Marseille, France
Marseille, France

Aix-Marseille University is a public research university located in Provence, southern France. With roots dating back to 1409, the university was formed by the merger of the University of Provence, the University of the Mediterranean and Paul Cézanne University. The merger became effective on 1 January 2012, resulting in the creation of the largest university in France and the French-speaking world, with about 70,000 students. AMU has the largest financial endowment of any academic institution in the Francophone world, standing at €650 million.The university is organized around five main campuses situated in Aix-en-Provence and Marseille. Apart from its major campuses, AMU owns and operates facilities in Arles, Aubagne, Avignon, Digne-les-Bains, Gap, La Ciotat, Lambesc and Salon-de-Provence. The university is headquartered at the Pharo, Marseille.AMU has produced many notable alumni in the fields of law, politics, business, economics and literature. To date, there have been four Nobel Laureates amongst its alumni and faculty, as well as a two-time recipient of the Pulitzer Prize, three César Award winners, several heads of state, parliamentary speakers, government ministers, ambassadors and members of the Institut de France.AMU has hundreds of research and teaching partnerships, including close collaboration with the French National Centre for Scientific Research and the French Atomic Energy and Alternative Energies Commission . AMU is a member of numerous academic organisations including the European University Association and the Mediterranean Universities Union . Wikipedia.

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Aix - Marseille University | Date: 2015-03-10

The invention relates to a chimeric peptide displaying the ganglioside-binding properties of both -synuclein and -amyloid peptide. Such peptide is useful in preventing or treating any condition which involves gangliosides as cell surface receptor sites, including neurodegenerative disorders, infectious diseases, or tumors.

French National Center for Scientific Research and Aix - Marseille University | Date: 2015-04-09

A device for quantifying a useful thermal energy available in a tank for storing a heated or cooled fluid or solid includes: a plurality of thermoelectric converters configured to be distributed in plural locations of the storage tank; an electric circuit interconnecting the thermoelectric converters; a device measuring a single electrical variable of the electric circuit; and a converter converting a single measurement of the single electrical variable into a value for quantification of the useful thermal energy available in the storage tank.

French Institute of Health, Medical Research, Aix - Marseille University and Gfrs Groupe Francophone Of Recherche Sur La Sclerodermie Systemique | Date: 2015-03-12

The present invention relates to an in vitro method for diagnosing lupus in a subject, said method comprising the step of detecting in a biological sample obtained from the subject the autoantibody recognizing the protein biomarker THEX1. More, the invention relates to kits and array useful for carrying out diagnosis methods according to the present invention.

Aix - Marseille University and French National Center for Scientific Research | Date: 2015-05-11

The present invention relates to a method for displaying a graphical interface having display areas including a reference area, wherein each file of a file set is displayed in the form of an icon in one of the display areas, and each file of the file set contains a unique identifier identifying the file, and processing a command for inserting into the file set a selected pre-existing file which does not belong to the file set, the processing of the insertion command including the steps of: generating a new file in the file set, from the content of the selected pre-existing file, generating a unique identifier identifying the new file, and inserting into the new file the generated unique identifier and a reference link generated from a file identifier corresponding to each icon located in the reference area.

French National Center for Scientific Research and Aix - Marseille University | Date: 2017-01-11

The present invention relates to a compound of formula (I) or (II) and its use for detecting and/or quantifying a solvent S_(1) in a solvent S_(2), S_(1) and S_(2) being distinct:_(1), R_(2), R_(3), R_(4), R_(5), R_(6), X, Y and n are as defined in claim 1.

French National Center for Scientific Research and Aix - Marseille University | Date: 2017-04-19

The disclosure relates to a layer comprising at least one hydrophilic part and at least one hydrophobic part, the layer comprising self-assembled amphiphilic molecules polymerized with each other on both the hydrophilic part and the hydrophobic part of the layer; a detecting device comprising a substrate and the above-mentioned layer; and a liposome, a micelle, transport system for a substance and a biomimetic system comprising the above-mentioned layer. The disclosure also relates to a process for producing a layer, the process comprising: providing amphiphilic molecules; allowing sufficient time for the amphiphilic molecules to self-assemble and form at least one hydrophilic part and at least one hydrophobic part of the layer; polymerizing the self-assembled amphiphilic molecules with each other on both the hydrophilic part and the hydrophobic part of the layer.

Speziale S.,Aix - Marseille University
Journal of Mathematical Physics | Year: 2017

We study the SL(2,C) Clebsch-Gordan coefficients appearing in the Lorentzian EPRL spin foam amplitudes for loop quantum gravity.We show how the amplitudes decompose into SU(2) nj-symbols at the vertices and integrals over boosts at the edges. The integrals define edge amplitudes that can be evaluated analytically using and adapting results in the literature, leading to a pure state sum model formulation. This procedure introduces virtual representations which, in a manner reminiscent of virtual momenta in Feynman amplitudes, are off-shell of the simplicity constraints present in the theory, but with the integrands that peak at the on-shell values.We point out some properties of the edge amplitudes which are helpful for numerical and analytical evaluations of spin foam amplitudes, and suggest among other things a simpler model useful for calculations of certain lowest order amplitudes. As an application, we estimate the large spin scaling behaviour of the simpler model, on a closed foam with all 4-valent edges and Euler characteristic X, to be N x-5E+V/2. The paper contains a review and an extension of the results on SL(2, C) Clebsch-Gordan coefficients among unitary representations of the principal series that can be useful beyond their application to quantum gravity considered here. Published by AIP Publishing.

Quintard A.,Aix - Marseille University | Rodriguez J.,Aix - Marseille University
Organic Letters | Year: 2017

Organocatalyzed enantioselective consecutive Michael addition of diethyl glutaconate to a nitro-olefin/reductive cyclization sequence has been developed, directly providing NH-free trans,trans-2,3,4-trisubstituted pyrrolidines with typically >88:12 dr and >90% ee. The obtained structures are closely related to several molecules with high biological profiles, holding great promise for medicinal chemistry. In addition, their potential as direct organocatalysts in the enantioselective Michael addition promoted by enamine activation is also reported. © 2017 American Chemical Society.

Lafage R.,Aix - Marseille University
Spine | Year: 2017

STUDY DESIGN.: Retrospective review OBJECTIVE.: Investigate the role of lower limbs compensation with progressive sagittal malalignment SUMMARY OF BACKGROUND DATA.: While lower limb compensatory mechanisms are an established response to progressive sagittal malalignment, their specific role and potential impact on surgical planning has not been evaluated. METHODS.: Single center retrospective review of full body xrays was performed in patients >20 yrs. Parameters were measured with dedicated software. Population was stratified by 50?mm intervals of SVA and one-way ANOVA was performed to compare P.shift (P.Shift=antero-posterior translation of the pelvis versus the feet) across SVA groups. Antero-posterior offset of each vertebra in relation to a vertical line extended from the distal tibial metaphysis (TM) was investigated. Linear regression was performed to predict Pelvic Tilt (PT) using Knee angle (KA) and P.Shift, while controlling for pelvic incidence minus lumbar lordosis mismatch (PI-LL) and SVA. RESULTS.: 2124 patient visits were included (PI=55.1?±?14.1°, PT=21.0?±?11°, PI-LL=6.3?±?17.3°, SVA=29?±?51?mm). With progressively increased SVA, P.shift decreased from 30 to −100?mm (all p?

STUDY DESIGN.: High resolution imaging and biomechanical investigation of ex-vivo vertebrae OBJECTIVE.: To assess bone microarchitecture of cadaveric vertebrae using ultra-high field (UHF) 7 Tesla magnetic resonance imaging (MRI) and to determine whether the corresponding microarchitecture parameters were related to BMD and bone strength assessed by dual energy X-ray absorptiometry (DXA) and mechanical compression tests. SUMMARY OF BACKGROUND DATA.: Limitations of DXA for the assessment of bone fragility and osteoporosis have been recognized and criteria of microarchitecture alteration have been included in the definition of osteoporosis. Although vertebral fracture is the most common osteoporotic fracture, no study has assessed directly vertebral trabecular bone. microarchitecture. METHODS.: BMD of twenty four vertebrae (L2, L3, L4) from eight cadavers were investigated using DXA. The bone volume fraction (BVF), trabecular thickness (Tb.Th), and trabecular spacing (Tb.Sp) of each vertebra was quantified using UHF MRI. Measurements were performed by two operators in order to characterize the inter-rater reliability. The whole set of specimens underwent mechanical compression tests to failure and the corresponding failure stress was calculated. RESULTS.: The inter-rater reliability for bone microarchitecture parameters was good withintraclass correlation coefficients ranging from 0.82 to 0.94. Failure load and stress were significantly correlated with BVF, Tb.Sp and BMD (p?

