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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.

Truffinet O.,University Paris Diderot
Journal of Pediatric Gastroenterology and Nutrition | Year: 2016

OBJECTIVES:: Tacrolimus is an immunosuppressive agent that has been proposed in the treatment of severe ulcerative colitis. This study examined the effectiveness and safety of tacrolimus in treating refractory Crohn Disease (CD) colitis in children. METHODS:: All children treated by oral tacrolimus for CD colitis at a tertiary pediatric center were included in the study. All patients were refractory to steroids and infliximab. Clinical response (decreased PCDAI >15 and PCDAI?

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.

This note presents a mechanistic explanation of the transition between the morphology of cephalochordates to that of amniotes. By a careful study of the morphogenetic movements which occur during the early stages of development of a typical amniote (a chicken embryo), we are able to show that the formation of a vertebrate body follows a sequence: first, formation of dorsal folds, then head and heart as dorsal and ventral folds, and finally another dorsal fold, which eventually builds up the chorion. This order has a physical origin linked to the velocity field of the tissue flow. These folds form at right angles to the flow direction, and the topology of the chordates flow is hyperbolic. This mechanism explains the differences between the successive bauplans, by the cumulate forward and backward movement of the flow. Eventually, the entire phenomenon can be described as a self-organized system of Russian dolls, by which the heart finds itself inside the embryo, and the embryo itself inside the chorion. In addition, the phenomenon has a mirror symmetry in the anterior and in the posterior part, thereby explaining naturally the existence of animals having a caudal heart. © 2010 Académie des sciences.

SALEZ J.,University Paris Diderot
Combinatorics Probability and Computing | Year: 2015

We consider large random graphs with prescribed degrees, as generated by the configuration model. In the regime where the empirical degree distribution approaches a limit μ with finite mean, we establish the systematic convergence of a broad class of graph parameters that includes the independence number, the maximum cut size, the logarithm of the Tutte polynomial, and the free energy of the anti-ferromagnetic Ising and Potts models. Contrary to previous works, our results are not a priori limited to the free energy of some prescribed graphical model. They apply more generally to any additive, Lipschitz and concave graph parameter. In addition, the corresponding limits are shown to be Lipschitz and concave in the degree distribution μ. This considerably extends the applicability of the celebrated interpolation method, introduced in the context of spin glasses, and recently related to the challenging question of right-convergence of sparse graphs. Copyright © Cambridge University Press 2015

Bommier V.,University Paris Diderot
Astronomy and Astrophysics | Year: 2012

Context: The context is the magnetic field measurement in external solar or stellar layers by interpreting line polarization measurements and the Hanle effect. Aims: The aim is to model the Hanle effect depolarization by integrating upon a star on the one hand, and by integrating along a line-of-sight through the solar corona on the other hand. Methods: The formalism of the atomic density matrix is recalled. Particular attention was devoted to the four axis rotations necessary to transform the magnetic field reference frame into that of the line-of-sight. Results: In the stellar case, the discrepancy between the results by López Ariste et al. (2011, A&A, 527, A120) and the symmetry considerations by Ignace etal. (2011, A&A, 530, A82) is resolved. In the solar case, the computations of the hydrogen Lyα polarization by Derouich et al. (2010, A&A, 511, A7) are revisited, owing to symmetry considerations. Conclusions: In the stellar case, we confirm that the effect integrated on a star leads to a non-vanishing magnetic depolarization due to the high non-linearity of the Hanle effect. In the solar case, we find that the Hanle sensitivity of hydrogen Lyβ and Lyα could be better adapted to the measurement of the coronal background magnetic field. They form a pair of lines of different and complementary sensitivity, which makes it possible to determine the full vector. Lyα would be instead adapted to the coronal loop magnetic field measurement, because this field is stronger and suited to the Lyα Hanle sensitivity. © ESO 2012.

Celerier M.-N.,University Paris Diderot
Astronomy and Astrophysics | Year: 2012

Context. During the past fifteen years, inhomogeneous cosmological models have been put forward to explain the observed dimming of the SNIa luminosity without resorting to dark energy. The simplest models are the spherically symmetric Lemaître-Tolman (LT) solutions with a central observer. Their use must be considered as a mere first step towards more sophisticated models. Spherical symmetry is but a mathematical simplification and one must consider spherical symmetric models as exhibiting an energy density smoothed out over angles around us. However, they have been taken at face value by some authors who tried to use them for either irrelevant purposes or to put them to the test as if they were robust models of our Universe. Aims. We wish to clarify how these models must be used in cosmology. Methods. We first use the results obtained by Iguchi and collaborators to derive the density profiles of the pure growing and decaying mode LT models. We then discuss the relevance of the different test proposals in the light of the interpretation given above. Results. We show that decaying-mode (parabolic) LT models always exhibit an overdensity near their centre and growing-mode (elliptic or hyperbolic) LT models, a void. This is at variance with some statements in the literature. We dismiss all previous proposals merely designed to test the spherical symmetry of the LT models, and we agree that the value of H 0 and the measurement of the redshift drift are valid tests of the models. However, we suspect that this last test, which is the best in principle, will be more complicated to implement than usually claimed. © 2012 ESO.

Leroy B.,University Paris Diderot
Astronomy and Astrophysics | Year: 2012

We present a code for the fast computation of the Lomb-Scargle periodogram that uses nonequispaced fast Fourier transforms (FFTs). The computation time has the classical O(Nlog N) behaviour of FFTs, but is shorter by about one order of magnitude than the "classical" fast algorithm by Press and Rybicki, and is about five times shorter that the best GPU-based implementations of the usual O(N 2) algorithm. This performance is achieved without sacrificing accuracy, as revealed by comparing the computations done with our FFT-based algorithm and a naïve one. © 2012 ESO.

Social networks have many different uses. Most young people use them for experimentation and innovation. Social networks help young people get familiar with the digital world, and develop themselves in interrelation with their peers. But social networks can also be used to avoid relationships in the real world, or to practice different forms of harassment. A specific danger lies in forgetting that a great number of people can have access to personal information posted online. Doctors should be particularly aware of this issue.

Revaz Y.,Ecole Polytechnique Federale de Lausanne | Jablonka P.,Ecole Polytechnique Federale de Lausanne | Jablonka P.,University Paris Diderot
Astronomy and Astrophysics | Year: 2012

We present the fully parallel chemo-dynamical Tree/SPH code GEAR, which allows us to perform high resolution simulations with detailed chemical diagnostics. Starting from the public version of Gadget-2, we included the complex treatment of the baryon physics: gas cooling, star formation law, chemical evolution, and supernova feedback. We qualified the performances of GEAR in the case of dwarf spheroidal galaxies (dSphs) galaxies. Our code GEAR conserves the total energy budget of the systems to better than 5% over 14 Gyr and provides an excellent convergence of the results with numerical resolution. We showed that models of dSphs in a static Euclidean space, where the expansion of the universe is neglected are valid. In addition, we tackled some existing open questions in the field, such as the stellar mass fraction of dSphs and its link to the predicted dark matter halo mass function, the effect of supernova feedback, the spatial distribution of the stellar populations, and the origin of the diversity in star formation histories and chemical abundance patterns. Strong supernova-driven winds seem incompatible with the observed metallicities and luminosities. Despite newly formed stars being preferentially found in the galaxy central parts, turbulent motions in the gas can quickly erase any metallicity gradient. The diversity in properties of dSph are related to a range of total masses, as well as a range of dispersion in the central densities, which is also seen in the halos emerging from a ΛCDM cosmogony. © 2012 ESO.

Sierra A.,University Paris Diderot
Journal of Pediatric Gastroenterology and Nutrition | Year: 2016

OBJECTIVES:: Intraduodenal hematoma (IDH) is an uncommon complication of endoscopic duodenal biopsy that can cause severe obstruction of the digestive, biliary, or pancreatic tracts. We aimed to analyze the risk factors and outcomes of biopsy-induced IDH in our series. METHODS:: Between 2010 and 2014, a retrospective chart review was conducted for all children younger than 18 years of age treated for IDH. We collected their data in our tertiary pediatric center and compared them to those of controls matched for age, sex, and pathology. RESULTS:: Among 2705 upper non-therapeutic endoscopies and 1163 duodenal biopsies, 7 IDH occurred in 6 children suspected of developing graft-versus-host disease after bone marrow transplantation (BMT) and in 1 patient with Noonan syndrome. The IDH prevalence was significantly higher after BMT compared to children who did not undergo grafting (7% versus 0.1%; P?=?7.9×10; odds ratio?=?82). After a median delay of 48?hours, patients developed intestinal obstruction with abdominal pain and vomiting. The diagnosis was confirmed by using ultrasonography or computed tomography scans. Acute pancreatitis was determined in 3 out of 7 patients. Conservative treatment allowed complete resolution in all patients. CONCLUSIONS:: IDH is not an infrequent complication of endoscopic duodenal biopsy, especially in patients who undergo bone marrow transplantation. Endoscopists should be especially careful during the duodenal biopsy procedure in these patients. With no early perforation due to post-biopsy IDH reported, the prognosis is good and conservative management generally leads to resolution of the symptoms in 2–3 weeks. © 2016 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

Schmidt M.,University Pierre and Marie Curie | Azoulay E.,Assistance Publique Hopitaux de Paris | Azoulay E.,University Paris Diderot
Current Opinion in Critical Care | Year: 2012

Purpose of review An appreciation of the post-ICU burden for family members, as well as the ways to prevent and minimize their symptoms of stress, anxiety, and depression. Recent findings The long-term consequences of critical illness are growing in importance as the aging population increases its demand for critical care, and as the short-term mortality after critical illness decreases. Recently, postintensive care syndrome family was proposed as a new term for this cluster of psychological complications. Critical care providers are now recognizing the need to also address the psychological needs of the relatives earlier after ICU admission. Summary A high proportion of family members present with symptoms of anxiety (70%) and depression (35%). Acute stress disorder and posttraumatic stress disorder (PTSD) related symptoms are also common. These symptoms are significantly more frequent when the relative is a spouse, or in bereaved family members. Few long-term data are available. However, in family members of dying patients, 1 year after the loss, up to 40% of them present with criteria for psychiatric illness such as generalized anxiety, major depressive disorders, or complicated grief. Prevention of post-ICU burden, mostly based on communication strategies, has been proposed to assist relatives. Copyright © Lippincott Williams & Wilkins.

To determine the efficacy in pain reduction of a topical 1% lidocaine compared to a placebo cream in patients with oral mucosal lesions due to trauma or minor oral aphthous ulcer. The design was a double-blind, randomized, placebo-controlled, six-center trial on 59 patients. Pain intensity and relief were measured using a 100-mm visual analog scale (VAS). One-tailed Student t test and ANOVA analyses were used for statistical analyses. Independent of the pain origin (oral mucosal trauma or minor oral aphthous ulcer), the application of the 1% lidocaine cream led to a mean reduction in VAS pain intensity of 29.4 mm ± 17.0, which was significantly greater than the decrease obtained with the placebo cream. Analysis showed a statistically significant efficacy of the 1% lidocaine cream (P = .0003). Its efficacy was not related to the type of lesion, and no adverse drug reaction, either local or systemic, was reported by any of the patients. A significant reduction in pain intensity occurred after application of 1% lidocaine cream and was significantly greater than that with the placebo cream. Taking into account the study's limitations, this product seems safe to use.

Farges O.,University Paris Diderot
Annals of surgery | Year: 2012

To evaluate at a national level the incidence of liver resection, postoperative mortality, and variables that predict this outcome. Data on indications of and results of liver resection are mainly derived from high-volume centers. Nationwide data are lacking. French health care databases were screened to identify all patients who had undergone elective hepatectomy between 2007 and 2010. The patients' age, address, associated conditions, indication and extent of hepatic (or extrahepatic) surgery and the hospital type, location, and hepatectomy caseload were retrieved. Logistic regression was used to measure the influence of these parameters on in-hospital and 90-day mortality rates. The model, created using patients operated on in 2007 and 2009, was tested in those operated on in 2008 and 2010. Overall, 28,708 hepatectomies were performed. The annual incidence (13.2 per 10 adult inhabitants) varied between regions, but the extremal quotient was limited to 2.2 because 15% of the operations took place outside the patients' home region. Hospitals performed a median of 4 resections per year but 53% of all resections were performed in institutions with a volume of more than 50 per year. Treatment for primary tumors and major resections correlated with hepatectomy caseload. In-hospital and 90-day mortality were 3.4% and 5.8%, respectively. The area under the receiver operating characteristic curve of the prognostic model was 0.78/0.77 in the training and validation sample. There were significant disparities in practice. In-hospital mortality underestimated true, postoperative mortality by more than 50%. The model created may be useful for more efficient regionalization of care and patient counseling.

Bonsor A.,Joseph Fourier University | Augereau J.-C.,Joseph Fourier University | Thebault P.,University Paris Diderot
Astronomy and Astrophysics | Year: 2012

High levels of exozodiacal dust are observed around a growing number of main sequence stars. The origin of such dust is not clear, given that it has a short lifetime against both collisions and radiative forces. Even a collisional cascade with km-sized parent bodies, as suggested to explain outer debris discs, cannot survive sufficiently long. In this work we investigate whether the observed exozodiacal dust could originate from an outer planetesimal belt. We investigate the scattering processes in stable planetary systems to determine whether sufficient material could be scattered inwards in order to retain the exozodiacal dust at its currently observed levels. We use N-body simulations to investigate the efficiency of this scattering and its dependence on the architecture of the planetary system. The results of these simulations can be used to assess the ability of hypothetical chains of planets to produce exozodi in observed systems. We find that for older (>100 Myr) stars with exozodiacal dust, a massive, large radii (>20 AU) outer belt and a chain of tightly packed, low-mass planets would be required to retain the dust at its currently observed levels. This brings into question how many, if any, real systems possess such a contrived architecture and are therefore capable of scattering at sufficiently high rates to retain exozodi dust on long timescales. © ESO, 2012.

Derrida B.,University Paris Diderot
Journal of Statistical Mechanics: Theory and Experiment | Year: 2011

The one-dimensional symmetric simple exclusion process (SSEP) is one of the very few exactly soluble models of non-equilibrium statistical physics. It describes a system of particles which diffuse with hard core repulsion on a onedimensional lattice in contact with two reservoirs of particles at unequal densities. The goal of this paper is to review the two main approaches which lead to the exact expression of the large deviation functional of the density of the SSEP in its steady state: a microscopic approach (based on the matrix product ansatz and an additivity property) and a macroscopic approach (based on the macroscopic fluctuation theory of Bertini, De Sole, Gabrielli, Jona-Lasinio and Landim). © 2011 IOP Publishing Ltd and SISSA.

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.

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.

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.

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..

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.

Bringuier E.,University Paris Diderot
Physica A: Statistical Mechanics and its Applications | Year: 2010

The motion of a linear polymer chain in a good solvent under a temperature gradient is examined theoretically by breaking up the flexible chain into Brownian rigid rods, and writing down an equation of motion for each rod. The motion is driven by two forces. The first one is Waldmann's thermophoretic force (stemming from the departure of the solvent's molecular-velocity distribution from Maxwell's equilibrium distribution) which here is extrapolated to a dense medium. The second force is due to the fact that the viscous friction varies with position owing to the temperature gradient, which brings an important correction to the Stokes law of friction. We use scaling considerations relying upon disparate length scales and omitting non-universal numerical prefactors. The present scaling theory is compared with recent experiments on the thermodiffusion of polymers and is shown to account for (i) the existence of both signs of the thermodiffusion coefficient of long chains, (ii) the order of magnitude of the coefficient, (iii) its independence of the chain length in the high-polymer limit and (iv) its dependence on the solvent viscosity. © 2010 Elsevier B.V. All rights reserved.

Granot R.,Ben - Gurion University of the Negev | Dyment J.,University Paris Diderot
Earth and Planetary Science Letters | Year: 2015

The separation of South America from Africa during the Cretaceous is poorly understood due to the long period of stable polarity of the geomagnetic field, the Cretaceous Normal Superchron (CNS, lasted between ~121 and 83.6 Myr ago). We present a new identification of magnetic anomalies located within the southern South Atlantic magnetic quiet zones that have arisen due to past variations in the strength of the dipolar geomagnetic field. Using these anomalies, together with fracture zone locations, we calculate the first set of magnetic anomalies-based finite rotation parameters for South America and Africa during that period. The kinematic solutions are generally consistent with fracture zone traces and magnetic anomalies outside the area used to construct them. The rotations indicate that seafloor spreading rates increased steadily throughout most of the Cretaceous and decreased sharply at around 80 Myr ago. A change in plate motion took place in the middle of the superchron, roughly 100 Myr ago, around the time of the final breakup (i.e., separation of continental-oceanic boundary in the Equatorial Atlantic). Prominent misfit between the calculated synthetic flowlines (older than Anomaly Q1) and the fracture zones straddling the African Plate in the central South Atlantic could only be explained by a combination of seafloor asymmetry and internal dextral motion (<100 km) within South America, west of the Rio Grande fracture zone. This process has lasted until ~92 Myr ago after which both Africa and South America (south of the equator) behaved rigidly. The clearing of the continental-oceanic boundaries within the Equatorial Atlantic Gateway was probably completed by ~95 Myr ago. The clearing was followed by a progressive widening and deepening of the passageway, leading to the emergence of north-south flow of intermediate and deep-water which might have triggered the global cooling of bottom water and the end for the Cretaceous greenhouse period. © 2015 Elsevier B.V.

Logeart D.,University Paris Diderot
European journal of heart failure | Year: 2013

To improve knowledge of epidemiological data, management, and clinical outcome of acute heart failure (AHF) in a real-life setting in France. We conducted an observational survey constituting a single-day snapshot of all unplanned hospitalizations because of AHF in 170 hospitals throughout France (the OFICA survey). A total of 1658 patients (median age 79 years, 55% male) were included. Family doctors were the first medical contact in 43% of cases, and patients were admitted through emergency departments in 64% of cases. Clinical scenarios were mainly acutely decompensated HF (48%) and acute pulmonary oedema (38%) with similar clinical and biological characteristics as well as outcome. Characteristics were different and severity higher in both shock and right HF. Infection and arrhythmia were the most frequent precipitating factors (27% and 24% of cases); diabetes and chronic pulmonary disease were the most frequent co-morbidities (31% and 21%). Over 80% of patients underwent both natriuretic peptide testing and echocardiography. LVEF was preserved (>50%) in 36% of patients and associated with specific characteristics and lower severity. Median hospital stay was 13 days; in-hospital mortality was 8.2%, and independent predictors were age, blood pressure, and creatinine. Treatment at discharge in patients with reduced LVEF included ACE inhibitors/ARBs, beta-blockers, and aldosterone inhibitors in 78, 67, and 27% cases. Non-surgical devices were reported in <20% of potential candidates. This comprehensive survey analysing AHF in real life emphasizes the heterogeneous nature and overall high severity of AHF. It could be a useful tool to identify unsolved medical issues and improve outcome. Trial registration: NCT01080937.

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.

Hu D.J.-K.,Columbia University | Baffet A.D.,Columbia University | Nayak T.,Columbia University | Akhmanova A.,University Utrecht | And 2 more authors.
Cell | Year: 2013

Radial glial progenitors (RGPs) are elongated epithelial cells that give rise to neurons, glia, and adult stem cells during brain development. RGP nuclei migrate basally during G1, apically using cytoplasmic dynein during G2, and undergo mitosis at the ventricular surface. By live imaging of in utero electroporated rat brain, we find that two distinct G2-specific mechanisms for dynein nuclear pore recruitment are essential for apical nuclear migration. The "RanBP2-BicD2" and "Nup133-CENP-F" pathways act sequentially, with Nup133 or CENP-F RNAi arresting nuclei close to the ventricular surface in a premitotic state. Forced targeting of dynein to the nuclear envelope rescues nuclear migration and cell-cycle progression, demonstrating that apical nuclear migration is not simply correlated with cell-cycle progression from G2 to mitosis, but rather, is a required event. These results reveal that cell-cycle control of apical nuclear migration occurs by motor protein recruitment and identify a role for nucleus- and centrosome-associated forces in mitotic entry. PaperClip © 2013 Elsevier Inc.

