopulation of the colonic bacterial flora.


Kuksin S.,University Paris Diderot | Maiocchi A.,Cergy-Pontoise University
Nonlinearity | Year: 2015

We consider the 2d quasigeostrophic equation on the β-plane for the stream function ψ, with dissipation and a random force: (+ K)ψt - pJ(ψψ) - βψx = lang;random force〉 ? k2ψ +ψ. (∗) Here ψ = ψ(t, x, y), x εℝ/2πLℤ, y ε ℝ/2πℤ. For typical values of the horizontal period L we prove that the law of the action-vector of a solution for (∗) (formed by the halves of the squared norms of its complex Fourier coefficients) converges, as β → ∞, to the law of an action-vector for solution of an auxiliary effective equation, and the stationary distribution of the action-vector for solutions of (∗) converges to that of the effective equation. Moreover, this convergence is uniform in κ ∈ (0, 1]. The effective equation is an infinite system of stochastic equations which splits into invariant subsystems of complex dimension 3; each of these subsystems is an integrable hamiltonian system, coupled with a Langevin thermostat. Under the iterated limits limL=ρ→∞limβ→∞ and limκ→0limβ→∞ we get similar systems. In particular, none of the three limiting systems exhibits the energy cascade to high frequencies. © 2015 IOP Publishing Ltd & London Mathematical Society.


Ciarletta P.,University Pierre and Marie Curie | Ben Amar M.,University Paris Diderot
Journal of the Mechanics and Physics of Solids | Year: 2012

Constrained growth processes in living materials result in a complex distribution of residual strains, which in certain geometries may induce a bifurcation in the elastic stability. In this work, we investigate the combined effects of growth and material anisotropy in the epithelial pattern formation of tubular tissues. In order to represent the structural organization of most organs, we adopt a strain energy density which accounts for the presence of a nonlinear reinforcement made of cross-ply fibers distributed inside a ground matrix. Using a canonical transformation in mixed polar coordinates, we transform the nonlinear elastic boundary value problem into a variational formulation, performing a straightforward derivation of the EulerLagrange equations for perturbations in circumferential and longitudinal directions. The corresponding curves of marginal stability are obtained numerically: the results demonstrate that both the three-dimensional distribution of residual strains and the mechanical properties of fiber reinforcements within the tissue are fundamental to determine the emergence of a specific instability pattern. In particular, different proportions of axial and circumferential residual strains can model the epithelial formation of mucosal folds in the esophagus and of plicae circulares in the small intestine. The theoretical predictions are compared with morphological data for embryonic intestinal tissues, suggesting that the volumetric growth of the epithelium can also drive the early stages of villi morphogenesis. © 2011 Elsevier Ltd. All rights reserved.


Mottez F.,University Paris Diderot | Genot V.,Roche Holding AG
Journal of Geophysical Research: Space Physics | Year: 2011

With the help of a 2.5-D particle-in-cell simulation code, we investigate the physics of the acceleration of auroral electrons, through the interaction of an isolated Alfvén wave packet with a plasma density cavity. The cavity is edged by density gradients perpendicular to the magnetic field. We show that a single passing of an isolated wave packet over a (infinite) cavity creates an electron beam. It triggers local current and beam-plasma instabilities and small-scale coherent electric structures. The energy flux of downgoing electrons is significantly increased, whereas upgoing electrons are also accelerated, even if no beam is formed. Accelerated electrons remain after the passage of the Alfvénic pulse, allowing the observation of energetic particles without any significant electromagnetic perturbation. The dependence of this process on the electron to ion mass ratio is consistent with its control by inertial effects. Copyright 2011 by the American Geophysical Union.


Frappart F.,French National Center for Scientific Research | Ramillien G.,French National Center for Scientific Research | Ronchail J.,University Paris Diderot
International Journal of Climatology | Year: 2013

This study examines how the interannual variability of rainfall impacts the land water storage in the Amazon basin during the 2003-2010 time span at monthly time-scale using respectively, Tropical Rainfall Measuring Mission (TRMM) and Gravity Recovery And Climate Experiment (GRACE) satellite observations. Monthly estimates of GRACE-based terrestrial water storage (TWS) are compared to (1) TRMM rainfall, (2) in situ discharges at the outlet of the major sub-basins of the Amazon over 2003-2010 to characterize the redistribution of precipitation on land water. The time-variations of land water storage derived from GRACE are consistent with those of rainfall and discharges at basin and sub-basin scales even at interannual time-scales (correlation generally greater than 0.7). The study of the relationship between these two quantities reveals large differences in terms of rainfall amount, water storage, time delays, resulting of the water transport among the sub-basins of the Amazon. The analysis of GRACE data has enabled identification of the signature of the recent extreme climatic events (droughts of 2005 and 2010, flood of 2009) on the land water storage, in terms of spatial patterns and intensity. These results are in good agreement with what was observed on independent datasets (water levels and discharges, vegetation activity, forest fires, and drought index), highlighting the interest of gravimetry from space missions for the characterization of the interannual variability of the TWS. GRACE data offer the unique opportunity to monitor the hydrological cycle in ungauged basins where reliable observations of rainfall and discharges are missing. © 2013 Royal Meteorological Society.


Birchler J.A.,University of Missouri | Veitia R.A.,French National Center for Scientific Research | Veitia R.A.,University Paris Diderot
New Phytologist | Year: 2010

The gene balance hypothesis states that the stoichiometry of members of multisubunit complexes affects the function of the whole because of the kinetics and mode of assembly. Gene regulatory mechanisms also would be governed by these principles. Here, we review the impact of this concept with regard to the effects on the genetics of quantitative traits, the fate of duplication of genes following polyploidization events or segmental duplication, the basis of aneuploid syndromes, the constraints on cis and trans variation in gene regulation and the potential involvement in hybrid incompatibilities. © The Authors (2009). Journal compilation © New Phytologist Trust (2009).


Herbert E.,University Paris Diderot | Mordant N.,French National Center for Scientific Research | Falcon E.,University Paris Diderot
Physical Review Letters | Year: 2010

We report experiments on gravity-capillary wave turbulence on the surface of a fluid. The wave amplitudes are measured simultaneously in time and space by using an optical method. The full space-time power spectrum shows that the wave energy is localized on several branches in the wave-vector-frequency space. The number of branches depends on the power injected within the waves. The measurement of the nonlinear dispersion relation is found to be well described by a law suggesting that the energy transfer mechanisms involved in wave turbulence are restricted not only to purely resonant interaction between nonlinear waves. The power-law scaling of the spatial spectrum and the probability distribution of the wave amplitudes at a given wave number are also measured and compared to the theoretical predictions. ©2010 The American Physical Society.


Mayer C.,Institute Pasteur Paris | Mayer C.,French National Center for Scientific Research | Mayer C.,University Paris Diderot | Janin Y.L.,Institute Pasteur Paris | Janin Y.L.,French National Center for Scientific Research
Chemical Reviews | Year: 2014

A remarkable number of series of inhibitors of novobiocin and fluoroquinolone antibiotics has been reported. The design of biochemical or cellular assays, amenable to high-throughput screenings, along with X-ray-derived structures of the early inhibitors bound to DNA gyrase, were instrumental in this. The difficult task of transforming good type IIA topoisomerase inhibitors into actual antibacterials provided a lot of insights into the delicate balance required between their lipophilicity and water solubility. Since a fully functional bacterial type IIA topoisomerase requires the assembly of a heterotetramer, it is reasonable to conceive the existence of peptides that would interfere with these protein-protein interactions and thus act as regulators of enzyme function. Concerning the effect of various divalent metals on type IIA topoisomerases, their catalytic properties are strongly dependent on the presence of magnesium salts as a cofactor.


Sapkota S.N.,National Seismic Center | Bollinger L.,CEA DAM Ile-de-France | Klinger Y.,University Paris Diderot | Tapponnier P.,Nanyang Technological University | And 2 more authors.
Nature Geoscience | Year: 2013

It is unclear where plate boundary thrusts generate giant rather than great earthquakes. Along the Himalayas, the source sizes and recurrence times of large seismic events are particularly uncertain, since no surface signatures were found for those that shook the range in the twentieth century. Here we challenge the consensus that these events remained blind and did not rupture the surface. We use geomorphological mapping of fluvial deposits, palaeo-seismological logging of river-cut cliffs and trench walls, and modelling of calibrated 14 C ages, to show that the M w 8.2 Bihar-Nepal earthquake on 15 January 1934 did break the surface: traces of the rupture are clear along at least 150 km of the Main Frontal Thrust fault in Nepal, between 8550′ and 8720′ E. Furthermore, we date collapse wedges in the Sir Valley and find that the 7 June AD 1255 earthquake, an event that devastated Kathmandu and mortally wounded the Nepalese King Abhaya Malla, also ruptured the surface along this stretch of the mega-thrust. Thus, in the past 1,000 years, two great earthquakes, 679 years apart, rather than one giant eleventh-century AD event, contributed to the frontal uplift of young river terraces in eastern Nepal. The rare surface expression of these earthquakes implies that surface ruptures of other reputedly blind great Himalayan events might exist. © 2013 Macmillan Publishers Limited. All rights reserved.


Serreau J.,University Paris Diderot | Tissier M.,University Pierre and Marie Curie
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2012

We propose a new one-parameter family of Landau gauges for Yang-Mills theories which can be formulated by means of functional integral methods and are thus well suited for analytic calculations, but which are free of Gribov ambiguities and avoid the Neuberger zero problem of the standard Faddeev-Popov construction. The resulting gauge-fixed theory is perturbatively renormalizable in four dimensions and, for what concerns the calculation of ghost and gauge field correlators, it reduces to a massive extension of the Faddeev-Popov action. We study the renormalization group flow of this theory at one-loop and show that it has no Landau pole in the infrared for some - including physically relevant - range of values of the renormalized parameters. © 2012.


Roman B.,University Paris Diderot | Pocheau A.,Aix - Marseille University | Pocheau A.,French National Center for Scientific Research
Physical Review Letters | Year: 2012

We address the crumpling of thin sheets in between large scale curved cylinders. In contrast with the usual crushing of a paper ball, one curvature of the sheet is fixed here by the cylinders radius, yielding an anisotropic compaction. As compaction proceeds, it is found that sheets first develop singular folds involving ridges or developable cones, but eventually turn to regular folds free of any geometrical singularities, without ever having entered the plastic regime. This surprising uncrumpling transition corresponds to a stress defocusing. It is understood from a balance between bending and stretching energies on regular states. © 2012 American Physical Society.


Mathis S.,University Paris Diderot | Mathis S.,University Pierre and Marie Curie
Lecture Notes in Physics | Year: 2013

Stars are rotating and magnetic bodies. Moreover, more and more constraints are obtained on such dynamical processes using, for example, seismology and spectropolarimetry. Therefore, it is now necessary to get a complete and coherent picture of dynamical processes in stellar interiors. However, to simulate such processes in a star in full details would require treating length scales and time scales spanning many orders of magnitude. This is clearly not feasible, even with the most powerful computers available today. This is the reason why it is nowadays necessary to use and couple 1-D, 2-D, and 3-D modelings to get a global picture of macroscopic MHD transport processes in stellar interiors. In this review, we report the state of the art of the modeling of transport processes in stellar interiors (both in radiation and in convection zones) aimed to study the stars angular momentum history, the related profile of differential rotation, and their magnetism. © Springer-Verlag Berlin Heidelberg 2013.


Piazza F.,University Paris Diderot | Piazza F.,Paris West University Nanterre La Défense | Vernizzi F.,CEA Saclay Nuclear Research Center | Vernizzi F.,French National Center for Scientific Research
Classical and Quantum Gravity | Year: 2013

The effective field theory of cosmological perturbations stems from considering a cosmological background solution as a state displaying spontaneous breaking of time translations and (adiabatic) perturbations as the related Nambu-Goldstone modes. With this insight, one can systematically develop a theory for the cosmological perturbations during inflation and, with minor modifications, also describe in full generality the gravitational interactions of dark energy, which are relevant for late-time cosmology. The formalism displays a unique set of Lagrangian operators containing an increasing number of cosmological perturbations and derivatives. We give an introductory description of the unitary gauge formalism for theories with broken gauge symmetry - that allows us to write down the most general Lagrangian - and of the Stückelberg 'trick' - that allows to recover gauge invariance and to make the scalar field explicit. We show how to apply this formalism to gravity and cosmology and we reproduce the detailed analysis of the action in the ADM variables. We also review some basic applications to inflation and dark energy. © 2013 IOP Publishing Ltd.


Amphipols (APols) are short amphiphilic polymers designed to handle membrane proteins (MPs) in aqueous solutions as an alternative to small surfactants (detergents). APols adsorb onto the transmembrane, hydrophobic surface of MPs, forming small, water-soluble complexes, in which the protein is biochemically stabilized. At variance with MP/detergent complexes, MP/APol ones remain stable even at extreme dilutions. Pure APol solutions self-associate into well-defined micelle-like globules comprising a few APol molecules, a rather unusual behavior for amphiphilic polymers, which typically form ill-defined assemblies. The best characterized APol to date, A8-35, is a random copolymer of acrylic acid, isopropylacrylamide, and octylacrylamide. In the present work, the concentration threshold for self-association of A8-35 in salty buffer (NaCl 100 mM, Tris/HCl 20 mM, pH 8.0) has been studied by Förster resonance energy transfer (FRET) measurements and tensiometry. In a 1:1 mol/mol mixture of APols grafted with either rhodamine or 7-nitro-1,2,3-benzoxadiazole, the FRET signal as a function of A8-35 concentration is essentially zero below a threshold concentration of 0.002 g ·L-1 and increases linearly with concentration above this threshold. This indicates that assembly takes place in a narrow concentration interval around 0.002 g ·L-1. Surface tension measurements decreases regularly with concentration until a threshold of ca. 0.004 g ·L-1, beyond which it reaches a plateau at ca. 30 mN ·m-1. Within experimental uncertainties, the two techniques thus yield a comparable estimate of the critical self-assembly concentration. The kinetics of variation of the surface tension was analyzed by dynamic surface tension measurements in the time window 10 ms-100 s. The rate of surface tension decrease was similar in solutions of A8-35 and of the anionic surfactant sodium dodecylsulfate when both compounds were at a similar molar concentration of n-alkyl moieties. Overall, the solution properties of APol "micelles" (in salty buffer) appear surprisingly similar to those of the micelles formed by small, nonpolymeric surfactants, a feature that was not anticipated owing to the polymeric and polydisperse nature of A8-35. The key to the remarkable stability to dilution of A8-35 globules, likely to include also that of MP/APol complexes, lies accordingly in the low value of the critical self-association concentration as compared to that of small amphiphilic analogues. © 2012 American Chemical Society.


Dumont J.,University Paris Diderot | Desai A.,Ludwig Institute for Cancer Research
Trends in Cell Biology | Year: 2012

The ability to reproduce relies in most eukaryotes on specialized cells called gametes. Gametes are formed by the process of meiosis in which, after a single round of replication, two successive cell divisions reduce the ploidy of the genome. Fusion of gametes at fertilization reconstitutes diploidy. In most animal species, chromosome segregation during female meiosis occurs on spindles assembled in the absence of the major microtubule-organizing center, the centrosome. In mammals, oocyte meiosis is error prone and underlies most birth aneuploidies. Here, we review recent work on acentrosomal spindle formation and chromosome alignment/separation during oocyte meiosis in different animal models. © 2012 Elsevier Ltd.


Hwang W.,Seoul National University | Arluison V.,French National Center for Scientific Research | Arluison V.,University Paris Diderot | Hohng S.,Seoul National University
Nucleic Acids Research | Year: 2011

Hfq is a key regulator involved in multiple aspects of stress tolerance and virulence of bacteria. There has been an intriguing question as to how this RNA chaperone achieves two completely opposite functions-annealing and unwinding-for different RNA substrates. To address this question, we studied the Hfq-mediated interaction of fragments of a non-coding RNA, DsrA, with its mRNA target rpoS by using single-molecule fluorescence techniques. These experiments permitted us to observe the mechanistic steps of Hfq-mediated RNA annealing/unwinding at the single-molecule level, for the first time. Our real-time observations reveal that, even if the ring-shaped Hfq displays multiple binding sites for its interaction with RNA, the regulatory RNA and the mRNA compete for the same binding site. The competition makes the RNA-Hfq interaction dynamic and, surprisingly, increases the overall annealing efficiency by properly aligning the two RNAs. We furthermore reveal that when Hfq specifically binds to only one of the two RNAs, the unwinding process dominates over the annealing process, thus shedding a new light on the substrate selectivity for annealing or unwinding. Finally, our results demonstrate for the first time that a single Hfq hexamer is sufficient to facilitate sRNA-mRNA annealing. © 2011 The Author(s).


Taboureau O.,Technical University of Denmark | Baell J.B.,Walter and Eliza Hall Institute of Medical Research | Fernandez-Recio J.,Barcelona Supercomputing Center | Villoutreix B.O.,University Paris Diderot
Chemistry and Biology | Year: 2012

Bioinformatics and chemoinformatics approaches contribute to hit discovery, hit-to-lead optimization, safety profiling, and target identification and enhance our overall understanding of the health and disease states. A vast repertoire of computational methods has been reported and increasingly combined in order to address more and more challenging targets or complex molecular mechanisms in the context of large-scale integration of structure and bioactivity data produced by private and public drug research. This review explores some key computational methods directly linked to drug discovery and chemical biology with a special emphasis on compound collection preparation, virtual screening, protein docking, and systems pharmacology. A list of generally freely available software packages and online resources is provided, and examples of successful applications are briefly commented upon. © 2012 Elsevier Ltd All rights reserved.


Bourgeron T.,Institute Pasteur Paris | Bourgeron T.,French National Center for Scientific Research | Bourgeron T.,University Paris Diderot
Nature Reviews Neuroscience | Year: 2015

Genetics studies of autism spectrum disorder (ASD) have identified several risk genes that are key regulators of synaptic plasticity. Indeed, many of the risk genes that have been linked to these disorders encode synaptic scaffolding proteins, receptors, cell adhesion molecules or proteins that are involved in chromatin remodelling, transcription, protein synthesis or degradation, or actin cytoskeleton dynamics. Changes in any of these proteins can increase or decrease synaptic strength or number and, ultimately, neuronal connectivity in the brain. In addition, when deleterious mutations occur, inefficient genetic buffering and impaired synaptic homeostasis may increase an individual's risk for ASD. © 2015 Macmillan Publishers Limited. All rights reserved.


Bendo G.J.,University of Manchester | Bendo G.J.,Imperial College London | Galliano F.,University Paris Diderot | Madden S.C.,University Paris Diderot
Monthly Notices of the Royal Astronomical Society | Year: 2012

We provide an overview of ancillary 24-, 70- and 160-μm data from the Multiband Imaging Photometer for Spitzer (MIPS) that are intended to complement the 70-500 μm Herschel Space Observatory photometry data for nearby galaxies obtained by the Herschel-SPIRE Local Galaxies Guaranteed Time Programs and the Herschel Virgo Cluster Survey. The MIPS data can be used to extend the photometry to wavebands that are not observed in these Herschel surveys and to check the photometry in cases where Herschel performs observations at the same wavelengths. Additionally, we measured globally integrated 24-160μm flux densities for the galaxies in the sample that can be used for the construction of spectral energy distributions. Using MIPS photometry published by other references, we have confirmed that we are obtaining accurate photometry for these galaxies. © 2012 The Authors Monthly Notices of the Royal Astronomical Society © 2012 RAS.