Amgoud L.,French National Center for Scientific Research | Nouioua F.,Aix - Marseille University
International Journal of Approximate Reasoning | Year: 2017

Rule-based argumentation systems are developed for reasoning about defeasible information. They take as input a theory made of a set of facts, a set of strict rules, which encode strict information, and a set of defeasible rules which describe general behavior with exceptional cases. They build arguments by chaining such rules, define attacks between them, use a semantics for evaluating the arguments, and finally identify the plausible conclusions that follow from the theory. Undercutting is one of the main attack relations of such systems. It consists of blocking the application of defeasible rules when their exceptional cases hold. In this paper, we consider this relation for capturing all the different conflicts in a theory. We present the first argumentation system that uses only undercutting, and show that it satisfies the rationality postulates proposed in the literature. Finally, we fully characterize both its extensions and its plausible conclusions under various acceptability semantics. Indeed, we show full correspondences between extensions and sub-theories of the theory under which the argumentation system is built. © 2017 Elsevier Inc.

Tardy A.,Aix - Marseille University | Nicolas J.,University Paris - Sud | Gigmes D.,Aix - Marseille University | Lefay C.,Aix - Marseille University | Guillaneuf Y.,Aix - Marseille University
Chemical Reviews | Year: 2017

Cyclic monomers bearing either vinyl or exomethylene groups have the ability to be polymerized through a radical pathway via a ring-opening mechanism (addition-fragmentation process), leading to the introduction of functionalities in the polymer backbone. Radical ring-opening polymerization (rROP) combines the advantages of both ring-opening polymerization and radical polymerization, that is the preparation of polymers bearing heteroatoms in the backbone but with the ease and robustness of a radical process. This current review presents a comprehensive description of rROP by detailing: (i) the various monomers that polymerize through rROP; (ii) the main parameters that govern the rROP mechanism; (iii) the copolymerization by conventional or controlled/living radical polymerization between rROP monomers and traditional vinyl monomers to obtain copolymers with advanced properties; (iv) the different applications (low shrinkage materials and preparation of (bio)degradable materials) of rROP monomer-containing materials, and (v) the main alternatives to rROP to induce degradability to materials obtained by a radical polymerization. © 2017 American Chemical Society.

Carrier A.,Aix - Marseille University
Antioxidants and Redox Signaling | Year: 2017

The worldwide epidemic of obesity is a major public health concern. Obesity is a major risk factor for noncommunicable diseases such as type 2 diabetes and cardiovascular diseases, clustered in the so-called metabolic syndrome (MS). Other main chronic illnesses are promoted by excessive body weight, including cancer and neurodegenerative pathologies, both affecting a number of people worldwide. In recent years, the primary role of an excess of reactive oxygen species (oxidative stress) resulting from altered redox control in the etiology of all of these pathologies has been unveiled. Interestingly, it appears that oxidative stress is both the cause and the consequence of obesity and associated disorders. This Forum features reviews that recapitulate the current knowledge on the link between oxidative stress and MS in the physiopathology of different biological systems. © Mary Ann Liebert, Inc. 2017.

Borel P.,Aix - Marseille University | Desmarchelier C.,Aix - Marseille University
Nutrients | Year: 2017

Blood concentration of vitamin A (VA), which is present as different molecules, i.e., mainly retinol and provitamin A carotenoids, plus retinyl esters in the postprandial period after a VA-containing meal, is affected by numerous factors: dietary VA intake, VA absorption efficiency, efficiency of provitamin A carotenoid conversion to VA, VA tissue uptake, etc. Most of these factors are in turn modulated by genetic variations in genes encoding proteins involved in VA metabolism. Genome-wide association studies (GWAS) and candidate gene association studies have identified single nucleotide polymorphisms (SNPs) associated with blood concentrations of retinol and β-carotene, as well as with β-carotene bioavailability. These genetic variations likely explain, at least in part, interindividual variability in VA status and in VA bioavailability. However, much work remains to be done to identify all of the SNPs involved in VA status and bioavailability and to assess the possible involvement of other kinds of genetic variations, e.g., copy number variants and insertions/deletions, in these phenotypes. Yet, the potential usefulness of this area of research is exciting regarding the proposition of more personalized dietary recommendations in VA, particularly in populations at risk of VA deficiency. © 2017 by the authors. Licensee MDPI, Basel, Switzerland.

Finsinger W.,French National Center for Scientific Research | Giesecke T.,University of Gottingen | Brewer S.,University of Utah | Leydet M.,Aix - Marseille University
Ecology Letters | Year: 2017

Plant communities are not stable over time and biological novelty is predicted to emerge due to climate change, the introduction of exotic species and land-use change. However, the rate at which this novelty may arise over longer time periods has so far received little attention. We reconstruct the emergence of novelty in Europe for a set of baseline conditions over the past 15 000 years to assess past rates of emergence and investigate underlying causes. The emergence of novelty is baseline specific and, during the early-Holocene, was mitigated by the rapid spread of plant taxa. Although novelty generally increases as a function of time, climate and human-induced landscape changes contributed to a non-linear post-glacial trajectory of novelty with jumps corresponding to periods of rapid changes. Emergence of novelty accelerated during the past 1000 years. Historical cultural landscapes experienced a faster novelty development due to the contribution from anthropogenic land-cover changes. © 2017 John Wiley & Sons Ltd/CNRS.

Verga A.D.,Aix - Marseille University
European Physical Journal B | Year: 2017

We investigate the effect of spatial disorder on the edge states localized at the interface between two topologically different regions. Rotation disorder can localize the quantum walk if it is strong enough to change the topology, otherwise the edge state is protected. Nonlinear spatial disorder, dependent on the walker’s state, attracts the walk to the interface even for very large coupling, preserving the ballistic transport characteristic of the clean regime. © 2017, EDP Sciences, SIF, Springer-Verlag Berlin Heidelberg.

Maciejowski J.,Aix - Marseille University | Gaillard P.-H.L.,Aix - Marseille University
Nature Reviews Molecular Cell Biology | Year: 2017

Structure-specific endonucleases (SSEs) have key roles in DNA replication, recombination and repair, and emerging roles in transcription. These enzymes have specificity for DNA secondary structure rather than for sequence, and therefore their activity must be precisely controlled to ensure genome stability. In this Review, we discuss how SSEs are controlled as part of genome maintenance pathways in eukaryotes, with an emphasis on the elaborate mechanisms that regulate the members of the major SSE families — including the xeroderma pigmentosum group F-complementing protein (XPF) and MMS and UV-sensitive protein 81 (MUS81)-dependent nucleases, and the flap endonuclease 1 (FEN1), XPG and XPG-like endonuclease 1 (GEN1) enzymes — during processes such as DNA adduct repair, Holliday junction processing and replication stress. We also discuss newly characterized connections between SSEs and other classes of DNA-remodelling enzymes and cell cycle control machineries, which reveal the importance of SSE scaffolds such as the synthetic lethal of unknown function 4 (SLX4) tumour suppressor for the maintenance of genome stability. © 2017 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

Weissker H.-C.,Aix - Marseille University
Nanotechnology Materials and Devices Conference, NMDC 2016 - Conference Proceedings | Year: 2016

Noble metal particles are interesting for a large number of reasons. On the one hand, they are used in a plethora of applications. On the other hand, they are of huge fundamental interest because they allow us to study the transition between very small molecule-like clusters with discrete electronic states and spectra, and larger nanoparticles where the electronic structure approaches that of the smooth bands of bulk metal. Many of these clusters, but by no means all, show a strong localized surface-plasmon resonance (LSPR) which classically corresponds to a collective oscillation of the electrons and dominates the visible absorption spectrum, depending on a variety of parameters such as size, material, surrounding, and chemical configuration (as in alloys). © 2016 IEEE.