Morel O.,University Paris Diderot
Journal of visceral surgery | Year: 2011

In cases of serious bleeding postpartum, resuscitation and surgical techniques are complementary and should be adapted to both the etiology and severity of bleeding. In extremely severe cases, the performance of a hysterectomy should not be delayed. For women with stable hemodynamic status, so-called "conservative" surgical techniques can instead be used. In this study, we describe and discuss the indications and feasibility of various techniques of vascular ligation. Uterine mattress suture compression techniques and abdomino-pelvic packing are also described. When conservative management is feasible, the first line approach should be bilateral distal ligation of the uterine arteries: this simple and low-risk technique is immediately effective in 80% of cases. If bleeding persists, uterine devascularization can be completed by a triple ligation as described by Tsirulnikov, with or without supplemental proximal ligation of the uterine arteries. This procedure should be performed in preference to the so-called "stepwise ligation sequence", which involves ligation of the ovarian pedicles and poses a risk of subsequent ovarian failure. Bilateral hypogastric artery ligation is also an effective and widely used first-line technique for experienced surgeons. This approach is technically challenging for less-experienced surgeons and is reserved for cases of failed triple ligation. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Gorodetzky P.,University Paris Diderot
Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment | Year: 2011

JEM-EUSO is a large telescope looking at the earth from the ISS. It uses a huge volume of the earth's night sky atmosphere in which an extremely energetic cosmic ray particle (E>1019eV) generates a straight-line N2 fluorescence signal on the path of the cascade shower moving at the speed of light for a length of 10100 km depending on the incident angle. The spacetime resolved calorimetry of showers is achieved with a large-aperture Fresnel lens optics and a large-area focal surface of detectors. Such a system in space is capable of detecting thousands of events with energy above 1020 eV (>1000 super-LHC) in a few years of operation on orbit, allowing a particle channel of astronomy and for research of fundamental physics in the universe. Neutrino interaction cross-sections at such high energies are expected to increase in the Standard Model, and EUSO expects a reasonable chance of observing the cosmogenic neutrino events among those detectable showers, because the atmospheric target mass of the EUSO TPC exceeds 1 trillion tons. This experiment JEM-EUSO is currently considered by the Japan Aerospace Exploration Agency (JAXA) for a possible payload on the Japan Experiment Module (JEM) of the International Space Station (ISS). © 2010 Elsevier B.V. All rights reserved.

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).

Ricard J.-D.,Hopitaux de Paris | Ricard J.-D.,University Paris Diderot | Ricard J.-D.,French Institute of Health and Medical Research
Minerva Anestesiologica | Year: 2012

Use of high flow nasal cannula oxygen (HFNC) is increasingly popular in adult ICUs for patients with acute hypoxemic respiratory failure. This is the result of the successful long-term use of HFNC in the neonatal field and recent clinical data in adults indicating beneficial effects of HFNC over conventional facemask oxygen therapy. HFNC rapidly alleviates symptoms of respiratory distress and improves oxygenation by several mechanisms, including deadspace washout, reduction in oxygen dilution and in inspiratory nasopharyngeal resistance, a moderate positive airway pressure effect that may generate alveolar recruitment and an overall greater tolerance and comfort with the interface and the heated and humidified inspired gases. Indications of HFNC are broad, encompassing most if not all causes of acute hypoxemic respiratory failure. HFNC can also provide oxygen during invasive procedures, and be used to prevent or treat postextubation respiratory failure. HFNC may also alleviate respiratory distress in patients at a palliative stage. Although observational studies suggest that HFNC might reduce the need for intubation in acute hypoxemic respiratory failure; such a reduction has not yet been demonstrated. Beyond this potential additional effect on outcome, the evidence already published argues in favor of the large use of HFNC as first line therapy for acute respiratory failure. © 2012 EDIZIONI MINERVA MEDICA.

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.

Saveant J.-M.,University Paris Diderot
Annual Review of Analytical Chemistry | Year: 2014

Proton-coupled electron transfers (PCET) are ubiquitous in natural and synthetic processes. This review focuses on reactions where the two events are concerted. Semiclassical models of such reactions allow their kinetic characterization through activation versus driving force relationships, estimates of reorganization energies, effects of the nature of the proton acceptor, and H/D kinetic isotope effect as well as their discrimination from stepwise pathways. Several homogeneous reactions (through stopped-flow and laser flash-quench techniques) and electrochemical processes are discussed in this framework. Once the way has been rid of the improper notion of pH-dependent driving force, water appears as a remarkable proton acceptor in terms of reorganization energy and pre-exponential factor, thanks to its H-bonded and H-bonding properties, similarly to purposely synthesized "H-bond train" molecules. The most recent developments are in modeling and description of emblematic concerted proton-electron transfer (CPET) reactions associated with the breaking of a heavy-atom bond in an all-concerted process. © Copyright ©2014 by Annual Reviews. All rights reserved.

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.

Lejoyeux M.,University Paris Diderot | Weinstein A.,Hadassah Medical Organization
American Journal of Drug and Alcohol Abuse | Year: 2010

Background: Compulsive buying is a chronic, repetitive purchasing that becomes a primary response to negative events and feelings, and may include symptoms equivalent to craving and withdrawal. Objectives: This article describes the addictive characteristics of compulsive buying, the psychiatric comorbidity, and the possibilities of treatment. Methods: Using PubMed and MedLine search engines, we performed a review of published literature over the period 19902010 using the keyword "compulsive buying". Results: A key feature distinguishing compulsive buyers from normal consumers, collectors, and hoarders is that the former focuses on the buying process itself, rather than the items bought. In this instance, the purchased items are usually never used, but tend to be hidden or thrown away. A recent screening study found that up to 5 of adult Americans appear to be afflicted with this compulsion. Compulsive buying results in adverse consequences, including financial and legal problems, psychological distress (depression, guilt), and interpersonal conflict. The most commonly associated comorbidities are depression and eating disorders. Nothing is known about the neurobiology and genetics of compulsive buying and relatively little about its treatment. Cognitive behavioral therapy has some efficacy, but no medication has been effective in controlled trials. Conclusions: Compulsive buying can be described as a behavioral dependence. A great deal of future research is needed to improve our understanding of compulsive buying. © 2010 Informa Healthcare USA, Inc.

Garrabe J.,University Paris Diderot
Annales Medico-Psychologiques | Year: 2011

The question of finding criteria to help classify diseases started arising from the middle of the 19th century onwards. As for mental diseases French (Morel) and German (Kahlbaum, Kraepelin) authors proposed several classifications. From the end of the 19th century the International Bureau of Statistics (Paris) started publishing an International Classification of Diseases, to be reviewed every ten years (J. Bertillon). The Health Bureau of the League of Nations (Geneva) continued this work in the years between the two world wars, then the WHO carried on after the second world war for the fifth edition onwards. A specific chapter V (F) was devoted to mental illness. Several national classifications have been revised and modified to establish a concordance with the successive editions of the ICD especially, regarding the area of child psychiatry, the French Classification of Child and Adolescent Mental Diseases in the 2010 version. © 2011 Elsevier Masson SAS.

Lomas J.S.,University Paris Diderot
Magnetic Resonance in Chemistry | Year: 2013

The proton NMR spectra of several 1,2-diols in benzene have been analysed so as to associate each magnetically nonequivalent proton with its chemical shift. The shifts and coupling constants of the OH and methylene protons of ethane-1,2-diol have been determined in a wide range of solvents. The conformer distribution and the proton NMR shifts of these 1,2-diols in benzene have been computed on the basis of density functional theory. The solvent is included using the integral-equation-formalism polarizable continuum model implemented in Gaussian 09. Relative Gibbs energies for all stable conformers are calculated at the Perdew, Burke and Enzerhof (PBE)0/6-311 + G(d,p) level, and shifts are calculated using the gauge-including atomic orbital method with the PBE0/6-311 + G(d,p) geometry but using the cc-pVTZ basis set. Previous calculations on ethane-1,2-diol and propane-1,2-diol have been corrected and extended. New calculations on tert-butylethane-1,2-diol, phenylethane-1,2-diol, butane-2,3-diols (dl and meso) and cyclohexane-1,2-diols (cis and trans) are presented. Overall, the computed NMR shifts are in good agreement with experimental values for the OH protons but remain systematically high for CH protons. Some results based on the Gaussian 03 solvation model are included for comparison. Copyright © 2012 John Wiley & Sons, Ltd.

Lomas J.S.,University Paris Diderot
Magnetic Resonance in Chemistry | Year: 2013

The proton nuclear magnetic resonance (NMR) spectra of propane-1,3-diol, 2-methylpropane-1,3-diol, 2,2-dimethylpropane-1,3-diol, butane-1,3-diol, 3-methylbutane-1,3-diol, pentane-2,4-diols (dl and meso), 2-methylpentane-2,4- diol and cyclohexane-1,3-diols (cis and trans) in benzene have been analysed. The conformer distribution and the NMR shifts of these diols have been computed on the basis of density functional theory, the solvent being included by means of the integral equation formalism phase continuum model (IEFPCM) implemented in Gaussian 09. Relative Gibbs energies of all conformers are calculated at the Perdew, Burke and Ernzerhof (PBE)0/6-311 + G(d,p) level, and NMR shifts by the gauge-including atomic orbital method with the PBE0/6-311 + G(d,p) geometry and the cc-pVTZ basis set. Vicinal coupling constants for 1,2- and 1,3-diols are rationalised in terms of relative conformer populations and geometries. The NMR shifts of hydrogen-bonded protons in individual conformers of alkane-1,n-diols show a very rough correlation with the OH⋯OH distances. The computed overall NMR shifts for CH protons in 1,2- and 1,3-diols are systematically high but correlate very well with the experimental values, with a gradient of 1.07 ± 0.01. Some values for nonequivalent methylene protons in 1,3-diols are reversed, calculation giving enhanced values for the proton anti to the COH bonds. Errors in the NMR shifts computed for the OH protons of nonsymmetrical diols appear to be related to relative populations of conformers where one or other of the OH groups is the donor. Some results based on the second-order Møller-Plesset approach, the Becke three-parameter Lee-Yang-Parr method and on the IEFPCM solvation model implemented in Gaussian 03 are included. Copyright © 2013 John Wiley & Sons, Ltd.

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

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.

Meheut H.,University of Bern | Meliani Z.,University Paris Diderot | Varniere P.,CNRS Astroparticle and Cosmology Lab | Benz W.,University of Bern
Astronomy and Astrophysics | Year: 2012

Context. One of the most challenging steps in planet formation theory is the one leading to the formation of planetesimals of kilometre size. A promising scenario involves the existence of vortices able to concentrate a large amount of dust and grains in their centres. Up to now this scenario has mostly been studied in 2D razor thin disks. A 3D study including, simultaneously, the formation and resulting dust concentration of the vortices with vertical settling, is still missing. Aims. The Rossby wave instability self-consistently forms 3D vortices, which have the unique quality of presenting a large-scale vertical velocity in their centre. Here we aim to study how this newly discovered effect can alter the dynamic evolution of the dust. Methods. We performed global 3D simulations of the RWI in a radially and vertically stratified disk using the code MPI-AMRVAC. After the growth phase of the instability, the gas and solid phases are modelled by a bi-fluid approach, where the dust is considered as a fluid without pressure. Both the drag force of the gas on the dust and the back reaction of the dust on the gas are included. Multiple grain sizes from 1 mm to 5 cm are used with a constant density distribution. Results. We obtain in a short timescale a high concentration of the largest grains in the vortices. Indeed, in 3 rotations the dust-to-gas density ratio grows from 10 -2 to unity leading to a concentration of mass up to that of Mars in one vortex. The presence of the radial drift is also at the origin of a dust pile-up at the radius of the vortices. Lastly, the vertical velocity of the gas in the vortex causes the sedimentation process to be reversed, the mm size dust is lifted and higher concentrations are obtained in the upper layer than in the midplane. Conclusions. The Rossby wave instability is a promising mechanism for planetesimal formation, and the results presented here can be of particular interest in the context of future observations of protoplanetary disks. © 2012 ESO.

Delgado-Inglada G.,National Autonomous University of Mexico | Morisset C.,National Autonomous University of Mexico | Stasinska G.,University Paris Diderot
Monthly Notices of the Royal Astronomical Society | Year: 2014

We compute a large grid of photoionization models that covers a wide range of physical parameters and is representative of most of the observed planetary nebulae (PNe). Using this grid, we derive new formulae for the ionization correction factors (ICFs) of He, O, N, Ne, S, Ar, Cl, and C. Analytical expressions to estimate the uncertainties arising from our ICFs are also provided. This should be useful since these uncertainties are usually not considered when estimating the error bars in element abundances. Our ICFs are valid over a variety of assumptions such as the input metallicities, the spectral energy distribution of the ionizing source, the gas distribution, or the presence of dust grains. Besides, the ICFs are adequate both for large aperture observations and for pencil-beam observations in the central zones of the nebulae.We test our ICFs on a large sample of observed PNe that extends as far as possible in ionization, central star temperature, and metallicity, by checking that the Ne/O, S/O, Ar/O, and Cl/O ratios showno trend with the degree of ionization. Our ICFs lead to significant differences in the derived abundance ratios as compared with previous determinations, especially for N/O, Ne/O, and Ar/O. © 2014 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.

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.

Oukhaled A.G.,CNRS Laboratory for Analysis and Modelling for Biology and Environment | Biance A.-L.,University Claude Bernard Lyon 1 | Pelta J.,CNRS Laboratory for Analysis and Modelling for Biology and Environment | Auvray L.,University Paris Diderot | Bacri L.,CNRS Laboratory for Analysis and Modelling for Biology and Environment
Physical Review Letters | Year: 2012

We investigate the entrance of single poly(ethylene glycol) chains into an I-hemolysin channel. We detect the frequency and duration of the current blockades induced by large neutral polymers, where chain radius is larger than pore diameter. In the semidilute regime, these chains pass only if the monomer concentration is larger than a well-defined threshold. Experiments are performed in a very large domain of concentration and molecular mass, up to 35% and 200kDa, respectively, which was previously unexplored. The variation of the dwell time as a function of molecular mass shows that the chains are extracted from the semidilute solution in contact with the pore by a reptation mechanism. © 2012 American Physical Society.

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.

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.

Dufaux J.-F.,University Paris Diderot
Physical Review Letters | Year: 2012

Cosmic superstrings interact generically with a tower of light and/or strongly coupled Kaluza-Klein (KK) modes associated with the geometry of the internal space. We study the production of KK particles by cosmic superstring loops, and show that it is constrained by big bang nucleosynthesis. We study the resulting constraints in the parameter space of the underlying string theory model and highlight their complementarity with the regions that can be probed by current and upcoming gravitational wave experiments. © 2012 American Physical Society.

Erlinger S.,University Paris Diderot
Clinics and Research in Hepatology and Gastroenterology | Year: 2011

We analyse a paper, which reports an entirely novel approach to the treatment of cystic fibrosis, consisting in " repairing" the defective mutant protein. Patients with cystic fibrosis have a mutation of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), an epithelial chloride channel involved in salt and fluid transport in multiple organs, including the lungs and pancreas. The mutations have different effects on the CFTR protein, such as misfolding for the ΔF508 mutation (the most common), or defective opening of the chloride channel for the G551D-CFTR mutation, found in 4 to 5% of the patients. The authors of this work have shown that VX-770, an agent known previously to increase the activity of wild-type and G551D-CFTR cell surface protein in vitro, was able, when given orally to 39 cystic fibrosis patients during 14 and 28 days, to partially restore chloride conductance, as measured by nasal epithelium potential difference. Similarly, the agent partially restored chloride transport in sweat glands, as measured by the sweat chloride concentration. Clinically, VX-770 increased the forced expiratory volume per second (FEVi). Side effects included macular skin rash, elevation of blood glucose concentration and glycosuria. All side effects resolved after discontinuation of the drug. VX-770 has also been shown to increase the activity of ΔF508-CFTR channels in vitro, provided they reach the cell surface. This study appears to be a milestone in the treatment of cystic fibrosis and possibly other genetic diseases. © 2011 Elsevier Masson SAS.

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).

Nicolis A.,Columbia University | Piazza F.,University Paris Diderot
Journal of High Energy Physics | Year: 2012

For relativistic quantum field theories, we consider Lorentz breaking, spatially homogeneous field configurations or states that evolve in time along a symmetry direction. We dub this situation "spontaneous symmetry probing" (SSP).We mainly focus on internal symmetries, i.e. on symmetries that commute with the Poincaré group. We prove that the fluctuations around SSP states have a Lagrangian that is explicitly time independent, and we provide the field space parameterization that makes this manifest. We show that there is always a gapless Goldstone excitation that perturbs the system in the direction of motion in field space. Perhaps more interestingly, we show that if such a direction is part of a non-Abelian group of symmetries, the Goldstone bosons associated with spontaneously broken generators that do not commute with the SSP one acquire a gap, proportional to the SSP state's "speed". We outline possible applications of this formalism to inflationary cosmology.

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.

Astier P.,University Paris Diderot
Reports on Progress in Physics | Year: 2012

Over the last 20 years, supernovae have become a key tool to constrain the expansion history of the Universe through the construction of Hubble diagrams, using luminosity distances to supernovae belonging to the Ia subtype. This technique was key for the discovery that the expansion of the Universe is now accelerating. We review the principle and difficulties of the measurements, the classification and diversity of supernovae, and the physics of explosion. We discuss the systematic uncertainties affecting the cosmological conclusions with some emphasis on photometric calibration. We describe the major supernova cosmology surveys, the presented analyses and their conclusions, together with the present status of the field. We conclude on the expectations for the near future. © 2012 IOP Publishing Ltd.

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.

Erlinger S.,University Paris Diderot
Clinics and Research in Hepatology and Gastroenterology | Year: 2014

The elegant paper by Fickert et al. on bile duct ligated mice provides convincing evidence for the hypothesis that bile acids retained in the serum during cholestasis and excreted through the kidneys are toxic to collecting duct cells. The authors propose that bile acids initiate a chain of reactions leading to tubulointerstitial nephritis and fibrosis. Mice with cholestasis were protected by prefeeding with the hydrophilic bile acid norursodeoxycholic acid, an observation which suggests a potential therapeutic option for cholemic nephropathy. © 2014.

Weil Olivier C.,University Paris Diderot
Medecine et Maladies Infectieuses | Year: 2013

In children, pneumococcus became the predominant infectious agent, after the routine use of the Hib conjugate vaccine dramatically decreased Haemophilus Influenzae type b prevalence. The incidence of invasive pneumococcal infections (IPI) and of non-invasive infections due to vaccine serotypes (VS) decreased by 80% in Europe along with a 30-40% decrease in the global incidence of IPI in this age group, after the implementation of Prevenar 7® routine immunization in children below 2years of age. The decrease of IPI due to VS in other age groups was an indirect benefit. The moderate increase of non-vaccinal serotype IPI incidence did not impede the benefit of the overall program. Serotype 19A was the most frequent and carried resistance to antibiotics. Prevenar 13®, a second-generation vaccine with six new serotypes, replaced Prevenar 7® in most countries after 2010, with available evidence of its effectiveness (United Kingdom, US, France). © 2013 Published by Elsevier Masson SAS.

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.

Chevalier N.R.,University Paris Diderot
Journal of Physical Chemistry C | Year: 2014

We study the effect of wetting properties on the propensity of a surface to heterogeneously nucleate or adsorb calcium carbonate from a saturated aqueous solution. Glass, silanized glass, and polyethylene surfaces are considered. UV-ozone is used to tune the wetting behavior from hydrophobic to hydrophilic by forming oxidized carbon groups (alcohol, aldehyde, carboxylic). For all substrates that do not promote any specific orientation of CaCO3 crystals, increasing hydrophilicity inhibits CaCO3 nucleation. Complete «104» and «001» crystal orientations relative to the substrate plane are obtained for silanized glass exposed to prolonged UV-ozone treatment; nucleation densities are then also considerably higher. Our results highlight the role of interfacial surface energies and orientation in heterogeneous crystal nucleation and adsorption phenomena and contribute to the rational design of antiscaling surface treatments. © 2014 American Chemical Society.