Ciarletta P.,University Pierre and Marie Curie | Ben Amar M.,University Paris Diderot
International Journal of Non-Linear Mechanics | Year: 2012

Morphoelastic theories have demonstrated that elastic instabilities can occur during the growth of soft materials, initiating the transition toward complex patterns. Within the framework of non-linear elasticity, the theory of incremental elastic deformations is classically employed for solving stability problems with finite strains. In this work, we define a variational method to study the bifurcation of growing cylinders with circular section. Accounting for a constant axial pre-stretch, we define a set of canonical transformations in mixed polar coordinates, providing a locally isochoric mapping. Introducing a generating function to derive an implicit gradient form of the mixed variables, the incompressibility constraint for the elastic deformation is solved exactly. The canonical representation allows to transform a generic boundary value problem, characterized by conservative body forces and surface traction loads, into a completely variational formulation. The proposed variational method gives a straightforward derivation of the linear stability analysis, which would otherwise require lengthy manipulations on the governing incremental equations. The definition of a generating function can also account for the presence of local singularities in the elastic solution. Bifurcation analysis is performed for few constrained growth problems of biomechanical interests, such as the mucosal folding of tubular tissues and surface instabilities in tumor growth. In a concluding section, the theoretical results are discussed for clarifying how anisotropy, residual strains and external constraints can affect the stability properties of soft tissues in growth and remodeling processes. © 2011 Elsevier Ltd. All rights reserved.


Kakkar A.K.,University College London | Cimminiello C.,Ospedale Civile di Vimercate | Goldhaber S.Z.,Harvard University | Parakh R.,Medicity | And 3 more authors.
New England Journal of Medicine | Year: 2011

BACKGROUND: Although thromboprophylaxis reduces the incidence of venous thromboembolism in acutely ill medical patients, an associated reduction in the rate of death from any cause has not been shown. METHODS: We conducted a double-blind, placebo-controlled, randomized trial to assess the effect of subcutaneous enoxaparin (40 mg daily) as compared with placebo - both administered for 10±4 days in patients who were wearing elastic stockings with graduated compression - on the rate of death from any cause among hospitalized, acutely ill medical patients at participating sites in China, India, Korea, Malaysia, Mexico, the Philippines, and Tunisia. Inclusion criteria were an age of at least 40 years and hospitalization for acute decompensated heart failure, severe systemic infection with at least one risk factor for venous thromboembolism, or active cancer. The primary efficacy outcome was the rate of death from any cause at 30 days after randomization. The primary safety outcome was the rate of major bleeding during and up to 48 hours after the treatment period. RESULTS: A total of 8307 patients were randomly assigned to receive enoxaparin plus elastic stockings with graduated compression (4171 patients) or placebo plus elastic stockings with graduated compression (4136 patients) and were included in the intentionto-treat population. The rate of death from any cause at day 30 was 4.9% in the enoxaparin group as compared with 4.8% in the placebo group (risk ratio, 1.0; 95% confidence interval [CI], 0.8 to 1.2; P = 0.83). The rate of major bleeding was 0.4% in the enoxaparin group and 0.3% in the placebo group (risk ratio, 1.4; 95% CI, 0.7 to 3.1; P = 0.35). CONCLUSIONS: The use of enoxaparin plus elastic stockings with graduated compression, as compared with elastic stockings with graduated compression alone, was not associated with a reduction in the rate of death from any cause among hospitalized, acutely ill medical patients. (Funded by Sanofi; LIFENOX ClinicalTrials.gov number, NCT00622648.) Copyright © 2011 Massachusetts Medical Society. All rights reserved.


Benayoun B.A.,French National Center for Scientific Research | Benayoun B.A.,University Paris Diderot | Caburet S.,French National Center for Scientific Research | Caburet S.,University Paris Diderot | And 2 more authors.
Trends in Genetics | Year: 2011

Forkhead box (FOX) proteins constitute an evolutionarily conserved family of transcription factors with a central role not only during development, but also in the adult organism. Thus, the misregulation and/or mutation of FOX genes often induce human genetic diseases, promote cancer or deregulate ageing. Indeed, germinal FOX gene mutations cause diseases ranging from infertility to language and/or speech disorders and immunological defects. Moreover, because of their central role in signalling pathways and in the regulation of homeostasis, somatic misregulation and/or mutation of FOX genes are associated with cancer. FOX proteins have undergone diversification in terms of their sequence, regulation and function. In addition to dedicated roles, evidence suggests that Forkhead factors have retained some functional redundancy. Thus, combinations of slightly defective alleles might induce disease phenotypes in humans, acting as quantitative trait loci. Uncovering such variants would be a big step towards understanding the functional interdependencies of different FOX members and their implications in complex pathologies. © 2011 Elsevier Ltd.


London G.M.,Manhes Hospital | London G.M.,National Health Research Institute | Marchais S.J.,Manhes Hospital | Guerin A.P.,National Health Research Institute | De Vernejoul M-C.,University Paris Diderot
Journal of the American Society of Nephrology | Year: 2015

An association between atherosclerosis and osteoporosis has been reported in several studies. This association could result from local intraosseous atherosclerosis and ischemia, which is shown by limb osteoporosis in patients with peripheral artery disease (PAD), but also could result from bidirectional communication between the skeleton and blood vessels. Systemic bone disorders and PAD are frequent in ESRD. Here, we investigated the possible interaction of these disorders. For 65 prevalent nondiabetic patients on hemodialysis, we measured ankle-brachial pressure index (ABix) and evaluated mineral and bone disorders with bone histomorphometry. In prevalent patients on hemodialysis, PAD (ABix<0.9 or >1.4/incompressible) was associated with low bone turnover and pronounced osteoblast resistance to parathyroid hormone (PTH), which is indicated by decreased double-labeled surface and osteoblast surface (P<0.001). Higher osteoblast resistance to PTH in patients with PAD was characterized by weaker correlation coefficients (slopes) between serum PTH and double-labeled surface (P=0.02) or osteoblast surface (P=0.03). The correlations between osteoclast number or eroded surface and serum mineral parameters, including PTH, did not differ for subjects with normal ABix and PAD. Common vascular risk factors (dyslipidemia, smoking, and sex) were similar for normal, low, and incompressible ABix. Patients with PAD were older and had high C-reactive protein levels and longer hemodialysis vintage. These results indicate that, in prevalent nondiabetic patients with ESRD, PAD associates with low bone turnover and pronounced osteoblast resistance to PTH. Copyright © 2015 by the American Society of Nepdfhrology.


Guillot S.,McGill University | Servillat M.,University Paris Diderot | Servillat M.,Harvard - Smithsonian Center for Astrophysics | Webb N.A.,Toulouse 1 University Capitole | And 2 more authors.
Astrophysical Journal | Year: 2013

This paper presents the measurement of the neutron star (NS) radius using the thermal spectra from quiescent low-mass X-ray binaries (qLMXBs) inside globular clusters (GCs). Recent observations of NSs have presented evidence that cold ultra dense matter - present in the core of NSs - is best described by "normal matter" equations of state (EoSs). Such EoSs predict that the radii of NSs, R NS, are quasi-constant (within measurement errors, of ∼10%) for astrophysically relevant masses (M NS>0.5 M ⊙). The present work adopts this theoretical prediction as an assumption, and uses it to constrain a single R NS value from five qLMXB targets with available high signal-to-noise X-ray spectroscopic data. Employing a Markov chain Monte-Carlo approach, we produce the marginalized posterior distribution for R NS, constrained to be the same value for all five NSs in the sample. An effort was made to include all quantifiable sources of uncertainty into the uncertainty of the quoted radius measurement. These include the uncertainties in the distances to the GCs, the uncertainties due to the Galactic absorption in the direction of the GCs, and the possibility of a hard power-law spectral component for count excesses at high photon energy, which are observed in some qLMXBs in the Galactic plane. Using conservative assumptions, we found that the radius, common to the five qLMXBs and constant for a wide range of masses, lies in the low range of possible NS radii, R NS = 9.1-1.5 +1.3 (90%-confidence). Such a value is consistent with low-R NS equations of state. We compare this result with previous radius measurements of NSs from various analyses of different types of systems. In addition, we compare the spectral analyses of individual qLMXBs to previous works. © 2013. The American Astronomical Society. All rights reserved..


Genin E.,French National Center for Scientific Research | Reboud-Ravaux M.,University Paris Diderot | Vidal J.,French National Center for Scientific Research
Current Topics in Medicinal Chemistry | Year: 2010

The search for proteasome inhibitors began fifteen years ago. These inhibitors proved to be powerful tools for investigating many important cellular processes regulated by the ubiquitin-proteasome pathway. Targeting the proteasome pathway can also lead to new treatments for disorders like cancer, muscular dystrophies, inflammation and immune diseases. This is already true for cancer; the FDA approved bortezomib, a potent proteasome inhibitor, for treating multiple myeloma in 2003, and mantle cell lymphoma in 2006. The chemical structures identified in some of the early proteasome inhibitors have led to the development of new anti-cancer drugs (CEP-18770, Carfilzomib, NPI-0052). All these molecules are covalent bonding inhibitors that react with the catalytic Thr1-Oγ of the three types of active site. This review covers recent developments in medicinal chemistry of natural and synthetic proteasome inhibitors. Advances in non-covalent inhibitors that have no reactive group will be highlighted as they should minimize side-effects. New structures and new modes of action have been recently identified that open the door to new drug candidates for treating a range of diseases. © 2010 Bentham Science Publishers Ltd.


Lausson S.,University Pierre and Marie Curie | Cressent M.,University Paris Diderot
Journal of Cellular Biochemistry | Year: 2011

Adrenomedullin (ADM) plays an important role in the regulation of osteoblastic cells through both a proliferative and an anti-apoptotic effects. The present study investigated mechanisms involved in the effect of ADM on survival. We report that ADM can act in osteoblasts both through a non-transcriptional action, by phosphorylation of different kinases and components, and through a transcriptional effect by activation of CREB. So, we observed by Western blot analysis, modifications in the downstream targets of ERK, the pro-apoptotic protein Bad, which is inactivated by increase in Ser155 phosphorylation, and the transcription factor CREB, which is activated by phosphorylation at Ser133. CREB activation was confirmed by a CRE-dependent gene transcription assay and an immunocytochemical study. This increase in CREB phosphorylation could lead to its enhanced transcriptional activity, as indicated by the induced expression of the proliferation marker, PCNA. Moreover, ADM could also activate the tyrosine kinase Src and the PI3-Kinase, both of which are implicated in survival. The use of specific pharmacological inhibitors allowed to establish that ADM could activate a signaling cascade involving Src, MEK, ERK, p90RSK, and that the effect of ADM, in particular on the CREB protein, greatly depends on the regulatory control of interfering signaling pathways. Moreover, as Wnt signaling plays an important role in the control of osteoblast apoptosis, we explored a major component of this pathway, protein GSK3β. ADM-induced inactivation of GSK3β by phosphorylation at Ser9, highly suggests that ADM could also exert its survival effect in osteoblast via components of the Wnt pathway. © 2011 Wiley Periodicals, Inc.


Bamba M.,University Paris Diderot | Imamoglu A.,ETH Zurich | Carusotto I.,University of Trento | Ciuti C.,University Paris Diderot
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2011

In a recent work it was numerically shown that a resonantly driven photonic "molecule" consisting of two coupled cavities can exhibit strong photon antibunching with a surprisingly weak Kerr nonlinearity. Here, we analytically identify the subtle quantum interference effect that is responsible for the predicted efficient photon blockade effect. We then extend the theory to the experimentally relevant Jaynes-Cummings system consisting of a single quantum emitter in a coupled-cavity structure and predict the strong antibunching even for single-atom cooperativity on the order of or smaller than unity. The potential of this quantum interference effect in the realization of strongly correlated photonic systems with only weak material nonlinearities is assessed by comparing on-site and inter-site correlations in a ring of three coupled photonic molecules. © 2011 American Physical Society.


Miotto B.,University Paris Diderot | Graba Y.,French National Center for Scientific Research
BioEssays | Year: 2010

Hox proteins are well-known as developmental transcription factors controlling cell and tissue identity, but recent findings suggest that they are also part of the cell replication machinery. Hox-mediated control of transcription and replication may ensure coordinated control of cell growth and differentiation, two processes that need to be tightly and precisely coordinated to allow proper organ formation and patterning. In this review we summarize the available data linking Hox proteins to the replication machinery and discuss the developmental and pathological implications of this new facet of Hox protein function. © 2010 Wiley Periodicals, Inc.


Veitia R.A.,French National Center for Scientific Research | Veitia R.A.,University Paris Diderot
BioEssays | Year: 2010

Testis determination in most mammals is regulated by a genetic hierarchy initiated by the SRY gene. Early ovarian development has long been thought of as a default pathway switched on passively by the absence of SRY. Recent studies challenge this view and show that the ovary constantly represses male-specific genes, from embryonic stages to adulthood. Notably, the absence of the crucial ovarian transcription factor FOXL2 (alone or in combination with other factors) induces a derepression of male-specific genes during development, postnatally and, even more interestingly, during adulthood. Strikingly, in the adult, targeted ablation of Foxl2 leads to a molecular transdifferentiation of the supporting cells of the ovary, which acquire cytological and transcriptomic characteristics of the supporting cells of the testes. These studies bring many answers to the field of gonadal determination, differentiation and maintenance, but also open many questions. © 2010 WILEY Periodicals, Inc.


De Commer K.,Cergy-Pontoise University | Freslon A.,University Paris Diderot | Yamashita M.,Copenhagen University
Communications in Mathematical Physics | Year: 2014

We show that the discrete duals of the free orthogonal quantum groups have the Haagerup property and the completely contractive approximation property. Analogous results hold for the free unitary quantum groups and the quantum automorphism groups of finite-dimensional C*-algebras. The proof relies on the monoidal equivalence between free orthogonal quantum groups and SUq(2) quantum groups, on the construction of a sufficient supply of bounded central functionals for SUq(2) quantum groups, and on the free product techniques of Ricard and Xu. Our results generalize previous work in the Kac setting due to Brannan on the Haagerup property, and due to the second author on the CCAP. © 2014 Springer-Verlag Berlin Heidelberg.


Cournac A.,University Pierre and Marie Curie | Plumbridge J.,University Paris Diderot
Journal of Bacteriology | Year: 2013

Transcriptional regulation is at the heart of biological functions such as adaptation to a changing environment or to new carbon sources. One of the mechanisms which has been found to modulate transcription, either positively (activation) or negatively (repression), involves the formation of DNA loops. A DNA loop occurs when a protein or a complex of proteins simultaneously binds to two different sites on DNA with looping out of the intervening DNA. This simple mechanism is central to the regulation of several operons in the genome of the bacterium Escherichia coli, like the lac operon, one of the paradigms of genetic regulation. The aim of this review is to gather and discuss concepts and ideas from experimental biology and theoretical physics concerning DNA looping in genetic regulation. We first describe experimental techniques designed to show the formation of a DNA loop. We then present the benefits that can or could be derived from a mechanism involving DNA looping. Some of these are already experimentally proven, but others are theoretical predictions and merit experimental investigation. Then, we try to identify other genetic systems that could be regulated by a DNA looping mechanism in the genome of Escherichia coli. We found many operons that, according to our set of criteria, have a good chance to be regulated with a DNA loop. Finally, we discuss the proposition recently made by both biologists and physicists that this mechanism could also act at the genomic scale and play a crucial role in the spatial organization of genomes. © 2013, American Society for Microbiology.


Veitia R.A.,French National Center for Scientific Research | Veitia R.A.,University Paris Diderot | Birchler J.A.,University of Missouri
Journal of Pathology | Year: 2010

The classical concept of genetic dominance is a simplification of a more quantitative reality. This is clearly exemplified by aneuploid syndromes, of which the best known case is trisomy 21. Moreover, there is an increasing number of clinical conditions due to reduced dosage (haploinsufficiency) of genes encoding transcription factors and other proteins involved in signal transduction and macromolecular complexes. In such genetic diseases, a high degree of phenotypic variability is observed, which calls for an explanation. The sources of dominance are heterogeneous and difficult to cover in a brief review. Here, we will focus on the molecular bases of dosage-sensitive syndromes from the perspective of the gene dosage balance hypothesis, which postulates that stoichiometric alterations of macromolecular complexes or cellular networks are responsible for dominant phenotypes, because of the existing non-linear relationships between the genotypic and phenotypic values with which they are associated. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Hube F.,University Paris Diderot | Velasco G.,University Paris Diderot | Rollin J.,University of Tours | Furling D.,University Pierre and Marie Curie | Francastel C.,University Paris Diderot
Nucleic Acids Research | Year: 2011

The steroid receptor RNA activator (SRA) has the unusual property to function as both a non-coding RNA (ncRNA) and a protein SRAP. SRA ncRNA is known to increase the activity of a range of nuclear receptors as well as the master regulator of muscle differentiation MyoD. The contribution of SRA to either a ncRNA or a protein is influenced by alternative splicing of the first intron, the retention of which disrupts the SRAP open reading frame. We reported here that the ratio between non-coding and coding SRA isoforms increased during myogenic differentiation of human satellite cells but not myotonic dystrophy patient satellite cells, in which differentiation capacity is affected. Using constructs that exclusively produce SRA ncRNA or SRAP, we demonstrated that whereas SRA ncRNA was indeed an enhancer of myogenic differentiation and myogenic conversion of non-muscle cells through the co-activation of MyoD activity, SRAP prevented this SRA RNA-dependant co-activation. Interestingly, the SRAP inhibitory effect is mediated through the interaction of SRAP with its RNA counterpart via its RRM-like domain interacting with the functional sub-structure of SRA RNA, STR7. This study thus provides a new model for SRA-mediated regulation of MyoD transcriptional activity in the promotion of normal muscle differentiation, which takes into account the nature of SRA molecules present. © 2010 The Author(s).


Nicolas-Chanoine M.-H.,Service de Microbiologie | Nicolas-Chanoine M.-H.,University Paris Diderot | Bertrand X.,Service dHygiene Hospitaliere | Bertrand X.,University of Franche Comte | Madec J.-Y.,Unite Antibioresistance et Virulence Bacteriennes
Clinical Microbiology Reviews | Year: 2014

In 2008, a previously unknown Escherichia coli clonal group, sequence type 131 (ST131), was identified on three continents. Today, ST131 is the predominant E. coli lineage among extraintestinal pathogenic E. coli (ExPEC) isolates worldwide. Retrospective studies have suggested that it may originally have risen to prominence as early as 2003. Unlike other classical group B2 ExPEC isolates, ST131 isolates are commonly reported to produce extended- spectrum β-lactamases, such as CTX-M-15, and almost all are resistant to fluoroquinolones. Moreover, ST131 E. coli isolates are considered to be truly pathogenic, due to the spectrum of infections they cause in both community and hospital settings and the large number of virulence-associated genes they contain. ST131 isolates therefore seem to contradict the widely held view that high levels of antimicrobial resistance are necessarily associated with a fitness cost leading to a decrease in pathogenesis. Six years after the first description of E. coli ST131, this review outlines the principal traits of ST131 clonal group isolates, based on the growing body of published data, and highlights what is currently known and what we need to find out to provide public health authorities with better information to help combat ST131. © 2014, American Society for Microbiology. All Rights Reserved.


Marie P.J.,French Institute of Health and Medical Research | Marie P.J.,University Paris Diderot | Felsenberg D.,Center for Muscle and Bone Research | Brandi M.L.,University of Florence
Osteoporosis International | Year: 2011

Oestrogen deficiency increases the rate of bone remodelling which, in association with a negative remodelling balance (resorption exceeding formation), results in impaired bone architecture, mass and strength. Current antiosteoporotic drugs act on bone remodelling by inhibiting bone resorption or by promoting its formation. An alternative therapeutic approach is based on the concept of inducing opposite effects on bone resorption and formation. One therapeutic agent, strontium ranelate, was shown to induce opposite effects on bone resorption and formation in pre-clinical studies and to reduce fracture risk in postmenopausal osteoporotic patients. How strontium ranelate acts to improve bone strength in humans remains a matter of debate, however. This review of the most recent pre-clinical and clinical studies is a critical analysis of strontium ranelate's action on bone resorption and formation and how it increases bone mass, microarchitecture and strength in postmenopausal osteoporotic women. © International Osteoporosis Foundation and National Osteoporosis Foundation 2010.