Medail F.,Aix - Marseille University
Regional Environmental Change | Year: 2017

The numerous Mediterranean islands (>10,000) are very important from a biodiversity point of view, both in term of plant species (numerous endemics, presence of ‘climate relicts’) and of ecosystems’ assemblage. These patterns can be explained by complex interactions between a highly heterogeneous historical biogeography and ecological processes related to diverse island conditions. Furthermore, most of the ups and downs of this biodiversity were closely linked with human pressures which have changed many times through the long socio-ecological history of these island landscapes since the Neolithic period. At present, insular plant biodiversity and rural landscapes are threatened by diverse global environmental changes related to urbanization, habitat fragmentation, unsustainable tourism and other practices (e.g. overgrazing, forest fires), and by other more recent drivers such as climate warming and aridification, sea-level rise and biological invasions. Some of these impacts will be exacerbated on islands because of no (or highly limited) adjacent areas of expansion, notably on the smallest ones (i.e. size < ca. 1000 ha). With regards to the biome crisis facing the Mediterranean basin and induced by human activities, islands constitute key ecological systems and ‘current refugia’ to ensure the long-term preservation of coastal plant biodiversity. They also represent fascinating ecological systems to disentangle the role of environmental versus human pressures on spatially simplified communities of the Mediterranean coastal areas. Future detailed studies of these ‘natural island microcosms’ could greatly improve our knowledge of the functional and evolutionary processes induced by rapid environmental changes in this region. © 2017 Springer-Verlag Berlin Heidelberg

Krauzlis R.J.,U.S. National Institutes of Health | Goffart L.,Aix - Marseille University | Hafed Z.M.,Werner Reichardt Center for Integrative Neuroscience
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2017

Ocular fixation is a dynamic process that is actively controlled by many of the same brain structures involved in the control of eye movements, including the superior colliculus, cerebellum and reticular formation. In this article, we review several aspects of this active control. First, the decision to move the eyes not only depends on target-related signals from the peripheral visual field, but also on signals from the currently fixated target at the fovea, and involves mechanisms that are shared between saccades and smooth pursuit. Second, eye position during fixation is actively controlled and depends on bilateral activity in the superior colliculi and medio-posterior cerebellum; disruption of activity in these circuits causes systematic deviations in eye position during both fixation and smooth pursuit eye movements. Third, the eyes are not completely still during fixation but make continuous miniature movements, including ocular drift and microsaccades, which are controlled by the same neuronal mechanisms that generate larger saccades. Finally, fixational eye movements have large effects on visual perception. Ocular drift transforms the visual input in ways that increase spatial acuity; microsaccades not only improve vision by relocating the fovea but also cause momentary changes in vision analogous to those caused by larger saccades. © 2017 The Authors.

Perrinet L.U.,Aix - Marseille University
Proceedings of the 2016 6th European Workshop on Visual Information Processing, EUVIP 2016 | Year: 2016

Natural images follow statistics inherited by the structure of our physical (visual) environment. In particular, a prominent facet of this structure is that images can be described by a relatively sparse number of features. We designed a sparse coding algorithm biologically-inspired by the architecture of the primary visual cortex. We show here that coefficients of this representation exhibit a power-law distribution. For each image, the exponent of this distribution characterizes sparseness and varies from image to image. To investigate the role of this sparseness, we designed a new class of random textured stimuli with a controlled sparseness value inspired by measurements of natural images. Then, we provide with a method to synthesize random textures images with a given sparseness statistics that match that of some class of natural images and provide perspectives for their use in neurophysiology. © 2016 IEEE.

Stefanovic S.,Aix - Marseille University | Zaffran S.,Aix - Marseille University
Mechanisms of Development | Year: 2017

Substantial experimental and epidemiological data have highlighted the interplay between nutritional and genetic factors in the development of congenital heart defects. Retinoic acid (RA), a derivative of vitamin A, plays a key role during vertebrate development including the formation of the heart. Retinoids bind to RA and retinoid X receptors (RARs and RXRs) which then regulate tissue-specific genes. Here, we will focus on the roles of RA signaling and receptors in gene regulation during cardiogenesis, and the consequence of deregulated retinoid signaling on heart formation and congenital heart defects. © 2016 Elsevier Ireland Ltd

Jordan B.,Aix - Marseille University
Medecine/Sciences | Year: 2017

A novel gene editing procedure based on a nuclease from the Argonaute protein family was described in mid-2016 and appeared to provide significant advantages over the now widely used CRISPR-Cas9 system. Attempts by numerous groups to use this technique have however been unsuccessful; several negative reports have been published in addition to many accounts of failure found in the "grey literature". It is unclear at this point whether this reflects an (unknown) critical experimental factor or hints at data misinterpretation, possibly even at outright fabrication of results. © 2017 médecine/sciences-Inserm.

Duruisseau K.,Aix - Marseille University
BSGLg | Year: 2014

Energy system is confronted with two limits attached to its attributes: depletion of fossil and fissile energies and the global warming. It is also confronted with a sustained increase in the world's energy demand. These elements force the system to a new energy transition. The emerging concept of energy transition is becoming a research problem for the geography. The aim of this paper is to characterize the place of geography in the construction of this concept from the point of view of space and geographical scales.

Rosato J.,Aix - Marseille University
High Energy Density Physics | Year: 2017

A summary of results obtained at the third Spectral Line Shape in Plasmas code comparison workshop (SLSP3) is given. As in the SLSP1 and SLSP2, a standardized set of case problems was decided on in advance and then investigated at the workshop. A presentation of these cases, together with a discussion of selected results, is provided here. © 2017 Elsevier B.V.

Chepoi V.,Aix - Marseille University | Dragan F.F.,Kent State University | Vaxes Y.,Aix - Marseille University
Proceedings of the Annual ACM-SIAM Symposium on Discrete Algorithms | Year: 2017

We investigate the impact the negative curvature has on the trafic congestion in large-scale networks. We prove that every Gromov hyperbolic network G admits a core, thus answering in the positive a conjecture by Jonckheere, Lou, Bonahon, and Baryshnikov, Internet Mathematics, 7 (2011) which is based on the experimental observation by Narayan and Saniee, Physical Review E, 84 (2011) that real-world networks with small hyperbolicity have a core congestion. Namely, we prove that for every subset X of vertices of a graph with δ-thin geodesic triangles (in particular, of a δ-hyperbolic graph) G there exists a vertex m of G such that the ball B(m; 4δ) of radius 4δ centered at m intercepts at least one half of the total ow between all pairs of vertices of X, where the ow between two vertices x; y 2 X is carried by geodesic (or quasi-geodesic) (x; y)-paths. Moreover, we prove a primal- dual result showing that, for any commodity graph R on X and any r ≥ 8δ; the size σr(R) of the least r-multi-core (i.e., the number of balls of radius r) intercepting all pairs of R is upper bounded by the maximum number of pairwise (2r-5δ)- Apart pairs of R and that an r-multi-core of size σr5δ(R) can be computed in polynomial time for every finite set X. Our result about total r-multi-cores is based on a Helly- type theorem for quasiconvex sets in δ-hyperbolic graphs (this is our second main result). Namely, we show that for any finite collection Q of pairwise intersecting δ-quasiconvex sets of a δ-hyperbolic graph G there exists a single ball B(c; 2ϵ + 5δ) intersecting all sets of Q. More generally, we prove that if Q is a collection of 2r-close (i.e., any two sets of Q are at distance ≤ 2r) δ-quasiconvex sets of a δ-hyperbolic graph G, then there exists a ball B(c; rϵ) of radius rϵ := maxf2ϵ + 5δ r + ϵ + 3δg intersecting all sets of Q. These kind of Helly-type results are also useful in geometric group theory. Using the Helly theorem for quasiconvex sets and a primal-dual approach, we show algorithmically that the mini- mum number of balls of radius 2ϵ + 5δ intersecting all sets of a family Q of δ-quasiconvex sets does not exceed the packing number of Q (maximum number of pairwise disjoint sets of Q). We extend the covering and packing result to set-families κQ in which each set is a union of at most κ ϵ-quasiconvex sets of a δ-hyperbolic graph G. Namely, we show that if r 2κ2πr and r(Q) is the maximum number of mutually 2r-apart members of κQ, then the minimum number of balls of radius r+2ϵ+6δ intersecting all members of κQ is at most 2κ2πr(κQ) and such a hitting set and a packing can be constructed in polynomial time for every finite κQ (this is our third main result). For set- families consisting of unions of κ balls in δ-hyperbolic graphs a similar result was obtained by Chepoi and Estellon (2007). In case of κ = 0 (trees) and δ = r = 0; (subtrees of a tree) we recover the result of Alon (2002) about the transversal and packing numbers of a set-family in which each set is a union of at most ϵ subtrees of a tree. Copyright © by SIAM.