Objective: Retrace the history regarding the classification of diseases, notably mental diseases, from the birth of psychiatry at the beginning of the 19th century and up to the 10th revision of the International Classification of diseases published by the WHO (in 1993). Method: Study the classifications proposed successively by the nosographists during this period. Results: In the 18th century, physicians classified diseases in the same way as animal and vegetal species (Carl von Linné). In the 19th century, following several attempts in France and Germany to classify mental diseases according to known or suspected aetiological and pathogenic factors (B.-A. Morel, Griesinger), psychiatrists classified psychosis and neurosis according to their clinical symptomatology and their development over time, from their onset up to the terminal stage. In 1893, J. Bertillon proposed a "Nomenclature of diseases" during the International Congress of Statistics in Chicago that permitted their classification, so as to classify-collect statistical epidemiological data on international level. Revisions were made between the two world wars by the Office of Health of the Society of Nations (Geneva). Following the foundation in 1948 of the WHO, it was the latter that continued the revisions of the International classification of diseases (ICD), Chapter V (F) of which is dedicated to disorders. Discussion: The debate on the question of classifications in psychiatry has always taken place during the World Congress on Psychiatry since its initiation in Paris in 1951. In 1976, during the sixth congress in Honolulu, a resolution was adopted requesting the national psychiatric societies that had a classification of mental diseases to revise the latter so that they tallied with Chapter V(F) of the ICD. The American Psychiatric Association revised its Diagnosis and Statistical Manuel of mental disorders (DSM) and published the DSM III. In France, a group of pedopsychiatrists published a French classification of Mental disorders in children and adolescents (Classification Française des Troubles Mentaux de l'Enfant et de l'Adolescent- CFTMEA), the last revision of which was published in 2012 (CFTMEA R 2012). Conclusion: This study shows that it is not possible to propose a classification of mental diseases, in particular according to the development of psychiatry at the time it is drawn up; it can only be of value within the cultural context of the country in which it is to be used. © 2013 Elsevier Masson SAS.

Kiladjian J.-J.,Center dinvestigations cliniques | Kiladjian J.-J.,University Paris Diderot | Kiladjian J.-J.,French Institute of Health and Medical Research | Mesa R.A.,Mayo Medical School | Hoffman R.,Mount Sinai School of Medicine
Blood | Year: 2011

IFNα has been used to treat malignant and viral disorders for more than 25 years. Its efficacy is likely the consequence of its broad range of biologic activities, including direct effects on malignant cells, enhancement of anti-tumor immune responses, induction of proapoptotic genes, inhibition of angiogenesis, and promotion of the cycling of dormant malignant stem cells. Because of the recent development of "targeted" therapies, the use of IFN has been dramatically reduced over the last decade. The increasing awareness of the multistep pathogenesis of many malignancies has suggested, however, that such an approach using target-specific agents is not universally effective. These observations have resulted in a number of recent clinical trials utilizing IFNα in patients with chronic myeloid leukemia (CML), systemic mast cell disease, hypereosinophilic syndrome and the Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) with promising outcomes. These reports provide evidence that IFNα, alone or in combination with other agents, can induce surprisingly robust molecular response rates and possibly improve survival. Although IFNα at present remains an experimental form of therapy for patients with myeloid malignancies, these promising results suggest that it may become again an important component of the therapeutic arsenal for this group of hematologic malignancies. © 2011 by The American Society of Hematology.

Down syndrome is a complex disease that has challenged molecular and cellular research for more than 50 years. UnDerstanding the molecular bases of morphological, cellular, and functional alterations resulting from the presence of an additional complete chromosome 21 would aid in targeting specific genes and pathways for rescuing some phenotypes. Recently, progress has been made by characterization of brain alterations in mouse models of Down syndrome. This review will highlight the main molecular and cellular findings recently described for these models, particularly with respect to their relationship to Down syndrome phenotypes. © Copyright 2012 Nicole Créau.

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

In this paper, we explore worst-case solutions for the problems of pattern and multi-pattern matching on strings in the RAM model with word length w. In the first problem, we have a pattern p of length m over an alphabet of size σ, and given any text T of length n, where each character is encoded using log σ bit, we wish to find all occurrences of p. For the multi-pattern matching problem we have a set S of d patterns of total length m and a query on a text T consists in finding all the occurrences in T of the patterns in S (in the following we refer by occ to the number of reported occurrences). As each character of the text is encoded using log σ bits and we can read w bits in constant time in the RAM model, the best query time for the two problems which can only possibly be achieved by reading Θ(w/ log σ) consecutive characters, is O(nlog σ/w + occ). In this paper, we present two results. The first result is that using O(m) words of space, single pattern matching queries can be answered in time O(n(log m/m + log σ/w + occ, and multiple pattern matching queries answered in time O(n(log d+log y +log log m/y + log σ/w) + occ), where y is the length of the shortest pattern. Our second result is a variant of the first result which uses the four Russian technique to remove the dependence on the shortest pattern length at the expense of using an additional space t. It answers to multi-pattern matching queries in time O(n(log d+log logσ t+log log m/logσ t + occ) using O(m + t) words of space. © 2011 Springer-Verlag.

Alecian E.,University Paris Diderot
Lecture Notes in Physics | Year: 2013

In this chapter I first present the pre-main sequence stars around which accretion disks are observed and summarise the main observed characteristics of the classical T Tauri and Herbig Ae/Be stars. I then review the theoretical and empirical reasons that lead many scientists to conclude that the objects of this class are surrounded by accretion disk. Finally I review the basic characteristics of the disks of these stars, and expose the observations that lead us to derive them.

Zouali M.,University Paris Diderot
Annals of the New York Academy of Sciences | Year: 2011

Accumulating epidemiological, clinical, and experimental evidence supports the conclusion of a critical role of epigenetic factors in immune programming. This understanding provides the basis for elucidating how the intricate interactions of the genome, epigenome, and transcriptome shape immune responses and maintain immune tolerance to self-antigens. Deciphering the precise contribution of epigenetic factors to autoimmunity, and in particular to lupus, has become an active research area. On one hand, it is well established that environmental factors have an impact on the epigenome and, therefore, on the transcriptional and translational machinery of specific cell types; on the other, the environment also plays an important role in the severity of lupus and other autoimmunity diseases. Determining how epigenetics "connects" the environment to cell biology and to autoreactivity will be key for advancing our understanding in this field and, possibly, for developing novel preventive strategies. © 2011 New York Academy of Sciences.

Marie P.J.,University Paris Diderot
Gene | Year: 2012

Fibroblast Growth Factors (FGFs) regulate prenatal and postnatal bone formation through activation of FGF receptors (FGFR) and downstream signaling events. During the last decade, major advances have been made in our understanding of the mechanisms by which FGF/FGFR signaling controls osteoprogenitor cell replication and osteoblast differentiation and function. The analysis of the phenotype induced by FGF invalidation and mutations in FGFR allowed to delineate key FGF signaling pathways that regulate osteoblastogenesis. Molecular genomic studies led to identify target genes that are controlled by FGF/FGFR signaling and govern osteoblasts. The analysis of intracellular signaling pathways showed the importance of functional crosstalks between FGF signaling and other pathways in the regulation of bone formation. These recent progresses in the mechanisms underlying FGF/FGFR signaling may provide a molecular basis for developing therapeutic strategies in human skeletal dysplasias. © 2012 Elsevier B.V.

Cates M.E.,University of Edinburgh | Tailleur J.,University Paris Diderot
EPL | Year: 2013

Active Brownian particles (ABPs, such as self-phoretic colloids) swim at fixed speed v along a body-axis u that rotates by slow angular diffusion. Run-and-tumble particles (RTPs, such as motile bacteria) swim with constant u until a random tumble event suddenly decorrelates the orientation. We show that when the motility parameters depend on density ρ but not on u, the coarse-grained fluctuating hydrodynamics of interacting ABPs and RTPs can be mapped onto each other and are thus strictly equivalent. In both cases, a steeply enough decreasing v(ρ) causes phase separation in dimensions d = 2,3, even when no attractive forces act between the particles. This points to a generic role for motility-induced phase separation in active matter. However, we show that the ABP/RTP equivalence does not automatically extend to the more general case of u-dependent motilities. Copyright © EPLA, 2013.

Carusotto I.,University of Trento | Ciuti C.,University Paris Diderot
Reviews of Modern Physics | Year: 2013

This article reviews recent theoretical and experimental advances in the fundamental understanding and active control of quantum fluids of light in nonlinear optical systems. In the presence of effective photon-photon interactions induced by the optical nonlinearity of the medium, a many-photon system can behave collectively as a quantum fluid with a number of novel features stemming from its intrinsically nonequilibrium nature. A rich variety of recently observed photon hydrodynamical effects is presented, from the superfluid flow around a defect at low speeds, to the appearance of a Mach-Cherenkov cone in a supersonic flow, to the hydrodynamic formation of topological excitations such as quantized vortices and dark solitons at the surface of large impenetrable obstacles. While the review is mostly focused on a specific class of semiconductor systems that have been extensively studied in recent years (planar semiconductor microcavities in the strong light-matter coupling regime having cavity polaritons as elementary excitations), the very concept of quantum fluids of light applies to a broad spectrum of systems, ranging from bulk nonlinear crystals, to atomic clouds embedded in optical fibers and cavities, to photonic crystal cavities, to superconducting quantum circuits based on Josephson junctions. The conclusive part of the article is devoted to a review of the future perspectives in the direction of strongly correlated photon gases and of artificial gauge fields for photons. In particular, several mechanisms to obtain efficient photon blockade are presented, together with their application to the generation of novel quantum phases. © 2013 American Physical Society.

Bouya I.,University Paris Diderot | Dormy E.,Ecole Normale Superieure de Paris
Physics of Fluids | Year: 2013

The Arnol'd-Beltrami-Childress flow is a prototype for fast dynamo action, essential to the origin of magnetic field in large astrophysical objects. Probably the most studied configuration is the classical 1: 1: 1 flow. We investigate its dynamo properties varying the magnetic Reynolds number Rm. We identify two kinks in the growth rate, which correspond, respectively, to an eigenvalue crossing and to an eigenvalue coalescence. The dominant eigenvalue becomes purely real for a finite value of the control parameter. Finally, we show that even for Rm = 25 000, the dominant eigenvalue has not yet reached an asymptotic behaviour. It still varies very significantly with the controlling parameter. Even at these very large values of Rm the fast dynamo property of this flow cannot yet be established. © 2013 American Institute of Physics.

Boleslawski E.,University Paris Diderot
Annals of Surgery | Year: 2014

RESULTS:: Between January 2013 and September 2013, 651 hepatectomies were included. Inflow occlusion was performed in 58% (intermittent in 32%, continuous in 24%) and was not performed in 42%. PST-AST (336 IU/L; interquartile range: 204–573) and PST-ALT (336 IU/L; interquartile range: 205–557) occurred on postoperative day 1. PST was not correlated with the duration of inflow occlusion (ρ-AST = 0.20, P < 0.01; ρ-ALT = 0.18, P < 0.01). PST was not independently associated with morbidity. Receiver operating characteristic curve identified a cutoff of 450 IU/L but this predictionʼs accuracy was low: area under the receiver operating characteristic curve for PST-AST: 0.61, confidence interval: 0.56–0.66, P < 0.01, and area under the receiver operating characteristic curve for PST-ALT: 0.57, confidence interval: 0.52–0.62, P = 0.01.CONCLUSIONS:: PST is not correlated with ischemia time and should not be used as a surrogate of postoperative outcome.OBJECTIVES:: Determine whether inflow occlusion is correlated with peak-postoperative serum-transaminases (PSTs) and whether PST is predictive of outcome after liver resections.BACKGROUND:: PST is used as the surrogate of ischemia reperfusion and as the main endpoint in prospective trials of inflow occlusion. This assumption has, however, not been validated. Furthermore, the impact of PST on the postoperative course is unknown.METHODS:: This prospectively designed registered study included consecutive adult patients undergoing elective hepatectomy in 9 HPB centers. Primary outcome was PST of aspartate-amino-transferase (AST) and alanine-amino-transferase (ALT). Secondary outcome was 90-day morbidity (Dindo-Clavien grades) and length of stay. Explanatory variables were preoperative (including age, sex, body mass index, comorbidities, cirrhosis, and chemotherapy), and intraoperative variables (including procedure performed, inflow occlusion and its duration, length of surgery, vasoactive drugs used, blood loss, and transfusion) were collected prospectively on a dedicated Web site. Multivariable regression models were used to identify independent predictors of PST and of morbidity. © 2014 by Lippincott Williams & Wilkins.

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.

Ballen K.K.,Massachusetts General Hospital | Gluckman E.,University Paris Diderot | Broxmeyer H.E.,Indiana University
Blood | Year: 2013

Umbilical cord blood is an alternative hematopoietic stem cell source for patients with hematologic diseases who can be cured by allogeneic hematopoietic cell transplantation. Initially, umbilical cord blood transplantation was limited to children, given the low cell dose infused. Both related and unrelated cord blood transplants have been performed with high rates of success for a variety of hematologic disorders and metabolic storage diseases in the pediatric setting. The results for adult umbilical cord blood transplantation have improved, with greater emphasis on cord blood units of sufficient cell dose and human leukocyte antigen match and with the use of double umbilical cord blood units and improved supportive care techniques. Cord blood expansion trials have recently shown improvement in time to engraftment. Umbilical cord blood is being compared with other graft sources in both retrospective and prospective trials. The growth of the field over the last 25 years and the plans for future exploration are discussed. Copyright © 2011 by The American Society of Hematology; all rights reserved.

Charles N.,University Paris Diderot | Rivera J.,U.S. National Institutes of Health
Current Allergy and Asthma Reports | Year: 2011

Systemic lupus erythematosus (SLE) is a heterogeneous disease that can affect multiple organs. A hallmark of this disease, as is the case for other autoimmune diseases, is the presence of large numbers of autoantibodies. As such, SLE is considered to be a B-cell disease perpetuated by the expansion of autoreactive T and B cells. The T cells involved have long been considered to be T-helper type 1 (Th1) and Th17 cells, as these potent proinflammatory cells can be found in the tissues of SLE patients. Recent advances point to a role for the Th2 environment in contributing to SLE through promotion of autoantibody production. Here we describe the recent work focusing on autoreactive IgE and the activation of basophils as promoting the production of autoantibodies in SLE. The findings, both in a murine model of SLE and in humans with SLE, support the concept that the activation of the basophil by autoreactive IgE-containing immune complexes serves to amplify the production of autoantibodies and contributes to the pathogenesis of disease. We propose that therapeutic targeting of this amplification loop by reducing the levels of circulating autoreactive IgE may have benefit in SLE. © Springer Science+Business Media, LLC (outside the USA) 2011.

Piazza F.,University Paris Diderot | Piazza F.,Paris West University Nanterre La Defense | 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.

Kervestin S.,University Paris Diderot | Jacobson A.,University of Massachusetts Medical School
Nature Reviews Molecular Cell Biology | Year: 2012

Although most mRNA molecules derived from protein-coding genes are destined to be translated into functional polypeptides, some are eliminated by cellular quality control pathways that collectively perform the task of mRNA surveillance. In the nonsense-mediated decay (NMD) pathway premature translation termination promotes the recruitment of a set of factors that destabilize a targeted mRNA. The same factors also seem to have key roles in repressing the translation of the mRNA, dissociating its terminating ribosome and messenger ribonucleoproteins (mRNPs), promoting the degradation of its truncated polypeptide product and possibly even feeding back to the site of transcription to interfere with splicing of the primary transcript. © 2012 Macmillan Publishers Limited. All rights reserved.

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.

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.

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.

Popot J.-L.,University Paris Diderot
Archives of Biochemistry and Biophysics | Year: 2014

Thirty-three years have elapsed since the first membrane protein (MP) was brought back in vitro to its native state starting from the completely unfolded polypeptide. Folding MPs is as useful from a practical point of view as it is thought-provoking from a theoretical one. Yet, this activity is considered as a high-risk, time-consuming endeavor, full of pitfalls, its path littered with the broken careers of graduate students sacrificed on the altar of a long shot that never paid off. In fact, a surprisingly high number of MPs have actually been folded or refolded in vitro. Analysis of the literature indicates (i) that the endeavor is not as desperate as it may seem, (ii) that techniques are diversifying and improving, and (iii) that many MPs do not need the cellular biosynthetic apparatus, nor even a membrane environment, to reach a functional 3D structure. A compilation, hopefully close to complete, is presented of MPs that have been (re)folded in vitro to-date, with the conditions of their synthesis, the denaturant(s) used, if any, and the (re)folding conditions, along with a few comments. The hope is that this analysis will encourage membrane protein biochemists to consider producing their target proteins in this way, help them decide about an experimental course, and stimulate the reflection about which environments favor membrane protein folding and why. © 2014 Elsevier B.V. All rights reserved.

Lomas J.S.,University Paris Diderot
Journal of Physical Organic Chemistry | Year: 2011

The 1H NMR titration method is used to investigate through-space and through-bond effects on the association of diols with pyridine in benzene. Alkan-1,n-diols (n goes from 2 to 10), DL and meso isomers of butan-2,3-, pentan-2,4- and hexan-2,5-diols, two adamantane diols and a bicyclo[2.2.2]octane diol are compared with alkanols. The -CH2OH groups of the tri- and bicyclic compounds behave as if they were independent, with limiting OH proton shifts (at very low concentration) and both the first and the second association constants similar to those of a primary alcohol. In contrast, the alkane diols, with n=2-4, display unusually high limiting shifts, ranging from 1.0 to 1.5ppm (2.1ppm for one methyl-substituted diol). For these diols the first dissociation constant and the sum of the OH proton shifts in the 1:1 pyridine: diol complex are enhanced. This may be attributed to small cooperative effects, implying intramolecular hydrogen bonding, for n=3 and 4, but for n=2 a through-bond effect accounts for most of the increase. Substituent interaction falls off sharply for n=5 and is practically negligible for n=10, for which the second association constant is close to the first. A sterically hindered BiEDOT diol, 2,2′-bis{(3,4-ethylenedioxythienyl)-5-[3-(2,2,4,4-tetramethylpentan-3-ol)] } behaves like the polycyclic compounds, with the two -C(t-Bu)2OH groups independent. Short-chain diols (n=2-4) show small cooperative effects in their association with pyridine in benzene. Copyright © 2010 John Wiley & Sons, Ltd.

Farhi D.,University Paris Diderot
Drugs of Today | Year: 2010

Ustekinumab, a fully human monoclonal antibody that binds to the p40 subunit of IL-12 and IL-23, has been recently approved in Europe and the U.S. for the treatment of moderate to severe plaque psoriasis. The efficacy and safety of ustekinumab have been demonstrated in three randomized phase III clinical trials, which are reviewed herein. In the PHOENIX 1 and 2 trials, significantly more patients achieved a PASI 75 response at week 12 on ustekinumab 45 mg (67.1% and 66.7%, respectively) or 90 mg (66.4% and 75.7%, respectively) than on placebo (3.1% and 3.7%, respectively; P < 0.0001 for each comparison versus placebo, in both trials). In the ACCEPT trial, PASI 75 was achieved at week 12 by 67.5% of patients on ustekinumab 45 mg, 73.8% on ustekinumab 90 mg and 56.8% on etanercept (comparison versus etanercept: P = 0.01 and P < 0.001, respectively). Injection-site reactions were significantly more common on etanercept than on ustekinumab. These results show that ustekinumab is significantly more effective than placebo and etanercept in the short-term treatment of moderate to severe psoriasis. Its safety has also been demonstrated during 76 weeks in patients without active infection or malignancy. Long-term safety data should be provided by the ongoing follow-up of the PHOENIX 1 and 2 cohorts. Copyright © 2010 Prous Science, S.A.U. or its licensors. All rights reserved.

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.

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).

Colcombet T.,University Paris Diderot
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2011

The objective of this survey is to present the ideal theory of monoids, the so-called Green's relations, and to illustrate the usefulness of this tool for solving automata related questions. We use Green's relations for proving four classical results related to automata theory: The result of Schützenberger characterizing star-free languages, the theorem of factorization forests of Simon, the characterization of infinite words of decidable monadic theory due to Semenov, and the r esult of determinization of automata over infinite words of McNaughton. © 2011 Springer-Verlag.

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.

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.