Piquemal J.-Y.,University Paris Diderot | Briot E.,University Pierre and Marie Curie | Bregeault J.-M.,University Pierre and Marie Curie
Dalton Transactions | Year: 2013

Based on selected examples from the literature, this perspective aims to provide a short overview of synthetic methods using hydrogen peroxide and/or peroxidic species for the elaboration of discrete or zero-dimensional species, as well as mono-, bi- and tri-dimensional materials. There are several advantages in using peroxidic species: no foreign ion or organic ligand is introduced in the reaction medium, they are relatively cheap compared to costly alkoxides, for example, and in certain favorable cases these methods allow the selective formation of a given oxide polymorph. The materials prepared are used in several important technological applications such as electrochromism, gas sensing and electrochemistry but, in this review, special emphasis is placed on oxidation catalysis. Indeed, the deposition of peroxo species on or into oxide supports generally leads to catalytic materials that display higher activities related to a better dispersion of the active metal species in the host matrix. This review also focuses on the use of hydrogen peroxide for the recycling of toxic metal-containing spent materials such as those found in batteries for portable electronic devices. © The Royal Society of Chemistry 2013.


Verlhac M.-H.,University Pierre and Marie Curie | Terret M.-E.,University Pierre and Marie Curie | Pintard L.,University Paris Diderot
Current Opinion in Cell Biology | Year: 2010

In metazoans the oocyte-to-embryo transition occurs in the absence of mRNA transcription and relies entirely on maternally provided mRNA and proteins. We review here recent findings illustrating the importance of degradation of key proteins allowing essential cell cycle transitions as well as important remodelling of the oocyte to produce a totipotent zygote. By following the chronological order of events, we update recent discoveries on the instrumental role of the cullin-RING and APC/C ubiquitin-ligases in promoting meiosis resumption and the oocyte-to-embryo transition. © 2010 Elsevier Ltd.


Retaux S.,French National Center for Scientific Research | Casane D.,University Paris Diderot
EvoDevo | Year: 2013

Animals inhabiting the darkness of caves are generally blind and de-pigmented, regardless of the phylum they belong to. Survival in this environment is an enormous challenge, the most obvious being to find food and mates without the help of vision, and the loss of eyes in cave animals is often accompanied by an enhancement of other sensory apparatuses. Here we review the recent literature describing developmental biology and molecular evolution studies in order to discuss the evolutionary mechanisms underlying adaptation to life in the dark. We conclude that both genetic drift (neutral hypothesis) and direct and indirect selection (selective hypothesis) occurred together during the loss of eyes in cave animals. We also identify some future directions of research to better understand adaptation to total darkness, for which integrative analyses relying on evo-devo approaches associated with thorough ecological and population genomic studies should shed some light. © 2013 Rétaux and Casane; licensee BioMed Central Ltd.


Liu Y.-J.,University Pierre and Marie Curie | Le Berre M.,University Pierre and Marie Curie | Lautenschlaeger F.,University Pierre and Marie Curie | Lautenschlaeger F.,Saarland University | And 6 more authors.
Cell | Year: 2015

The mesenchymal-amoeboid transition (MAT) was proposed as a mechanism for cancer cells to adapt their migration mode to their environment. While the molecular pathways involved in this transition are well documented, the role of the microenvironment in the MAT is still poorly understood. Here, we investigated how confinement and adhesion affect this transition. We report that, in the absence of focal adhesions and under conditions of confinement, mesenchymal cells can spontaneously switch to a fast amoeboid migration phenotype. We identified two main types of fast migration - one involving a local protrusion and a second involving a myosin-II-dependent mechanical instability of the cell cortex that leads to a global cortical flow. Interestingly, transformed cells are more prone to adopt this fast migration mode. Finally, we propose a generic model that explains migration transitions and predicts a phase diagram of migration phenotypes based on three main control parameters: confinement, adhesion, and contractility. © 2015 Elsevier Inc.


Eriksson E.,Heinrich Heine University Düsseldorf | Mora C.,University Paris Diderot | Zazunov A.,Heinrich Heine University Düsseldorf | Egger R.,Heinrich Heine University Düsseldorf
Physical Review Letters | Year: 2014

We propose and study a setup realizing a stable manifold of non-Fermi-liquid states. The device consists of a mesoscopic superconducting island hosting N≥3 Majorana bound states tunnel coupled to normal leads, with a Josephson contact to a bulk superconductor. We find a nontrivial interplay between multichannel Kondo and resonant Andreev reflection processes, which results in the fixed point manifold. The scaling dimension of the leading irrelevant perturbation changes continuously within the manifold and determines the power-law scaling of the temperature-dependent conductance. © 2014 American Physical Society.


Von Filseck J.M.,University of Nice Sophia Antipolis | Copic A.,University Paris Diderot | Delfosse V.,French Institute of Health and Medical Research | Delfosse V.,French National Center for Scientific Research | And 5 more authors.
Science | Year: 2015

In eukaryotic cells, phosphatidylserine (PS) is synthesized in the endoplasmic reticulum (ER) but is highly enriched in the plasma membrane (PM), where it contributes negative charge and to specific recruitment of signaling proteins. This distribution relies on transport mechanisms whose nature remains elusive. Here, we found that the PS transporter Osh6p extracted phosphatidylinositol 4-phosphate (PI4P) and exchanged PS for PI4P between two membranes. We solved the crystal structure of Osh6p:PI4P complex and demonstrated that the transport of PS by Osh6p depends on PI4P recognition in vivo. Finally, we showed that the PI4P-phosphatase Sac1p, by maintaining a PI4P gradient at the ER/PM interface, drove PS transport. Thus, PS transport by oxysterol-binding protein-related protein (ORP)/oxysterol-binding homology (Osh) proteins is fueled by PI4P metabolism through PS/PI4P exchange cycles. Copyright 2015 by the American Association for the Advancement of Science.


Nivaskumar M.,Institute Pasteur Paris | Nivaskumar M.,French National Center for Scientific Research | Nivaskumar M.,University Paris Diderot | Francetic O.,Institute Pasteur Paris | Francetic O.,French National Center for Scientific Research
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2014

Type II protein secretion systems (T2SS) are molecular machines that promote specific transport of folded periplasmic proteins in Gram-negative bacteria, across a dedicated channel in the outer membrane. Secreted substrates, released to the milieu or displayed on the cell surface, contribute to bacterial adaptation to a range of habitats, from deep-sea waters to animal and plant tissues. The past decade has seen remarkable progress in structural, biochemical and functional analysis of T2SS and related systems, bringing new mechanistic insights into these dynamic complexes. This review focuses on recent advances in the field, and discusses open questions regarding the secretion mechanism. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey. © 2013 Elsevier B.V.


Peretto N.,University of Manchester | Peretto N.,University Paris Diderot | Fuller G.A.,University of Manchester
Astrophysical Journal | Year: 2010

How and when the mass distribution of stars in the Galaxy is set is one of the main issues of modern astronomy. Here, we present a statistical study of mass and density distributions of infrared dark clouds (IRDCs) and fragments within them. These regions are pristine molecular gas structures and progenitors of stars and so provide insights into the initial conditions of star formation. This study makes use of an IRDC catalog, the largest sample of IRDC column density maps to date, containing a total of ∼11,000 IRDCs with column densities exceeding NH2 = 1×1022 cm-2 and over 50,000 single-peaked IRDC fragments. The large number of objects constitutes an important strength of this study, allowing a detailed analysis of the completeness of the sample and so statistically robust conclusions. Using a statistical approach to assigning distances to clouds, the mass and density distributions of the clouds and the fragments within them are constructed. The mass distributions show a steepening of the slope when switching from IRDCs to fragments, in agreement with previous results of similar structures. IRDCs and fragments are divided into unbound/bound objects by assuming Larson's relation and calculating their virial parameter. IRDCs are mostly gravitationally bound, while a significant fraction of the fragments are not. The density distribution of gravitationally unbound fragments shows a steep characteristic slope such as Δ/Δlog(n) ∝n-4.0±0.5, rather independent of the range of fragment mass. However, the incompleteness limit at a number density of ∼103 cm-3 does not allow us to exclude a potential lognormal density distribution. In contrast, gravitationally bound fragments show a characteristic density peak at n ≃ 104 cm -3 but the shape of the density distributions changes with the range of fragment masses. An explanation for this could be the differential dynamical evolution of the fragment density with respect to their mass as more massive fragments contract more rapidly. The IRDC properties reported here provide a representative view of the density and mass structure of dense molecular clouds before and during the earliest stages of star formation. These should serve as constraints on any theoretical or numerical model to identify the physical processes involved in the formation and evolution of structure in molecular clouds. © 2010. The American Astronomical Society.


Veitia R.A.,French National Center for Scientific Research | Veitia R.A.,University Paris Diderot | Bottani S.,University Paris Diderot | Birchler J.A.,University of Missouri
Trends in Genetics | Year: 2013

High-throughput genomic analyses have shown that many mutations, including loss-of-function (LOF) mutations, are present in diseased as well as in healthy individuals. Gene dosage effects due to deletions, duplications, and LOF mutations provide avenues to explore oligo- and multigenic inheritance. Here, we focus on several mechanisms that mediate gene dosage effects and analyze biochemical interactions among multiple gene products that are sources of nonlinear relations connecting genotypes and phenotypes. We also explore potential mechanisms that compensate for gene dosage effects. Understanding these issues is critical to understanding why an individual bearing a few damaging mutations can be severely diseased, whereas others harboring tens of potentially deleterious mutations can appear quite healthy. © 2013 Elsevier Ltd.


Casane D.,French National Center for Scientific Research | Casane D.,University Paris Diderot | Laurenti P.,French National Center for Scientific Research | Laurenti P.,University Paris Diderot
BioEssays | Year: 2013

A series of recent studies on extant coelacanths has emphasised the slow rate of molecular and morphological evolution in these species. These studies were based on the assumption that a coelacanth is a 'living fossil' that has shown little morphological change since the Devonian, and they proposed a causal link between low molecular evolutionary rate and morphological stasis. Here, we have examined the available molecular and morphological data and show that: (i) low intra-specific molecular diversity does not imply low mutation rate, (ii) studies not showing low substitution rates in coelacanth are often neglected, (iii) the morphological stability of coelacanths is not supported by paleontological evidence. We recall that intra-species levels of molecular diversity, inter-species genome divergence rates and morphological divergence rates are under different constraints and they are not necessarily correlated. Finally, we emphasise that concepts such as 'living fossil', 'basal lineage', or 'primitive extant species' do not make sense from a tree-thinking perspective. © 2013 WILEY Periodicals, Inc.


Blanchet L.,University Pierre and Marie Curie | Novak J.,University Paris Diderot
Monthly Notices of the Royal Astronomical Society | Year: 2011

The modified Newtonian dynamics (MOND) have been formulated as a modification of the Poisson equation for the Newtonian gravitational field. This theory generically predicts a violation of the strong version of the equivalence principle and as a result, the gravitational dynamics of a system depend on the external gravitational field in which the system is embedded. This so-called external field effect has been recently shown to imply the existence of an anomalous quadrupolar correction, along the direction of the external galactic field, in the gravitational potential felt by planets in the Solar system. In this paper, we confirm the existence of this effect by a numerical integration of the MOND equation in the presence of an external field and compute the secular precession of the perihelion of planets induced by this effect. We find that the precession effect is rather large for outer gaseous planets and in the case of Saturn, it is comparable to published residuals of precession obtained by Saturn range tracking data. The effect is much smaller for inner planets, but in the case of the Earth, it appears to be in conflict for most of the MOND functions μ(y) with the very good constraint on the perihelion precession obtained from Jupiter very long baseline interferometry data. The MOND functions that are compatible with this constraint appear to have a very rapid transition from the MONDian regime to the Newtonian one. © 2011 The Authors Monthly Notices of the Royal Astronomical Society © 2011 RAS.


Doig A.J.,University of Manchester | Derreumaux P.,University Paris Diderot | Derreumaux P.,Institut Universitaire de France
Current Opinion in Structural Biology | Year: 2015

For decades, drug after drug has failed to slow the progression of Alzheimer's disease in human trials. How compounds reducing fibril formation in vitro and toxicity in transgenic mice and flies bind to the Aβ toxic oligomers, is unknown. This account reviews recent drugs mainly targeting Aβ, how they were identified and report their successes from in vitro and in vivo experimental studies and their current status in clinical trials. We then focus on recent in vitro and simulation results on how inhibitors interact with Aβ monomers and oligomers, highly desirable knowledge for predicting new efficient drugs. We conclude with a perspective on the future of the inhibition of amyloid formation by small molecules. © 2014 Elsevier Ltd.


Debiec H.,University Pierre and Marie Curie | Lefeu F.,University Pierre and Marie Curie | Kemper M.J.,University of Hamburg | Niaudet P.,University of Paris Descartes | And 4 more authors.
New England Journal of Medicine | Year: 2011

BACKGROUND: The M-type phospholipase A 2 receptor (PLA 2R) was recently identified as a candidate antigen in 70% of cases of idiopathic membranous nephropathy, a common form of the nephrotic syndrome. The nature of antigens involved in other idiopathic and secondary membranous nephropathies remains unclear. METHODS: We searched for antibodies against bovine serum albumin and circulating bovine serum albumin by means of enzyme-linked immunosorbent assay and Western blotting in serum specimens obtained from 50 patients with membranous nephropathy and 172 controls. The properties of immunopurified circulating bovine serum albumin obtained from serum specimens were analyzed with the use of two-dimensional sodium dodecyl sulfate-polyacrylamide-gel electrophoresis. We detected bovine serum albumin in glomerular deposits and analyzed the reactivity of eluted IgG. RESULTS: Eleven patients, including four children, had high levels of circulating anti-bovine serum albumin antibodies, of both the IgG1 and IgG4 subclasses. These patients also had elevated levels of circulating bovine serum albumin, without an increase in circulating immune complex levels. Bovine serum albumin immunopurified from the serum specimens of these four children migrated in the basic range of pH, whereas the bovine serum albumin from adult patients migrated in neutral regions as native bovine serum albumin. Bovine serum albumin was detected in subepithelial immune deposits only in the children with both high levels of cationic circulating bovine serum albumin and bovine serum albumin-specific antibodies, and it colocalized with IgG in the absence of PLA2R. IgG eluted from such deposits was specific for bovine serum albumin. CONCLUSIONS: Some patients with childhood membranous nephropathy have both circulating cationic bovine serum albumin and anti-bovine serum albumin antibodies. Bovine serum albumin is present in immune deposits, suggesting that cationic bovine serum albumin is pathogenic through binding to the anionic glomerular capillary wall and in situ formation of immune complexes, as shown in experimental models. Copyright © 2011 Massachusetts Medical Society. All rights reserved.


Castera L.,University Paris Diderot | Pinzani M.,University of Florence | Bosch J.,University of Barcelona
Journal of Hepatology | Year: 2012

The development of portal hypertension is a common consequence of chronic liver diseases leading to the formation of esophageal and gastric varices responsible for variceal bleeding, associated with a high mortality rate, as well as other severe complications such as portosystemic encephalopathy and sepsis. Measurement of hepatic venous pressure gradient (HVPG) and upper GI endoscopy are considered the gold standards for portal hypertension assessment in patients with cirrhosis. However, both types of investigation are invasive and HVPG measurement is routinely available and/or performed with adequate standards only in expert centres. There is thus a need for non invasive methods able to predict, with acceptable diagnostic accuracy, the progression of portal hypertension toward the levels of clinically significant (i.e. HVPG ≥10 mmHg) and severe (HVPG ≥12 mmHg) as well as the presence and the size of oesophageal varices. Transient elastography (TE) is a novel non invasive technology that allows measuring liver stiffness and that has gained popularity over the past few years. Although TE has been initially proposed to assess liver fibrosis, a good correlation has been reported between liver stiffness values and HVPG as well as the presence of oesophageal varices, suggesting that it could be an interesting tool for the non invasive evaluation of portal hypertension. This review is aimed at discussing the advantages and limits of TE and the perspectives for its rationale use in clinical practice for the management of patients with portal hypertension. © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.


Patent
French Institute of Health, Medical Research, University Paris Diderot, University of Paris Descartes, University Pierre, Marie Curie and Assistance Publique Hopitaux De Paris | Date: 2014-09-11

An in vitro method for quantifying a target-specific test antibody in a test sample, comprising the steps of: a) performing an immunoassay using a target immobilized on a support which is brought into contact with the test sample, the immunoassay comprising a step of measuring the binding of the target-specific test antibody to the immobilized target by using a detectable non-antibody ligand that binds to the Fc region or to a light chain of an antibody, whereby a concentration-related value of the target-specific test antibody in the test sample is obtained, and b) comparing the concentration-related value obtained at step a) with a reference value obtained by performing an immunoassay using the target immobilized on a support which is brought into contact with a calibration sample comprising a known concentration of a target-specific calibration antibody, the immunoassay comprising a step of measuring the binding of the target-specific calibration antibody to the immobilized target by using the detectable non-antibody ligand of step a), and wherein: (i) the target-specific test antibody of step a) and the target-specific calibration antibody of step b) are identical, or (ii) the target-specific test antibody of step a) and the target-specific calibration antibody of step b) are distinct.


Patent
French Institute of Health, Medical Research, University of Paris Descartes, French National Center for Scientific Research and University Paris Diderot | Date: 2013-01-25

Novel antibodies and peptides relating to HIV are disclosed, as are vaccine compositions containing such antibodies and peptides. The compounds and compositions of the invention are of use in prevention and treatment of HIV, and in particular for inducing mucosal immunity to HIV.


Patent
French Institute of Health, Medical Research, University of Paris Descartes, University Paris Diderot, University Pierre, Marie Curie and Assistance Publique Hopitaux De Paris | Date: 2013-01-21

The present invention relates to an in vitro method for the prognosis of the survival time of a patient suffering from a solid cancer, comprising the quantification of the cell density of follicular B cells present in tumor-induced lymphoid structures from said patient, wherein a high density of follicular B cells indicates that the patient has a favorable prognosis and a low density of follicular B cells indicates that the patient has a poor prognosis.


Patent
French National Center for Scientific Research, French Institute of Health, Medical Research, University Paris Diderot and University Paul Sabatier | Date: 2012-02-08

This invention relates to the use of cells of a medullary or extra-medullary white adipose tissue, in particular of an extra-medullary stromal vascular fraction (SVF) and/or mature dedifferentiated adipocytes of any origin for initiating the formation of a functional vascularisation.


Patent
French Institute of Health, Medical Research, French National Center for Scientific Research and University Paris Diderot | Date: 2014-12-19

The present invention concerns an inhibitor of an interaction between CD300a and an aminophospholipid for use in preventing or treating a virus infection by inhibition of the interaction between CD300a and viral aminophospholipid.


Patent
University Paris Diderot and French National Center for Scientific Research | Date: 2015-01-07

A photodetector for the detection of a light beam, comprising:


Patent
French National Center for Scientific Research and University Paris Diderot | Date: 2014-04-02

A wave shaping device which comprises a tunable impedance surface and a controller connected to the surface in order to control its impedance. The shaping device further comprises a transmission module for receiving a pilot signal used to control the impedance of the surface.