Gry C.,Aix - Marseille University | Jenkins E.B.,Princeton University
Astronomy and Astrophysics | Year: 2017

Aims. Our aim is to characterize the conditions in the nearest interstellar cloud. Methods. We analyze interstellar absorption features in the full UV spectrum of the nearby (d = 24 pc) B8 IVn star α Leo (Regulus). Observations were obtained with STIS at high resolution and high signal-to-noise ratio by the HST ASTRAL Treasury program. We derive column densities for many key atomic species and interpret their partial ionizations. Results. The gas in front of α Leo exhibits two absorption components. The main one is kinematically identified as the local interstellar cloud (LIC) that surrounds the Sun. The second component is shifted by +5.6 km s-1 relative to the main component, in agreement with results for other lines of sight in this region of the sky, and shares its ionization and physical conditions. The excitation of the C II fine-structure levels and the ratio of Mg I to Mg II reveal a temperature T = 6500 (+750, -600) K and electron density n(e) = 0.11 (+0.025, -0.03) cm-3. Our investigation of the ionization balance yields the ion fractions for 10 different atoms and indicates that about 1/3 of the hydrogen atoms are ionized. Metals are significantly depleted onto grains, with sulfur showing [S/H] ∼ -0.27. N(H I) = 1.9 (+0.9, -0.6) × 1018 cm-3, which indicates that this partly neutral gas occupies only 2 to 8 parsecs (about 13%) of the space toward the star, with the remaining volume being filled with a hot gas that emits soft X-rays. We do not detect any absorption features from the highly ionized species that could be produced in an interface between the warm medium and the surrounding hot gas, possibly because of non-equilibrium conditions or a particular magnetic field orientation that reduces thermal conduction. Finally, the radial velocity of the LIC agrees with that of the Local Leo Cold Cloud, indicating that they may be physically related. © ESO, 2017.

Boussaa D.,Aix - Marseille University
Mechanics of Materials | Year: 2017

This study investigates the effects that an initial local eigenstrain field, when superimposed on the thermal eigenstrain field, has on the overall thermal expansion coefficients and heat capacities of thermoelastic composites. The study can also be seen as an investigation into how a local residual stress field affects these overall moduli, as initial eigenstrains are generally a source of residual stresses. The approach taken is thermodynamic. Expressions that include the superimposed eigenstrain field are developed for the overall moduli within the framework of small strain thermoelasticity with temperature dependent materials. These expressions, which are written in terms of the concentration tensors and residual fields (stress and strain fields given rise to by the eigenstrains under zero overall stress and strain, respectively), contain correction terms that are absent in the expressions developed within linear thermoelasticity. Taking into account the temperature dependence of the constituent moduli is shown to be essential to capture the effects of the superimposed eigenstrain field. A Ti–6Al–4V/ZrO2 composite is investigated for which the correction terms are found to be negligible for the heat capacities but significant for the thermal expansion coefficients. This suggests that, for applications with large temperature changes, using the linear-thermoelasticity-based expressions can affect the accuracy of the estimates of the overall moduli, and therefore the accuracy of thermostructural analyses of composite structures. The proposed expressions can be of use to estimate the overall thermoelastic moduli in contexts in which the strains remain small, temperature changes are large, and superimposed eigenstrains may be present. © 2016 Elsevier Ltd

Mouelhi A.E.,Aix - Marseille University
Proceedings - 2016 IEEE 28th International Conference on Tools with Artificial Intelligence, ICTAI 2016 | Year: 2016

Identifying tractable classes of constraint satisfaction problems (CSPs) has been studied over the past two decades, and is now a very active research domain. Recently, some works have shown the interest of these tractable classes from a different viewpoint. For example, it is known that if there is no broken triangle on each two values of a given variable in an arcconsistent binary CSP, then this variable can be eliminated without changing its satisfiability. Next, it has been proved that even when this rule cannot be applied, it may be the case that for a given pair of values no broken triangle occurs, if this is the case, then we can perform a domain-reduction operation which consists in merging these values while preserving satisfiability. In this paper, we show that partial or total presence of tractable properties in non-binary constraints is sufficient for them to be decomposable into a set of lower arity constraints while preserving equivalence. More precisely, we prove that the presence of bijection or Dual Broken Triangle Property in non-binary constraint permits to decompose it while preserving equivalence. © 2016 IEEE.

Consalvi J.-L.,Aix - Marseille University
AIP Conference Proceedings | Year: 2017

The time-averaged Radiative Transfer Equation (RTE) introduces two unclosed terms, known as 'absorption Turbulence Radiation Interaction (TRI)' and 'emission TRI'. Emission TRI is related to the non-linear coupling between fluctuations of the absorption coefficient and fluctuations of the Planck function and can be described without introduction any approximation by using a transported PDF method. In this study, a hybrid flamelet/ Stochastic Eulerian Field Model is used to solve the transport equation of the one-point one-time PDF. In this formulation, the steady laminar flamelet model (SLF) is coupled to a joint Probability Density Function (PDF) of mixture fraction, enthalpy defect, scalar dissipation rate, and soot quantities and the PDF transport equation is solved by using a Stochastic Eulerian Field (SEF) method. Soot production is modeled by a semi-empirical model and the spectral dependence of the radiatively participating species, namely combustion products and soot, are computed by using a Narrow Band Correlated-k (NBCK) model. The model is applied to simulate an ethylene/methane turbulent jet flame burning in an oxygen-enriched environment. Model results are compared with the experiments and the effects of taken into account Emission TRI on flame structure, soot production and radiative loss are discussed. © 2017 Author(s).

BACKGROUND:: Gemcitabine remains a pillar in pancreatic cancer treatment. However, toxicities are frequently observed. Dose adjustment based on therapeutic drug monitoring might help decrease the occurrence of toxicities. In this context, this work aims at describing the pharmacokinetics (PK) of gemcitabine and its metabolite dFdU in pancreatic cancer patients and at identifying the main sources of their PK variability using a population pharmacokinetics approach, despite a sparse sampled-population and heterogeneous administration and sampling protocols. METHODS:: Data from 38 patients were included in the analysis. The three optimal sampling times were determined using KineticPro® and the population PK analysis was performed on Monolix®. Available patient characteristics, including cytidine deaminase (CDA) status, were tested as covariates. Correlation between PK parameters and occurrence of severe hematological toxicities was also investigated. RESULTS:: A two-compartment model best fitted the gemcitabine and dFdU PK data (volume of distribution and clearance for gemcitabine: V1 = 45 L and CL1 = 4.03 L/min; for dFdU: V2 = 36 L and CL2 = 0.226 L/min). Renal function was found to influence gemcitabine clearance, and body surface area (BSA) to impact the volume of distribution of dFdU. However, neither CDA status nor the occurrence of toxicities was correlated to PK parameters. CONCLUSIONS:: Despite sparse sampling and heterogeneous administration and sampling protocols, population and individual PK parameters of gemcitabine and dFdU were successfully estimated using Monolix® population PK software. The estimated parameters were consistent with previously published results. Surprisingly, CDA activity did not influence gemcitabine PK, which was explained by the absence of CDA-deficient patients enrolled in the study. This work suggests that even sparse data are valuable to estimate population and individual PK parameters in patients, which will be usable to individualize the dose for an optimized benefit to risk ratio. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

Fournier P.-E.,Aix - Marseille University
Microbiology Spectrum | Year: 2016

The origins of human infectious diseases have long fascinated scientists worldwide. Paleomicrobiology offers a unique access to the history of these infections and sheds light on ancient and historical epidemics. In this chapter, we review the paleomicrobiological evidence for Bartonella infections. © 2016 American Society for Microbiology.