Pickering G.,French Institute of Health and Medical Research | Leplege A.,University Paris Diderot
Pain Practice | Year: 2011

Herpes zoster pain and postherpetic neuralgia (PHN) particularly affect older persons. This literature review presents how quality of life is evaluated and the consequences of shingles and PHN on the quality of life of older persons. Although more than 150 articles have been published on herpes zoster and its consequences, specific studies focusing on the older population are needed, in several domains like epidemiology, preventive medicine, neuropsychology, and pharmacology. © 2010 The Authors. Pain Practice © 2010 World Institute of Pain.

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.

Bolejko K.,University of Oxford | Celerier M.-N.,University Paris Diderot | Krasinski A.,Nicolaus Copernicus Astronomical Center
Classical and Quantum Gravity | Year: 2011

Recently, inhomogeneous generalizations of the Friedmann-Lematre-Robertson- Walker (FLRW) cosmological models have gained interest in the astrophysical community and are more often employed to study cosmological phenomena. However, in many papers the inhomogeneous cosmological models are treated as an alternative to the FLRW models. In fact, they are not an alternative, but an exact perturbation of the latter, and are gradually becoming a necessity in modern cosmology. The assumption of homogeneity is just a first approximation introduced to simplify equations. So far this assumption is commonly believed to have worked well, but future and more precise observations will not be properly analysed unless inhomogeneities are taken into account. This paper reviews recent developments in the field and shows the importance of an inhomogeneous framework in the analysis of cosmological observations. © 2011 IOP Publishing Ltd.

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.

Mucciarelli A.,University of Bologna | Salaris M.,Liverpool John Moores University | Bonifacio P.,University Paris Diderot
Monthly Notices of the Royal Astronomical Society | Year: 2012

The discrepancy between cosmological Li abundance inferred from Population II dwarf stars and that derived from big bang nucleosynthesis calculations is still far from being satisfactorily solved. We investigated, as an alternative route, the use of Li abundances in Population II lower red giant branch stars as empirical diagnostic of the cosmological Li. Both theory and observations suggest that the surface Li abundance in metal-poor red giants after the completion of the first dredge-up and before the red giant branch bump is significantly less sensitive to the efficiency of atomic diffusion, compared with dwarf stars. The surface Li abundances in these objects - after the dilution caused by the first dredge-up - are predicted to be sensitive to the total Li content left in the star, i.e. they are affected only by the total amount of Li eventually burned during the previous main-sequence phase. Standard stellar models computed under different physical assumptions show that the inclusion of the atomic diffusion has an impact of about 0.07dex in the determination of the primordial Li abundance - much smaller than the case of metal-poor main-sequence turnoff stars - and it is basically unaffected by reasonable variations of other parameters (overshooting, age, initial He abundance and mixing length). We have determined from spectroscopy the surface Li content of 17 halo lower red giant branch stars, in the metallicity range between [Fe/H] ~- 3.4 and ~- 1.4dex, evolving before the extramixing episode that sets in at the red giant branch bump. The initial Li (customarily taken as estimate of the cosmological Li abundance A(Li) 0) has then been inferred by accounting for the difference between initial and post-dredge-up Li abundances in the appropriate stellar models. It depends mainly on the T eff scale adopted in the spectroscopic analysis, and is only weakly sensitive to the efficiency of atomic diffusion in the models, so long as one neglects Li destruction caused by the process competing with atomic diffusion. Our final A(Li) 0 estimate spans a relatively narrow range, between 2.28 and 2.46dex, and is ~0.3-0.4dex lower than predictions from big bang nucleosynthesis calculations. These values of A(Li) 0 are corroborated by the analysis of samples of red giants in the Galactic globular clusters NGC6397, NGC6752 and M4. Our result provides an independent quantitative estimate of the difference with the big bang value, and sets a very robust constraint for the physical processes invoked to resolve this discrepancy. © 2011 The Authors Monthly Notices of the Royal Astronomical Society © 2011 RAS.

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.

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.

BACKGROUND: Adherence to anti-osteoporosis treatments is poor, exposing treated women to increased fracture risk. Determinants of poor adherence are poorly understood. The study aims to determine physician- and patient- rated treatment compliance with osteoporosis treatments and to evaluate factors influencing compliance. METHODS: This was an observational, cross-sectional pharmacoepidemiological study with a randomly-selected sample of 420 GPs, 154 rheumatologists and 110 gynaecologists practicing in France. Investigators included post-menopausal women with a diagnosis of osteoporosis and a treatment initiated in the previous six months. Investigators completed a questionnaire on clinical features, treatments and medical history, and on patient compliance. Patients completed a questionnaire on sociodemographic features, lifestyle, attitudes and knowledge about osteoporosis, treatment compliance, treatment satisfaction and quality of life. Treatment compliance was evaluated with the Morisky Medication-taking Adherence Scale. Variables collected in the questionnaires were evaluated for association with compliance using multivariate logistic regression analysis. RESULTS: 785 women were evaluated. Physicians considered 95.4% of the sample to be compliant, but only 65.5% of women considered themselves compliant. The correlation between patient and physician perceptions of compliance was low (κ: 0.11 [95% CI: 0.06 to 0.16]). Patient-rated compliance was highest for monthly bisphosphonates (79.7%) and lowest for hormone substitution therapy (50.0%). Six variables were associated with compliance: treatment administration frequency, perceptions of long-term treatment acceptability, perceptions of health consequences of osteoporosis, perceptions of knowledge about osteoporosis, exercise and mental quality of life. CONCLUSION: Compliance to anti-osteoporosis treatments is poor. Reduction of dosing regimen frequency and patient education may be useful ways of improving compliance.

Loeuille N.,University Paris Diderot
Functional Ecology | Year: 2010

Selective pressures acting on foraging activities constrain the strength of interaction, hence the stability and energetic availability in food webs. 2. Because such selective pressures are usually measured at the individual level and because most experimental and theoretical works focus on simple settings, linking adaptive foraging with community scale patterns is still a far stretch. 3. Some recent models incorporate foraging adaptation in diverse communities. The models vary in the way they incorporate adaptation, via evolutionary or behavioural changes, and define individual fitness in various ways. 4. In spite of these differences, some general results linking adaptation to community structure and functioning emerge. In the present article, I introduce these different models and highlight their common results. 5. Adaptive foraging provides stability to large food web models and predicts successfully interaction patterns within food webs as well as other topological features such as food chain length. 6. The relationships between adaptive foraging and other structuring factors particularly depend on how well connected the local community is with surrounding communities (metacommunity aspect). © 2010 British Ecological Society.

Deruelle N.,University Paris Diderot
General Relativity and Gravitation | Year: 2011

General Relativity obeys the three equivalence principles, the "weak" one (all test bodies fall the same way in a given gravitational field), the "Einstein" one (gravity is locally effaced in a freely falling reference frame) and the "strong" one (the gravitational mass of a system equals its inertial mass to which all forms of energy, including gravitational energy, contribute). The first principle holds because matter is minimally coupled to the metric of a curved spacetime so that test bodies follow geodesics. The second holds because Minkowskian coordinates can be used in the vicinity of any event. The fact that the latter, strong, principle holds is ultimately due to the existence of superpotentials which allow to define the inertial mass of a gravitating system by means of its asymptotic gravitational field, that is, in terms of its gravitational mass. Nordström's theory of gravity, which describes gravity by a scalar field in flat spacetime, is observationally ruled out. It is however the only theory of gravity with General Relativity to obey the strong equivalence principle. I show in this paper that this remarkable property is true beyond post-newtonian level and can be related to the existence of a "Nordström-Katz" superpotential. © 2011 Springer Science+Business Media, LLC.

Langlois D.,University Paris Diderot
Progress of Theoretical Physics Supplement | Year: 2011

This contribution gives an overview on primordial non-Gaussianities from a theoretical perspective. After presenting a general formalism to describe nonlinear cosmological perturbations, several classes of models, illustrated with examples, are discussed: multi-field inflation with non-standard Lagrangians, modulaton fields, curvaton fields. In the latter case, a special emphasis is put on the isocurvature perturbations, which could leave a specific signature in non-Gaussianities.

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.

Lehoucq R.,University Paris Diderot
European Journal of Physics | Year: 2011

The blackbody is one of the first topics the students face at the beginning of their studies on modern physics. The usual framework supposes that a blackbody emits radiation in a 3D space in the form of massless bosons (photons). This paper investigates the blackbody radiation in a more general context in order to discuss the physical hypotheses underlying it. After exposing in a nutshell standard calculations about blackbody radiation, this paper investigates the influence of a non-zero photon mass and of the dimensionality of space on the blackbody radiation. It also discusses the possibility of a fermion-emitting blackbody. The aim of this paper is mainly pedagogical because experimental evidence points towards a massless photon propagating in a 3D space: exploring hypothetical worlds can help better understand our world. © 2011 IOP Publishing Ltd.

Polo S.E.,University Paris Diderot
Journal of Molecular Biology | Year: 2015

DNA damage signaling and repair machineries operate in a nuclear environment where DNA is wrapped around histone proteins and packaged into chromatin. Understanding how chromatin structure is restored together with the DNA sequence during DNA damage repair has been a topic of intense research. Indeed, chromatin integrity is central to cell functions and identity. However, chromatin shows remarkable plasticity in response to DNA damage. This review presents our current knowledge of chromatin dynamics in the mammalian cell nucleus in response to DNA double strand breaks and UV lesions. I provide an overview of the key players involved in regulating histone dynamics in damaged chromatin regions, focusing on histone chaperones and their concerted action with histone modifiers, chromatin remodelers and repair factors. I also discuss how these dynamics contribute to reshaping chromatin and, by altering the chromatin landscape, may affect the maintenance of epigenetic information. © 2014 Elsevier Ltd.

The increased levels of fine particles in the atmosphere are suspected of aggravating cardiopulmonary diseases, but the determinants of particle toxicity are poorly understood. This work aims at studying the role of composition and size in the toxicity of size-segregated particulate matter (PM) collected at different sites on human bronchial epithelial cells. PM were sampled at a traffic urban site (Urb S) and a rural site (Rur S) during the pesticide-spreading period. Ultrafine (UF), fine (F), and coarse (C) PM were characterized by their shape and chemical composition. Whatever the site, the finest PM (UF and F) induced the mRNA expression of CYP1A1, a biomarker of polyaromatic hydrocarbons (PAH) exposure, NQO-1 and heme HO-1, two antioxidant responsive element-driven genes; and two effect biomarkers, GM-CSF, a proinflammatory cytokine and amphiregulin (AR), a growth factor. C PM have a low or no effect. Interestingly, AR is more strongly induced by rural PM at the same mass exposure. These discrepancies suggest involvement of PM chemical composition: rural PM bearing the characteristics of aged aerosols with a high content of water-soluble components, and PM at urban kerbside sites containing mainly water-insoluble components. To conclude, we provide evidence that the finest PM fractions, whatever their origin, are more prone to induce exposure and effect biomarkers. The AR differential expression suggests a source-dependent effect requiring further investigation because of the role of this growth factor in airway remodeling, a characteristic feature of chronic lung respiratory diseases exacerbated by particulate pollution.

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.

Khoury A.Z.,Federal University of Fluminense | Milman P.,CNRS Orsay Institute for Molecular Science | Milman P.,University Paris Diderot
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2011

We propose a polarization to orbital angular momentum teleportation scheme using entangled photon pairs generated by spontaneous parametric down-conversion. By making a joint detection of the polarization and angular momentum parity of a single photon, we are able to detect all the Bell states and perform, in principle, perfect teleportation from a discrete to a continuous system using minimal resources. The proposed protocol implementation demands experimental resources that are currently available in quantum optics laboratories. © 2011 American Physical Society.

Lefevere R.,University Paris Diderot
Archive for Rational Mechanics and Analysis | Year: 2015

We provide a proof that the stationary macroscopic current of particles in a random lattice Lorentz gas satisfies Fick’s law when connected to particles reservoirs. We consider a box on a d + 1-dimensional lattice and when $${d\geqq7}$$d≧7, we show that under a diffusive rescaling of space and time, the probability of finding a current different from its stationary value is exponentially small in time. Its stationary value is given by the conductivity times the difference of chemical potentials of the reservoirs. The proof is based on the fact that in a high dimension, random walks have a small probability of making loops or intersecting each other when starting sufficiently far apart. © 2014, Springer-Verlag Berlin Heidelberg.

Leyronas X.,University Paris Diderot
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2011

We present a field theoretic method for the calculation of the second and third virial coefficients b2 and b3 of two-species fermions interacting via a contact interaction. The method is mostly analytic. We find a closed expression for b3 in terms of the two- and three-body T matrices. We recover numerically, at unitarity, and also in the whole Bose-Einstein-condensate-BCS crossover, previous numerical results for the third virial coefficient b3. © 2011 American Physical Society.

Plumbridge J.,University Paris Diderot
Journal of Molecular Microbiology and Biotechnology | Year: 2015

Amino sugars are dual-purpose compounds in bacteria: they are essential components of the outer wall peptidoglycan (PG) and the outer membrane of Gram-negative bacteria and, in addition, when supplied exogenously their catabolism contributes valuable supplies of energy, carbon and nitrogen to the cell. The enzymes for both the synthesis and degradation of glucosamine (GlcN) and N-acetylglucosamine (GlcNAc) are highly conserved but during evolution have become subject to different regulatory regimes. Escherichia coli grows more rapidly using GlcNAc as a carbon source than with GlcN. On the other hand, Bacillus subtilis, but not other Bacilli tested, grows more efficiently on GlcN than GlcNAc. The more rapid growth on this sugar is associated with the presence of a second, GlcN-specific operon, which is unique to this species. A single locus is associated with the genes for catabolism of GlcNAc and GlcN in E. Coli, although they enter the cell via different transporters. In E. Coli the amino sugar transport and catabolic genes have also been requisitioned as part of the PG recycling process. Although PG recycling likely occurs in B. subtilis, it appears to have different characteristics. © 2015 S. Karger AG, Basel.

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.

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.

Akar S.,University Paris Diderot
Journal of Physics: Conference Series | Year: 2014

We present recent results from the BABAR Collaboration on radiative decays. These include searches for new physics via measurements of several observables such as the time- dependent CP asymmetry in B0 → K0 Sπ-π+γ exclusive decays, as well as direct CP asymmetries and branching fractions in B → Xsγ and B → Xsℓ+ℓ- inclusive decays. © Published under licence by IOP Publishing Ltd.

Thebault P.,University Paris Diderot
Astronomy and Astrophysics | Year: 2016

Context. The surface energy constraint puts a limit on the smallest fragment ssurf that can be produced after a collision. Based on analytical considerations, this mechanism has been recently identified as being having the potential to prevent the production of small dust grains in debris discs and to cut off their size distribution at sizes larger than the blow-out size. Aims. We numerically investigate the importance of this effect to find out under which conditions it can leave a signature in the small-size end of a disc's particle size distribution (PSD). An important part of this work is to map out, in a disc at steady-state, what is the most likely collisional origin for μm-sized dust grains, in terms of the sizes of their collisional progenitors. Methods. For the first time, we implement the surface energy constraint into a collisional evolution code. We consider a typical debris disc extending from 50 to 100 au and two different stellar types: sun-like and A star. We also consider two levels of stirring in the disc: dynamically "hot" (e=0.075) and "cold" (e= 0.01). In all cases, we derive ssurf maps as a function of target and projectile sizes, st and sp, and compare them to equivalent maps for the dust-production rate. We then compute disc-integrated profiles of the PSD and estimate the imprint of the surface energy constraint. Results. We find that the (sp,st) regions of high ssurf values do not coincide with those of high dust production rates. As a consequence, the surface energy constraint generally has a weak effect on the system's PSD. The maximum ssurf-induced depletion of μm-sized grains is ∼30% and is obtained for a sun-like star and a dynamically "hot" case. For the e = 0.01 cases, the surface energy effect is negligible compared to the massive small grain depletion that is induced by another mechanism: the "natural" imbalance between dust production and destruction rates in low-stirring discs. © ESO, 2016.

Agostino L.,University Paris Diderot
Journal of Physics: Conference Series | Year: 2014

The LAGUNA/LBNO collaboration proposes a new generation neutrino experiment to address fundamental questions in particle and astroparticle physics. The experiment consists of a far detector, Liquid Argon (LAr) double phase Time TPC (Time Projection Chamber), the fiducial mass of the detector is set to 20 kt in its first stage. The detector will be situated at 2300 km from CERN: this long baseline provides a unique opportunity to study the neutrino flavour oscillations over the first and second oscillation maxima and to explore the L/E (Length over energy) behaviour. The near detector is based on a high-pressure argon gas TPC situated at CERN. I will detail the physics potential of this experiment for determining without ambiguity the mass hierarchy (MH) in its first stage and discovering CP violation (CPV) using the CERN SPS beam with a power of 750 kw. The impact of the assumptions on the knowledge of the oscillation parameters and the systematic errors are very important and will be shown in detail to prove the force of the experiment assuming realistic and conservative parameter values. © Published under licence by IOP Publishing Ltd.

The use of mesenchymal stem cells (MSCs) for tissue regeneration is often hampered by modest engraftment in host tissue. This study was designed to quantitatively compare MSCs engraftment rates after delivery using a polysaccharide-based porous scaffold or endocardial (EC) injection in a rat myocardial infarction model. Cellular engraftment was measured by quantitative reverse transcription-polymerase chain reaction using MSCs previously transduced with a lentiviral vector that expresses green fluorescent protein (GFP). The use of a scaffold promoted local cellular engraftment and survival. The number of residual GFP(+) cells was greater with the scaffold than after EC injection (9.7% vs. 5.1% at 1 month and 16.3% vs. 6.1% at 2 months, respectively [n=5]). This concurred with a significant increase in mRNA vascular endothelial growth factor level in the scaffold group (p<0.05). Clusters of GFP+ cells were detected in the peri-infarct area, mainly phenotypically consistent with immature MSCs. Functional assessment by echocardiography at 2 months postinfarct also showed a trend toward a lower left ventricular dilatation and a reduced fibrosis in the scaffold group in comparison to direct injection group (n=10). These findings demonstrate that using a porous biodegradable scaffold is a promising method to improve cell delivery and engraftment into damaged myocardium.

Marie P.J.,University Paris Diderot
Osteoporosis International | Year: 2011

Improving bone repair remains an important and challenging issue. Therapeutic approaches to amplify osteogenic cell pool or function include cell and gene therapies. We identified genes that promote human mesenchymal cell differentiation and bone formation. Targeting these or other genes may improve the efficacy of cell therapy for bone repair. © International Osteoporosis Foundation and National Osteoporosis Foundation 2011.

Alexakis A.,University Paris Diderot
Journal of Fluid Mechanics | Year: 2015

The steady state of a forced Taylor-Green flow is investigated in a rotating frame of reference. The investigation involves the results of 184 numerical simulations for different Reynolds numbers ReF and Rossby numbers RoF. The large number of examined runs allows a systematic study that enables the mapping of the different behaviours observed to the parameter space ( ReF,RoF), and the examination of different limiting procedures for approaching the large ReF small RoF limit. Four distinctly different states were identified: laminar, intermittent bursts, quasi-two-dimensional condensates and weakly rotating turbulence. These four different states are separated by power-law boundaries RoF ∝ ReF -γ in the small RoF limit. In this limit, the predictions of asymptotic expansions can be directly compared with the results of the direct numerical simulations. While the first-order expansion is in good agreement with the results of the linear stability theory, it fails to reproduce the dynamical behaviour of the quasi-two-dimensional part of the flow in the nonlinear regime, indicating that higher-order terms in the expansion need to be taken into account. The large number of simulations allows also to investigate the scaling that relates the amplitude of the fluctuations with the energy dissipation rate and the control parameters of the system for the different states of the flow. Different scaling was observed for different states of the flow, that are discussed in detail. The present results clearly demonstrate that the limits of small Rossby and large Reynolds numbers do not commute and it is important to specify the order in which they are taken. © 2015 Cambridge University Press.