Patent
University Paris Diderot and French National Center for Scientific Research | Date: 2013-10-04

The present invention relates to catalysts for the production of CO gas through electrochemical CO_(2 )reduction. In particular, the present invention relates to an electrochemical cell comprising an iron porphyrin as the catalyst for the CO_(2 )reduction into CO, a method of performing electrochemical reduction of CO_(2 )using said electrochemical cell thereby producing CO gas, and a method of performing electrochemical reduction of CO_(2 )using said iron porphyrin catalyst thereby producing CO gas.


Patent
Vivatech, French National Center for Scientific Research, University Paris Diderot and Mohammed V University | Date: 2013-03-29

The invention relates to methods of diagnosis or prognosis of a tissue or organ fibrosis (e.g., skin fibrosis, hypertrophic scar or a keloid) in a reparative or reactive process comprising the step of determining the levels of expression of genes encoding different molecular markers in a sample of a tissue or organ from a mammalian, wherein different genes markers are studied.


Patent
University Paris Diderot, French National Center for Scientific Research and Ecole Normale Superieure de Cachan | Date: 2013-06-12

The invention relates to a method for quantifying linear forms of the DNA genome of the human immunodeficiency virus 1 (HIV-1) in a sample, wherein: a ligation reaction is performed with a double-stranded oligonucleotide suitable for ligation with the linear form of the HIV-1 DNA genome having a mature 3 end and/or the linear form of the HIV-1 DNA genome having a non-mature 3 end; a quantitative PCR is carried out from the ligation product obtained in the previous step; and the quantity of the linear form of the HIV-1 DNA genome having a mature 3 end and/or the quantity of the linear form of the HIV-1 DNA genome having a non-mature 3 end in the sample are deduced therefrom.


Patent
Vivatech, French National Center for Scientific Research, University Paris Diderot and Mohammed V University | Date: 2013-03-29

The present invention relates to a method and kit for the classification and prognosis of wounds of mammalian, in particular in human. The method defines a molecular signature that enables one to characterize a pathological wound healing such as chronic or non-healing wound.


Patent
French Institute of Health, Medical Research, University Pierre, Marie Curie, University Paris Diderot, University of Paris Descartes and Assistance Publique Hopitaux De Paris | Date: 2013-06-06

The present invention relates to a soluble peptide comprising the amino acids sequence: KRFYVVMWKK (SEQ ID NO: 1) or a function-conservative variant thereof for use in the treatment of cancer. The invention also relates to a pharmaceutical composition for use in the treatment of cancer comprising at least one soluble peptide according to the invention or at least one acid nucleic according to the invention or at least one expression vector according to the invention, or at least one host cell according to the invention and a pharmaceutically acceptable carrier.


Patent
University Paris Diderot, French National Center for Scientific Research, French Institute of Health, Medical Research, University of Paris Descartes and Assistance Publique Hopitaux De Paris | Date: 2014-03-24

The present invention is in the technical field of transplantation, and more particularly relates to the prognosis of a renal transplantation, and to the prevention of renal ischemia and reperfusion injury (IRI) prior to renal transplantation. The invention is more particularly based on the findings that the circulating level of ferritin in a patient is predictive of the outcome of renal transplantation, and that an iron administration to said patient prior to transplantation can prevent IRI.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2009.8.0 | Award Amount: 2.31M | Year: 2010

This project will demonstrate an integrated terahertz (THz) emitter at room temperature, based on a parametric optical process in an AlGaAs device, combining strong material nonlinearity and high optical confinement. The approach followed is based on a quasi-phasematching scheme in the whispering-gallery cavity of a microcylinder containing self-assembled quantum-dots. Compared to existing THz sources like photoconductive antennas, photo-mixers, quantum cascade lasers and optical parametric generators, the TREASURE source will bring together several crucial advantages: room-temperature operation, electrical pumping, compactness, THz power above ~0.3 W from a single emitter (1 W in an array) , custom emission wavelength, spectral purity, an the perspectives of coherent detection and two-dimensional array schemes. This will be accomplished with the complementary competences of four world-class research groups, plus an industrial partner, leader in the THz technology.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2011.9.1 | Award Amount: 2.87M | Year: 2012

Despite significant research efforts during the past 10 years, the terahertz (THz) spectral range remains vastly underexploited, owing essentially to the insufficient signal-to-noise ratio (SNR) achievable with present technology. The projects aim is to address this problem by building a new technological platform enabling the generation of high power, broad bandwidth, THz frequency combs (FCs) with a high frequency stability. The demonstration of FCs in the visible and near-IR spectral ranges has been among the main breakthroughs in the field of optics in the past decade. FCs are commonly generated by mode-locked lasers. In the frequency domain they consist of a broad spectrum of narrow lines, separated by a constant frequency interval, corresponding, in the time domain, to the repetition rate of the emitted pulse train. The time duration of the emitted pulses is roughly given by the inverse of the spectral bandwidth. Due to the lack of mode-locked lasers, FCs in the THz range are nowadays generated by inherently inefficient non-linear conversion techniques. This is the main cause for the low SNR of present THz systems. The THz FCs envisioned in this project will be based on THz quantum cascade lasers (QCLs), a novel, compact and powerful THz semiconductor laser source. THz FCs will be generated by mode-locked THz QCLs, and/or by using THz QCLs as semiconductor amplifiers. This will allow the production of FCs with average powers in excess of 10mW, with a spectral bandwidth > 1THz, and a corresponding pulse duration < 1ps. Such high power THz FCs will be combined with highly sensitive coherent detection techniques based on compact fs-fiber lasers that will be developed ad hoc in this project. The ultimate goal is the realization of an enabling THz technology, which may be adapted for a wide variety of applications in fields such as Physics, Chemistry, Biology and Medicine.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2009.8.0 | Award Amount: 2.21M | Year: 2010

Quantum Information Science (QIS) is a young, highly interdisciplinary field touching on the foundations of both computer science and quantum physics It provides a new model of computation that is both physically feasible and more powerful than conventional computing. If a quantum computer is built, we will be able to solve computational problems that are hard for ordinary computers. Quantum information also enables communication and cryptography protocols that are impossible in the classical world. These facts have created enormous interest in QIS.\n\nWe propose research on computer science aspects of QIS, with a strong interdisciplinary collaboration between computer scientists and physicists that makes our consortium unique in Europe. We will apply ideas from computer science to solve problems in quantum information science and the ideas from quantum information and physics to solve problems in classical computer science.\n\nOur goals include new methods for building quantum algorithms (e.g., by harnessing quantum\nwalks) and understanding the general structure of quantum algorithms (e.g., the interplay between their quantum and classical components). In quantum communication, we will integrate the computer science and physics perspectives, with implications for a variety of models: quantum games, communication complexity, interactive proofs and cryptographic protocols.\n\nWe will also study the mathematical structures that are common to classical and quantum computing, with applications to both fields.\n\nWe believe that our approach is the most timely answer to:\nA) the challenges presently facing the theory of QIS which needs both a strengthening of its foundations and the development of new applications; and\nB) the exciting but as yet barely explored opportunity of applying the new tools developped\nwithin QIS to classical computer science.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2007.1.2 | Award Amount: 4.43M | Year: 2008

Mancoosi aims to develop the scientific knowledge and build the tools necessary to manage the complexity of the open source infrastructure, which is one of the essential building blocks of tomorrows software architectures: the success of LAMP (Linux, Apache, Mysql, Php) inside and outside the data centers is clear evidence of this. Yet, this infrastructure undergoes a fast-paced and distributed evolution that is too often maintained in ad-hoc ways using tools and processes that have clearly attained their limits today: we need new and innovative technology.\n\nWe explicitly target the difficult problems that arise when one wants to efficiently and safely upgrade a set of software components in complex software infrastructures, like those found in open source software distributions, among the most complex software systems known, made of tens of thousands of components that evolve over time without centralized design.\n\nMancoosi will provide: a model of the infrastructure, and the transformations it undergoes when adding or removing components; advanced algorithm to choose efficient evolution paths when updating a platform; a forum to attract leading experts by organizing an international competition; tools that incorporate these findings and advance the state of the art in the field.\n\nMancoosi is precisely focused on Objective ICT-2007.1.2 (c) of the present call, by enabling mastery of complexity, dependability and behavioral stability in the complex system of software infrastructures evolving over time without central design.\n\nWe bring together innovative industries from the Open Source world with deep first-hand experience in the practical issues of the problem, members of the Open Source community that are able to provide high-quality access to the community, and leading researchers that have the knowledge necessary to elaborate the sophisticated models and algorithms needed to solve the underlying problems.


Patent
French Institute of Health, Medical Research, University Pierre, Marie Curie, University Paris Diderot, University of Paris Descartes and Assistance Publique Hopitaux De Paris | Date: 2015-10-05

The present invention relates to a soluble peptide comprising the amino acids sequence: KRFYVVMWKK (SEQ ID NO: 1) or a function-conservative variant thereof for use in the treatment of cancer. The invention also relates to a pharmaceutical composition for use in the treatment of cancer comprising at least one soluble peptide according to the invention or at least one acid nucleic according to the invention or at least one expression vector according to the invention, or at least one host cell according to the invention and a pharmaceutically acceptable carrier.


Patent
Super Sonic Imagine, University Paris Diderot and French National Center for Scientific Research | Date: 2010-04-20

An imaging method using shear waves for observing a viscoelastic medium, comprising: several successive excitation steps j during which elastic shear waves are generated respectively at different excitation loci (Lj) in the viscoelastic medium by an imaging device, the different excitation loci being separated from one another by a maximum distance Dm, an imaging step corresponding to each excitation step j, in which a set j of successive raw images Imj(tk) of the viscoelastic medium at times tk are determined during propagation of the shear wave, the raw images having a resolution R which is larger than the maximum distance Dm, an averaging step in which raw images Imj(tk) corresponding to the same relative time tk are averaged to determine an average image Im(tk).


Patent
French National Center for Scientific Research, University of Reims Champagne Ardenne and University Paris Diderot | Date: 2013-12-18

The present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt, solvate or hydrate thereof, in which: X_(3 )is F, OH or SH, Y_(3 )is F, OH or SH, X_(1), X_(2), X_(4), X_(5), Y_(1), Y_(2), Y_(4 )and Y_(5 )are, independently of one another, H, F, Cl, Br, OH or SH, and 1 to 2 groups among the X_(1), X_(2), X_(4 )and X_(5 )radicals are other than H and/or 1 to 2 groups among the Y_(1), Y_(2), Y_(4 )and Y_(5 )radicals are other than H. The present invention also relates to a compound of formula (I) for use as a medicament, in particular in the prevention and/or treatment of cognitive disorders associated with a dysfunction of the Dyrk1A protein.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2010-ITN | Award Amount: 3.25M | Year: 2011

The recent identification of tumor initiating (TIC) or cancer stem cells (CSC) has opened a new area of research for scientists interested in cancer. Understanding the biology of cancer stem cells has already unraveled pathways and potential targets. However, accumulating data has underscored the complexity of the CSC research area and prompts hence the need for well-structured networks to provide expert platforms, rapid exchange of information to train future researchers in this new concept. 10 laboratories from 6 member states with 4 expert enterprises, all at the highest level of cancer stem cell research will unit in a European Cancer Stem Cell Training Network (EuroCSCTraining). Partners, from the public and private sector, have complementary expert experience in this new area, are active members of CSC research, and share dedication in training and dissemination. The EuroCSCTraining coordinator is one of the present coordinators of the Paris CSC Consortium and director of the Institute of PhD schools of University Paris-Diderot. The main goal of this Network is to foster translaboratory and transPhD school training in this new area of Cancer Research. The EurosCSCTraining supervisory board will bring together supervisors of the private and public sector along with representatives of PhD schools to provide eligibility criteria of recruitment, monitor training, and set up individual tutorship for PCD. The research projects on cancer stem cells will be advertised simultaneously through the EuroCSCTraining Network and the partners University. It is anticipated that the EuroCSCTraining network will create a multidisciplinary and multisector structure of training for a new area of research in cancer which will develop research in Europe, foster European collaborations and provide the basis to harmonise initial research training in cancer research amongst partner Institutions.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: FETPROACT-01-2016 | Award Amount: 5.82M | Year: 2017

Social media and the digitization of news and discussion fora are having far-reaching effects on the way individuals and communities communicate, organize, and express themselves. Can the information circulating on these platforms be tapped to better understand and analyze the enormous problems facing our contemporary society? Could this help us to better monitor the growing number of social crises due to cultural differences and diverging world-views? Would this facilitate early detection and perhaps even ways to resolve conflicts before they lead to violence? The Odycceus project answers all these questions affirmatively. It will develop the conceptual foundations, methodologies, and tools to translate this bold vision into reality and demonstrate its power in a large number of cases. Specifically, the project seeks conceptual breakthroughs in Global Systems Science, including a fine-grained representation of cultural conflicts based on conceptual spaces and sophisticated text analysis, extensions of game theory to handle games with both divergent interests and divergent mindsets, and new models of alignment and polarization dynamics. The project will also develop an open modular platform, called Penelope, that integrates tools for the complete pipeline, from data scraped from social media and digital sources, to visualization of the analyses and models developed by the project. The platform features an infrastructure allowing developers to provide new plug-ins for additional steps in the pipeline, share them with others, and jointly develop the platform as an open source community. Finally, the project will build two innovative participatory tools, the Opinion Observatory and the Opinion Facilitator, which allow citizens to monitor, visualize and influence the dynamics of conflict situations that involve heterogeneous cultural biases and non-transparent entanglements of multilateral interests.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2011.9.9 | Award Amount: 2.57M | Year: 2013

We will study the algorithmic aspects of quantum information. Our goal is to find new algorithms for quantum computers and new quantum communication protocols that are more efficient than the classical protocols. We will pursue this goal in a number of different ways.\n\nFirstly, we will study concrete problems that may have fast quantum algorithms and develop methods for constructing quantum algorithms. We will investigate the use of quantum walks (quantum counterparts of random walks) and learning graphs (a very new method which appeared less than a year ago) to construct quantum algorithms. We will also study two promising application areas for new quantum algorithms: hidden shift problems and property testing.\n\nSecondly, we will investigate general properties of quantum algorithms, such as the role of various resources (e.g., quantum entanglement or quantum discord) in quantum algorithms. We will study restricted forms of quantum computation, to find the minimum conditions under which universal quantum computation is possible. We will investigate the role of structure in input data in quantum speedups, by studying the maximum quantum speedups achievable in various settings.\n\nThirdly, we will study the counterparts of those questions in the communication setting. We will work on designing quantum protocols that solve communication tasks more efficiently than any classical protocol and investigate quantum communication in a game-theoretic setting where parties act to maximize their self-interest.\n\nLastly, we will investigate applications of quantum information concepts in other areas, namely to solve classical problems in computer science and to understand the computational complexity of problems in quantum physics. One of the major applications of a future quantum computer is to simulate quantum physical systems. Our goal is to understand this area in terms of complexity and possible quantum algorithms and to compare these with classical computational techniques.


Patent
Institute Pasteur Paris, French National Center for Scientific Research and University Paris Diderot | Date: 2014-09-17

The present invention relates to a subunit vaccine platform based on multimeric ribonucleoproteins (RNPs) comprising nucleoproteins of a non- segmented negative-strand ribonucleic acid (RNA) virus as carriers of heterologous polypeptides. The present invention also relates to multimeric RNPs resulting from the assembly of at least 200 fusion proteins with a cellular RNA, or to recombinant yeasts or yeast lysates expressing these multimeric RNPs. It also concerns a process for the preparation of these multimeric RNPs or recombinant yeasts or yeast lysates. In particular, the present invention relates to their use as active ingredient for the in vitro production of an immunogenic composition or in eliciting a protective prophylactic or a therapeutic immune response against said heterologous polypeptide in a host in need thereof. Recombinant yeasts or yeast lysates of the invention can also be used as expression and vector systems for delivery to a host.


Patent
French National Center for Scientific Research, University Paris Diderot, Ecole Normale Superieure de Lyon, University Pierre and Marie Curie | Date: 2012-03-21

This method comprises bringing drops to be separated into contact with an interface (40) suitable for allowing an osmotic equilibrium between the content of each drop to be separated. The method comprises an osmotic flow between the drops (20A) of the first group of drops through the interface (40) in order to modify the density of each drop (20A) of the first group of drops and the separation of the drops (20A, 20B) according to the density thereof or a combination of the density and the volume in order to isolate the drops (20A) of the first group of drops from the drops (20B) of a second group of drops.


Patent
French Institute of Health, Medical Research, Université de Sherbrooke, University of Paris Descartes, University Pierre, Marie Curie, Assistance Publique Hopitaux De Paris and University Paris Diderot | Date: 2013-03-26

The present invention relates to methods and compositions for the prevention or treatment of ischemia related organ damage.


Belazzougui D.,University Paris Diderot | Venturini R.,CNR Institute of Information Science and Technologies Alessandro Faedo
Proceedings of the Annual ACM-SIAM Symposium on Discrete Algorithms | Year: 2013

Given a set of integer keys from a bounded universe along with associated data, the dictionary problem asks to answer two queries: membership and retrieval. Membership has to tell whether a given element is in the dictionary or not; Retrieval has to return the data associated with the searched key. In this paper we provide time and space optimal solutions for three well-established relaxations of this basic problem: (Compressed) Static functions, Approximate membership and Relative membership. Copyright © SIAM.


Fadili M.J.,University of Caen Lower Normandy | Starck J.-L.,University Paris Diderot | Bobin J.,California Institute of Technology | Moudden Y.,CEA Saclay Nuclear Research Center
Proceedings of the IEEE | Year: 2010

This paper gives essential insights into the use of sparsity and morphological diversity in image decomposition and source separation by reviewing our recent work in this field. The idea to morphologically decompose a signal into its building blocks is an important problem in signal processing and has far-reaching applications in science and technology. Starck, proposed a novel decomposition methodmorphological component analysis (MCA)based on sparse representation of signals. MCA assumes that each (monochannel) signal is the linear mixture of several layers, the so-called morphological components, that are morphologically distinct, e.g., sines and bumps. The success of this method relies on two tenets: sparsity and morphological diversity. That is, each morphological component is sparsely represented in a specific transform domain, and the latter is highly inefficient in representing the other content in the mixture. Once such transforms are identified, MCA is an iterative thresholding algorithm that is capable of decoupling the signal content. Sparsity and morphological diversity have also been used as a novel and effective source of diversity for blind source separation (BSS), hence extending the MCA to multichannel data. Building on these ingredients, we will provide an overview the generalized MCA introduced by the authors in and as a fast and efficient BSS method. We will illustrate the application of these algorithms on several real examples. We conclude our tour by briefly describing our software toolboxes made available for download on the Internet for sparse signal and image decomposition and separation. © 2009 IEEE.


Mora C.,University Paris Diderot | Chevy F.,Kastler-Brossel Laboratory
Physical Review Letters | Year: 2010

Recent experiments on imbalanced Fermi gases have raised interest in the physics of an impurity immersed in a Fermi sea, the so-called Fermi polaron. In this Letter, a simple theory is devised to describe dilute Fermi-polaron ensembles corresponding to the normal phase of an imbalanced Fermi gas. An exact formula is obtained for the dominant interaction between polarons, expressed solely in terms of a single-polaron parameter. The physics of this interaction is identified as a signature of the Pauli exclusion principle. © 2010 The American Physical Society.


Castin Y.,Kastler-Brossel Laboratory | Mora C.,University Paris Diderot | Pricoupenko L.,CNRS Condensed Matter Physics Laboratory
Physical Review Letters | Year: 2010

We study three same-spin-state fermions of mass M interacting with a distinguishable particle of mass m in the unitary limit where the interaction has a zero range and an infinite s-wave scattering length. We predict an interval of mass ratio 13.384


Guerrouache M.,CNRS East Paris Institute of Chemistry and Materials Science | Mahouche-Chergui S.,University Paris Diderot | Chehimi M.M.,University Paris Diderot | Carbonnier B.,CNRS East Paris Institute of Chemistry and Materials Science
Chemical Communications | Year: 2012

A monolith surface with alkyne functionality was reacted with cysteamine through radical-mediated thiol-yne addition reaction providing a hydrophilic and chelating interface. Photochemical initiation affords spatial control over the reaction site and further site-specific immobilisation of gold nanoparticles. © 2012 The Royal Society of Chemistry.