Raoult D.,Aix - Marseille University
Microbiology Spectrum | Year: 2016

We have been involved in the field of paleomicrobiology since 1998, when we used dental pulp to identify Yersinia pestis as the causative agent of the great plague of Marseille (1720). We recently designed a specific technique, "suicide PCR," that can prevent contamination. A controversy arose between two teams, with one claiming that DNA must be altered to amplify it and the other group claiming that demographic data did not support the role of Y. pestis in the Black Death (i.e., the great plague of the Middle Ages). These controversies led us to evaluate other epidemiological models and to propose the body louse as the vector of this pandemic. This proposal was substantiated by experimental models, the recovery of Y. pestis from lice in the Congo, and the identification of epidemics involving both Y. pestis and Bartonella quintana (the agent of trench fever, transmitted by the body louse) in ancient corpses from mass graves. Paleomicrobiology has led to a re-evaluation of plague pandemics. © 2016 American Society for Microbiology.

Drancourt M.,Aix - Marseille University
Microbiology Spectrum | Year: 2016

The authenticity of some of the very first works in the field of paleopathology has been questioned, and standards have been progressively established for the experiments and the interpretation of data. Whereas most problems initially arose from the contamination of ancient specimens with modern human DNA, the situation is different in the field of paleomicrobiology, in which the risk for contamination is well-known and adequately managed by any laboratory team with expertise in the routine diagnosis of modern-day infections. Indeed, the exploration of ancient microbiota and pathogens is best done by such laboratory teams, with research directed toward the discovery and implementation of new techniques and the interpretation of data. © 2016 American Society for Microbiology.

Lawrence T.,Aix - Marseille University
Microbiology Spectrum | Year: 2016

The functional and phenotypic diversity of macrophages has long been appreciated, and it is now clear that it reflects a complex interplay between hard-wired differentiation pathways and instructive signals in specific tissues (Lawrence T, Natoli G. 2011, Nat Rev Immunol 11:750-761). Recent studies have begun to unravel the molecular basis for the integration of these intrinsic developmental pathways with extracellular signals from the tissue microenvironment that confer the distinct phenotypes of tissue-resident macrophages (Lavin Y et al. 2014. Cell 159:1312-1326; Gosselin D et al. 2014. Cell 159:1327-1340). Macrophage phenotype and function is particularly dynamic during inflammation or infection, as blood monocytes are recruited into tissues and differentiate into macrophages, and depending on the nature of the inflammatory stimulus, they may acquire distinct functional phenotypes (Xue J et al. 2014. Immunity 40:274-288; Murray PJ et al. 2014. Immunity 41:14-20). Furthermore, these functional activation states can be rapidly modified in response to a changing microenvironment. Here we will discuss several key signaling pathways that drive macrophage activation during the inflammatory response and discuss how these pathways are integrated to "fine-tune" macrophage phenotype and function. © 2016 American Society for Microbiology. All rights reserved.

Aboudharam G.,Aix - Marseille University
Microbiology Spectrum | Year: 2016

The Paleomicrobiology establishes the diagnosis of ancient infectious diseases by studying ancient pathogens. This recent science also analyzes the evolution of these pathogens, virulence, and their adaptation to their habitat and their vectors. The DNA persists a long time after the death of an organism despite the chemical and enzymatic degradation. The possibility of sequencing bacterial, viral, parasitic and archaeal DNA molecules persists over time. Various sources are used for these studies: frozen tissue and particularly human tissue are a exceptional source for the analysis because at very low temperatures, all biological activity is suspended. The coprolites are a source of choice for studying the human microbiome. Other sources, the ancient bones are the most abundant, however, they may contain only small amounts of DNA due to natural leaching. When the use of the tooth is possible, is a particularly interesting source because of its highly mineralized structure, which gives greater persistence than bone. The calcified tartar deposited on teeth is a source of interest for the study of oral microbiome. All these sources are subject to precautions (gloves and masks hat) at the time of sampling to avoid cross contamination and also be listed in the most precise way because they are precious and rare. © 2016 American Society for Microbiology.

Daulat A.M.,Aix - Marseille University | Borg J.-P.,Aix - Marseille University
Trends in Cancer | Year: 2017

Cancer cells are addicted to a large spectrum of extracellular cues implicated in initiation, stem cell renewal, tumor growth, dissemination in the body, and resistance to treatment. Wingless/Int-1 (Wnt) ligands and their associated signaling cascades contribute to most of these processes, paving the way for opportunities in therapeutic development. The developmental Wnt/planar cell polarity (PCP) pathway is the most recently described branch of Wnt signaling strongly implicated in cancer development at early and late stages. We describe here some of the latest knowledge accumulated on this pathway and the pending questions, present the most convincing findings about its role in cancer, and review the most promising strategies currently designed to target its components. Noncanonical Wingless/Int-1 (Wnt)/planar cell polarity (PCP) signaling is known to control the orientation of the epithelial sheet orthogonal to the apicobasal polarity and convergent-extension movements at the early stage of gastrulation during vertebrate development. An evolutionarily conserved group of molecules called core PCP proteins regulates these processes through poorly known mechanisms.Wnt/PCP has been documented to control cancer cell proliferation, migration, and resistance to cell death.Elevation of the expression of the core components of Wnt/PCP during cancer progression is often correlated with poor patient outcome.Therapeutics designed to target the Wnt/PCP pathway are currently under investigation in clinical trials. © 2017 Elsevier Inc.

Mattalia J.-M.R.,Aix - Marseille University
Beilstein Journal of Organic Chemistry | Year: 2017

This review presents an overview of the reductive decyanation reaction with a special interest for recent developments. This transformation allows synthetic chemists to take advantages of the nitrile functional group before its removal. Mechanistic details and applications to organic synthesis are provided. © 2017 Mattalia; licensee Beilstein-Institut.

Zhang D.,East China Normal University | Zhang D.,Ecole Normale Superieure de Lyon | Martinez A.,Ecole Normale Superieure de Lyon | Martinez A.,Aix - Marseille University | Dutasta J.-P.,Ecole Normale Superieure de Lyon
Chemical Reviews | Year: 2017

In the wide area of host-guest chemistry, hemicryptophanes, combining a cyclotribenzylene (or cyclotriveratrylene CTV) unit with another different C3-symmetrical moiety, appears as a recent family of molecular cages. The synthesis and recognition properties of the first hemicryptophane were reported in 1982 by Collet and Lehn, but the very little attention received by this class of host compounds in the 20 years following this first promising result can account for their apparent novelty. Indeed, in the last 10 years hemicryptophanes have aroused growing interest, and new aspects have been developed. Thanks to the rigid shaping unit of the north part (CTV) and also the variable and easily functionalized south moiety, hemicryptophanes are revealed to be inherently chiral ditopic host compounds, able to encapsulate various guests, including charged and neutral species. They also enter the field of stimuli-responsive supramolecular systems exhibiting controlled functions. Moreover, endohedral functionalization of their inner cavity leads to supramolecular catalysts. The confinement of the catalytic center affords nanoreactors with improved catalytic activities or selectivities when compared to model systems without a cavity. The current trend shows that reactions in the confined space of synthetic hosts, mimicking enzyme behavior, will expand rapidly in the near future. © 2017 American Chemical Society.

Adam F.,University of Avignon | Abert-Vian M.,University of Avignon | Peltier G.,Aix - Marseille University | Chemat F.,University of Avignon
Bioresource Technology | Year: 2012

In order to comply with criteria of green chemistry concepts and sustainability, a new procedure has been performed for solvent-free ultrasound-assisted extraction (UAE) to extract lipids from fresh Nannochloropsis oculata biomass. Through response surface methodology (RSM) parameters affecting the oil recovery were optimized. Optimum conditions for oil extraction were estimated as follows: (i) 1000. W ultrasonic power, (ii) 30. min extraction time and (iii) biomass dry weight content at 5%. Yields were calculated by the total fatty acids methyl esters amounts analyzed by GC-FID-MS. The maximum oil recovery was around 0.21%. This value was compared with the one obtained with the conventional extraction method (Bligh and Dyer). Furthermore, effect of temperature on the yield was also investigated. The overall results show an innovative and effective extraction method adapted for microalgae oil recovery, without using solvent and with an enable scaling up. © 2012 Elsevier Ltd.