Hure J.,University Paris Diderot | Audoly B.,CNRS Jean Le Rond dAlembert Institute
Journal of the Mechanics and Physics of Solids | Year: 2013

We present a combined theoretical and experimental study of the buckling of a thin film wrapped around a sphere under the action of capillary forces. A rigid sphere is coated with a wetting liquid, and then wrapped by a thin film having an approximately cylindrical shape. The equilibrium of the film is governed by the competing effects of elasticity and capillarity: elasticity tends to keep the film developable while capillarity tends to curve it in both directions so as to maximize the area of contact with the sphere. In the experiments, the region of contact between the film and the sphere has cylindrical symmetry when the sphere radius is small, but destabilizes to a non-symmetric, wrinkled configuration when the radius is larger than a critical value. We combine the Donnell equations for near-cylindrical shells to include a unilateral constraint with the impenetrable sphere, and the capillary forces acting along a moving edge. A non-linear solution describing the axisymmetric configuration of the film is derived. A linear stability analysis is then presented, which successfully captures the wrinkling instability, the symmetry of the unstable mode, the instability threshold and the critical wavelength. The motion of the free boundary at the edge of the region of contact, which has an effect on the instability, is treated without any approximation. © 2012 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.

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.

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.

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.

Strong spatial variations in soil weathering processes were identified in the uplands and piedmont zones of the Baturité massif (Ceará, NE Brazil), a medium-elevation tropical mountain characterized by a steep ecocline between humid climate of the summit zone and semi-arid conditions of the erosional piedmont. With the combined help of field surveys and laboratory analyses, involving micromorphological observations as well as geochemical and mineralogical investigations, this study demonstrates a close spatial correlation between soil weathering processes and present-day water balance (WBI) variations: (i) in the humid massif (WBI>500mm·y -1), monosiallitization is exclusive in soil and upper saprolite horizons and leads to the neoformation of 1:1 clay minerals (well-crystallized kaolinite) with minor amounts of gibbsite; (ii) in the subhumid peripheral area of the massif (50

Zouali M.,French Institute of Health and Medical Research | Zouali M.,University Paris Diderot
FEBS Letters | Year: 2013

Despite frequent exposures to a variety of potential triggers, including antigens produced by pathogens or commensal microbiota, B-lymphocytes are able to mount highly protective responses to a variety of threats, while remaining tolerant to self-components. A number of cytokines, signaling pathways and transcription factors have been characterized to elucidate the mechanisms underlying B cell tolerance to self. It is, however, unclear how the signals received by B-lymphocytes are converted into complex and sustained patterns of gene expression that can allow production of protective antibodies and maintain immune tolerance to self-components. Mounting evidence now suggests an important role for epigenetic mechanisms in modulating and transmitting signals for B lymphocyte tolerization to self-antigens. It is likely that a better insight into epigenetic regulation of B cell tolerance will lead to development of gene-specific therapeutic approaches that optimize host defense mechanisms to exogenous threats, while preventing development and/or progression of autoimmune inflammatory diseases. © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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.

We discuss the case of lines formed by scattering, which comprises both coherent and incoherent scattering. Both processes contribute to form the line profiles in the so-called second solar spectrum, which is the spectrum of the linear polarization of such lines observed close to the solar limb. However, most of the lines cannot be simply modeled with a two-level or two-term atom model, and we present a generalized formalism for this purpose. Aims. The aim is to obtain a formalism that is able to describe scattering in line centers (resonant scattering or incoherent scattering) and in far wings (Rayleigh/Raman scattering or coherent scattering) for a multilevel and multiline atom. Methods. The method is designed to overcome the Markov approximation, which is often performed in the atom-photon interaction description. The method was already presented in the two first papers of this series, but the final equations of those papers were for a two-level atom. Results. We present here the final equations generalized for the multilevel and multiline atom. We describe the main steps of the theoretical development, and, in particular, how we performed the series development to overcome the Markov approximation. Conclusions. The statistical equilibrium equations for the atomic density matrix and the radiative transfer equation coefficients are obtained with line profiles. The Doppler redistribution is also taken into account because we show that the statistical equilibrium equations must be solved for each atomic velocity class. © 2016 ESO.

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.

Receiving people in situation of psychological vulnerability in foster families implies, beside a shared everyday life, a concern for these persons and for their well-being, in other words a form of care, different from cure treatments. The current development of "theories of care", in the field of moral and political philosophy, helps to specify the dimensions of care, including its intrinsic ethical dimension. These ones turn out to be relevant in the context of foster families. People take care not only of other people, but also of the shared and everyday world in which they live together. This care of the shared world is to be itself shared. © 2013 Elsevier Masson SAS.

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.

Erlinger S.,University Paris Diderot
Clinics and Research in Hepatology and Gastroenterology | Year: 2012

Low phospholipid-associated cholestasis and cholelithiasis (LPAC) is a genetic disorder characterized by cholesterol gallbladder and intrahepatic stones. It is caused by a mutation of the gene . ABCB4, which encodes the canalicular protein ABCB4/MDR3, a flippase that plays an essential role in the secretion of phosphatidylcholine into bile. Failure of this protein leads to secretion of bile that is poor in phospholipids and, hence, highly lithogenic, with potent detergent properties. This, in turn, leads to cholangiocyte luminal membrane injury and biliary lesions causing cholestasis. The diagnosis should be suspected when at least two of the following criteria are present: onset of symptoms before the age of 40 years; recurrence of biliary symptoms (biliary colic, jaundice, cholangitis, acute pancreatitis) after cholecystectomy; presence of echogenic foci within the liver indicative of intrahepatic stones or biliary sludge; previous episode(s) of intrahepatic cholestasis of pregnancy; and family history of gallstones in first-degree relatives. Intrahepatic stones can be demonstrated by ultrasonography with color Doppler examination, computed tomography and magnetic resonance imaging with magnetic resonance cholangiography, and the diagnosis confirmed by . ABCB4 genotyping. Therapy with ursodeoxycholic acid offers prompt relief of symptoms and usually prevents complications. In some cases, however, surgery may be necessary. © 2012 Elsevier Masson SAS.

Issa S.P.,University Paris Diderot
Journal of Pediatric Orthopaedics | Year: 2016

BACKGROUND:: The incidence of surgical site infections (SSI) after adolescent idiopathic scoliosis (AIS) surgery ranges from 0.5% to 7%. There is currently a regain of interest in hybrid constructs, combining lumbar pedicle screws and thoracic sublaminar bands, but some authors have raised concerns about the risk of SSI and the difficulty of bacterial eradication. The goal of this study was therefore to assess the outcomes of SSI after AIS surgery using sublaminar bands. METHODS:: A total of 524 consecutive patients operated for AIS using sublaminar bands between June 2006 and June 2014 were included. SSI cases were identified and analyzed retrospectively. Radiologic and functional outcomes were evaluated at follow-up using EOS imaging and SRS 30 scores, and compared with a control group. RESULTS:: The overall SSI rate was 5.3%, with a majority of monomicrobial (86%) infections occurring in the first 6 weeks postoperative (93%). The most frequent pathogens were skin germs (Staphylococcus aureus and Propionibacterium acnes) with a community profile. Patients were treated successfully with surgical debridement without implants removal, associated with 6 weeks of antibiotherapy. However, 25% of patients required >1 surgical debridement. Instrumentation removal was decided in the 2 cases with late SSI, and performed uneventfully. Radiologic and functional outcomes at follow-up were not affected by the occurrence of SSI. CONCLUSIONS:: Sublaminar bands are not associated with a higher risk of infection. However, the SSI rate in the current study stands in the upper range of the literature, and other preventive strategies should be considered. In case of early infection, bands removal is not necessary to obtain pathogen eradication, but the sublaminar implants can be pulled out safely in case of late SSI. The occurrence of SSI does not alter the outcomes at follow-up. LEVEL OF EVIDENCE:: Level III. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

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.

Luminet J.-P.,University Paris Diderot
Gravitation and Cosmology | Year: 2014

What is the shape of the Universe? Is it finite or infinite? Is space multi-connected to create ghost images of faraway cosmic sources? After a "dark age" period, the field of cosmic topology has now become one of the major concerns in astronomy and cosmology, not only from theorists but also from observational astronomers. Here I give a personal account of the spectacular progress in the field since the beginning of the 1990s, when I started to work in it. © 2014 Pleiades Publishing, Ltd.

Kotera K.,University of Chicago | Allard D.,University Paris Diderot | Olinto A.V.,University of Chicago
Journal of Cosmology and Astroparticle Physics | Year: 2010

While propagating from their source to the observer, ultrahigh energy cosmic rays interact with cosmological photon backgrounds and generate to the so-called "cosmogenic neutrinos". Here we study the parameter space of the cosmogenic neutrino flux given recent cosmic ray data and updates on plausible source evolution models. The shape and normalization of the cosmogenic neutrino flux are very sensitive to some of the current unknowns of ultrahigh energy cosmic ray sources and composition. We investigate various chemical compositions and maximum proton acceleration energies Ep,max which are allowed by current observations. We consider different models of source evolution in redshift and three possible scenarios for the Galactic to extragalactic transition. We summarize the parameter space for cosmogenic neutrinos into three regions: an optimistic scenario that is currently being constrained by observations, a plausible range of models in which we base many of our rate estimates, and a pessimistic scenario that will postpone detection for decades to come. We present the implications of these three scenarios for the detection of cosmogenic neutrinos from PeV to ZeV (1014-21 eV) with the existing and upcoming instruments. In the plausible range of parameters, the narrow flux variability in the EeV energy region assures low but detectable rates for IceCube (0.06-0.2 neutrino per year) and the Pierre Auger Observatory (0.03-0.06 neutrino per year), and detection should happen in the next decade. If EeV neutrinos are detected, PeV information can help select between competing models of cosmic ray composition at the highest energy and the Galactic to extragalactic transition at ankle energies. With improved sensitivity, ZeV neutrino observatories, such as ANITA and JEM-EUSO could explore and place limits on the maximum acceleration energy. © 2010 IOP Publishing Ltd and SISSA.

Richette P.,University Paris Diderot
Rheumatology (Oxford, England) | Year: 2010

To determine the effects of iron depletion on serum levels of joint biomarkers and on joint symptoms in patients with hereditary haemochromatosis (HH). Levels of biomarkers were measured in 18 patients with HH at the time of diagnosis and after iron depletion. The markers were type II collagen degradation (Coll2-1) and its nitrated form (Coll2-1NO(2)), type II procollagen synthesis (CPII), MPO, COMP and HA. For each patient, demographic data were collected and the global joint pain (visual analogue scale) was assessed before and after iron depletion by phlebotomy. A total of 18 patients [10 males; mean (s.d.) age 48 (11) years] were homozygous for the C282Y mutation. No patient had liver dysfunction. Ferritin level before iron removal was 627.5 (range 133-3276) microg/l, and duration of the iron depletion phase was 295 (70-670) days. Serum levels of both Coll2-1 and CPII were significantly increased from diagnosis after iron depletion: 80.1 (55.6-113.5) vs 96.0 (48.8-136.3) nM (P = 0.004) and 731.4 (374.2-1012.3) vs 812.8 (535.8-1165.6) ng/ml (P = 0.03), respectively. Levels of other biomarkers were not modified by iron depletion. Ferritin level, which at baseline was correlated with body iron store (r = 0.63; P = 0.008), was significantly correlated with HA level measured before iron depletion (r = 0.60; P = 0.01). Global joint pain was not correlated with ferritin concentration and did not significantly decrease after iron depletion: 43 (19-73) vs 36 (16-67) mm (P = 0.07). In patients with HH, cartilage homoeostasis is modified by iron excess and an increase in type II collagen turnover occurs after excess iron removal.

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.

Madler T.,University Paris Diderot
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

Perturbations of the linearized vacuum Einstein equations in the Bondi-Sachs formulation of general relativity can be derived from a single master function with spin weight two, which is related to the Weyl scalar Ψ0, and which is determined by a simple wave equation. By utilizing a standard spin representation of tensors on a sphere and two different approaches to solve the master equation, we are able to determine two simple and explicitly time-dependent solutions. Both solutions, of which one is asymptotically flat, comply with the regularity conditions at the vertex of the null cone. For the asymptotically flat solution we calculate the corresponding linearized perturbations, describing all multipoles of spin-2 waves that propagate on a Minkowskian background spacetime. We also analyze the asymptotic behavior of this solution at null infinity using a Penrose compactification and calculate the Weyl scalar Ψ4. Because of its simplicity, the asymptotically flat solution presented here is ideally suited for test bed calculations in the Bondi-Sachs formulation of numerical relativity. It may be considered as a sibling of the Bergmann-Sachs or Teukolsky-Rinne solutions, on spacelike hypersurfaces, for a metric adapted to null hypersurfaces. © 2013 American Physical Society.

Briand C.,University Paris Diderot
Journal of Plasma Physics | Year: 2015

All the bodies of the solar system are embedded in the supersonic flux of energetic particles emitted by the Sun. Since the advent of the space age, the models to describe the interaction of this plasma flow with the planets, asteroids, comets etc. have drastically progressed. The possibilities of in situ measurements of the particle distributions and electromagnetic fields have enabled the plasma theories to be tested under astrophysical conditions. Energy transfer from the Sun to the outermost regions of the heliosphere as well as the processes leading to the dissipation of this energy are central questions for heliophysicists. Understanding the dynamics of the particles is thus critical. It is a particularly complicated subject since the medium is (almost) non-collisional. Thus, next to the description of the particles, the development of waves must be considered. Indeed, they participate to the exchange of energy between different species that would not interact otherwise. In other words, waves may play the role of collisions. This paper concentrates on Langmuir waves for their strong links with the electron dynamics. The basic processes of growth and saturation of the Langmuir waves are reviewed to stress their diagnostic capabilities. Then, the characteristics of the waves are described in the several heliophysical contexts: the planetary environments (in particular the ionosphere, the magnetotail and the foreshock) and in the interplanetary medium (in quiescent conditions of the solar wind or during transient events). A particular emphasis is given to results obtained in the last 15 years. Copyright © Cambridge University Press 2015.

Perrot-Applanat M.,French Institute of Health and Medical Research | Perrot-Applanat M.,University Paris Diderot | Di Benedetto M.,French Institute of Health and Medical Research
Cell Adhesion and Migration | Year: 2012

Vascular endothelial growth factor A (VEGF-A) is well known for its key roles in blood vessel growth. Although most studies on VEGF and VEGF receptors have been focused on their functions in angiogenesis and in endothelial cells, the role of VEGF in cancer biology appears as an emerging area of importance. In this context, the presence of VEGF receptors in tumor cells strongly suggests that VEGF-A also promotes a wide range of functions, both in vitro and in vivo, all autocrine functions on tumor cells, including adhesion, survival, migration and invasion. Ultimately, refining our knowledge of VEGF signaling pathways in tumor cells should help us to understand why the current used treatments targeting the VEGF pathway in cancer are not universally effective in inhibiting metastasis tumors, and it should also provide new avenues for future therapies. © 2012 Landes Bioscience.

Portha B.,University Paris Diderot
Methods in molecular biology (Clifton, N.J.) | Year: 2012

Type 2 diabetes mellitus (T2D) arises when the endocrine pancreas fails to secrete sufficient insulin to cope with the metabolic demand because of β-cell secretory dysfunction and/or decreased β-cell mass. Defining the nature of the pancreatic islet defects present in T2D has been difficult, in part because human islets are inaccessible for direct study. This review is aimed to illustrate to what extent the Goto Kakizaki rat, one of the best characterized animal models of spontaneous T2D, has proved to be a valuable tool offering sufficient commonalities to study this aspect. A comprehensive compendium of the multiple functional GK abnormalities so far identified is proposed in this perspective, together with their time-course and interactions. A special focus is given toward the pathogenesis of defective β-cell number and function in the GK model. It is proposed that the development of T2D in the GK model results from the complex interaction of multiple events: (1) several susceptibility loci containing genes responsible for some diabetic traits; (2) gestational metabolic impairment inducing an epigenetic programming of the offspring pancreas and the major insulin target tissues; and (3) environmentally induced loss of β-cell differentiation due to chronic exposure to hyperglycemia/hyperlipidemia, inflammation, and oxidative stress.

Casandjian J.-M.,University Paris Diderot
Astrophysical Journal | Year: 2015

Cosmic-ray (CR) electrons and nuclei interact with the Galactic interstellar gas and produce high-energy γ-rays. The γ-ray emission rate per hydrogen atom, called emissivity, provides a unique indirect probe of the CR flux. We present the measurement and the interpretation of the emissivity in the solar neighborhood for γ-ray energy from 50 MeV to 50 GeV. We analyzed a subset of 4 yr of observations from the Large Area Telescope (LAT) aboard the Fermi Gamma-ray Space Telescope (Fermi) restricted to absolute latitudes 10° < |b| < 70°. From a fit to the LAT data including atomic, molecular, and ionized hydrogen column density templates, as well as a dust optical depth map, we derived the emissivities, the molecular hydrogen-to-CO conversion factor XCO = (0.902 ± 0.007) × 1020 cm-2 (K km s-1)-1, and the dust-to-gas ratio XDUST = (41.4 ± 0.3)× 1020 cm-2 mag-1. Moreover, we detected for the first time γ-ray emission from ionized hydrogen. We compared the extracted emissivities to those calculated from γ-ray production cross sections and to CR spectra measured in the heliosphere. We observed that the experimental emissivities are reproduced only if the solar modulation is accounted for. This provides a direct detection of solar modulation observed previously through the anticorrelation between CR fluxes and solar activity. Finally, we fitted a parameterized spectral form to the heliospheric CR observations and to the Fermi-LAT emissivity and obtained compatible local interstellar spectra for proton and helium kinetic energy per nucleon between between 1 and 100 GeV and for electron-positrons between 0.1 and 100 GeV. © 2015. The American Astronomical Society. All rights reserved.

Serreau J.,University Paris Diderot
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2014

We compute the renormalization group flow of O(N) scalar field theories in de Sitter space using nonperturbative renormalization group techniques in the local potential approximation. We obtain the flow of the effective potential on superhorizon scales for arbitrary space-time dimension D = d + 1. We show that, due to strong infrared fluctuations, the latter is qualitatively similar to the corresponding one in Euclidean space RD with D = 0. It follows that spontaneously broken symmetries are radiatively restored in any space-time dimension and for any value of N. © 2014 The Author.

Van Elewyck V.,University Paris Diderot
Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment | Year: 2014

The ANTARES neutrino telescope is currently the largest operating water Cherenkov detector and the largest neutrino detector in the Northern Hemisphere. Its main scientific target is the detection of high-energy (TeV and beyond) neutrinos from cosmic accelerators, as predicted by hadronic interaction models, and the measurement of the diffuse neutrino flux. Its location allows for surveying a large part of the Galactic Plane, including the Galactic Centre. In addition to the standalone searches for point-like and diffuse high-energy neutrino signals, ANTARES has developed a range of multi-messenger strategies to exploit the close connection between neutrinos and other cosmic messengers such as gamma-rays, charged cosmic rays and gravitational waves. This contribution provides an overview of the recently conducted analyses, including a search for neutrinos from the Fermi bubbles region, searches for optical counterparts with the TAToO program, and searches for neutrinos in correlation with gamma-ray bursts, blazars, and microquasars. Further topics of investigation, covering e.g. the search for neutrinos from dark matter annihilation, searches for exotic particles and the measurement of neutrino oscillations, are also reviewed. © 2014 Published by Elsevier B.V.

Le Tiec A.,University Paris Diderot
Classical and Quantum Gravity | Year: 2014

The Hamilton-Jacobi equation for test particles in the Kerr geometry is separable. Using action-angle variables, we establish several relations between various physical quantities that characterize bound timelike geodesic orbits around a spinning black hole, including the particle's rest mass, energy, angular momentum, mean redshift and fundamental frequencies. These relations are explicitly checked to hold true in the particular case of equatorial circular orbits. An application to the gravitational wave-driven, adiabatic inspiral of extreme-mass-ratio compact binaries is briefly discussed. © 2014 IOP Publishing Ltd.