Jansen P.,VU University Amsterdam | Xu L.-H.,University of New Brunswick | Kleiner I.,University Paris Diderot | Ubachs W.,VU University Amsterdam | Bethlem H.L.,VU University Amsterdam
Physical Review Letters | Year: 2011

The 6.7 and 12.2 GHz masers, corresponding to the 51→6 0A+ and 20→3-1E transitions in methanol (CH3OH), respectively, are among the brightest radio objects in the sky. We present calculations for the sensitivity of these and other transitions in the ground state of methanol to a variation of the proton-to-electron mass ratio. We show that the sensitivity is greatly enhanced due to a cancellation of energies associated with the hindered internal rotation and the overall rotation of the molecule. We find sensitivities of K μ=-42 and Kμ=-33, for the 51→6 0A+ and 20→3-1E transitions, respectively. The sensitivities of other transitions in the different isotopologues of methanol range from -88 to 330. This makes methanol a sensitive probe for spatial and temporal variations of the proton-to-electron mass ratio. © 2011 American Physical Society.


Hartle J.,University of California at Santa Barbara | Hawking S.W.,DAMTP | Hertog T.,University Paris Diderot | Hertog T.,Solvay Group
Physical Review Letters | Year: 2011

We consider landscape models that admit several regions where the conditions for eternal inflation hold. It is shown that one can use the no-boundary wave function to calculate small departures from homogeneity within our past light cone despite the possibility of much larger fluctuations on super horizon scales. The dominant contribution comes from the history exiting eternal inflation at the lowest value of the potential. In a class of landscape models this predicts a tensor to scalar ratio of about 10%. In this way the no-boundary wave function defines a measure for the prediction of local cosmological observations. © 2011 American Physical Society.


Delande D.,Kastler-Brossel Laboratory | Orso G.,University Paris Diderot
Physical Review Letters | Year: 2014

Using the transfer-matrix method, we numerically compute the precise position of the mobility edge of atoms exposed to a laser speckle potential and study its dependence versus the disorder strength and correlation function. Our results deviate significantly from previous theoretical estimates using an approximate, self-consistent approach of localization. In particular, we find that the position of the mobility edge in blue-detuned speckles is much lower than in the red-detuned counterpart, pointing out the crucial role played by the asymmetric on-site distribution of speckle patterns. © 2014 American Physical Society.


Cacciari M.,CNRS Theoretical and High Energy Physics | Cacciari M.,University Paris Diderot | Salam G.P.,CNRS Theoretical and High Energy Physics | Salam G.P.,CERN | And 2 more authors.
European Physical Journal C | Year: 2012

FastJet is a C++ package that provides a broad range of jet finding and analysis tools. It includes efficient native implementations of all widely used 2→1 sequential recombination jet algorithms for pp and e +e - collisions, as well as access to 3rd party jet algorithms through a plugin mechanism, including all currently used cone algorithms. FastJet also provides means to facilitate the manipulation of jet substructure, including some common boosted heavy-object taggers, as well as tools for estimation of pileup and underlying-event noise levels, determination of jet areas and subtraction or suppression of noise in jets. © 2012 The Author(s).


Rossi R.,University Paris Diderot | Werner F.,Kastler-Brossel Laboratory
Journal of Physics A: Mathematical and Theoretical | Year: 2015

Recently, Kozik, Ferrero and Georges discovered numerically that for a family of fundamental models of interacting fermions, the self-energy S[G] is a multi-valued functional of the fully dressed single-particle propagator G, and that the skeleton diagrammatic series σbold [G] converges to the wrong branch above a critical interaction strength. We consider the zero space-time dimensional case, where the same mathematical phenomena appear from elementary algebra. We also find a similar phenomenology for the fully bold formalism built on the fully dressed single-particle propagator and pair propagator. © 2015 IOP Publishing Ltd Printed in the UK.


Laurent S.,Kastler-Brossel Laboratory | Leyronas X.,University Paris Diderot | Chevy F.,Kastler-Brossel Laboratory
Physical Review Letters | Year: 2014

Using a combination of Boltzmann's equation and virial expansion, we study the effect of three-body losses and interactions on the momentum distribution of a homogeneous unitary Bose gas in the dilute limit where quantum correlations are negligible. The comparison of our results to the recent measurement made at JILA on a unitary gas of Rb85 allows us to determine an experimental fugacity z=0.5(1). © 2014 American Physical Society.


Lepine J.-P.,University Paris Diderot | Briley M.,NeuroBiz Consulting and Communication
Neuropsychiatric Disease and Treatment | Year: 2011

Recent epidemiological surveys conducted in general populations have found that the lifetime prevalence of depression is in the range of 10% to 15%. Mood disorders, as defined by the World Mental Health and the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, have a 12-month prevalence which varies from 3% in Japan to over 9% in the US. A recent American survey found the prevalence of current depression to be 9% and the rate of current major depression to be 3.4%. All studies of depressive disorders have stressed the importance of the mortality and morbidity associated with depression. The mortality risk for suicide in depressed patients is more than 20-fold greater than in the general population. Recent studies have also shown the importance of depression as a risk factor for cardiovascular death. The risk of cardiac mortality after an initial myocardial infarction is greater in patients with depression and related to the severity of the depressive episode. Greater severity of depressive symptoms has been found to be associated with significantly higher risk of all-cause mortality including cardiovascular death and stroke. In addition to mortality, functional impairment and disability associated with depression have been consistently reported. Depression increases the risk of decreased workplace productivity and absenteeism resulting in lowered income or unemployment. Absenteeism and presenteeism (being physically present at work but functioning suboptimally) have been estimated to result in a loss of $36.6 billion per year in the US. Worldwide projections by the World Health Organization for the year 2030 identify unipolar major depression as the leading cause of disease burden. This article is a brief overview of how depression affects the quality of life of the subject and is also a huge burden for both the family of the depressed patient and for society at large. © 2011 Lépine and Briley.


Starck J.-L.,University Paris Diderot | Bobin J.,California Institute of Technology
Proceedings of the IEEE | Year: 2010

Wavelets have been used extensively for several years now in astronomy for many purposes, ranging from data filtering and deconvolution to star and galaxy detection or cosmic-ray removal. More recent sparse representations such as ridgelets or curvelets have also been proposed for the detection of anisotropic features such as cosmic strings in the cosmic microwave background. We review in this paper a range of methods based on sparsity that have been proposed for astronomical data analysis. We also discuss the impact of compressed sensing, the new sampling theory, in astronomy for collecting the data, transferring them to earth or reconstructing an image from incomplete measurements. © 2009 IEEE.


Durand A.,University Paris Diderot | Kontinen J.,University of Helsinki
ACM Transactions on Computational Logic | Year: 2012

We study fragments D(k∀) and D(k-dep) of dependence logic defined either by restricting the number k of universal quantifiers or the width of dependence atoms in formulas. We find the sublogics of existential second-order logic corresponding to these fragments of dependence logic. We also show that, for any fixed signature, the fragments D(k∀) give rise to an infinite hierarchy with respect to expressive power. On the other hand, for the fragments D(k-dep), a hierarchy theorem is otained only in the case the signature is also allowed to vary. For any fixed signature, this question is open and is related to the so-called Spectrum Arity Hierarchy Conjecture. © 2012 ACM.


Moussaieff A.,Hebrew University of Jerusalem | Kogan N.M.,Hebrew University of Jerusalem | Aberdam D.,French Institute of Health and Medical Research | Aberdam D.,University Paris Diderot
Stem Cells | Year: 2015

Recent studies suggest that the metabolic network is an important part of the molecular circuitry that underlies pluripotency. Of the metabolic pathways that were implicated in the pluripotency balance, "energy" metabolism is particularly notable. Its mechanism of action on pluripotency-regulating genes has been partially elucidated when three metabolites, namely acetate, S-adenosylmethionine, and O-linked β-N-acetylglucosamine were recently shown to link cytosolic signals to pluripotent gene expression. The cytosolic levels of these metabolites are the result of environmental perturbations, making them sensitive messengers, which are assumed to diffuse through the nuclear pores, being small molecules. Recent work also suggests that the modulation of the levels of these metabolites in pluripotent cells controls the balance between pluripotency and early commitment via epigenetic modifications. Here, we review recent studies that link metabolism and pluripotency via epigenetic modifications that occur through these three metabolites. Stem Cells 2015;33:2374-2380 © 2015 AlphaMed Press.


Socie G.,Hospital Saint Louis | Socie G.,University Paris Diderot | Socie G.,French Institute of Health and Medical Research | Ritz J.,Dana-Farber Cancer Institute | Ritz J.,Harvard University
Blood | Year: 2014

Chronic graft-versus-host disease (GVHD) is a frequent and potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation. Increased transplantation of older patients and the more frequent use of unrelated donors has led to increased numbers of patients with this painful complication. Recent advances have been made in understanding the pathophysiology of chronic GVHD and in establishing precise criteria for diagnosis and classification of disease manifestations. These advances will hopefully pave the way for improving both the prophylaxis and treatment of chronic GVHD. © 2014 by The American Society of Hematology.


Taylor A.M.,Dublin Institute for Advanced Studies | Gabici S.,University Paris Diderot | Aharonian F.,Dublin Institute for Advanced Studies | Aharonian F.,Max Planck Institute for Nuclear Physics | Aharonian F.,Gran Sasso Science Institute
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2014

Recent IceCube results suggest that the first detection of very high energy astrophysical neutrinos have been accomplished. We consider these results at face value in a Galactic origin context. Emission scenarios from both the Fermi bubble and broader halo region are considered. We motivate that such an intensity of diffuse neutrino emission could be Galactic in origin if it is produced from an outflow into the halo region. This scenario requires cosmic ray transport within the outflow environment to be different to that inferred locally within the disk and that activity in the central part of the Galaxy accelerates cosmic rays to trans-"knee" energies before they escape into an outflow. The presence of a large reservoir of gas in a very extended halo around the Galaxy, recently inferred from x-ray observations, implies that the relatively modest acceleration power of 1039 erg s-1 in PeV energy cosmic rays may be sufficient to explain the observed neutrino flux. Such a luminosity is compatible with that required to explain the observed intensity of cosmic rays around the knee. © 2014 American Physical Society.


Chatzimpiros P.,University Paris Diderot | Barles S.,CITES
Biogeosciences | Year: 2013

Human foods typically contain a minor fraction of the nitrogen (N) used in agricultural production. The major fraction is lost to the environment and interferes with all current environmental problems and global change issues. Food is also generally consumed far from its production location and associated N losses remain unknown unless connected to products through consumption-based indicators. We develop the N food-print as an indicator to connect N flows and losses in livestock systems to the consumption of dietary N in the form of beef, pork and fresh milk in France. This N food-print of a product is the N loss associated with its agricultural production. The conversions of N, from field application to recovery in vegetal and animal proteins, are calculated from statistical data on crop and animal production and through modelling of feed rations for cattle and swine. Beef farming to feed an individual in France uses 11.1 kg N cap-1 yr-1, out of which 3.8 kg N cap-1 yr-1 (or 35%) is the N food-print, 7% is recovered in retail products, 3% is slaughter waste and 55% returns to agriculture as manure. Pork and dairy production use 7.5 and 2.3 kg N cap-1 yr-1, respectively, out of which 53 and 48% is the N food-print, respectively; about 11% is recovered in retail products and 35% returns to agriculture as manure. In total, more than 75% of the N food-print relates to crop cultivation for feed and much of these losses (80% for dairy and pork production, 20% for beef production) occur in crop farms far from where the livestock is reared. Regional and national policies to reduce N losses should take into account that trade in feed implies causal relationships among N losses in agrosystems distant from each other. © Author(s) 2013.


Danelutto M.,University of Pisa | Di Cosmo R.,University Paris Diderot
Procedia Computer Science | Year: 2012

We discuss the implementation of a minimalist parallel library in OCaml. The library provides parallel map and fold (reduce) higher order functions and targets standard cache coherent shared memory multi-cores. Our Parmap.parmap and Parmap.parfold functions may be used to seamlessly replace OCaml List map and fold standard functions preserving their full functional semantics while achieving nearly optimal speedup on standard multi-core architectures. We discuss the design of the Parmap module, the main implementation features and we present some experimental results assessing the efficiency of the Parmap parallel functions. Overall, Parmap represents a perfect incarnation of the "propagate the concept with minimal disruption" principle introduced in Cole's algorithmic skeleton manifesto. © 2012 Published by Elsevier Ltd.


Cid Fernandes R.,Federal University of Santa Catarina | Stasinska G.,University Paris Diderot | Mateus A.,Federal University of Santa Catarina | Vale Asari N.,Federal University of Santa Catarina
Monthly Notices of the Royal Astronomical Society | Year: 2011

We use the WHα versus [Nii]/Hα (WHAN) diagram introduced by us in previous work to provide a comprehensive emission-line classification of Sloan Digital Sky Survey galaxies. This classification is able to cope with the large population of weak line galaxies that do not appear in traditional diagrams due to a lack of some of the diagnostic lines. A further advantage of the WHAN diagram is to allow the differentiation between two very distinct classes that overlap in the low-ionization nuclear emission-line region (LINER) region of traditional diagnostic diagrams. These are galaxies hosting a weakly active galactic nucleus (wAGN) and 'retired galaxies' (RGs), i.e. galaxies that have stopped forming stars and are ionized by their hot low-mass evolved stars. A useful criterion to distinguish true from fake AGN (i.e. the RGs) is the value of ξ, which measures the ratio of the extinction-corrected Hα luminosity with respect to the Hα luminosity expected from photoionization by stellar populations older than 108yr. We find that ξ follows a markedly bimodal distribution, with a ξ≫ 1 population composed by systems undergoing star formation and/or nuclear activity, and a peak at ξ~ 1 corresponding to the prediction of the RG model. We base our classification scheme not on ξ but on a more readily available and model-independent quantity which provides an excellent observational proxy for ξ: the equivalent width of Hα. Based on the bimodal distribution of WHα, we set the practical division between wAGN and RGs at WHα= 3Å. Five classes of galaxies are identified within the WHAN diagram: (i) pure star-forming galaxies: and WHα > 3Å; (ii) strong AGN (i.e. Seyferts): and WHα > 6Å; (iii) weak AGN: and WHα between 3 and 6Å; (iv) RGs (i.e. fake AGN): WHα < 3Å; (v) passive galaxies (actually, lineless galaxies): WHα and W[Nii] < 0.5Å. A comparative analysis of star formation histories and of other physical and observational properties in these different classes of galaxies corroborates our proposed differentiation between RGs and wAGN in the LINER-like family. This analysis also shows similarities between strong and weak AGN on the one hand, and retired and passive galaxies on the other. © 2011 The Authors. Monthly Notices of the Royal Astronomical Society © 2011 RAS.


Castagnetti M.,University of Padua | El-Ghoneimi A.,University Paris Diderot
Journal of Urology | Year: 2010

Purpose: We systematically reviewed the literature published during the last 20 years on the treatment of primary proximal hypospadias associated with severe ventral curvature. Materials and Methods: We reviewed studies published between 1990 and December 2009, searching for "hypospadias" in MEDLINE®/PubMed®, EMBASE®, Web of Science® and the Cochrane Library. Results: The search yielded 69 pertinent studies. These studies were generally of low quality (69.5% surgical series). Based on the literature, curvature should be addressed stepwise starting with ventral dissection that extends underneath the urethral plate (urethral plate mobilization). Contrary to former practice, urethral plate division seems to have more of a role if significant curvature persists. Dorsal plication seems sufficient to correct only minor degrees of curvature, while a minority of cases require ventral lengthening. No urethroplasty techniques appear to be definitively superior. After urethral plate division a staged urethroplasty has lower complication rates but a second operation is required, which might otherwise be avoided in approximately 70% of cases. Conclusions: The present systematic review shows the weak evidence backing current management of primary severe hypospadias. We even lack a clear-cut definition of severe hypospadias and associated curvature. Hence, while we developed general recommendations for treatment based on our review of available evidence, we emphasize the need to establish shared criteria for accurate preoperative or introperative patient stratification, and to define objective outcome measures and followup intervals for data reporting to make comparison of surgical approaches reliable. © 2010 American Urological Association Education and Research, Inc.


Perrier A.,University Paris Diderot | Maurel F.,University Paris Diderot | Jacquemin D.,University of Nantes
Accounts of Chemical Research | Year: 2012

In single photochromes, the two isomers that are interconverted in photoinduced reactions can serve as on and off states in a molecular switching device. The addition of several photochromic moieties onto a single molecule can allow the processing of more complex logical patterns. For example, an asymmetric triad could, in principle, store a byte, rather than a bit, of data. Because of the potential impact of multiphotochromic molecules in many research areas, over the past decade several groups have synthesized these coupled structures. The targets are easily addressable molecules that display increased contrast between the on and off states and in which all isomers have significantly distinguishable optical signatures.In this Account, we provide an overview of the multiswitchable molecular systems that incorporate at least one diarylethene group, which is the most successful thermally stable (P-type) organic photochrome. Up to this point, most systems have presented significant limitations. First of all, the reversibility of the processes is hindered by several side reactions more frequently than for single photochromes. Second, switching one part of the compound impedes the photoreactivity of other fragments in approximately 50% of the cases, and maximizing the electronic communication increases the probability of partial activity. In addition, most of the few synthesized operative systems only demonstrate cumulative absorption spectra rather than new features. Finally, it is impossible to selectively induce a chosen conversion because one wavelength might trigger several processes. We also emphasize the promising successes of asymmetric diarylethene dimers and trimers and molecules that combine two families of photochromes, such as diarylethene added to fulgimide or phenoxy-naphthacenequinone.In that framework, theoretical simulations offer complementary tools to investigate these structures, both to obtain structure/property relationships and to propose paths for the design of more efficient molecules. However, due to the size of the systems, researchers can only apply semiquantitative models. The investigation of the absorption spectra of the photochromes with time-dependent density functional theory (TD-DFT), the analysis of the topology of the LUMO + n (typically n = 1) of the closed-open hybrid, and an estimate of the steric stress in the hypothetical (ground-state) closed-closed structure serve as a useful combination of parameters to obtain initial insights regarding the photocyclization of the different open diarylethene groups. Nevertheless, because a first-order qualitative approach does not explore the potential energy surface of the photoexcited states, it remains inadequate for the investigation of some molecules. © 2012 American Chemical Society.


Patent
Alchimedics and University Paris Diderot | Date: 2011-09-23

The use of at least one diazonium salt bearing an initiator function, for forming an undercoat obtained by grafting a graft derived from the diazonium salt and bearing an initiator function at the surface of a conductive or semiconductive material on the undercoat, and for forming on the undercoat a polymeric layer obtained by polymerization, in particular free radical polymerization, in situ of at least one monomer, initiated from the initiator function.