Kuhnt W.,University of Kiel | Holbourn A.,University of Kiel | Moullade M.,Aix - Marseille University
Geology | Year: 2011

The onset of the early Aptian oceanic anoxic event (OAE) 1a (ca. 120 Ma) coincided with a major perturbation of the carbon cycle, which is reflected in the sedimentary carbon isotope record. Triggering mechanisms, duration, and climatic repercussions of this episode of accelerated organic matter burial remain poorly constrained. Here, we present millennialscale bulk rock carbon and oxygen isotope data from a marly subtropical intrashelf basin (La Bédoule, southeast France) with unusually high sedimentation rates, which track the onset of OAE1a in unprecedented resolution. Our record reveals that the negative, low-amplitude δ13C excursion preceding OAE1a lasted >100 k.y., implying that enhanced volcanic CO2 emission and/or pulsed methane dissociation over a prolonged time span were instrumental in triggering OAE1a. The main positive carbon isotope shift at the onset of OAE1a, previously regarded as continuous, occurred stepwise over an extended period of >300 k.y. Transient climate cooling during the initial δ13C increase probably reflects ephemeral high-latitude glaciation, triggered by changes in radiative forcing and drawdown of atmospheric CO2. © 2011 Geological Society of America.

Chinot O.L.,Aix - Marseille University | Wick W.,German Cancer Research Center | Mason W.,Princess Margaret Hospital | Henriksson R.,Regional Cancer Center | And 12 more authors.
New England Journal of Medicine | Year: 2014

BACKGROUND: Standard therapy for newly diagnosed glioblastoma is radiotherapy plus temozolomide. In this phase 3 study, we evaluated the effect of the addition of bevacizumab to radiotherapy-temozolomide for the treatment of newly diagnosed glioblastoma. METHODS: We randomly assigned patients with supratentorial glioblastoma to receive intravenous bevacizumab (10 mg per kilogram of body weight every 2 weeks) or placebo, plus radiotherapy (2 Gy 5 days a week; maximum, 60 Gy) and oral temozolomide (75 mg per square meter of body-surface area per day) for 6 weeks. After a 28-day treatment break, maintenance bevacizumab (10 mg per kilogram intravenously every 2 weeks) or placebo, plus temozolomide (150 to 200 mg per square meter per day for 5 days), was continued for six 4-week cycles, followed by bevacizumab monotherapy (15 mg per kilogram intravenously every 3 weeks) or placebo until the disease progressed or unacceptable toxic effects developed. The coprimary end points were investigator-assessed progression-free survival and overall survival. RESULTS: A total of 458 patients were assigned to the bevacizumab group, and 463 patients to the placebo group. The median progression-free survival was longer in the bevacizumab group than in the placebo group (10.6 months vs. 6.2 months; stratified hazard ratio for progression or death, 0.64; 95% confidence interval [CI], 0.55 to 0.74; P<0.001). The benefit with respect to progression-free survival was observed across subgroups. Overall survival did not differ significantly between groups (stratified hazard ratio for death, 0.88; 95% CI, 0.76 to 1.02; P = 0.10). The respective overall survival rates with bevacizumab and placebo were 72.4% and 66.3% at 1 year (P = 0.049) and 33.9% and 30.1% at 2 years (P = 0.24). Baseline health-related quality of life and performance status were maintained longer in the bevacizumab group, and the glucocorticoid requirement was lower. More patients in the bevacizumab group than in the placebo group had grade 3 or higher adverse events (66.8% vs. 51.3%) and grade 3 or higher adverse events often associated with bevacizumab (32.5% vs. 15.8%). CONCLUSIONS: The addition of bevacizumab to radiotherapy-temozolomide did not improve survival in patients with glioblastoma. Improved progression-free survival and maintenance of baseline quality of life and performance status were observed with bevacizumab; however, the rate of adverse events was higher with bevacizumab than with placebo. Copyright © 2014 Massachusetts Medical Society.

Roques L.,French National Institute for Agricultural Research | Cristofol M.,Aix - Marseille University
Nonlinearity | Year: 2010

This paper is devoted to the analysis of some uniqueness properties of a classical reaction-diffusion equation of the Fisher-KPP type, coming from population dynamics in heterogeneous environments. We work in a one-dimensional interval (a, b) and we assume a nonlinear term of the form u (μ(x) - γu) where μ belongs to a fixed subset of C0([a, b]). We prove that the knowledge of u at t = 0 and of u, ux at a single point x0 and for small times t ∈ (0, ε) is sufficient to completely determine the couple (u(t, x), μ(x)) provided γ is known. Additionally, if uxx(t, x0) is also measured for t ∈ (0, ε), the triplet (u(t, x), μ(x), γ) is also completely determined. Those analytical results are completed with numerical simulations which show that, in practice, measurements of u and ux at a single point x0 (and for t ∈ (0, ε)) are sufficient to obtain a good approximation of the coefficient μ(x). These numerical simulations also show that the measurement of the derivative ux is essential in order to accurately determine μ(x). © 2010 IOP Publishing Ltd and London Mathematical Society.

Hernandez S.B.,University of Seville | Cota I.,University of Seville | Ducret A.,Aix - Marseille University | Aussel L.,Aix - Marseille University | Casadesus J.,University of Seville
PLoS Genetics | Year: 2012

Bile possesses antibacterial activity because bile salts disrupt membranes, denature proteins, and damage DNA. This study describes mechanisms employed by the bacterium Salmonella enterica to survive bile. Sublethal concentrations of the bile salt sodium deoxycholate (DOC) adapt Salmonella to survive lethal concentrations of bile. Adaptation seems to be associated to multiple changes in gene expression, which include upregulation of the RpoS-dependent general stress response and other stress responses. The crucial role of the general stress response in adaptation to bile is supported by the observation that RpoS - mutants are bile-sensitive. While adaptation to bile involves a response by the bacterial population, individual cells can become bile-resistant without adaptation: plating of a non-adapted S. enterica culture on medium containing a lethal concentration of bile yields bile-resistant colonies at frequencies between 10 -6 and 10 -7 per cell and generation. Fluctuation analysis indicates that such colonies derive from bile-resistant cells present in the previous culture. A fraction of such isolates are stable, indicating that bile resistance can be acquired by mutation. Full genome sequencing of bile-resistant mutants shows that alteration of the lipopolysaccharide transport machinery is a frequent cause of mutational bile resistance. However, selection on lethal concentrations of bile also provides bile-resistant isolates that are not mutants. We propose that such isolates derive from rare cells whose physiological state permitted survival upon encountering bile. This view is supported by single cell analysis of gene expression using a microscope fluidic system: batch cultures of Salmonella contain cells that activate stress response genes in the absence of DOC. This phenomenon underscores the existence of phenotypic heterogeneity in clonal populations of bacteria and may illustrate the adaptive value of gene expression fluctuations. © 2012 Hernández et al.

Borel P.,French National Institute for Agricultural Research | Borel P.,French Institute of Health and Medical Research | Borel P.,Aix - Marseille University
Molecular Nutrition and Food Research | Year: 2012

As shown in most clinical studies dedicated to carotenoids, there is a huge interindividual variability in absorption, and blood and tissue responses, of dietary carotenoids. The recent discovery that several proteins are involved in carotenoid metabolism in humans has prompted a possible explanation for this phenomenon: genetic variants in genes encoding for these proteins may affect their expression or activity, and in turn carotenoid metabolism and carotenoid status. The proteins clearly identified so far are (i) the carotene oxygenases β,β-carotene-15,15′-monooxygenase (BCMO1) and β,β-carotene-9′,10′-oxygenase (BCDO2), which are involved in carotenoid cleavage, (ii) scavenger receptor class B type I (SR-BI), cluster determinant 36 (CD36), and Niemann Pick C1-like 1 (NPC1L1), which are involved in carotenoid uptake by cells, and (iii) glutathione S-transferase Pi 1 (GSTP1) and human retinal lutein-binding protein (HR-LBP), which are involved in the transport of xanthophylls in the retina. Other proteins, such as ATP-binding cassette subfamily G member 5 (ABCG5) and the fatty acid-binding proteins (FABPs) are also apparently involved although firmer evidence is still required. A genome-wide association study, as well as several candidate gene association studies, has shown that groups of subjects bearing different alleles in single nucleotide polymorphisms located in or near several of the above-mentioned genes display different blood and/or tissue concentrations of carotenoids. Further studies are needed to identify all the proteins involved in carotenoid metabolism and assess whether other types of genetic variation, e.g. copy number variants and epigenetic modifications, can modulate carotenoid status. One potential application of such research could be personalized dietary guidelines for carotenoids according to individual genetic characteristics. © 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Robaglia C.,Aix - Marseille University | Thomas M.,University Paris - Sud | Meyer C.,French National Institute for Agricultural Research
Current Opinion in Plant Biology | Year: 2012