Billoir P.,University Paris Diderot
Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment | Year: 2014

The Pierre Auger Observatory detects the atmospheric showers induced by cosmic rays of ultra-high energy (UHE). It is the first one to use the hybrid technique. A set of telescopes observes the fluorescence of the nitrogen molecules on clear moonless nights, giving access to the longitudinal profile of the shower. These telescopes surround a giant array of 1600 water Cherenkov tanks (covering more than 3000 km2), which works continuously and samples the particles reaching the ground (mainly muons, photons and electrons/positrons); the light produced within the water is recorded into FADC (Fast Analog to Digital Convertes) traces. A subsample of hybrid events provides a cross calibration of the two components. We describe the structure of the Cherenkov detectors, their sensitivity to different particles and the information they can give on the direction of origin, the energy and the nature of the primary UHE object; we discuss also their discrimination power for rare events (UHE photons or neutrinos). To cope with the variability of weather conditions and the limitations of the communication system, the procedures for trigger and real time calibration have been shared between local processors and a central acquisition system. The overall system has been working almost continuously for 10 years, while being progressively completed and increased by the creation of a dense "infill" subarray. © 2014 Elsevier B.V.

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.

The prevention of perinatal neurological disabilities remains a major challenge for public health, and no neuroprotective treatment to date has proven clinically useful in reducing the lesions leading to these disabilities. Efforts are, therefore, urgently needed to test other neuroprotective strategies including cell therapies. Although stem cells have raised great hopes as an inexhaustible source of therapeutic products that could be used for neuroprotection and neuroregeneration in disorders affecting the brain and spinal cord, certain sources of stem cells are associated with potential ethical issues. The human umbilical cord (hUC) is a rich source of stem and progenitor cells including mesenchymal stem cells (MSCs) derived either from the cord or from cord blood. hUC MSCs (hUC-MSCs) have several advantages as compared to other types and sources of stem cells. In this review, we will summarize the most recent findings regarding the technical aspects and the preclinical investigation of these promising cells in neuroprotection and neuroregeneration, and their potential use in the developing human brain. However, extensive studies are needed to optimize the administration protocol, safety parameters, and potential preinjection cell manipulations before designing a controlled trial in human neonates.

Klimann I.,University Paris Diderot
Leibniz International Proceedings in Informatics, LIPIcs | Year: 2013

We prove that a semigroup generated by a reversible two-state Mealy automaton is either finite or free of rank 2. This fact leads to the decidability of finiteness for groups generated by twostate or two-letter invertible-reversible Mealy automata and to the decidability of freeness for semigroups generated by two-state invertible-reversible Mealy automata.

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.

The morphogenesis of vertebrate body parts remains an open question. It is not clear whether the existence of different structures, such as a head, can be addressed by fundamental laws of tissue movement and deformation, or whether they are only a sequence of stop-and-go genetic instructions. i have filmed by time-lapse microscopy the formation of the presumptive head territory in chicken embryos. i show that the early lateral evagination of the eye cups and of the mesencephalic plate is a consequence of a sudden change in boundary conditions of the initial cell flow occurring in these embryos. Due to tissue flow, and collision of the two halves of the embryo, the tissue sheet movement is first dipolar, and next quadrupolar. In vivo air puff tonometry reveals a simple visco-elastic behaviour of the living material. The jump from a dipolar to a quadrupolar flow changes the topology of the early morphogenetic field which is observed towards a complex vortex winding with a trail (the eye cups and brain folds). The hydrodynamical model accounts for the discontinuity of the vector field at the moment of collision of the left and right halves of the embryo, at a quantitative level. This suggests a possible mechanism for the morphogenesis of the head of amniotes, as compared to cephalochordates and anamniotes. © EDP Sciences.

Rothwell P.M.,University of Oxford | 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.

Strani M.,University Paris Diderot
Nonlinearity | Year: 2015

We study the one-dimensional metastable dynamics of internal interfaces for the initial boundary value problem for the following convection-reactiondiffusion equation 2 Metastable behaviour appears when the time-dependent solution develops into a layered function in a relatively short time, and subsequently approaches its steady state in a very long time interval. A rigorous analysis is used to study such behaviour by means of the construction of a one-parameter family {(U)e (x;e)}e of approximate stationary solutions and of a linearisation of the original system around an element of this family. We obtain a system consisting of an ODE for the parameter î, describing the position of the interface coupled with a PDE for the perturbation v and defined as the difference v:=U-ue. The key of our analysis are the spectral properties of the linearised operator around an element of the family {U}e : the presence of a first eigenvalue, small with respect to a, leads to metastable behaviour when σ≥1. © 2015 IOP Publishing Ltd & London Mathematical Society Printed in the UK.

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.

Hanini A.,University Paris Diderot
International journal of nanomedicine | Year: 2011

Nanotechnology is an exciting field of investigation for the development of new treatments for many human diseases. However, it is necessary to assess the biocompatibility of nanoparticles in vitro and in vivo before considering clinical applications. Our characterization of polyol-produced maghemite γ-Fe(2)O(3) nanoparticles showed high structural quality. The particles showed a homogeneous spherical size around 10 nm and could form aggregates depending on the dispersion conditions. Such nanoparticles were efficiently taken up in vitro by human endothelial cells, which represent the first biological barrier to nanoparticles in vivo. However, γ-Fe(2)O(3) can cause cell death within 24 hours of exposure, most likely through oxidative stress. Further in vivo exploration suggests that although γ-Fe(2)O(3) nanoparticles are rapidly cleared through the urine, they can lead to toxicity in the liver, kidneys and lungs, while the brain and heart remain unaffected. In conclusion, γ-Fe(2)O(3) could exhibit harmful properties and therefore surface coating, cellular targeting, and local exposure should be considered before developing clinical applications.

Mandelbrot L.,University Paris Diderot
Gynecologie Obstetrique Fertilite | Year: 2012

With antiretroviral therapy, the risk of HIV transmission from an infected person to a stable heterosexual partner is very low when a sustained undetectable viral load is achieved, in the absence of associated genital tract infections. However, epidemiological data do not prove that there is no risk at all. Virological data confirm that when the blood viral load is undetectable for several months, the viral load in semen usually becomes undetectable, but viral shedding can persist in some cases. Two different issues are involved: 1): Can we do without assisted reproductive in HIV sero-different couples who want to have a child? and; 2): can couples in which one or both members are HIV positive entirely stop using condoms? The current French guidelines consider natural conception to be a reasonable option for these couples, recommending self-insemination when the woman is HIV positive and timed unprotected intercourse when the man is HIV positive. Preconceptional care should be available, including viral load monitoring, detection of genital infections and an estimation of the couple's potential fertility. On the other hand, we must strongly discourage unprotected sex in high-risk situations. The best prevention of risk behavior is to offer complete information and appropriate support to people with HIV who wish to conceive. © 2011 Elsevier Masson SAS. All rights reserved.

Kakkar A.K.,University College London | Cimminiello C.,Ospedale Civile di Vimercate | Goldhaber S.Z.,Harvard University | Parakh R.,Medicity | And 2 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.

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.

Ilharreborde B.,University Paris Diderot
Orthopaedics and Traumatology: Surgery and Research | Year: 2015

The epidemiology and diagnosis of osteoarticular infections (OAI) have changed considerably in recent years, partly due to the development of molecular biology. Kingella kingae is now recognized as the most frequent pathogen in children under 4years of age, while methicillin-resistant Staphylococcus aureus (SA) has been increasingly reported. Although the clinical course of OAI is mostly benign, with shorter antibiotic regimens and simplified treatments, serious functional impairments and life-threatening complications can still occur, especially in case of delayed diagnosis or infection caused by Panton-Valentine leukocidin-producing strains of SA. Newborns and patients with sickle cell disease have greater risk of orthopaedic sequelae, which need to be detected and managed early. The main sequelae of osteomyelitis are angular limb deformity, due to partial growth arrest, and lower limb discrepancy. Therapeutic options are guided by the patient's age and predictions at maturity. The main complications of septic arthritis are joint stiffness and osteonecrosis. The procedures to consider are arthrodesis, joint reconstruction in immature children, and arthroplasty at the end of growth. © 2014.

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.

Cates M.E.,University of Edinburgh | Tailleur J.,University Paris Diderot
Annual Review of Condensed Matter Physics | Year: 2015

Self-propelled particles include both self-phoretic synthetic colloids and various microorganisms. By continually consuming energy, they bypass the laws of equilibrium thermodynamics. These laws enforce the Boltzmann distribution in thermal equilibrium: The steady state is then independent of kinetic parameters. In contrast, self-propelled particles tend to accumulate where they move more slowly. They may also slow down at high density for either biochemical or steric reasons. This creates positive feedback, which can lead to motility-induced phase separation (MIPS) between dense and dilute fluid phases. At leading order in gradients, a mapping relates variable-speed, self-propelled particles to passive particles with attractions. This deep link to equilibrium phase separation is confirmed by simulations but generally breaks down at higher order in gradients: New effects, with no equilibrium counterpart, then emerge. We give a selective overview of the fast-developing field of MIPS, focusing on theory and simulation but including a brief speculative survey of its experimental implications. © 2015 by Annual Reviews.

Marangon I.,University Paris Diderot
Journal of visualized experiments : JoVE | Year: 2013

Carbon-based nanomaterials, like carbon nanotubes (CNTs), belong to this type of nanoparticles which are very difficult to discriminate from carbon-rich cell structures and de facto there is still no quantitative method to assess their distribution at cell and tissue levels. What we propose here is an innovative method allowing the detection and quantification of CNTs in cells using a multispectral imaging flow cytometer (ImageStream, Amnis). This newly developed device integrates both a high-throughput of cells and high resolution imaging, providing thus images for each cell directly in flow and therefore statistically relevant image analysis. Each cell image is acquired on bright-field (BF), dark-field (DF), and fluorescent channels, giving access respectively to the level and the distribution of light absorption, light scattered and fluorescence for each cell. The analysis consists then in a pixel-by-pixel comparison of each image, of the 7,000-10,000 cells acquired for each condition of the experiment. Localization and quantification of CNTs is made possible thanks to some particular intrinsic properties of CNTs: strong light absorbance and scattering; indeed CNTs appear as strongly absorbed dark spots on BF and bright spots on DF with a precise colocalization. This methodology could have a considerable impact on studies about interactions between nanomaterials and cells given that this protocol is applicable for a large range of nanomaterials, insofar as they are capable of absorbing (and/or scattering) strongly enough the light.

Kapoutsis C.A.,University Paris Diderot
Information and Computation | Year: 2013

On every n-long input, every two-way finite automaton (2fa) can reverse its input head O(n) times before halting. A 2fa with few reversals is an automaton where this number is only o(n). For every h, we exhibit a language that can be recognized by an h-state nondeterministic 2fa with few reversals, but requires Ω(2h) states on every deterministic 2fa with few reversals. © 2012 Elsevier Inc. All rights reserved.

Belazzougui D.,University Paris Diderot | Navarro G.,University of Chile | Valenzuela D.,University of Chile
Journal of Discrete Algorithms | Year: 2013

We give new space/time tradeoffs for compressed indexes that answer document retrieval queries on general sequences. On a collection of D documents of total length n, current approaches require at least |CSA|+O(nlgDlglgD) or 2|CSA|+o(n) bits of space, where CSA is a full-text index. Using monotone minimal perfect hash functions (mmphfs), we give new algorithms for document listing with frequencies and top-k document retrieval using just |CSA|+O(nlglglgD) bits. We also improve current solutions that use 2|CSA|+o(n) bits, and consider other problems such as colored range listing, top-k most important documents, and computing arbitrary frequencies. We give proof-of-concept experimental results that show that using mmphfs may provide relevant practical tradeoffs for document listing with frequencies. © 2012 Elsevier B.V.

Munck A.,University Paris Diderot
International Journal of Biochemistry and Cell Biology | Year: 2014

Cystic fibrosis (CF) gut manifestations are predominantly secondary to cystic fibrosis transmembrane regulator protein (CFTR) dysfunction. The CFTR gene is expressed throughout the intestinal tract. Because the intestine is difficult to assess in humans, there exists a lack of data on the underlying mechanisms of intestinal dysfunction. A more tractable approach involves the use of mouse models of CF, created by gene targeting techniques, to describe the consequences of CFTR dysfunction in the intestinal tissues, including mucus accumulation, disturbed motility, small bowel bacterial overgrowth and inflammation with altered innate immune responses, that are likely to be interrelated. We will focus on the latter. Recently, in people with CF, even in the absence of overt gastrointestinal symptoms, chronic intestinal inflammation and abnormal balance of the microbiota have been evidenced. Because chronic gut inflammation may be a driver for systemic inflammation, the prevention and control of intestinal inflammation represents a promising research strategy. This article is part of a Directed Issue entitled: Cystic Fibrosis: From o-mics to cell biology, physiology, and therapeutic advances. © 2014 Elsevier Ltd.

Belazzougui D.,University Paris Diderot
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2010

The problem of dictionary matching is a classical problem in string matching: given a set S of d strings of total length n characters over an (not necessarily constant) alphabet of size σ, build a data structure so that we can match in a any text T all occurrences of strings belonging to S. The classical solution for this problem is the Aho-Corasick automaton which finds all occ occurrences in a text T in time O(|T| + occ) using a representation that occupies O(mlogm) bits of space where m ≤ n + 1 is the number of states in the automaton. In this paper we show that the Aho-Corasick automaton can be represented in just m(log σ + O(1)) + O(d log(n/d)) bits of space while still maintaining the ability to answer to queries in O(|T|+occ) time. To the best of our knowledge, the currently fastest succinct data structure for the dictionary matching problem uses O(n log σ) bits of space while answering queries in O(|T| log log n + occ) time. In the paper we also show how the space occupancy can be reduced to m(H0+O(1))+O(d log(n/d)) where H 0 is the empirical entropy of the characters appearing in the trie representation of the set S, provided that σ

Miotto B.,Harvard University | Miotto B.,University Paris Diderot | Struhl K.,Harvard University
Molecular Cell | Year: 2011

In response to environmental stresses, cells activate stress-response genes and inhibit DNA replication. HBO1 histone acetylase is a coactivator both for AP-1 transcription factors responding to stress-activated JNK kinases and also for the Cdt1 licensing factor that ensures that DNA is replicated exactly once per cell cycle. In response to nongenotoxic stress, JNK phosphorylates Jun, an AP-1 transcription factor, leading to increased recruitment of HBO1 and increased transcription of target genes. In addition, JNK phosphorylates Cdt1 on threonine 29, leading to rapid dissociation of HBO1 from replication origins, thereby blocking initiation of DNA replication. Upon relief of stress, HBO1 reassociates with replication origins. Thus, regulated and reciprocal recruitment of the HBO1 coactivator to target genes and replication origins via JNK-mediated phosphorylation of the recruiting transcription and replication licensing factors coordinates the transcriptional and DNA replication response to cellular stress. © 2011 Elsevier Inc.

This study aimed to assess the results of segmental reversal of the small bowel (SRSB) in patients with short bowel syndrome (SBS) who were "permanently" dependent on parenteral nutrition (PN) and to identify possible prognostic factors for weaning. SRSB is a nontransplant surgical option for patients with SBS who require long-term PN. Few studies have reported outcomes in humans. : All patients who were permanently dependent on PN and underwent a SRSB between 1985 and 2010 for SBS were included. The data were retrospectively retrieved. Thirty-eight patients underwent SRSB. The median age was 55.5 years (range, 18-76). The median length of the small bowel remnant was 49 cm (20-140), including a reversed segment of 10 cm (6-15). The median follow-up was 57.7 months (1-304). At the 5-year follow-up, 17 patients had been weaned from PN (45%). In the remaining patients, PN dependency had decreased from 7 ± 1 to 4 ± 1 days per week. The survival rate was 84%. The prognostic factors for weaning were a short time between subtotal enterectomy and SRSB (P = 0.036), a longer than typical stay in the nutrition unit (P = 0.035), and an SRSB longer than 10 cm (P = 0.024). SRSB has a role as a conservative alternative to small bowel transplantation in patients with SBS permanently dependent on PN. With a segmental reversal of 10 to 12 cm, almost half of the patients can be expected to be weaned from PN.

Down syndrome is a complex disease that has challenged molecular and cellular research for more than 50 years. Understanding the molecular bases of morphological, cellular, and functional alterations resulting from the presence of an additional complete chromosome 21 would aid in targeting specific genes and pathways for rescuing some phenotypes. Recently, progress has been made by characterization of brain alterations in mouse models of Down syndrome. This review will highlight the main molecular and cellular findings recently described for these models, particularly with respect to their relationship to Down syndrome phenotypes.

Ehrhard T.,University Paris Diderot
Proceedings - Symposium on Logic in Computer Science | Year: 2010

We study the Taylor expansion of lambda-terms in a non-deterministic or algebraic setting, where terms can be added. The target language is a resource lambda calculus based on a differential lambda-calculus that we introduced recently. This operation is not possible in the general untyped case where reduction can produce unbounded coefficients. We endow resource terms with a finiteness structure (in the sense of our earlier work on finiteness spaces) and show that the Taylor expansions of terms typeable in Girard's system F are finitary by a reducibility method. © 2010 IEEE.

Deledalle C.-A.,Telecom ParisTech | Duval V.,Telecom ParisTech | Salmon J.,University Paris Diderot
Journal of Mathematical Imaging and Vision | Year: 2012

We propose in this paper an extension of the Non-Local Means (NL-Means) denoising algorithm. The idea is to replace the usual square patches used to compare pixel neighborhoods with various shapes that can take advantage of the local geometry of the image. We provide a fast algorithm to compute the NL-Means with arbitrary shapes thanks to the Fast Fourier Transform. We then consider local combinations of the estimators associated with various shapes by using Stein's Unbiased Risk Estimate (SURE). Experimental results show that this algorithm improve the standard NL-Means performance and is close to state-of-the-art methods, both in terms of visual quality and numerical results. Moreover, common visual artifacts usually observed by denoising with NL-Means are reduced or suppressed thanks to our approach. © 2011 Springer Science+Business Media, LLC.

Erlinger S.,University Paris Diderot
Clinics and Research in Hepatology and Gastroenterology | Year: 2014

The authors report the case of a child with extreme elevation of serum bile acid concentration, without pruritus, symptomatic cholestasis, liver disease, or abnormalities of liver function tests. Sequencing of the SLC10A1 gene, encoding NTCP (the sinusoidal uptake transporter of conjugated bile acids) revealed a single homozygous point mutation in the coding sequence of the gene resulting in an arginine to histidine substitution at position 252. This mutation resulted in a markedly reduced uptake activity of taurocholic acid. This is the first report of a new inborn error of bile acid transport, due to a mutation of NTCP. © 2014.

Elinger S.,University Paris Diderot
Clinics and Research in Hepatology and Gastroenterology | Year: 2014

Several recent papers support the view that Na-taurocholate cotransporting polypeptide (NTCP), the sinusoidal bile acid transporter of hepatocytes, is a cell surface receptor enabling entry into these cells of the hepatitis B virus (HBV). This major advance in the understanding of the HBV life cycle paves the way to new therapeutic strategies aimed at blocking HBV entry into hepatocytes. © 2014.

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.

Bodirsky M.,Ecole Polytechnique - Palaiseau | Pinsker M.,University Paris Diderot
Proceedings of the Annual ACM Symposium on Theory of Computing | Year: 2011

Schaefer's theorem is a complexity classification result for so-called Boolean constraint satisfaction problems: it states that every Boolean constraint satisfaction problem is either contained in one out of six classes and can be solved in polynomial time, or is NP-complete. We present an analog of this dichotomy result for the propositional logic of graphs instead of Boolean logic. In this generalization of Schaefer's result, the input consists of a set W of variables and a conjunction Phi of statements ("constraints") about these variables in the language of graphs, where each statement is taken from a fixed finite set Psi of allowed quantifier-free first-order formulas; the question is whether Phi is satisfiable in a graph. We prove that either Psi is contained in one out of 17 classes of graph formulas and the corresponding problem can be solved in polynomial time, or the problem is NP-complete. This is achieved by a universal-algebraic approach, which in turn allows us to use structural Ramsey theory. To apply the universal-algebraic approach, we formulate the computational problems under consideration as constraint satisfaction problems (CSPs) whose templates are first-order definable in the countably infinite random graph. Our method to classify the computational complexity of those CSPs produces many statements of independent mathematical interest. © 2011 ACM.