Schinazi R.,Emory University | Halfon P.,Hopital Europeen and Laboratoire Alphabio Marseille | Marcellin P.,University Paris Diderot | Asselah T.,University Paris Diderot
Liver International | Year: 2014

For HCV infection, there have been major advancements during last several years with large numbers of ongoing trials with various direct-acting antivirals (DAA) showing high potency, favourable tolerability profile, higher barrier to resistance, shortened treatment duration, all oral regimen, pan-genotypic, fewer drug interactions and reduced pill burden. By 2014, several DAAs are anticipated to complete successful phase III trials and will be commercially available. Initially, a wave of IFN-based regimen (sofosbuvir, faldaprevir and simeprevir) will be available for treatment of HCV genotype 1. In the near future, combination of antiviral agents with additive potency that lack cross-resistance with good safety profile will likely be the new recommended regimens, making HCV, the first chronic viral infection to be eradicated worldwide with a finite duration of combination DAA therapy without IFN or ribavirin. The aim of this review was to summarize the results obtained from recent DAA combination studies without IFN. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Bucher M.,University Paris Diderot | Louis T.,University Paris Diderot | Louis T.,Laboratoire Of Physique
Monthly Notices of the Royal Astronomical Society | Year: 2012

For analysing maps of the cosmic microwave background sky, it is necessary to mask out the region around the Galactic equator where the parasitic foreground emission is strongest as well as the brightest compact sources. Since many of the analyses of the data, particularly those searching for non-Gaussianity of a primordial origin, are most straightforwardly carried out on full-sky maps, it is of great interest to develop efficient algorithms for filling in the missing information in a plausible way. In this paper, we explore algorithms for filling in based on constrained Gaussian realizations. The non-trivial step in such a filling-in procedure is to find the maximum likelihood configuration for the masked pixels given the data for the unmasked pixels. We reformulate the problem in terms of an integral equation involving a short-range kernel and show that in the far interior of a masked region the maximum likelihood configuration very nearly obeys the Laplace equation. Although carrying out constrained Gaussian realizations is in principle straightforward, for finely pixelized maps as will be required for the Planck analysis, a direct brute force method is not numerically tractable. Here we present some concrete solutions to this problem, both on a spatially flat sky with periodic boundary conditions and on the pixelized sphere. One approach is to solve the linear system using an appropriately preconditioned conjugate gradient method. While this approach was successfully implemented on a rectangular domain with periodic boundary conditions and converged rapidly even for very wide masked regions, we found that the method failed on the pixelized sphere for reasons that we explain here. We present an approach that works for full-sky pixelized maps on the sphere involving a kernel-based multiresolution Laplace solver followed by a series of conjugate gradient corrections near the boundary of the mask. © 2012 The Authors. Monthly Notices of the Royal Astronomical Society © 2012 RAS.


Bosnjakl Z.,University Paris Diderot | Kumar P.,University of Texas at Austin
Monthly Notices of the Royal Astronomical Society: Letters | Year: 2012

Photons of energy larger than 100MeV from long GRBs arrive a few seconds after >10MeV photons do. We show that this delay is a natural consequence of a magnetic-dominated relativistic jet. The much slower acceleration of a magnetic jet with radius (compared with a hot baryonic outflow) results in high-energy γ-ray photons to be converted to electron-positron pairs out to a larger radius, whereas lower energy γ-rays of energy less than ~10MeV can escape when the jet crosses the Thomson photosphere. The resulting delay for the arrival of high-energy photons is found to be similar to the value observed by the Fermi satellite for a number of GRBs. A prediction of this model is that the delay should increase with photon energy (E) as ~E 0.17 for E < 100MeV. The delay depends almost linearly on burst redshift, and on the distance from the central compact object where the jet is launched (R 0). Therefore, the delay in arrival of <10 2 MeV photons can be used to estimate burst redshift if the magnetic jet model for γ-ray generation is correct and R 0 is roughly the same for long GRBs. ©2012 The Authors Monthly Notices of the Royal Astronomical Society. © 2012 RAS.


Rojas X.,University Paris Diderot | Haziot A.,University Paris Diderot | Bapst V.,University Paris Diderot | Balibar S.,University Paris Diderot | Maris H.J.,Brown University
Physical Review Letters | Year: 2010

We have measured the elasticity of high quality ultrapure He4 single crystals in the low temperature region where supersolidity is supposed to occur. At 20He4 mK, our results are consistent with elastic coefficients previously measured at 1.2He4 K. As the temperature increases from 20 to 100He4 mK, a large softening occurs because dislocations unpin from He3 impurities. In the absence of He3 impurities, dislocations are free to move down to 20He4 mK; the crystals are soft. The large magnitude of this anomalous softening shows that dislocations form a mobile mosaic structure. It illustrates the remarkable quantum plasticity of He4 crystals. ©2010 The American Physical Society.


Wiviott S.D.,Harvard University | Steg P.G.,Alliance University | Steg P.G.,University Paris Diderot | Steg P.G.,French Institute of Health and Medical Research | Steg P.G.,Imperial College London
The Lancet | Year: 2015

Platelet-mediated thrombosis is a major pathophysiological mechanism that underlies acute coronary syndromes, and therefore, antiplatelet therapy is an important foundation in the treatment and prevention of recurrence of these syndromes. Nearly 30 years ago, aspirin was the first agent to show a benefit for acute coronary syndromes and is still a key therapeutic agent. The landmark CURE trial showed that the addition of a P2Y12 antagonist, clopidogrel, to aspirin was beneficial in the treatment of acute coronary syndromes. Despite substantial benefits with clopidogrel, limitations include the slow speed of onset, variable response, and a modest antiplatelet effect. Next-generation P2Y12 antagonists, prasugrel and ticagrelor, overcome these limitations and have been shown, in large-scale clinical trials for acute coronary syndromes, to reduce ischaemic events more than clopidogrel, at the expense of an increase in bleeding. Additional agents that target platelets by alternate mechanisms, including the protease-activated receptor-1 antagonist vorapaxar, have shown ischaemic benefit. These large-scale trials inform treatment decisions that need to balance ischaemic benefit and bleeding risk in patients with acute coronary syndromes. This Series paper describes major trial results, implications for clinical practice, and summarises continuing controversy. © 2015 Elsevier Ltd.


Venet F.,Immunology Laboratory | Lukaszewicz A.-C.,University Paris Diderot | Payen D.,University Paris Diderot | Hotchkiss R.,University of Washington | Monneret G.,Immunology Laboratory
Current Opinion in Immunology | Year: 2013

Preliminary studies suggest that a subgroup of septic patients with severe immune alterations is at high risk of death or nosocomial infection and therefore could benefit from adjunctive immune stimulating therapies. There is thus an urgent need for robust biomarkers usable in routine conditions evaluating rapidly evolving immune status in patients. Although functional testing remains a gold standard, its standardization remains challenging. Therefore, surrogate markers such as monocyte HLA-DR expression, are being developed. Such biomarkers of immune functionality will enable a novel approach in the design of clinical trials evaluating immunostimulating therapies in sepsis at the right time and in the right patient. © 2013 Elsevier Ltd.


Loirat C.,University Paris Diderot | Fremeaux-Bacchi V.,Assistance Publique Hopitaux de Paris
Orphanet Journal of Rare Diseases | Year: 2011

Hemolytic uremic syndrome (HUS) is defined by the triad of mechanical hemolytic anemia, thrombocytopenia and renal impairment. Atypical HUS (aHUS) defines non Shiga-toxin-HUS and even if some authors include secondary aHUS due to Streptococcus pneumoniae or other causes, aHUS designates a primary disease due to a disorder in complement alternative pathway regulation. Atypical HUS represents 5 -10% of HUS in children, but the majority of HUS in adults. The incidence of complement-aHUS is not known precisely. However, more than 1000 aHUS patients investigated for complement abnormalities have been reported. Onset is from the neonatal period to the adult age. Most patients present with hemolytic anemia, thrombocytopenia and renal failure and 20% have extra renal manifestations. Two to 10% die and one third progress to end-stage renal failure at first episode. Half of patients have relapses. Mutations in the genes encoding complement regulatory proteins factor H, membrane cofactor protein (MCP), factor I or thrombomodulin have been demonstrated in 20-30%, 5-15%, 4-10% and 3-5% of patients respectively, and mutations in the genes of C3 convertase proteins, C3 and factor B, in 2-10% and 1-4%. In addition, 6-10% of patients have anti-factor H antibodies. Diagnosis of aHUS relies on 1) No associated disease 2) No criteria for Shigatoxin-HUS (stool culture and PCR for Shiga-toxins; serology for anti-lipopolysaccharides antibodies) 3) No criteria for thrombotic thrombocytopenic purpura (serum ADAMTS 13 activity > 10%). Investigation of the complement system is required (C3, C4, factor H and factor I plasma concentration, MCP expression on leukocytes and anti-factor H antibodies; genetic screening to identify risk factors). The disease is familial in approximately 20% of pedigrees, with an autosomal recessive or dominant mode of transmission. As penetrance of the disease is 50%, genetic counseling is difficult. Plasmatherapy has been first line treatment until presently, without unquestionable demonstration of efficiency. There is a high risk of post-transplant recurrence, except in MCP-HUS. Case reports and two phase II trials show an impressive efficacy of the complement C5 blocker eculizumab, suggesting it will be the next standard of care. Except for patients treated by intensive plasmatherapy or eculizumab, the worst prognosis is in factor H-HUS, as mortality can reach 20% and 50% of survivors do not recover renal function. Half of factor I-HUS progress to end-stage renal failure. Conversely, most patients with MCP-HUS have preserved renal function. Anti-factor H antibodies-HUS has favourable outcome if treated early. © 2011Loirat and Frémeaux-Bacchi; licensee BioMed Central Ltd.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: GC.NMP.2010-1 | Award Amount: 4.94M | Year: 2011

For vehicle applications, it is desirable to have devices with high energy density, high power density, long cycle and shelf life, and low cost. Supercapacitors are considered one of the newest innovations in the field of electrical energy storage. In hybrid electric vehicle, supercapacitors can be coupled with fuel cells or batteries to deliver the high power needed during acceleration as well as to recover the available energy during regenerative braking. To design a supercapacitor for a specific application that requires high energy density or high power density or both, proper electrode materials and a suitable electrolyte are to be chosen. The combination of graphene and graphene-based material as electrode materials, and the use of room temperature ionic liquids (RTILs) may exhibit excellent performance in supercapacitors. Graphene based materials can be obtained by a bottom-up approach in a more controllable fashion. The enhanced capacitive behaviour of this material may be obtained by the proper alignment of graphene sheets as well as the interconnected nanoscale channels. However, these studies are still at the primary stage, and further studies are necessary. The ElectroGraph project follows a technology driven approach. It is thus obvious that the development of both electrode materials as well as the electrolyte solutions is required in order to optimize the overall performance of the supercapacitor. The main novelty of the technical development is the optimised production of graphene with its properties specifically defined and adjusted for application as electrode material in energy storage devices. This would be achieved through defining of processing parameters to tailor-made graphene with a specific surface area, size and corresponding electrical properties is a new consideration. The ElectroGraph will use an integrated approach in development of both electrode materials as well as the electrolyte solutions as required for optimising the overall performance of supercapacitors.


Fischer A.,German Cancer Research Center | Zalvide J.,University of Santiago de Compostela | Faurobert E.,Joseph Fourier University | Albiges-Rizo C.,Joseph Fourier University | And 2 more authors.
Trends in Molecular Medicine | Year: 2013

Cerebral cavernous malformations (CCMs) are vascular lesions that can occur sporadically or as a consequence of inherited loss-of-function mutations, predominantly in the genes CCM1 (KRIT1), CCM2 (MGC4607, OSM, Malcavernin), or CCM3 (PDCD10, TFAR15). Inherited, familial CCM is characterized by the development of multiple lesions throughout a patient's life leading to recurrent cerebral hemorrhages. Recently, roles for the CCM proteins in maintaining vascular barrier functions and quiescence have been elucidated, and in this review we summarize the genetics and pathophysiology of this disease and discuss the molecular mechanisms through which CCM proteins may act within blood vessels. © 2013 Elsevier Ltd.


Patent
French Institute of Health, Medical Research, University Paris Diderot, University of Paris 13 and Assistance Publique Hopitaux De Paris | Date: 2013-06-19

The present invention provides peptides corresponding to fragments of CD31 that inhibit platelet and leukocyte activation, and to their use in the treatment of thrombotic disease. These peptides find use as therapeutic agents in the treatment of inflammatory diseases and thrombotic diseases such as atherothrombosis, in particular when immobilised onto solid supports.


Patent
French Institute of Health, Medical Research, University Paris Diderot, University of Versailles, University of Paris Descartes and Assistance Publique Hopitaux De Paris | Date: 2013-01-28

The present invention relates to a method for determining whether a patient with cirrhosis is at risk of having clinically significant portal hypertension comprising the steps consisting of i) quantifying the levels of leuko-endothelial (CD31+/41), pan-leukocyte (CD11a+), lymphocyte (CD4+), erythrocyte (CD235a+) and hepatocyte-derived (cytokeratin-18+) microparticles in a blood sample obtained from the patient and ii) comparing said levels with predetermined reference values wherein a difference between the levels quantified at step i) and the predetermined reference values is indicative whether the patient is at risk of having clinically significant portal hypertension.


Patent
French Institute of Health, Medical Research, Pharmaleads, Assistance Publique Hopitaux De Paris and University Paris Diderot | Date: 2016-01-20

The present invention is directed to the use of an irreversible ligand of a serine protease selected from the group consisting of leukocyte elastase, thrombin, tissue plasminogen activator (t-PA) and plasmin for the molecular imaging of said serine protease and the diagnosis of pathophysiological conditions associated with said serine protease activity.


Patent
Institute Pasteur Paris, French Institute of Health, Medical Research, University Paris Diderot and Assistance Publique Hopitaux De Paris | Date: 2014-08-08

A massive clonal expansion of activated CD8^(+) T-cells with increased frequency of HPV 16-specific CD8^(+) T-cells was discovered to be a characteristic of oral lichen planus (OLP), indicating a causal link between HPV infection and the dysimmune process. The invention relates to compositions and methods for the diagnosis and treatment of OLP patients.


Patent
Institute Pasteur Paris, French Institute of Health, Medical Research, University Paris Diderot and Assistance Publique Hopitaux De Paris | Date: 2014-08-08

A massive clonal expansion of activated CD8^(+) T-cells with increased frequency of HPV 16-specific CD8^(+) T-cells was discovered to be a characteristic of oral lichen planus (OLP), indicating a causal link between HPV infection and the dysimmune process. The invention relates to compositions and methods for the diagnosis and treatment of OLP patients.


Hussain S.,University Paris Diderot | Vanoirbeek J.A.J.,Catholic University of Leuven | Hoet P.H.M.,National Health Research Institute
Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology | Year: 2012

Evaluation of the immunomodulatory potentials of nanomaterials is essential for developing safe and consumer-friendly nanotechnology. Various nanomaterials interact with the immune system, in a beneficial or deleterious way, but mechanistic details about such interactions are scarce. A lack of agreed-upon guidelines for evaluating the immunotoxicity of nanoparticles (NPs) adds to the complexity of the issue. Various review articles have summarized the immune system interactions of biodegradable NPs (with pharmaceutical uses), but such information is largely lacking for nonbiodegradable NPs. Here we give an overview of interactions of nonbiodegradable, persistent NPs with the immune system. Particular emphases include key factors that shape such interactions, cell-specific responses, allergy and immune-sensitive respiratory disorders. © 2011 Wiley Periodicals, Inc.


Lehnert M.D.,CNRS Paris Institute of Astrophysics | Di Matteo P.,University Paris Diderot | Haywood M.,University Paris Diderot | Snaith O.N.,University of Alabama
Astrophysical Journal Letters | Year: 2014

We compare the star formation history and dynamics of the Milky Way (MW) with the properties of distant disk galaxies. During the first 4 Gyr of its evolution, the MW formed stars with a high star formation intensity (SFI), ΣSFR 0.6 M yr-1 kpc-2 and as a result, generated outflows and high turbulence in its interstellar medium (ISM). This intense phase of star formation corresponds to the formation of the thick disk. The formation of the thick disk is a crucial phase that enables the MW to have formed approximately half of its total stellar mass by z 1 which is similar to "MW progenitor galaxies" selected by abundance matching. This agreement suggests that the formation of the thick disk may be a generic evolutionary phase in disk galaxies. Using a simple energy injection-kinetic energy relationship between the one-dimensional velocity dispersion and SFI, we can reproduce the average perpendicular dispersion in stellar velocities of the MW with age. This relationship, its inferred evolution, and required efficiency are consistent with observations of galaxies from z 0-3. The high turbulence generated by intense star formation naturally resulted in a thick disk, a chemically well-mixed ISM, and is the mechanism that links the evolution of MW to the observed characteristics of distant disk galaxies. © 2014. The American Astronomical Society. All rights reserved..


Chevalier M.F.,Institute Pasteur Paris | Chevalier M.F.,University Paris Diderot | Weiss L.,Institute Pasteur Paris | Weiss L.,University of Paris Descartes
Blood | Year: 2013

Natural regulatory T cells (Tregs) participate in responses to various chronic infections including HIV. HIV infection is associated with a progressive CD4 lymphopenia and defective HIV-specific CD8 responses known to play a key role in the control of viral replication. Persistent immune activation is a hallmark of HIV infection and is involved in disease progression independent of viral load. The consequences of Treg expansion, observed in HIV infection, could be either beneficial, by suppressing generalized T-cell activation, or detrimental, by weakening HIV-specific responses and thus contributing to viral persistence. The resulting balance between Tregs contrasting outcomes might have critical implications in pathogenesis. Topics covered in this review include HIV-induced alterations of Tregs, Treg cell dynamics in blood and tissues, Treg-suppressive function, and the relationship between Tregs and immune activation. This review also provides a focus on the role of CD39+ Tregs and other regulatory cell subsets. All these issues will be explored in different situations including acute and chronic infection, antiretroviral treatment-mediated viral control, and spontaneous viral control. Results must be interpreted with regard to both the Treg definition used in context and to the setting of the disease in an attempt to draw clearer conclusions from the apparently conflicting results. © 2013 by The American Society of Hematology.


Antunes A.,Institute Pasteur Paris | Martin-Verstraete I.,Institute Pasteur Paris | Martin-Verstraete I.,University Paris Diderot | Dupuy B.,Institute Pasteur Paris
Molecular Microbiology | Year: 2011

The presence of glucose or other rapidly metabolizable carbon sources in the bacterial growth medium strongly represses Clostridium difficile toxin synthesis independently of strain origin. In Gram-positive bacteria, carbon catabolite repression (CCR) is generally regarded as a regulatory mechanism that responds to carbohydrate availability. In the C. difficile genome all elements involved in CCR are present. To elucidate in vivo the role of CCR in C. difficile toxin synthesis, we used the ClosTron gene knockout system to construct mutants of strain JIR8094 that were unable to produce the major components of the CCR signal transduction pathway: the phosphotransferase system (PTS) proteins (Enzyme I and HPr), the HPr kinase/phosphorylase (HprK/P) and the catabolite control protein A, CcpA. Inactivation of the ptsI, ptsH and ccpA genes resulted in derepression of toxin gene expression in the presence of glucose, whereas repression of toxin production was still observed in the hprK mutant, indicating that uptake of glucose is required for repression but that phosphorylation of HPr by HprK is not. C. difficile CcpA was found to bind to the regulatory regions of the tcdA and tcdB genes but not through a consensus cre site motif. Moreover in vivo and in vitro results confirmed that HPr-Ser45-P does not stimulate CcpA-dependent binding to DNA targets. However, fructose-1,6-biphosphate (FBP) alone did increase CcpA binding affinity in the absence of HPr-Ser45-P. These results showed that CcpA represses toxin expression in response to PTS sugar availability, thus linking carbon source utilization to virulence gene expression in C. difficile. © 2010 Blackwell Publishing Ltd.