The perception of nutrient and energy levels inside and outside the cell is crucial to adjust growth and metabolism to available resources. The signaling pathways centered on the conserved TOR and SnRK1/Snf1/AMPK kinases have crucial and numerous roles in nutrient and energy sensing and in translating this information into metabolic and developmental adaptations. In plants evidence is mounting that, like in other eukaryotes, these signaling pathways have pivotal and antagonistic roles in connecting external or intracellular cues to many biological processes, including ribosome biogenesis, regulation of translation, cell division, accumulation of reserves and autophagy. Data on the plant TOR pathway have been hitherto rather scarce but recent findings have shed new light on its roles in plants. Moreover, the distinctive energy metabolism of photosynthetic organisms may reveal new features of these ancestral eukaryotic signaling elements. © 2012 Elsevier Ltd.

Vacher H.,French Institute of Health and Medical Research | Vacher H.,Aix - Marseille University | Trimmer J.S.,University of California at Davis
Pflugers Archiv European Journal of Physiology | Year: 2011

Voltage-gated ion channels are a diverse family of signaling proteins that mediate rapid electrical signaling events. Among these, voltage-gated potassium or Kv channels are the most diverse partly due to the large number of principal (or α) subunits and auxiliary subunits that can assemble in different combinations to generate Kv channel complexes with distinct structures and functions. The diversity of Kv channels underlies much of the variability in the active properties between different mammalian central neurons and the dynamic changes that lead to experience-dependent plasticity in intrinsic excitability. Recent studies have revealed that Kv channel α subunits and auxiliary subunits are extensively phosphorylated, contributing to additional structural and functional diversity. Here, we highlight recent studies that show that auxiliary subunits exert some of their profound effects on dendritic Kv4 and axonal Kv1 channels through phosphorylation-dependent mechanisms, either due to phosphorylation on the auxiliary subunit itself or by influencing the extent and/or impact of α subunit phosphorylation. The complex effects of auxiliary subunits and phosphorylation provide a potent mechanism to generate additional diversity in the structure and function of Kv4 and Kv1 channels, as well as allowing for dynamic reversible regulation of these important ion channels. © 2011 Springer-Verlag.

Vieux F.,Aix - Marseille University | Soler L.-G.,French National Institute for Agricultural Research | Touazi D.,French National Institute for Agricultural Research | Darmon N.,Aix - Marseille University | Darmon N.,French Institute of Health and Medical Research
American Journal of Clinical Nutrition | Year: 2013

Background: Healthy diets are supposed to be more environmentally friendly because they rely mainly on plant-based foods, which have lower greenhouse gas emissions (GHGEs) per unit weight than do animal-based foods. Objectives: The objectives were to estimate the GHGEs associated with the consumption of self-selected diets in France and to analyze their relation with the nutritional quality of diets. Design: For each adult in the national dietary Individual and National Survey on Food Consumption (n = 1918), the GHGEs of his or her diet were estimated based on the GHGEs of 391 foods. Highestnutritional- quality diets were defined as those having simultaneously 1) an energy density below the median, 2) a mean adequacy ratio (MAR) above the median, and 3) a mean excess ratio (MER, percentage of maximum recommended values for nutrients for which intake should be limited) below the median. Results: MAR was positively correlated and MER was negatively correlated with diet-related GHGEs. High-nutritional-quality diets contained more plant-based foods, notably fruit and vegetables, and fewer sweets and salted snacks than did low-quality diets. After adjustment for age, sex, and energy intake, the consumption of sweets and salted snacks was negatively correlated with diet-related GHGEs, whereas the consumption of animal products and of fruit and vegetables was positively associated with them. After adjustment for energy intake, high-nutritional- quality diets had significantly higher GHGEs (+9% and +22% for men and women, respectively) than did lownutritional- quality diets. Conclusion: Despite containing large amounts of plant-based foods, self-selected diets of the highest nutritional quality are currently not those with the lowest diet-related GHGEs. © 2013 American Society for Nutrition.

Vieux F.,Aix - Marseille University | Darmon N.,Aix - Marseille University | Touazi D.,French National Institute for Agricultural Research | Soler L.G.,French National Institute for Agricultural Research
Ecological Economics | Year: 2012

The aim was to estimate the greenhouse gas emissions (GHGE) associated with self-selected diets and to evaluate the impact of modifying dietary structures on diet-associated GHGE. Food consumption data from 1918 adults participating in the French national dietary survey and GHGE of 73 highly consumed foods (in g CO 2e/100g of edible food) were used to estimate the GHGE of each individual diet. The mean diet-associated GHGE was 4170g CO 2e/day and a high inter-individual variability was observed. When the total caloric intakes were reduced to meet the individual energy needs, the diet-associated GHGE decreased by either 10.7% or 2.4%, depending on the assumption made on the average physical activity level of the population. The meat and deli meat food group represented the strongest diet-associated GHGE contributor, but the impact of different meat reduction scenarios was modest. In particular, when fruit and vegetables were iso-calorically substituted for meat, either null or even positive diet-associated GHGE variations were observed because the needed amounts of fruit and vegetables to maintain the caloric content of the diet were high. Therefore, substituting fruit and vegetables for meat (especially deli meat) may be desirable for health but is not necessarily the best approach to decreasing diet-associated GHGE. © 2012 Elsevier B.V.

Lombard V.,CNRS Architecture and Functions of Biological Macromolecules Lab | Lombard V.,Aix - Marseille University | Golaconda Ramulu H.,CNRS Architecture and Functions of Biological Macromolecules Lab | Golaconda Ramulu H.,Aix - Marseille University | And 6 more authors.
Nucleic Acids Research | Year: 2014

The Carbohydrate-Active Enzymes database (CAZy; provides online and continuously updated access to a sequence-based family classification linking the sequence to the specificity and 3D structure of the enzymes that assemble, modify and breakdown oligo- and polysaccharides. Functional and 3D structural information is added and curated on a regular basis based on the available literature. In addition to the use of the database by enzymologists seeking curated information on CAZymes, the dissemination of a stable nomenclature for these enzymes is probably a major contribution of CAZy. The past few years have seen the expansion of the CAZy classification scheme to new families, the development of subfamilies in several families and the power of CAZy for the analysis of genomes and metagenomes. This article outlines the changes that have occurred in CAZy during the past 5 years and presents our novel effort to display the resolution and the carbohydrate ligands in crystallographic complexes of CAZymes. © 2013 The Author(s). Published by Oxford University Press.

Roques L.,French National Institute for Agricultural Research | Cristofol M.,Aix - Marseille University
Inverse Problems | Year: 2012

In this paper, we prove a uniqueness result in the inverse problem of determining several non-constant coefficients of a system of two parabolic equations, which corresponds to a Lotka-Volterra competition model. Our result gives a sufficient condition for the uniqueness of the determination of four coefficients of the system. This sufficient condition only involves pointwise measurements of the solution (u, v) of the system and of the spatial derivative u/x or v/x of one component at a single point x 0, during a time interval (0, ε). Our results are illustrated by numerical computations. © 2012 IOP Publishing Ltd.