Floege J.,RWTH Aachen | Moura I.C.,French Institute of Health and Medical Research | Moura I.C.,University Paris Diderot | Daha M.R.,Leiden University
Seminars in Immunopathology | Year: 2014

IgA nephropathy (IgAN) is the most common diagnosis amongst primary glomerular diseases in most countries where renal biopsies are regularly performed. Only a fraction of these patients is at high risk of losing glomerular filtration rate (GFR) in particular those with high grade proteinuria, uncontrolled hypertension or already impaired GFR at diagnosis, and those with renal scars in the renal biopsy. Genetic modifiers of IgAN onset and/or course are emerging. Spontaneous animal models of IgAN are problematic given considerable species differences between the rodent and human IgA system. However, new transgenic models help to better understand the pathogenesis. A key pathogenetic role appears to be played by underglycated IgA1 as well as autoantibodies to these IgA glycoforms and IgA receptors such as CD89 and transferrin receptor 1. Once IgA and/or IgA-containing immune complexes are deposited or formed in the mesangium, secondary effector mechanisms become important including complement activation, release of mesangial growth factors (in particular platelet-derived growth factor), and finally non-IgAN-specific events that culminate in glomerular and subsequently renal tubulointerstitial scaring. Here, we review these processes and describe potential novel therapeutic targets in IgAN. © 2014 Springer-Verlag.

Langlois D.,University Paris Diderot | Takahashi T.,Saga University
Journal of Cosmology and Astroparticle Physics | Year: 2013

We study density perturbations, including their non-Gaussianity, in models in which the decay rate of the curvaton depends on another light scalar field, denoted the modulaton. Although this model shares some similarities with the standard curvaton and modulated reheating scenarios, it exhibits interesting predictions for fNL and gNL that are specific to this model. We also discuss the possibility that both modulaton and curvaton fluctuations contribute to the final curvature perturbation. Our results naturally include the standard curvaton and modulated reheating scenarios as specific limits and are thus useful to present a unified treatment of these models and their variants.© 2013 IOP Publishing Ltd and Sissa Medialab srl.

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.

Membrane proteins (MPs) are usually handled in aqueous solutions as protein/detergent complexes. Detergents, however, tend to be inactivating. This situation has prompted the design of alternative surfactants that can be substituted for detergents once target proteins have been extracted from biological membranes and that keep them soluble in aqueous buffers while stabilizing them. The present review focuses on three such systems: Amphipols (APols) are amphipathic polymers that adsorb onto the hydrophobic transmembrane surface of MPs; nanodiscs (NDs) are small patches of lipid bilayer whose rim is stabilized by amphipathic proteins; fluorinated surfactants (FSs) resemble detergents but interfere less than detergents do with stabilizing protein/protein and protein/lipid interactions. The structure and properties of each of these three systems are described, as well as those of the complexes they form with MPs. Their respective usefulness, constraints, and prospects for functional and structural studies of MPs are discussed. © 2010 by Annual Reviews. All rights reserved.

De Prost N.,Hopitaux de Paris | Dreyfuss D.,University Paris Diderot | Dreyfuss D.,French Institute of Health and Medical Research
Minerva Anestesiologica | Year: 2012

The experimental evidence that ventilator could injure lungs through the application of excessive end-inspiratory volumes and transpulmonary pressures has led to major changes in the clinical management of patients suffering from the acute respiratory distress syndrome (ARDS). The prevention of ventilator-induced lung injury has become one of the main goals of current ventilator strategies for patients with ARDS as well as for patients with normal lungs that require mechanical ventilation. Tidal volume reduction allowed for a reduction in mortality that confirmed the clinical relevance of ventilator-induced lung injury. In contrast, strategies for setting positive end-expiratory pressure (PEEP) have been proposed but the optimal PEEP level remains unsettled. Considerable efforts have been made within the last decades to try to develop new ventilator strategies as well as pharmacological and mechanical measures in order to prevent VILI and further improve the outcome of ARDS patients. This review will strive to describe seminal experimental and clinical studies that aimed at preventing the development of VILI. © 2012 EDIZIONI MINERVA MEDICA.

Richette P.,University Paris Diderot | Perez-Ruiz F.,Hospital Universitario Cruces
Current Medical Research and Opinion | Year: 2013

Objectives: This review presents the information available on the role of uric acid (UA) on metabolic risk and on the link between hyperuricemia and metabolic syndrome. Methods: Key papers for inclusion were identified by a PubMed search and articles were selected according to their relevance for the topic, according to the authors' judgment. Results and conclusions: An elevated UA is both strongly associated and predictive of the metabolic syndrome, and increasing evidence suggests that UA may have a causal role. The classical viewpoint that UA is simply an innocuous marker of metabolic syndrome that should not even be measured will likely have to be modified. Lowering UA may be a novel treatment target for preventing diabetes and justify prospective clinical trials on the possible benefits of the measurement and lowering of serum UA on multiple chronic disease end points. © 2013 Informa UK Ltd.

Labro M.-T.,University Paris Diderot
Expert Review of Anti-Infective Therapy | Year: 2012

Antiparasitic and antifungal drugs have not received the same high level of recognition as antimicrobial drugs. They are comparatively few in number, the great majority of them were developed more than a century ago, they have many adverse side effects and are subject to the emergence of drug resistance. The second part of the review, devoted to the immunomodulatory effects of antimicrobial agents, addresses the interference of antiparasitic and antifungal agents with the host natural defenses and the deleterious or beneficial consequences of these properties. © 2012 Expert Reviews Ltd.

Peluffo A.E.,University Paris Diderot
Genetics | Year: 2015

The metaphor of the “genetic program,” indicating the genome as a set of instructions required to build a phenotype, has been very influential in biology despite various criticisms over the years. This metaphor, first published in 1961, is thought to have been invented independently in two different articles, one by Ernst Mayr and the other by François Jacob and Jacques Monod. Here, after a detailed analysis of what both parties meant by “genetic program,” I show, using unpublished archives, the strong resemblance between the ideas of Mayr and Monod and suggest that their idea of genetic program probably shares a common origin. I explore the possibility that the two men met before 1961 and also exchanged their ideas through common friends and colleagues in the field of molecular biology. Based on unpublished correspondence of Jacob and Monod, I highlight the important events that influenced the preparation of their influential paper, which introduced the concept of the genetic program. Finally, I suggest that the genetic program metaphor may have preceded both papers and that it was probably used informally before 1961. © 2015 by the Genetics Society of America.

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.

Mora C.,University Paris Diderot | Le Hur K.,Ecole Polytechnique - Palaiseau
Physical Review B - Condensed Matter and Materials Physics | Year: 2013

We investigate the admittance of a metallic quantum RC circuit with a spinful single-channel lead or equally with two conducting spin-polarized channels, in which Majorana fermions play a crucial role in the charge dynamics. We address how the two-channel Kondo physics and its emergent Majoranas arise. The existence of a single unscreened Majorana mode results in non-Fermi-liquid features and we determine the universal crossover function describing the Fermi-liquid to non-Fermi-liquid region. Remarkably, the same universal form emerges both at weak transmission and large transmission. We find that the charge relaxation resistance strongly increases in the non-Fermi-liquid realm. Our findings can be measured using current technology assuming a large cavity. © 2013 American Physical Society.

Castera L.,University Paris Diderot
Best Practice and Research: Clinical Gastroenterology | Year: 2011

Chronic liver diseases represent a major public health problem, accounting for significant morbidity and mortality worldwide. Their prognosis and management greatly depend on the amount and progression of liver fibrosis with the risk of developing cirrhosis. Liver biopsy, traditionally considered as the reference standard for staging of fibrosis, has been challenged over the past decade by the development of novel non invasive methodologies. These methods rely on two distinct but complementary approaches: i) a 'biological' approach based on the dosage of serum biomarkers of fibrosis; ii) a 'physical' approach based on the measurement of liver stiffness using transient elastography (TE). Non invasive methods have been initially studied and validated in chronic hepatitis C but are now increasingly used in other chronic liver diseases, resulting in a significant decrease in the need for liver biopsy. However, they will likely not completely abolish the need for liver biopsy and they should rather be employed as an integrated system with liver biopsy. This review is aimed at discussing the advantages and inconveniences of non invasive methods in comparison with liver biopsy for the management of patients with chronic liver diseases. © 2011 Elsevier Ltd. All rights reserved.

Castera L.,Bordeaux University Hospital Center | Bedossa P.,University Paris Diderot
Liver International | Year: 2011

The assessment of liver fibrosis is a major issue in the management of patients with chronic hepatitis C. Liver biopsy has traditionally been considered the gold standard for the evaluation of tissue damage, including fibrosis. In addition, it detects associated lesions such as steatosis, steatohepatitis or iron overload, which provide useful information for patient management and prognosis. Liver biopsy is, however, an invasive procedure, with a risk of rare but potentially life-threatening complications and it is prone to sampling errors. These limitations have led to the development of non-invasive methods. Currently available tests rely on two different but complementary approaches: (i) a 'biological' approach based on the dosage of serum biomarkers of fibrosis; (ii) a 'physical' approach based on the measurement of liver stiffness, using transient elastography. Although significant progress has been made in the non-invasive diagnosis of fibrosis, it is increasingly clear that these methods will not completely replace liver biopsy. Instead, non-invasive methods and liver biopsy should be used in an integrated approach for more efficient and convenient management of patients with chronic hepatitis C. The aim of this review is to discuss the advantages and limitations of liver biopsy and non-invasive methods and the perspectives for their use in clinical practice. © 2011 John Wiley & Sons A/S.

Horowitz G.,University Paris Diderot
EPJ Applied Physics | Year: 2011

Since they first appearance at the end of the 1980's, organic transistors have been experiencing a growing interest from both academic and industrial institutions. In this short review, we address the current state-of-the-art of this new kind of electronic device. In particular, we try to define what characterizes an organic semiconductor, and in what it differs from its inorganic counterpart. As far as the applications are concerned, we show that the organic transistor must not be viewed as a direct competitor to silicon; instead, its future lies in the opportunity to implement new low-cost fabrications techniques, and in the possibility to realize flexible devices on polymer substrates. © EDP Sciences, 2011.

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.

Binetruy P.,University Paris Diderot
Astronomy and Astrophysics Review | Year: 2013

The acceleration of the expansion of the Universe which has been identified in recent years has deep connections with some of the most central issues in fundamental physics. At present, the most plausible explanation is some form of vacuum energy. The puzzle of vacuum energy is a central question which lies at the interface between quantum theory and general relativity. Solving it will presumably require to construct a quantum theory of gravity and a correspondingly consistent picture of spacetime. To account for the acceleration of the expansion, one may also think of more dynamical forms of energy, what is known as dark energy, or modifications of gravity. In what follows, we review the vacuum energy problem as well as the basic models for dark energy or modification of gravity. We emphasize the conceptual aspects rather than the techniques involved. We also discuss the difficulties encountered in each approach. This review is intended for astrophysicists or physicists not specialized in particle physics, who are interested in apprehending the issues at stake in fundamental physics. © 2013 Springer-Verlag Berlin Heidelberg.

Cock-Rada A.,University of Antioquia | Weitzman J.B.,University Paris Diderot
Biology of the Cell | Year: 2013

The metastatic cascade which leads to the death of cancer patients results from a multi-step process of tumour progression caused by genetic and epigenetic alterations in key regulatory molecules. It is, therefore, crucial to improve our understanding of the regulation of genes controlling the metastatic process to identify predictive biomarkers and to develop more effective therapies to treat advanced disease. The study of epigenetic mechanisms of gene regulation offers a novel approach for innovative diagnosis and treatment of cancer patients. Recent discoveries provide compelling evidence that the methylation landscape (changes in both DNA methylation and histone post-translational modifications) is profoundly altered in cancer cells and contributes to the altered expression of genes regulating tumour phenotypes. However, the impact of methylation events specifically on the advanced metastatic process is poorly understood compared with the initial oncogenic events. Moreover, the characterisation of a large number of histone-modifying enzymes has revealed their active roles in cancer progression, via the regulation of specific target genes controlling different metastatic phenotypes. Here, we discuss two main methylating events (DNA methylation and histone-tail methylation) involved in oncogenesis and metastasis formation. The potential reversibility of these molecular events makes them promising biomarkers of metastatic potential and potential therapeutic targets. © 2013 Soçiété Française des Microscopies and Soçiété de Biologie Cellulaire de France.

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..

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.

Costa D.,Ecole Nationale Superieure de Chimie de Paris | Garrain P.-A.,Ecole Nationale Superieure 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.

Vandembroucq D.,University Paris Diderot | Roux S.,Ecole Normale Superieure de Cachan
Physical Review B - Condensed Matter and Materials Physics | Year: 2011

We discuss aging and localization in a simple "Eshelby" mesoscopic model of amorphous plasticity. Plastic deformation is assumed to occur through a series of local reorganizations. Using a discretization of the mechanical fields on a discrete lattice, local reorganizations are modeled as local slip events. Local yield stresses are randomly distributed in space and invariant in time. Each plastic slip event induces a long-ranged elastic stress redistribution. Mimicking the effect of aging, we focus on the behavior of the model when the initial state is characterized by a distribution of high local yield stress values. A dramatic effect on the localization behavior is obtained: the system first spontaneously self-traps to form a shear band, which then only slowly broadens. The higher the "age" parameter the more localized the plastic strain field. Two-time correlations computed on the stress field show a divergent correlation time with the age parameter. The amplitude of a local slip event (the prefactor of the Eshelby singularity) as compared to the yield stress distribution width acts here as a mechanical effective temperaturelike parameter: the lower the slip increment, the higher the localization and the decorrelation time. © 2011 American Physical Society.

Northern Morocco, a region long marginalized, is experiencing unprecedented development brought by large projects such as the "Tangier Med" harbor complex. Its impressive facilities (three harbors, processing and logistics areas, road and rail networks) have profoundly affected both slopes dynamics of the hinterland and the life of local residents without any proper preliminary assessment. Based on a detailed field study and land mapping, this study provides an inventory and a precise description of areas heavily impacted by the development of the harbor complex, taking as examples the wadis Ghlala and Laouiyed catchments.

Gluckman E.,University Paris Diderot
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2013

Sickle cell disease (SCD) is the most common inherited hemoglobinopathy. Despite antenatal counseling and neonatal screening programs implemented in higher income countries, SCD is still associated with multiple morbidities and early mortality. To date, the only curative approach to SCD is hematopoietic stem cell transplantation, but this therapy is not yet established worldwide. The registries of the European Blood and Marrow Transplant (EBMT) and the Centre for International Blood and Marrow Transplant Research (CIBMTR) account, respectively, for 611 and 627 patients receiving transplantations for SCD. Most of these patients were transplanted with grafts from an HLA-identical sibling donor. The main obstacles to increasing the number of transplantations are a lack of awareness on the part of physicians and families, the absence of reliable prognostic factors for severity, and the perceived risk that transplantation complications may outweigh the benefits of early transplantation. Results show that more than 90% of patients having undergone an HLA-identical sibling transplantation after myeloablative conditioning are cured, with very limited complications. Major improvement is expected from the use of new reduced-toxicity conditioning regimens and the use of alternative donors, including unrelated cord blood transplantations and related haploidentical bone marrow or peripheral blood stem cell transplantations.

Jaupart C.,University Paris Diderot | Mareschal J.-C.,University of Quebec at Montreal
Earth and Planetary Science Letters | Year: 2015

The post-orogenic thermal evolution of newborn cratons in the Archean is marked by high-temperature metamorphism and plutonic activity that lag accretion by several tens of million years. The source of the heat that is required remains controversial. Here, we show that such late activity is consistent with the thermal evolution of new continental crust that adjusts to heat released by radioactive decay. Quantitative results depend on the total amount of radioactive elements in the newborn crust. Using heat flow and heat production data from the Archean Superior Province of the Canadian Shield, we show that temperatures ≈800-900 °C were reached in the lower crust a few tens of million years after the final accretion event. The timing of post-orogenic metamorphism is sensitive to the thermal structure acquired at the end of accretion. For the Superior Province, the relatively short time-lag between the end of accretion and metamorphism suggests that the lithosphere was thin or had been heated up by sustained magma percolation. © 2015 Elsevier B.V.

Marie P.J.,University Paris Diderot | Marie P.J.,Paris West University Nanterre La Defense
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.

Habib M.,University Paris Diderot | Paul C.,Montpellier University
Computer Science Review | Year: 2010

Modular decomposition is a technique that applies to (but is not restricted to) graphs. The notion of a module naturally appears in the proofs of many graph theoretical theorems. Computing the modular decomposition tree is an important preprocessing step to solve a large number of combinatorial optimization problems. Since the first polynomial time algorithm in the early 1970's, the algorithmic of the modular decomposition has known an important development. This paper survey the ideas and techniques that arose from this line of research. © 2010.

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.

Kiritsis E.,University of Crete | Kiritsis E.,University Paris Diderot | Kofinas G.,University of Crete
Journal of High Energy Physics | Year: 2010

The most general spherically symmetric solution with zero shift is found in the non-projectable Hořava-Lifshitz class of theories with general coupling constants for the quadratic terms (with the Cotton tensor 2 as the only cubic terms and without terms with derivatives of the lapse). It contains as special cases, spherically symmetric solutions found by other authors earlier. It is found that the generic solution has conventional (AdS, dS or flat) asymptotics with a universal 1/r tail. There are several special cases where the asymptotics differ, including the detailed balance choice of couplings. The conventional thermodynamics of this general class of solutions is established by calculating the energy, temperature and entropy. Although several of the solutions have conventional horizons, for particles with ultra-luminal dispersion relations such solutions appear to be horizonless. © SISSA 2010.

Mazur A.K.,University Paris Diderot
Journal of Physical Chemistry B | Year: 2013

In aqueous solutions, the helical twist of DNA decreases with temperature. This phenomenon was noticed and studied experimentally several decades ago, but its physical origin remains elusive. The present paper shows that the thermal untwisting can be predicted from the specific properties of the torsional elasticity of the double helix revealed in recent computational studies. The temperature coefficient of untwisting estimated using coarse-grained models fitted to all-atom MD data accounts for the experimental results nearly quantitatively. The agreement is further improved with the computed torsional rigidity scaled to remove the discrepancy from experiment. The results confirm that the torsional rigidity of DNA is strongly anharmonic. They indicate that for random DNA, its value grows with small twisting and decreases with untwisting. © 2013 American Chemical Society.

Anabalon A.,Adolfo Ibanez University | Deruelle N.,University Paris Diderot
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

We show that the asymptotically flat hairy black holes, solutions of the Einstein field equations minimally coupled to a scalar field, previously discovered by one of us, present mode instability against linear radial perturbations. It is also shown that the number of unstable modes is finite and their frequencies can be made arbitrarily small. © 2013 American Physical Society.

Bousser M.-G.,University Paris Diderot
Frontiers of Medicine in China | Year: 2012

Stroke is a personal, familial, and social disaster. It is the third cause of death worldwide, the first cause of acquired disability, the second cause of dementia, and its cost is astronomic. The burden of stroke is likely to increase given the aging of the population and the growing incidence of many vascular risk factors. Prevention of stroke includes-as for all other diseases-a "mass approach" aiming at decreasing the risk at the society level and an individual approach, aiming at reducing the risk in a given subject. The mass approach is primarily based on the identification and treatment of vascular risk factors and, if possible, in the implementation of protective factors. These measures are the basis of primary prevention but most of them have now been shown to be also effective in secondary prevention. The individual approach combines a vascular risk factor modification and various treatments addressing the specific subtypes of stroke, such as antiplatelet drugs for the prevention of cerebral infarction in large and small artery diseases of the brain, carotid endarterectomy or stenting for tight carotid artery stenosis, and oral anticoagulants for the prevention of cardiac emboli. There is a growing awareness of the huge evidence-to-practice gap that exists in stroke prevention largely due to socio-economic factors. Recent approaches include low cost intervention packages to reduce blood pressure and cheap "polypills" combining in a single tablet aspirin and several drugs to lower blood pressure and cholesterol. Polypill intake should however not lead to abandon the healthy life-style measures which remain the mainstay of stroke prevention. © Higher Education Press and Springer-Verlag Berlin Heidelberg 2012.

Youssef A.,University Paris Diderot
Physical Review Letters | Year: 2011

We study the infrared (long-distance) behavior of the free photon field in deSitter spacetime. Using a two-parameter family of gauge-fixing terms, we show that the infrared (IR) behavior of the two-point function is highly gauge-dependent and ranges from vanishing to growing. This situation is in disagreement with its counterpart in flat spacetime, where the two-point function vanishes in the IR region for any choice of the gauge-fixing parameters. A criterion to isolate the physical part of the two-point function is given and is shown to lead to a well-behaved two-point function in the IR region. © 2011 American Physical Society.