Toro R.,Institute Pasteur Paris | Toro R.,University Paris Diderot
Evolutionary Biology | Year: 2012

The human brain is unique among primates in its complexity and variability. Here I argue that this variability is, however, strongly constrained by developmental processes common to all mammals. Comparative analyses of grey and white matter volume, cortical surface area and cortical folding show that the rostro-caudal axis of the central nervous system is a main direction along which mammalian neuroanatomical diversity is organised. Phylogenetically, rostral structures are often disproportionately larger and more differentiated in large mammals compared with small ones. Ontogenetically, caudal structures differentiate earlier but show less variation among species than rostral structures, which differentiate later and for a longer period. Theoretical considerations suggest that growth oriented along the rostro-caudal axis should produce non-linear differences in white matter volume and cortical folding. Growth appears then as a fundamental parameter to understand mammalian neuroanatomical variability, whose effects should be common to all species. This seems to be indeed the case for humans: the volume of different brain structures as well as changes in the extension and folding of the cerebral cortex resemble the trends observed across mammals. A strong global pattern of coordinated variability emerges, where differences in total brain volume are non-linearly related to local neuroanatomical changes. Finally, I review evidence suggesting that the changes related to this global pattern of variability may have an influence on the organisation of behaviour, modulating the development of certain cognitive traits or even affecting the susceptibility to psychiatric disorders. © 2012 Springer Science+Business Media New York.


Moreau H.D.,Institute Pasteur Paris | Moreau H.D.,French Institute of Health and Medical Research | Moreau H.D.,University Paris Diderot | Bousso P.,Institute Pasteur Paris | Bousso P.,French Institute of Health and Medical Research
Current Opinion in Immunology | Year: 2014

A decade ago the first movies depicting T cell behavior in vivo with the help of two-photon microscopy were generated. These initial experiments revealed that T cells migrate rapidly and randomly in secondary lymphoid organs at steady state and profoundly alter their behavior during antigen recognition, establishing both transient and stable contacts with antigen-presenting cells (APCs). Since then, in vivo imaging has continuously improved our understanding of T cell activation. In particular, recent studies uncovered how T cells may be guided in their search for the best APCs. Additionally, the development of more sophisticated fluorescent tools has permitted not only to visualize T cell-APC contacts but also to probe their functional impact on T cell activation. These recent progresses are providing new insights into how T cells sense antigen, collect activation signals during distinct types of interaction and integrate information over successive encounters. © 2013 Elsevier Ltd.


Solon A.P.,University Paris Diderot | Fily Y.,Brandeis University | Baskaran A.,Brandeis University | Cates M.E.,University of Edinburgh | And 3 more authors.
Nature Physics | Year: 2015

Pressure is the mechanical force per unit area that a confined system exerts on its container. In thermal equilibrium, it depends only on bulk properties - such as density and temperature - through an equation of state. Here we show that in a wide class of active systems the pressure depends on the precise interactions between the active particles and the confining walls. In general, therefore, active fluids have no equation of state. Their mechanical pressure exhibits anomalous properties that defy the familiar thermodynamic reasoning that holds in equilibrium. The pressure remains a function of state, however, in some specific and well-studied active models that tacitly restrict the character of the particle-wall and/or particle-particle interactions. © 2015 Macmillan Publishers Limited.


Sorbadere F.,CNRS Magmas and Volcanoes Laboratory | Schiano P.,CNRS Magmas and Volcanoes Laboratory | Metrich N.,University Paris Diderot
Journal of Petrology | Year: 2013

Here we address the question of the origin of rare nepheline-normative arc magmas through a systematic study of major, minor and trace elements in primitive olivine-hosted melt inclusions, together with literature data. The host-rocks of the inclusions are Mg-rich basalts to ankaramite lavas and scoria from several intra-oceanic volcanic arcs (Vanuatu, Lesser Antilles, Indonesian, Luzon and Aeolian arcs). The studied melt inclusions display trace element patterns typical of subduction-related calc-alkaline basalts, with variable enrichments in large ion lithophile elements and Sc (20-91 ppm), and La/Yb and Nb/Y ratios ranging from 1 to 18 and from 0·1 to 0·3, respectively. In CMAS projections, the melt inclusions delineate a trend linking two well-defined end-members, which are strongly and weakly enriched in the diopside component, respectively. The melt inclusions provide snapshots of the compositions of instantaneous melts, recording compositional diversity in the primitive magma batches, which requires mixing between melts generated by partial melting of peridotite and amphibole-bearing clinopyroxene-rich lithologies, possibly at a pressure of ~1 GPa and between 1200 and 1300°C. This hypothesis is supported by trace element modeling, and particularly by the correlation of Sc with incompatible element ratios. We propose that amphibole-bearing clinopyroxenites, occurring as cumulates at the base of the crust and/or as metasomatic veins in the upper mantle of island arcs, represent a suitable source for the Ne-normative melt inclusions variably enriched in CaO, observed in arc environments. © The Author 2012. Published by Oxford University Press. All rights reserved.


Raynaud-Simon A.,University Paris Diderot | Revel-Delhom C.,Haute Autorite de Sante | Hebuterne X.,University of Nice Sophia Antipolis
Clinical Nutrition | Year: 2011

These guidelines were produced at the request of the General Directorate of Health within the scope of the French Nutrition and Health Program (PNNS). They concern the management of malnutrition in elderly persons living at home, in institutional care, or in hospital. They belong to a recent series of studies published by ANAES. 11ANAES: French National Agency for Accreditation and Evaluation in Healthcare, merged into HAS in 2005. or HAS. Preceding studies concerned the "Diagnostic assessment of protein-energy malnutrition in hospitalized adults" (ANAES, September 2003) and the work conducted by the Committee for the Assessment of Devices and Health Technologies (CEPP) on "Reimbursement procedures for dietary foods for special medical purposes for nutritional supplementation and home enteral nutrition" (HAS, September 2006).The objective of these guidelines is to develop a tool for identifying and managing elderly subjects who are malnourished or at risk of malnutrition. © 2010.


Wioland H.,University of Cambridge | Wioland H.,University Paris Diderot | Woodhouse F.G.,University of Cambridge | Woodhouse F.G.,University of Western Australia | And 2 more authors.
Nature Physics | Year: 2016

Despite their inherently non-equilibrium nature, living systems can self-organize in highly ordered collective states that share striking similarities with the thermodynamic equilibrium phases of conventional condensed-matter and fluid systems. Examples range from the liquid-crystal-like arrangements of bacterial colonies, microbial suspensions and tissues to the coherent macro-scale dynamics in schools of fish and flocks of birds. Yet, the generic mathematical principles that govern the emergence of structure in such artificial and biological systems are elusive. It is not clear when, or even whether, well-established theoretical concepts describing universal thermostatistics of equilibrium systems can capture and classify ordered states of living matter. Here, we connect these two previously disparate regimes: through microfluidic experiments and mathematical modelling, we demonstrate that lattices of hydrodynamically coupled bacterial vortices can spontaneously organize into distinct patterns characterized by ferro- and antiferromagnetic order. The coupling between adjacent vortices can be controlled by tuning the inter-cavity gap widths. The emergence of opposing order regimes is tightly linked to the existence of geometry-induced edge currents, reminiscent of those in quantum systems. Our experimental observations can be rationalized in terms of a generic lattice field theory, suggesting that bacterial spin networks belong to the same universality class as a wide range of equilibrium systems. © 2015 Macmillan Publishers Limited. All rights reserved.


Wandersman C.,Institute Pasteur Paris | Delepelaire P.,University Paris Diderot
Molecular Microbiology | Year: 2012

Haem is the major iron source for bacteria that develop in higher organisms. In these hosts, bacteria have to cope with nutritional immunity imposed by the host, since haem and iron are tightly bound to carrier and storage proteins. Siderophores were the first recognized fighters in the battle for iron between bacteria and host. They are non-proteinaceus organic molecules having an extremely high affinity for Fe3+ and able to extract it from host proteins. Haemophores, that display functional analogy with siderophores, were more recently discovered. They are a class of secreted proteins with a high affinity for haem; they are able to extract haem from host haemoproteins and deliver it to specific receptors that internalize haem. In the past few years, a wealth of data has accumulated on haem acquisition systems that are dependent on surface exposed/secreted bacterial proteins. They promote haem transfer from its initial source (in most cases, a eukaryotic haem binding protein) to the transporter that carries out the membrane crossing step. Here we review recent discoveries in this field, with particular emphasis on similar and dissimilar mechanisms in haemophores and siderophores, from the initial host source to the binding protein/receptor at the cell surface. © 2012 Blackwell Publishing Ltd.


Solon A.P.,University Paris Diderot | Stenhammar J.,University of Edinburgh | Wittkowski R.,University of Edinburgh | Kardar M.,Massachusetts Institute of Technology | And 3 more authors.
Physical Review Letters | Year: 2015

We derive a microscopic expression for the mechanical pressure P in a system of spherical active Brownian particles at density ρ. Our exact result relates P, defined as the force per unit area on a bounding wall, to bulk correlation functions evaluated far away from the wall. It shows that (i) P(ρ) is a state function, independent of the particle-wall interaction; (ii) interactions contribute two terms to P, one encoding the slow-down that drives motility-induced phase separation, and the other a direct contribution well known for passive systems; and (iii) P is equal in coexisting phases. We discuss the consequences of these results for the motility-induced phase separation of active Brownian particles and show that the densities at coexistence do not satisfy a Maxwell construction on P. © 2015 American Physical Society.


Baaden M.,University Paris Diderot | Marrink S.J.,Zernike Institute for Advanced Materials
Current Opinion in Structural Biology | Year: 2013

Here, we review recent advances towards the modelling of protein-protein interactions (PPI) at the coarse-grained (CG) level, a technique that is now widely used to understand protein affinity, aggregation and self-assembly behaviour. PPI models of soluble proteins and membrane proteins are separately described, but we note the parallel development that is present in both research fields with three important themes: firstly, combining CG modelling with knowledge-based approaches to predict and refine protein-protein complexes; secondly, using physics-based CG models for de novo prediction of protein-protein complexes; and thirdly modelling of large scale protein aggregates. © 2013 Elsevier Ltd.


Huguet G.,Institute Pasteur Paris | Huguet G.,University Paris Diderot | Ey E.,Institute Pasteur Paris | Ey E.,University Paris Diderot | And 2 more authors.
Annual Review of Genomics and Human Genetics | Year: 2013

The autism spectrum disorders (ASD) are characterized by impairments in social interaction and stereotyped behaviors. For the majority of individuals with ASD, the causes of the disorder remain unknown; however, in up to 25% of cases, a genetic cause can be identified. Chromosomal rearrangements as well as rare and de novo copy-number variants are present in ∼10-20% of individuals with ASD, compared with 1-2% in the general population and/or unaffected siblings. Rare and de novo coding-sequence mutations affecting neuronal genes have also been identified in ∼5-10% of individuals with ASD. Common variants such as single-nucleotide polymorphisms seem to contribute to ASD susceptibility, but, taken individually, their effects appear to be small. Despite a heterogeneous genetic landscape, the genes implicated thus far-which are involved in chromatin remodeling, metabolism, mRNA translation, and synaptic function-seem to converge in common pathways affecting neuronal and synaptic homeostasis. Animal models developed to study these genes should lead to a better understanding of the diversity of the genetic landscapes of ASD. Copyright © 2013 by Annual Reviews. All rights reserved.


Gazeau J.P.,University Paris Diderot | Szafraniec F.H.,University Jagielloski
Journal of Physics A: Mathematical and Theoretical | Year: 2011

One more coherent state quantization of a complex plane is presented. Although the complex plane is equipped with a non-rotationally invariant measure, we still obtain a canonical commutation rule (up to a simple rescaling). We explain how the involved coherent states, built from holomorphic continuations of Hermite polynomials, are related to the non-commutative plane. © 2011 IOP Publishing Ltd.


Patent
French Institute of Health, Medical Research, University of Bordeaux Segalen and University Paris Diderot | Date: 2015-06-02

The present invention relate to three dimensional porous polysaccharide matrices able to induce mineralisation of a tissue in osseous site, as well as in non-osseous site, in the absence of stent cells or growth factors.


Marie P.J.,University Paris Diderot | Marie P.J.,Paris West University Nanterre La Défense
Nature Reviews Endocrinology | Year: 2013

The ageing skeleton experiences a progressive decline in the rate of bone formation, which can eventually result in osteoporosis - a common disease characterized by reduced bone mass and altered bone microarchitecture which can result in fractures. One emerging therapy involves the identification of molecules that target bone-marrow mesenchymal stromal cells (MSCs) and promote their differentiation into osteoblasts, thereby counteracting bone loss. This Review highlights the discovery that some integrins, a family of heterodimeric transmembrane proteins that can interact with matrix proteins and generate intracellular signals, can be targeted to promote homing of MSCs to bone, osteogenic differentiation and bone formation. Specifically, priming of the α 5 β 1 integrin, which is required for osteoblastic differentiation of MSCs, leads to increased bone formation and improved bone repair in mice. Additionally, treatment with a peptidomimetic ligand of the α 4 β 1 integrin coupled to an agent with a high affinity for bone improves the homing of MSCs to bone and promotes osteoblast differentiation and bone formation, leading to increased bone mass in osteopenic mice. Strategies that target key integrins expressed by MSCs might, therefore, translate into improved therapies for age-related bone loss and possibly other disorders.© 2013 Macmillan Publishers Limited. All rights reserved.


Soyer P.,Hopital Lariboisiere APHP 2 | Soyer P.,University Paris Diderot
European Radiology | Year: 2012

A paper reports the results of a retrospective study that was designed to evaluate the potential role of video capsule endoscopy (VCE) in elucidating the cause of bleeding in patients with obscure gastrointestinal bleeding (OGIB) for whom CT enterography was negative. The authors highlight the limitations of dual-phase CT enterography for the detection of flat lesions of the small bowel such as ulcers, angiodysplasias or arteriovenous malformations, and confirm the superiority of VCE for the detection of this category of lesions. This commentary discusses some of the issues raised. Key Points • Video capsule endoscopy surpasses CT enterography in detecting flat small bowel lesions. • Retrospective VCE and CTenterography findings in obscure bleeding need further evaluation. • A fair and unbiased comparison of the two investigations is still needed. © European Society of Radiology 2012.


Marie P.J.,Paris West University Nanterre La Défense | Marie P.J.,University Paris Diderot
Cellular and Molecular Life Sciences | Year: 2015

Several metabolic, genetic and oncogenic bone diseases are characterized by defective or excessive bone formation. These abnormalities are caused by dysfunctions in the commitment, differentiation or survival of cells of the osteoblast lineage. During the recent years, significant advances have been made in our understanding of the cellular and molecular mechanisms underlying the osteoblast dysfunctions in osteoporosis, skeletal dysplasias and primary bone tumors. This led to suggest novel therapeutic approaches to correct these abnormalities such as the modulation of WNT signaling, the pharmacological modulation of proteasome-mediated protein degradation, the induction of osteoprogenitor cell differentiation, the repression of cancer cell proliferation and the manipulation of epigenetic mechanisms. This article reviews our current understanding of the major cellular and molecular mechanisms inducing osteoblastic cell abnormalities in age-related bone loss, genetic skeletal dysplasias and primary bone tumors, and discusses emerging therapeutic strategies to counteract the osteoblast abnormalities in these disorders of bone formation. © 2014 Springer.


Livermore P.W.,University of Leeds | Fournier A.,University Paris Diderot | Gallet Y.,University Paris Diderot
Earth and Planetary Science Letters | Year: 2014

Recent studies (Ben-Yosef et al., 2009; Shaar et al., 2011) propose extreme archeomagnetic intensity changes (termed spikes) in the range ~4-5μT/year c.a. 1000 BC in the Near East, around 40 to 50 times larger than values typical of the present-day. In order to investigate whether such extreme changes are consistent with a model of the source region of the magnetic field, namely the fluid flow at the surface of Earth's core, we construct upper bounds for instantaneous magnetic intensity change at an arbitrary site on the Earth's surface. These bounds are constrained by the amount of kinetic energy available to sustain the change, taken here to be a prescribed value for the root-mean-squared surface velocity of 13 km/yr as inferred from the current state of the core. Further, we focus attention on two end-members of optimised core surface flow structure: unrestricted and purely-toroidal. As the derivation of the bounds demands complete knowledge of the geomagnetic field at the core surface, we model the unknown field by means of a Monte Carlo approach, extending to high degree the CHAOS-4 (epoch 2010 AD) and CALS10k1.b (epoch 1000 BC) geomagnetic field models.Using 2000 realisations for each family of stochastic field models, we find that optimised core flows are always large-scale and that they tend to generate a non-dipole, quadrupole-dominated secular variation at the Earth's surface. The dependence of the upper bounds as a function of site location reflects the large-scale structure of the intensity itself: stronger field permits more rapid change. For the site in the Near East, purely-toroidal flows have upper bounds of approximately 0.62 ± 0.02μT/year, whereas unrestricted flows increase this bound to 1.20 ± 0.02μT/year. We favour the former as more geophysically sound, on the account of a large body of previous results from core surface flow inversions and consistency with the existence of a stratified layer at the top of the core. Even if we allow for a generous threefold increase in the prescribed rms velocity (and a concomitant threefold increase in the bound), we conclude that the reported occurrences of extreme intensity changes as suggested in the Near East are not compatible with the commonly accepted structure of core-surface flow. However, it may be that an explanation for spikes lies beyond our current perception of core-dynamics and future work would be further motivated by seeking corroborative evidence of rapid intensity change from sites elsewhere on Earth's surface; we therefore also discuss the form that the secular variation would take in the case of simultanenous archeomagnetic spikes. © 2013 The Authors.


Richette P.,University Paris Diderot | Clerson P.,Orgametrie Biostatistiques | Perissin L.,Menarini | Flipo R.-M.,Lille 2 University of Health and Law | Bardin T.,University Paris Diderot
Annals of the Rheumatic Diseases | Year: 2015

Objectives: The reciprocal links between comorbidities and gout are complex. We used cluster analysis to attempt to identify different phenotypes on the basis of comorbidities in a large cohort of patients with gout.Methods: This was a cross-sectional multicentre study of 2763 gout patients conducted from November 2010 to May 2011. Cluster analysis was conducted separately for variables and for observations in patients, measuring proximity between variables and identifying homogeneous subgroups of patients. Variables used in both analyses were hypertension, obesity, diabetes, dyslipidaemia, heart failure, coronary heart disease, renal failure, liver disorders and cancer.Results: Comorbidities were common in this large cohort of patients with gout. Abdominal obesity, hypertension, metabolic syndrome and dyslipidaemia increased with gout duration, even after adjustment for age and sex. Five clusters (C1-C5) were found. Cluster C1 (n=332, 12%) consisted of patients with isolated gout and few comorbidities. In C2 (n=483, 17%), all patients were obese, with a high prevalence of hypertension. C3 (n=664, 24%) had the greatest proportion of patients with type 2 diabetes (75%). In C4 (n=782, 28%), almost all patients presented with dyslipidaemia (98%). Finally, C5 (n=502, 18%) consisted of almost all patients with a history of cardiovascular disease and renal failure, with a high rate of patients receiving diuretics.Conclusions: Cluster analysis of comorbidities in gout allowed us to identify five different clinical phenotypes, which may reflect different pathophysiological processes in gout.