Benhamou M.,French Institute of Health and Medical Research | Blank U.,University Paris Diderot
FEBS Letters | Year: 2010

Stimulation of mast cells through their high affinity IgE receptor (FcεRI) leads to the secretion of pre- and neoformed soluble mediators through vesicular carriers. This process is highly regulated in order to adapt the secretion of these potentially dangerous factors to the physiological needs. This regulation requires numerous essential effectors that are necessary to transmit the initial signal of FcεRI aggregation and couple it to the sophisticated secretory machinery of membrane fusion. Studies in recent years have led to the discovery of a series of new effector molecules that link FcεRI to secretion. We describe here some of the new developments that have allowed to obtain a clearer picture of stimulus/secretion coupling in mast cells. © 2010 Federation of European Biochemical Societies.

Girard M.P.,University Paris Diderot | Tam J.S.,World Health Organization | Assossou O.M.,Unite de Recherche Clinique Lariboisiere St Louis | Kieny M.P.,World Health Organization
Vaccine | Year: 2010

In March and early April 2009 a new swine-origin influenza virus (S-OIV), A (H1N1), emerged in Mexico and the USA. The virus quickly spread worldwide through human-to-human transmission. In view of the number of countries and communities which were reporting human cases, the World Health Organization raised the influenza pandemic alert to the highest level (level 6) on June 11, 2009. The propensity of the virus to primarily affect children, young adults and pregnant women, especially those with an underlying lung or cardiac disease condition, and the substantial increase in rate of hospitalizations, prompted the efforts of the pharmaceutical industry, including new manufacturers from China, Thailand, India and South America, to develop pandemic H1N1 influenza vaccines. All currently registered vaccines were tested for safety and immunogenicity in clinical trials on human volunteers. All were found to be safe and to elicit potentially protective antibody responses after the administration of a single dose of vaccine, including split inactivated vaccines with or without adjuvant, whole-virion vaccines and live-attenuated vaccines. The need for an increased surveillance of influenza virus circulation in swine is outlined. © 2010.

Duca M.,Leiden University | Duca M.,University Paris Diderot | Koper M.T.M.,Leiden University
Energy and Environmental Science | Year: 2012

Imbalances in the nitrogen cycle caused by human activities (combustion, fertiliser-intensive agriculture) have resulted in alarmingly increased levels of nitrate in groundwater and other water bodies, with potentially health-threatening consequences. The electrocatalytic removal of nitrate from polluted water is a promising alternative to bacterial denitrification, provided that full selectivity to harmless N2, which can be returned to the atmosphere, is achieved. This perspective article discusses the state-of-the-art of research on electrocatalytic denitrification, critically evaluating the obstacles still hampering large-scale application of this technique. The milestones of fundamental research focussing on the cathode reaction will first be dealt with, followed by their translation into electrochemical reactors of practical interest. Finally, a short foray into the novel field of bioelectrochemical reactors will close the article. Challenges and opportunities pertaining to these three topics will be analysed. © The Royal Society of Chemistry 2013.

Patients with unresectable pancreatic adenocarcinoma often develop biliary and/or duodenal obstruction during the course of their disease. Jaundice, pruritis, nausea and vomiting impact negatively on the quality of life and chemotherapy must often be withheld until these symptoms are resolved. In the past, an open surgical palliative bypass was proposed, but the development of endoprosthetic stents has changed the management of these patients. The success rate for placement of duodenal and biliary stents is greater than 90% with low morbidity. Classical surgical bypass surgery includes biliary-digestive and gastro-jejunal anastomoses. Many studies have compared endoscopic and surgical treatment, and there is a clear advantage to endoscopic treatment in terms of quality of life and cost. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Hohmann C.,University of Tubingen | Winkler E.,University of Tubingen | Morin G.,University Paris Diderot | Kappler A.,University of Tubingen
Environmental Science and Technology | Year: 2010

More than 100 million individuals worldwide are exposed to arsenic-contaminated water, making the investigation of arsenic mobility in aquatic systems of utmost importance. Iron (hydr)oxides play a key role in preventing arsenic release in aquifers and soils due to their strong arsenic sorption and are even used to remove arsenic in water treatment. Neutrophilic Fe(II)-oxidizing bacteria produce Fe(III) minerals and therefore have the potential to affect arsenic mobility. In the present study, we demonstrate that the metabolism of anaerobic nitrate-reducing and phototrophic Fe(II)-oxidizing bacteria is not significantly affected by arsenate concentrations of up to 500 μ M (37.5 mg/L). Even in the presence of the more toxic arsenic species, arsenite, cell metabolism was significantly impaired only at the highest arsenite concentration (500 μ M) for one of the Fe(II)-oxidizers. All Fe(II)-oxidizing bacteria tested effectively immobilized arsenic during Fe(II) oxidation (>96%), lowering the remaining dissolved arsenic concentrations to values close to or even lower than the current drinking water limit of 10 μ g/L. Since the minerals formed by these bacteria included highly crystalline Fe(III) minerals that are hardly reducible by Fe(III)-reducing bacteria, stimulation of arsenic immobilization by Fe(II)-oxidizing bacteria can potentially support water treatment systems or even be applied as an effective remediation strategy. © 2010 American Chemical Society.

Meas T.,French Institute of Health and Medical Research | Meas T.,University Paris Diderot
Diabetes and Metabolism | Year: 2010

For several years now, the epidemiological data have shown an inverse relationship between birth-weight and the development in later life of cardiovascular disease and metabolic disorders. The term "small for gestational age" (SGA) describes a neonate whose birth-weight is two standard deviations (SD) below the reference mean, corrected for gestational age and gender. SGA is associated with increased risks of developing hypertension, insulin resistance and type 2 diabetes. However, the association with an atherogenic lipid profile is less clear. Nevertheless, all of the components of the metabolic syndrome are present. Yet, in spite of the large body of data in the literature, the biological mechanisms underlying this association are still unclear. To explain the association, various hypotheses have been proposed, pointing to the role of a detrimental fetal environment or genetic susceptibility, or interaction between the two, and to the particular dynamic changes in adiposity that occur during catch-up growth. However, not only quantitative, but also qualitative, abnormalities of adipose tissue have been observed, suggesting a critical role of this organ in the development of metabolic complications. © 2009 Elsevier Masson SAS. All rights reserved.

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.

Portha B.,University Paris Diderot
Advances in Experimental Medicine and Biology | Year: 2010

Type 2 diabetes mellitus (T2D) arises when the endocrine pancreas fails to secrete sufficient insulin to cope with the metabolic demand because of β-cell secretory dysfunction and/or decreased β-cell mass. Defining the nature of the pancreatic islet defects present in T2D has been difficult, in part because human islets are inaccessible for direct study. This review is aimed to illustrate to what extent the Goto-Kakizaki rat, one of the best characterized animal models of spontaneous T2D, has proved to be a valuable tool offering sufficient commonalities to study this aspect. A comprehensive compendium of themultiple functional GK islet abnormalities so far identified is proposed in this perspective. The pathogenesis of defective β-cell number and function in the GK model is also discussed. It is proposed that the development of T2D in the GK model results from the complex interaction of multiple events: (i) several susceptibility loci containing genes responsible for some diabetic traits (distinct loci encoding impairment of β-cell metabolism and insulin exocytosis, but no quantitative trait locus for decreased β-cell mass); (ii) gestational metabolic impairment inducing an epigenetic programming of the offspring pancreas (decreased β-cell neogenesis and proliferation) transmitted over generations; and (iii) loss of β-cell differentiation related to chronic exposure to hyperglycaemia/ hyperlipidaemia, islet inflammation, islet oxidative stress, islet fibrosis and perturbed islet vasculature. © Springer Science+Business Media B.V. 2010.

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.

Marie P.J.,University Paris Diderot
Molecular Interventions | Year: 2010

Osteoporosis is characterized by reduced bone mass and deterioration of bone microarchitecture, resulting in bone fragility and increased susceptibility to fractures. Current antiosteoporotic treatments depend on antiresorptive or anabolic drugs, but a novel modality of treatment appears to be mediated by strontium ranelate, which has been shown to act by opposing bone resorption and formation in vitro. This review article addresses the cellular and molecular mechanisms that have been implicated in the therapeutic strengthening of bone observed upon administration of strontium ranelate to osteoporotic patients. These mechanisms relate to specific pathways of calcium signaling, including complex networks involving nuclear factor of activated T cells (NFAT) and Wnt signaling.

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.

Guinamard R.,University of Caen Lower Normandy | Demion M.,Montpellier University | Launay P.,University Paris Diderot
Physiology | Year: 2010

Calcium-activated nonselective cationic currents have been known for 30 years, but their physiological implications have remained unresolved until the recent cloning of the TRPM4 ion channel. Since then, TRPM4 has been identified as a key modulator of numerous calcium-dependent mechanisms such as the immune response, insulin secretion, cerebral artery constriction, respiratory rhythm, and cardiac conduction. © 2010 Int. Union Physiol. Sci./Am. Physiol. Soc.

Ricard J.-D.,University Paris Diderot
Current Opinion in Pulmonary Medicine | Year: 2012

PURPOSE OF REVIEW: Acute respiratory tract infections are a key public health problem, and represent a major cause of death worldwide. The dramatic shortage of new antibiotics combined with the increasing number of antibiotic-resistant bacteria constitutes a worrisome threat for the global population and a critical challenge for healthcare institutions. Over recent years, a better understanding of bacterial growth, metabolism, and virulence has offered several potential targets for nonantibiotic antimicrobial therapies. RECENT FINDINGS: Several leads have been investigated, targeting adhesion, communication, toxins, virulence factors, direct bacterial killing by bacteriophages, and vaccine strategies. Promising results have been obtained with these different targets, including inhibition of quorum sensing, use of pilicide compounds to inhibit bacterial adhesion, prevention and treatment of Pseudomonas aeruginosa pneumonia by bacteriophages, effective protection against P. aeruginosa lung infection with mucosal vaccination, use of anti-PcrV antibodies in P. aeruginosa-induced sepsis. SUMMARY: Expectations are high regarding the translation of these experimental results into true clinical benefits for the patients. Importantly, clinical studies are ongoing in some areas, and promising preliminary results have already been obtained in some instances. © 2012 Lippincott Williams & Wilkins, Inc.

Hagberg H.,Gothenburg University | Hagberg H.,Imperial College London | Gressens P.,Imperial College London | Gressens P.,French Institute of Health and Medical Research | And 2 more authors.
Annals of Neurology | Year: 2012

Inflammation is increasingly recognized as being of both physiological and pathological importance in the immature brain. The rationale of this review is to present an update on this topic with focus on long-term consequences of inflammation during childhood and in adults. The immature brain can be exposed to inflammation in connection with viral or bacterial infection during pregnancy or as a result of sterile central nervous system (CNS) insults. Through efficient anti-inflammatory and reparative processes, inflammation may resolve without any harmful effects on the brain. Alternatively, inflammation contributes to injury or enhances CNS vulnerability. Acute inflammation can also be shifted to a chronic inflammatory state and/or adversely affect brain development. Hypothetically, microglia are the main immunocompetent cells in the immature CNS, and depending on the stimulus, molecular context, and timing, these cells will acquire various phenotypes, which will be critical regarding the CNS consequences of inflammation. Inflammation has long-term consequences and could speculatively modify the risk of a variety of neurological disorders, including cerebral palsy, autism spectrum disorders, schizophrenia, multiple sclerosis, cognitive impairment, and Parkinson disease. So far, the picture is incomplete, and data mostly experimental. Further studies are required to strengthen the associations in humans and to determine whether novel therapeutic interventions during the perinatal period can influence the occurrence of neurological disease later in life. Copyright © 2012 American Neurological Association.

Lepoutre T.,University Paris Diderot
Evolution Psychiatrique | Year: 2014

This paper is a clinical contribution to the problem of schizophrenic negativism. The author tries to highlight the ambiguity of this symptom, because both its semiological acceptation and his importance in schizophrenic symptomatology are not properly qualified. The study of its clinical manifestations leads to call into question both its accepted meaning and its interpretation. While most authors seem to agree that negativistic behavior is an effect of the withdrawal of object love and seems therefore to reinforce the autistic position of schizophrenic patient, the author underlines what is left unexplained by such theories: the common alternation between states of negativism and states of complete submission to an all-powerful object. This frequent reversal of the sign of the object relation shows that negativism could be precisely understood as an attempt to re-establish an object cathexis, that is to say, an attempt to heal. © 2012 Elsevier Masson SAS.

Guedj F.,Mother Infant Research Institute | Bianchi D.W.,Mother Infant Research Institute | Delabar J.-M.,University Paris Diderot
Current Opinion in Obstetrics and Gynecology | Year: 2014

PURPOSE OF REVIEW: Down syndrome affects more than 5 million people globally. During the last 10 years, there has been a dramatic increase in the research efforts focused on therapeutic interventions to improve learning and memory in Down syndrome. RECENT FINDINGS: This review summarizes the different functional abnormalities targeted by researchers in mouse models of Down syndrome. Three main strategies have been used: neural stem cell implantation; environmental enrichment and physical exercise; and pharmacotherapy. Pharmacological targets include the choline pathway, GABA and NMDA receptors, DYRK1A protein, oxidative stress and pathways involved in development and neurogenesis. Many strategies have improved learning and memory as well as electrophysiological and molecular alterations in affected animals. To date, eight molecules have been tested in human adult clinical trials. No studies have yet been performed on infants. However, compelling studies reveal that permanent brain alterations originate during fetal life in Down syndrome. Early prenatal diagnosis offers a 28 weeks window to positively impact brain development and improve postnatal cognitive outcome in affected individuals. Only a few approaches (Epigallocatechine gallate, NAP/SAL, fluoxetine, and apigenin) have been used to treat mice in utero; these showed therapeutic effects that persisted to adulthood. SUMMARY: In this article, we discuss the challenges, recent progress, and lessons learned that pave the way for new therapeutic approaches in Down syndrome. © 2014 Wolters Kluwer Health - Lippincott Williams & Wilkins.

To test the validity of the use of the Douleur Neuropathique en 4 Questions (DN4) questionnaire for burning mouth syndrome (BMS) patients, and to differentiate patients by measuring the time course of the pain in BMS patients over a period of 7 days with a visual analog scale (VAS). Patients completed the DN4 questionnaire and a VAS every hour for 7 days. The data were expressed as mean ± SEM. Correlations were searched using the Spearman correlation test with a significance level at P < .05. Data were fully analyzed for the 22 patients (21 females, 1 male, mean [± SEM] age 62.7 ± 2.3 years) for the DN4 and 17 patients for the VAS. DN4 scores ranged from 2 to 7 (mean score: 3.9 ± 0.3), and 59% of the patients had a DN4 score ≥ 4. Burning was found in all the patients, followed by pricking pain (pins and needles) and allodynia (pain on brushing) (both 68%), tingling (45%), numbness (32%), itching (27%), and electrical discharges (23%). Monitoring the hourly time-course of the pain led to the identification of two groups with intermittent or constant pain. In the latter, averaging the VAS for 7 days enabled plotting a curve, the slope of which could be calculated. The range of the slopes was 0.00 to 0.59, and a regular increase of pain during the day was seen for the majority of the patients. The findings support the use of DN4 as a tool for screening BMS and reinforce the view that BMS is a clinical manifestation of a neuropathic disease. The methodology of this study can be used for a better description of the patients and the identification of subgroups.

Valla D.,University Paris Diderot
Seminars in Thrombosis and Hemostasis | Year: 2015

Splanchnic vein thrombosis includes thrombosis of the hepatic venous system (Budd-Chiari syndrome) and thrombosis of the portal venous system. Both conditions share uncommon prothrombotic disorders as causal factors, among which myeloproliferative neoplasms rank first. Budd-Chiari syndrome presents with acute or chronic, asymptomatic or severe liver disease. Diagnosis depends on noninvasive imaging of the obstructed hepatic venous outflow tract. A spontaneously fatal course can be prevented by a stepwise approach: (1) anticoagulation therapy, specific therapy for underlying disease, and medical or endoscopic management of liver-related complications, (2) angioplasty/stenting in a second step, and (3) eventually the insertion of transjugular intrahepatic stent shunt or liver transplantation. Recent portal vein thrombosis mostly jeopardizes the gut. Early anticoagulation prevents thrombus extension but is incompletely successful in achieving recanalization. Chronic portal vein thrombosis is complicated by bleeding related to portal hypertension, which can be prevented by usual pharmacological and endoscopic means. The prevention of recurrent thrombosis is achieved by anticoagulation therapy the impact of which on the risk of bleeding remains unclear. Portal vein thrombosis in patients with cirrhosis is likely neither a direct consequence of nor a direct cause for liver disease progression. Therefore, the indications and effects of anticoagulation therapy for portal vein thrombosis in patients with cirrhosis remain uncertain.

Burke B.,Singapore Institute of Medical Biology | Doye V.,University Paris Diderot
Cellular and Molecular Life Sciences | Year: 2010

The trafficking of macromolecules between the cytoplasm and the nucleus is controlled by the nuclear pore complexes (NPCs) and various transport factors that facilitate the movement of cargos through the NPCs and their accumulation in the target compartment. While their functions in transport are well established, an ever-growing number of observations have also linked components of the nuclear transport machinery to processes that control chromosome segregation during mitosis, including spindle assembly, kinetochore function, and the spindle assembly checkpoint. In this review, we will discuss this evolving area of study and emerging hypotheses that propose key roles for components of the nuclear transport apparatus in mitotic progression. © Springer Basel AG 2010.

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.

Cohen A.T.,Kings 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.

Krivine J.-L.,University Paris Diderot
Logical Methods in Computer Science | Year: 2012

Using the proof-program (Curry-Howard) correspondence, we give a new method to obtain models of ZF and relative consistency results in set theory. We show the relative consistency of ZF + DC + there exists a sequence of subsets of R the cardinals of which are strictly decreasing + other similar properties of R. These results seem not to have been previously obtained by forcing. © J.-L. Krivine.

Ehrhard T.,University Paris Diderot
Theoretical Computer Science | Year: 2012

We show that the extensional collapse of the relational model of linear logic is the model of prime-algebraic complete lattices, a natural extension to linear logic of the well known Scott semantics of the lambda-calculus. © 2011 Elsevier B.V. All rights reserved.

Steiner W.,University Paris Diderot
RAIRO - Theoretical Informatics and Applications | Year: 2012

The (-β)-integers are natural generalisations of the β-integers, and thus of the integers, for negative real bases. When β is the analogue of a Parry number, we describe the structure of the set of (-β)-integers by a fixed point of an anti-morphism. © 2011 EDP Sciences.

Lehman C.,University Paris Diderot
Osiris | Year: 2014

Despite recent studies of chemistry courses and of academic research at the beginning of the eighteenth century, the perception of chemistry in the French Enlightenment has often been overshadowed by Lavoisier’s works. This article proposes three specific case studies selected from Pierre Joseph Macquer’s (1718–84) rich career to show the continuous evolution of chemistry throughout the century: medicinal chemistry through the application of the Comte de La Garaye’s metallic salt solutions, the emergence of industrial chemistry through a few of Macquer’s evaluations at the Bureau du Commerce, and finally communal academic research through the experiments on diamonds using Tschirnhaus’s lens. These examples attempt to illustrate the innovative, creative, dynamic, multicultural, and multifaceted chemistry of the Enlightenment. © 2014 by The History of Science Society. 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.

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.

Duris D.,University Paris Diderot
Information Processing Letters | Year: 2012

The notions of γ and β-acyclicity are two classic generalizations of the acyclicity of graphs to hypergraphs. They satisfy the property that, if a hypergraph is γ-acyclic then it is β-acyclic, and the reverse is false. We give some new properties concerning these notions. First we show that we can strictly insert another notion of acyclicity between them, namely the fact of having a join tree with disjoint branches. And if we add a condition on the existence of such a join tree, we obtain a notion equivalent to γ-acyclicity. Then we present two characterizations, consisting in applying successively a small set of rules, deciding γ and β-acyclicity respectively. © 2012 Elsevier B.V.