Charousset C.,Institute Osteo Articulaire Paris Courcelles | Zaoui A.,University Paris Diderot | Bellaiche L.,Center dImage Medicale Bachaumont | Piterman M.,Aix - Marseille University
Arthroscopy - Journal of Arthroscopic and Related Surgery | Year: 2014

Purpose To evaluate the clinical and magnetic resonance imaging (MRI) outcome of arthroscopic rotator cuff repair with the use of leukocyte-platelet- rich plasma (L-PRP) in patients with large or massive rotator cuff tears. Methods A comparative cohort of patients with large or massive rotator cuff tears undergoing arthroscopic repair was studied. Two consecutive groups of patients were included: rotator cuff repairs with L-PRP injection (group 1, n = 35) and rotator cuff repairs without L-PRP injection (group 2, n = 35). A double-row cross-suture cuff repair was performed by a single surgeon with the same rehabilitation protocol. Patients were clinically evaluated with the Constant score; Simple Shoulder Test score; University of California, Los Angeles (UCLA) score; and strength measurements by use of a handheld dynamometer. Rotator cuff healing was evaluated by postoperative MRI using the Sugaya classification (type 1 to type 5). Results We prospectively evaluated the 2 groups at a minimum 2-year follow-up. The results did not show differences in cuff healing between the 2 groups (P =.16). The size of recurrent tears (type 4 v type 5), however, was significantly smaller in group 1 (P =.008). There was no statistically significant difference in the recurrent tear rate (types 4 and 5) between the 2 groups (P =.65). There was no significant difference between group 1 and group 2 in terms of University of California, Los Angeles score (29.1 and 30.3, respectively; P =.90); Simple Shoulder Test score (9.9 and 10.2, respectively; P =.94); Constant score (77.3 and 78.1, respectively; P =.82); and strength (7.5 and 7.0, respectively; P =.51). Conclusions In our study the use of autologous L-PRP did not improve the quality of tendon healing in patients undergoing arthroscopic repair of large or massive rotator cuff tears based on postoperative MRI evaluation. The only significant advantage was that the L-PRP patients had smaller iterative tears. However, the functional outcome was similar in the 2 groups of patients. Level of Evidence Level III, case-control study. © 2014 The Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.


Aim: To demonstrate non-inferiority of vildagliptin compared with gliclazide, as an add-on therapy, in patients with Type 2 diabetes inadequately controlled with metformin in a 52-week, randomized, double-blind, active-controlled study. Methods: Patients receiving a stable dose of metformin (≥ 1500 mg) were randomized (1 : 1) to receive vildagliptin (50 mg twice daily; n = 513) or gliclazide (up to 320 mg/day; n = 494). Results: Non-inferiority of vildagliptin was demonstrated (95% confidence interval -0.11%, 0.20%) with a mean change (se) from baseline glycated haemoglobin (HbA1c) (∼ 8.5% in both groups) to a 52-week endpoint of -0.81% (0.06) with vildagliptin and -0.85% (0.06) with gliclazide. Although a similar proportion of patients reached HbA1c < 7.0%, the total number of hypoglycaemic events was lower in the vildagliptin group (6 vs. 11 events). Vildagliptin was non-inferior (margin 0.6 mmol/l) to gliclazide in reducing fasting plasma glucose (1.31 vs. 1.52 mmol/l, P = 0.257). The overall incidence of any adverse events was similar in both groups (∼ 61%), but the number of serious adverse events was higher in the gliclazide group (8.7 vs. 6.7%). The number of patients who discontinued as a result of an unsatisfactory effect was higher in the vildagliptin group (n = 22 vs. 13, respectively) compared with gliclazide, but vildagliptin did not induce weight gain. Conclusion: In patients with Type 2 diabetes inadequately controlled with metformin, addition of vildagliptin provided similar HbA1c-lowering efficacy compared with gliclazide after 52 weeks of treatment. Although both treatments were well tolerated, vildagliptin-treated patients had fewer hypoglycaemic events and did not gain weight. © 2010 The Authors.AuthorsConclusions:In conclusion, in patients with Type 2 diabetes inadequately controlled with metformin monotherapy, the addition of vildagliptin provides similar HbA1c-lowering efficacy after 52 weeks of treatment compared with the addition of a sulphonylurea over a wide range of HbA1c levels. However, the relative benefit of vildagliptin compared with SUs [sulphonylureas] seems to be higher in patients with HbA1c <8.0%. This finding has important clinical implications in helping to identify those patients who might obtain the most benefit with vildagliptin treatment.AdverseEffects:32 (6.3%) patients had nasopharyngitis, 29 (5.7) hypertension, 26 (5.1) diarrhea, 16 (3.1) headache, 14 (2.7) pain in extremity, 11 (2.2) asthenia, 10 (2.0) bronchitis, 10 (2.0) fatigue, 9 (1.8) tremor, 7 (1.4) hyperhidrosis, 3 (0.6) gastrointestinal adverse events, 6 hypoglycemic events. 33 (6.7) patients had side effects leading to withdrawal.FreeText:Primary efficacy measure: change in glycated hemoglobin (HbA1c by ion exchange high performance liquid chromatography) from baseline to week 52. Secondary efficacy measures: proportion of patients achieving HbA1c targets of <7.0% and ≤6.5%, changes in fasting plasma glucose (FPG), body weight, B-cell function [fasting proinsulin, fasting proinsulin/insulin ratio, homeostasis model assessments B-cell function (HOMA-B)] and insulin resistance (IR; fasting insulin, HOMA-IR). Safety measures: monitoring and recording all adverse events (AEs) and serious adverse events, and regular assessments of vital signs, electrocardiography, physical condition and body weight. Concomitant drug: metformin ≥1500 mg.Patients:1007 outpatients, 524 males and 483 females; mean age 59.5 years (390 were ≥65 years); 84 Asian, 9 black, 788 Caucasian, 117 Hispanic or Latino, and 9 other. Galvus group: n=513; 268 males and 245 females; mean age 59.2 years (184 were ≥65 years); 43 Asian, 3 black, 405 Caucasian, 58 Hispanic or Latino, and 4 other. Gliclazide group: n=494, 256 males and 238 females; mean age 59.7 years (206 were ≥65 years); 41 Asian, 6 black, 383 Caucasian, 59 Hispanic or Latino, and 5 other. Dropouts: n=188 of whom 106 Galvus group (33 due to adverse events) and 82 gliclazide group (22 due to adverse events).TypeofStudy:A multicenter, randomized, double blind study comparing the efficacy, safety, and tolerability of Galvus versus (vs.) gliclazide in combination with metformin in patients with type 2 diabetes inadequately controlled with metformin alone.DosageDuration:50 mg bid (=100 mg daily). Duration: 52 weeks.ComparativeDrug:Gliclazide initially 80 mg daily, increased to maximum 320 mg daily if fasting plasma glucose was >7.0 mmol/l or fasting blood glucose was >6.3 mmol/l based on the fasting finger-stick capillary glucose measurement. Duration: 52 weeks.Results:Galvus was non-inferior to gliclazide with a mean change from baseline HbA1c (about 8.5% in both groups) to 52-week endpoint of -0.81% with Galvus and -0.85% with gliclazide. The greatest mean change from baseline in HbA1c was noted at week 24 in both groups (Galvus: -1.01%; gliclazide: -1.19%) with a slight increase in HbA1c from week 24 to week 52. The proportion of patients achieving HbA1c targets of <7.0% was similar in both groups (gliclazide: 31.9, Galvus: 29.6%), but the percentage of patients achieving HbA1c ≤6.5% was higher in gliclazide group (21.1 vs. 15.4%). Galvus was non-inferior (margin 0.6 mmol/l) to gliclazide in reducing FPG (1.31 vs. 1.52 mmol/l). The difference of mean decrease in fasting proinsulin levels between the 2 groups was remarkable, with a slight decrease from baseline to endpoint in Galvus group (-5.98 pmol/l) and an increase in gliclazide group (2.03 pmol/l). The proinsulin/insulin ratio reduced in both groups (Galvus: -0.11 and gliclazide: -0.03). A small decrease in mean fasting insulin from baseline to endpoint was noted in the Galvus group (-2.08 pmol/l), while a relatively large increase was noted in the gliclazide group (+10.2 pmol/l). Mean HOMA-IR reduced in both groups, with larger changes in the Galvus group than the gliclazide group (-0.67 vs. -0.11). Hypoglycemic events were lower in Galvus group (6 vs. 11). The overall incidence of AEs was similar in Galvus (61.8%) and gliclazide group (61.3%). The number of patients who discontinued as a result of an unsatisfactory effect was higher in Galvus (22 vs. 13), but Galvus did not induce weight gain. The proportion of patients with remarkable AEs was lower in the Galvus group (n=7 vs. 12). 3 in Galvus and 4 gliclazide had gastrointestinal AEs. Drug-related AEs and SAEs were higher in gliclazide than in the Galvus group (16.4 vs. 11.8% and 8.7 vs. 6.7%, respectively) but discontinuation because of AEs was slightly higher in the Galvus (6.7 vs. 4.7%).Indications:513 patients with refractory type 2 diabetes. Coexisting diseases: obesity (276), renal insufficiency (165; mild 156, moderate 9).


Ornitz D.M.,University of Washington | Marie P.J.,Paris West University Nanterre La Défense | Marie P.J.,University Paris Diderot
Genes and Development | Year: 2015

Fibroblast growth factor (FGF) signaling pathways are essential regulators of vertebrate skeletal development. FGF signaling regulates development of the limb bud and formation of the mesenchymal condensation and has key roles in regulating chondrogenesis, osteogenesis, and bone and mineral homeostasis. This review updates our review on FGFs in skeletal development published in Genes & Development in 2002, examines progress made on understanding the functions of the FGF signaling pathway during critical stages of skeletogenesis, and explores the mechanisms by which mutations in FGF signaling molecules cause skeletal malformations in humans. Links between FGF signaling pathways and other interacting pathways that are critical for skeletal development and could be exploited to treat genetic diseases and repair bone are also explored. © 2015 Ornitz and Marie.


Boronska K.,University of Leeds | Tuckerman L.S.,University Paris Diderot
Physical Review E - Statistical, Nonlinear, and Soft Matter Physics | Year: 2010

A large number of flows with distinctive patterns have been observed in experiments and simulations of Rayleigh-Bénard convection in a water-filled cylinder whose radius is twice the height. We have adapted a time-dependent pseudospectral code, first, to carry out Newton's method and branch continuation and, second, to carry out the exponential power method and Arnoldi iteration to calculate leading eigenpairs and determine the stability of the steady states. The resulting bifurcation diagram represents a compromise between the tendency in the bulk toward parallel rolls and the requirement imposed by the boundary conditions that primary bifurcations be toward states whose azimuthal dependence is trigonometric. The diagram contains 17 branches of stable and unstable steady states. These can be classified geometrically as roll states containing two, three, and four rolls; axisymmetric patterns with one or two tori; threefold-symmetric patterns called Mercedes, Mitsubishi, marigold, and cloverleaf; trigonometric patterns called dipole and pizza; and less symmetric patterns called CO and asymmetric three rolls. The convective branches are connected to the conductive state and to each other by 16 primary and secondary pitchfork bifurcations and turning points. In order to better understand this complicated bifurcation diagram, we have partitioned it according to azimuthal symmetry. We have been able to determine the bifurcation-theoretic origin from the conductive state of all the branches observed at high Rayleigh number. © 2010 The American Physical Society.


Mahr A.,University Paris Diderot | Mahr A.,Paris West University Nanterre La Défense | De Menthon M.,University Paris Diderot
Current Opinion in Rheumatology | Year: 2015

Purpose of review The classification of diseases reveals the relationships between conditions that are linked in some way. Such classification has been a challenge for vasculitis because of the heterogeneous and protean nature of the illnesses. Classification criteria are critical to homogenize patient populations with vasculitis who are included in basic and clinical research studies. Recent findings The most recent advance in vasculitis classification has been the revised 2012 Chapel Hill Consensus Conference (CHCC) nomenclature of vasculitis that, although mainly focusing on nomenclature, also included classification elements. Whereas still maintaining the caliber of the predominantly involved vessels as the main categorization criterion for primary systemic vasculitis, the 2012 CHCC nomenclature introduced a new category - variable-vessel vasculitis - to include Behçet's disease and Cogan's syndrome in the vasculitis spectrum. Another important feature was the expansion of the classification to secondary vasculitis and single-organ vasculitis. Similarly, classification criteria for several vasculitis entities have been altered and new criteria published, namely for Behçet's disease and cryoglobulinemic vasculitis. Summary The classification of vasculitis continues to be amended to account for advances in the general understanding of the nature of vasculitis and our ability to diagnose them. The relevance of the prevailing classification system, relying on affected vessel size as the primary discriminator of vasculitis entities, is still questionable for clinical practice. Clinically sound, widely accepted classification criteria are available for most vasculitis entities, although some areas remain ill-defined: polyarteritis nodosa, microscopic polyangiitis and adult immunoglobulin A vasculitis (Henoch-Schönlein). © 2014 Wolters Kluwer Health Lippincott Williams & Wilkins.


Felix M.-A.,University Paris Diderot | Braendle C.,Institute of Developmental Biology and Cancer
Current Biology | Year: 2010

In the laboratory, the nematode Caenorhabditis elegans lives on the surface of nutrient agar in Petri dishes, feeding on a lawn of the uracil auxotroph strain OP50, an Escherichia coli mutant strain. This sentence sums up the fundamentals of C. elegans ecology, as most of us know it. While over 15,000 articles on diverse biological aspects of C. elegans attest to the worm's undisputable virtues as a major model organism, its biology in the wild remains mysterious. To properly interpret and fully understand the available wealth of genetic, molecular and other biological observations made in the laboratory, it will be important to know its natural history and to place the species in its ecological and evolutionary context. With the aim of connecting the discoveries that have been made about C. elegans biology to its 'real life', we shall discuss recent studies on the worm's natural habitat and population biology, and outline key issues in attaining a modern natural history of C. elegans. © 2010 Elsevier Ltd.


Groheux D.,Paris West University Nanterre La Défense | Groheux D.,University Paris Diderot | Espie M.,Paris West University Nanterre La Défense | Giacchetti S.,Paris West University Nanterre La Défense | And 2 more authors.
Radiology | Year: 2013

In this analysis, the role of metabolic imaging with fuorine 18 fuorodeoxyglucose (FDG) in breast cancer is reviewed. The analysis was limited to recent works by using state-ofthe-art positron emission tomography (PET)/computed tomography (CT) technology. The strengths and limitations of FDG PET/CT are examined in various clinical settings, and the following questions are answered: Is FDG PET/CT useful to differentiate malignant from benign breast lesions? Can FDG PET/CT replace sentinel node biopsy for axillary staging? What is the role of FDG PET/CT in initial staging of inflammatory or locally advanced breast cancer? What is the role of FDG PET/CT in initial staging of clinical stage IIA and IIB and primary operable stage IIIA breast cancer? How does FDG PET/CT compare with conventional techniques in the restaging of cancer in patients who are suspected of having disease recurrence? What is the role of FDG PET/CT in the assessment of early response to neoadjuvant therapy and of response to therapy for metastatic disease? Some recommendations for clinical practice are given. © RSNA, 2012.


Marie P.J.,Institute National Of La Sante Et Of La Recherche Medicale Unite 606 | Marie P.J.,University Paris Diderot | Kassem M.,University of Southern Denmark | Kassem M.,King Saud University
Journal of Clinical Endocrinology and Metabolism | Year: 2011

Context: Age-related bone loss is associated with progressive changes in bone remodeling characterized by decreased bone formation relative to bone resorption. Both trabecular and periosteal bone formation decline with age in both sexes, which contributes to bone fragility and increased risk of fractures. Studies in rodents and humans revealed that, independent of sex hormone deficiency, the age-related decline in bone formation is characterized by decreased osteoblast number and lifespan and reduced bone-forming capacity of individual osteoblasts. An important clinical question is to identify the mechanisms involved in the age-related defective bone formation. Evidence Acquisition: The mechanisms discussed in this review are based on a PubMed search and knowledge of the authors in the field. Evidence Synthesis: Available basic and clinical studies indicate that multiple mechanisms are involved in the alterations of osteoblastogenesis and the resulting decline in bone formation with aging. Notably, the age-related osteoblast dysfunctions and defective bone formation are caused by a number of extrinsic clinical factors that inhibit anabolic signaling pathways in bone. Thus, targeting these pathways can abolish age-related bone loss. Conclusions: The identification of extrinsic mechanisms involved in osteoblast dysfunctions associated with aging improves our knowledge of age-related bone loss and provides a basis for therapeutic intervention to improve bone formation and bone mass in the aging population. Copyright © 2011 by The Endocrine Society.


Farrell F.D.C.,University of Edinburgh | Marchetti M.C.,Syracuse Biomaterials Institute | Marenduzzo D.,University of Edinburgh | Tailleur J.,University Paris Diderot
Physical Review Letters | Year: 2012

We study the behavior of interacting self-propelled particles, whose self-propulsion speed decreases with their local density. By combining direct simulations of the microscopic model with an analysis of the hydrodynamic equations obtained by explicitly coarse graining the model, we show that interactions lead generically to the formation of a host of patterns, including moving clumps, active lanes, and asters. This general mechanism could explain many of the patterns seen in recent experiments and simulations. © 2012 American Physical Society.


Bohe A.,Paris West University Nanterre La Défense | Bohe A.,University Paris Diderot
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2011

We investigate the effect of a large number of kinks on the gravitational power radiated by cosmic string loops. We show that the total power radiated by a loop with N left-moving and right-moving kinks is proportional to N and increases with the typical kink angle. We then apply these results to loops containing junctions which give rise to a proliferation of the number of sharp kinks. We show that the time of gravitational decay of these loops is smaller than previously assumed. In light of this, we revisit the gravitational wave burst predictions from a network containing such loops. We find there is no parameter regime in which the rate of individual kink bursts is enhanced with respect to standard networks. By contrast, there remains a region of parameter space for which the kink-kink bursts dominate the stochastic background. Finally, we discuss the order of magnitude of the typical number of sharp kinks resulting from kink proliferation on loops with junctions. © 2011 American Physical Society.


Mlynarczyk C.,University Paris Diderot | Fahraeus R.,University Paris Diderot | Fahraeus R.,Masaryk Memorial Cancer Institute
Nature Communications | Year: 2014

Endoplasmic reticulum (ER) stress occurs in poorly perfused tissues and activates the p53 isoform p53/47 to promote G2 arrest via 14-3-3σ. This contrasts with the p21 CDKN1A -dependent G1 arrest caused by p53 following DNA damage. It is not known how cells respond to conditions when both pathways are activated. Here we show that p53/47 prevents p53-induced p21 transcription during ER stress and that both isoforms repress p21 mRNA translation. This prevents p21 from promoting COP1-mediated 14-3-3σ degradation and leads to G2 arrest. DNA damage does not result in p53-dependent induction of p21 during ER stress and instead results in an increase in p53-induced apoptosis. This illustrates how p53 isoforms target an intrinsic balance between the G1 and G2 checkpoints for cell cycle coordination and demonstrates an ER stress-dependent p53 pathway that suppresses p21 and lowers the apoptotic threshold to genotoxic drugs. © 2014 Macmillan Publishers Limited. All rights reserved.


Buck-Koehntop B.A.,University of Utah | Defossez P.-A.,University Paris Diderot
Epigenetics | Year: 2013

DNA methylation is an epigenetic mark that is essential for the development of mammals; it is frequently altered in diseases ranging from cancer to psychiatric disorders. The presence of DNA methylation attracts specialized methyl-DNA binding factors that can then recruit chromatin modifiers. These methyl-CpG binding proteins (MBPs) have key biological roles and can be classified into three structural families: methyl-CpG binding domain (MBD), zinc finger, and SET and RING fingerassociated (SRA) domain. The structures of MBD and SRA proteins bound to methylated DNA have been previously determined and shown to exhibit two very different modes of methylated DNA recognition. The last piece of the puzzle has been recently revealed by the structural resolution of two different zinc finger proteins, Kaiso and ZFP57, in complex with methylated DNA. These structures show that the two methyl- CpG binding zinc finger proteins adopt differential methyl-CpG binding modes. Nonetheless, there are similarities with the MBD proteins suggesting some commonalities in methyl-CpG recognition across the various MBP domains. These fresh insights have consequences for the analysis of the many other zinc finger proteins present i