Levasseur A.,French National Institute for Agricultural Research | Levasseur A.,Universites Aix Marseille 1 et 2 | Pontarotti P.,Aix - Marseille University
Biology Direct | Year: 2011

Understanding the evolutionary plasticity of the genome requires a global, comparative approach in which genetic events are considered both in a phylogenetic framework and with regard to population genetics and environmental variables. In the mechanisms that generate adaptive and non-adaptive changes in genomes, segmental duplications (duplication of individual genes or genomic regions) and polyploidization (whole genome duplications) are well-known driving forces. The probability of fixation and maintenance of duplicates depends on many variables, including population sizes and selection regimes experienced by the corresponding genes: a combination of stochastic and adaptive mechanisms has shaped all genomes. A survey of experimental work shows that the distinction made between fixation and maintenance of duplicates still needs to be conceptualized and mathematically modeled. Here we review the mechanisms that increase or decrease the probability of fixation or maintenance of duplicated genes, and examine the outcome of these events on the adaptation of the organisms.Reviewers: This article was reviewed by Dr. Etienne Joly, Dr. Lutz Walter and Dr. W. Ford Doolittle. © 2011 Levasseur and Pontarotti; licensee BioMed Central Ltd.

Lim J.P.,National University of Singapore | Devaux J.,Aix - Marseille University | Yuki N.,National University of Singapore
Autoimmunity Reviews | Year: 2014

Guillain-Barré syndrome is classified into acute inflammatory demyelinating polyneuropathy and acute motor axonal neuropathy. Whereas autoantibodies to GM1 or GD1a induce the development of acute motor axonal neuropathy, pathogenic autoantibodies have yet to be identified in acute inflammatory demyelinating polyneuropathy and chronic inflammatory demyelinating polyneuropathy. This review highlights the importance of autoantibodies to peripheral nerve proteins in the physiopathology of acute and chronic inflammatory demyelinating polyneuropathies. Moreover, we listed up other potential antigens, which may become helpful biomarkers for acquired, dysimmune demyelinating neuropathies based on their critical functions during myelination and their implications in hereditary demyelinating neuropathies. © 2014 Elsevier B.V.

Chen S.-F.,Beijing Normal University | Ferre N.,Aix - Marseille University | Liu Y.-J.,Beijing Normal University
Chemistry - A European Journal | Year: 2013

Aequorea victoria is a type of jellyfish that is known by its famous protein, green fluorescent protein (GFP), which has been widely used as a probe in many fields. Aequorea has another important protein, aequorin, which is one of the members of the EF-hand calcium-binding protein family. Aequorin has been used for intracellular calcium measurements for three decades, but its bioluminescence mechanism remains largely unknown. One of the important reasons is the lack of clear and reliable knowledge about the light emitters, which are complex. Several neutral and anionic forms exist in chemiexcited, bioluminescent, and fluorescent states and are connected with the H-bond network of the binding cavity in the protein. We first theoretically investigated aequorin chemiluminescence, bioluminescence, and fluorescence in real proteins by performing hybrid quantum mechanics and molecular mechanics methods combined with a molecular dynamics method. For the first time, this study reported the origin and clear differences in the chemiluminescence, bioluminescence and fluorescence of aequorin, which is important for understanding the bioluminescence not only of jellyfish, but also of many other marine organisms (that have the same coelenterazine caved in different coelenterazine-type luciferases). See jellyfish in a new light: The origin and differences in the chemiluminescence, bioluminescence, and fluorescence of the proteins of the aequorin jellyfish were theoretically investigated by using hybrid quantum mechanics and molecular mechanics methods combined with a molecular dynamics method. The findings are important for understanding the bioluminescence of jellyfish and other marine organisms (see figure). Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Devaux J.J.,Aix - Marseille University | Odaka M.,Dokkyo Medical University | Yuki N.,National University of Singapore
Journal of the Peripheral Nervous System | Year: 2012

Neurofascin-186 (NF186), neuronal cell adhesion molecule (NrCAM), and gliomedin are adhesion molecules playing a central role in the formation of nodes of Ranvier. In Guillain-Barré syndrome (GBS), immune attack toward the nodes may participate in the disabilities. Autoantibodies to NF186 and gliomedin have been detected in a rat model of GBS. Here, we investigated the prevalence of antibodies against nodal adhesion molecules in patients with GBS or chronic inflammatory demyelinating polyneuropathy (CIDP). Sera from 100 GBS patients, 50 CIDP patients, 80 disease controls, and 50 healthy controls were tested for their ability to bind the nodes of Ranvier. To characterize the antigens, we performed cell binding assays against NF186, gliomedin, contactin, and NrCAM. We found that 43% of patients with GBS and 30% of patients with CIDP showed IgG fixation at nodes or paranodes. In eight patients with GBS or CIDP, we identified that IgG antibodies recognized the native extracellular domain of NF186, gliomedin, or contactin. Also, 29 patients showed IgM against nodal adhesion molecules. However, we did not detect IgM fixation at nodes or paranodes. Antibodies to gliomedin or NF186 were mostly detected in demyelinating and axonal GBS, respectively. The adsorption of the antibodies to their soluble antigens abolished IgG deposition at nodes and paranodes in nerves, indicating these were specific to NF186, gliomedin, and contactin. In conclusion, gliomedin, NF186, and contactin are novel target antigens in GBS. At nodes, additional epitopes are also the targets of IgG. These results suggest that antibody attack against nodal antigens participates in the etiology of GBS. © 2012 Peripheral Nerve Society.

Perry C.,Swinburne University of Technology | Ziegler J.C.,Aix - Marseille University | Zorzi M.,University of Padua
Cognitive Psychology | Year: 2010

Most words in English have more than one syllable, yet the most influential computational models of reading aloud are restricted to processing monosyllabic words. Here, we present CDP++, a new version of the Connectionist Dual Process model (Perry, Ziegler, & Zorzi, 2007). CDP++ is able to simulate the reading aloud of mono- and disyllabic words and nonwords, and learns to assign stress in exactly the same way as it learns to associate graphemes with phonemes. CDP++ is able to simulate the monosyllabic benchmark effects its predecessor could, and therefore shows full backwards compatibility. CDP++ also accounts for a number of novel effects specific to disyllabic words, including the effects of stress regularity and syllable number. In terms of database performance, CDP++ accounts for over 49% of the reaction time variance on items selected from the English Lexicon Project, a very large database of several thousand of words. With its lexicon of over 32,000 words, CDP++ is therefore a notable example of the successful scaling-up of a connectionist model to a size that more realistically approximates the human lexical system. © 2010 Elsevier Inc.

Perry C.,Swinburne University of Technology | Ziegler J.C.,Aix - Marseille University | Zorzi M.,University of Padua
Cognitive Science | Year: 2013

It is often assumed that graphemes are a crucial level of orthographic representation above letters. Current connectionist models of reading, however, do not address how the mapping from letters to graphemes is learned. One major challenge for computational modeling is therefore developing a model that learns this mapping and can assign the graphemes to linguistically meaningful categories such as the onset, vowel, and coda of a syllable. Here, we present a model that learns to do this in English for strings of any letter length and any number of syllables. The model is evaluated on error rates and further validated on the results of a behavioral experiment designed to examine ambiguities in the processing of graphemes. The results show that the model (a) chooses graphemes from letter strings with a high level of accuracy, even when trained on only a small portion of the English lexicon; (b) chooses a similar set of graphemes as people do in situations where different graphemes can potentially be selected; (c) predicts orthographic effects on segmentation which are found in human data; and (d) can be readily integrated into a full-blown model of multi-syllabic reading aloud such as CDP++ (Perry, Ziegler, & Zorzi, 2010). Altogether, these results suggest that the model provides a plausible hypothesis for the kind of computations that underlie the use of graphemes in skilled reading. © 2013 Cognitive Science Society, Inc.

Kelly R.G.,Aix - Marseille University | Buckingham M.E.,Institute Pasteur Paris
Cold Spring Harbor Perspectives in Medicine | Year: 2014

In this review,we focus on two important steps in the formation of the embryonic heart: (i) the progressive addition of late differentiating progenitor cells from the second heart field that drives heart tube extension during looping morphogenesis, and (ii) the emergence of patterned proliferation within the embryonicmyocardium that generates distinct cardiac chambers. During the transition between these steps, the major site of proliferation switches from progenitor cells outside the early heart to proliferation within the embryonic myocardium. The second heart field and ballooning morphogenesis concepts have major repercussions on our understanding of human heart development and disease. In particular, they provide a framework to dissect the origin of congenital heart defects and the regulation of myocardial proliferation and differentiation of relevance for cardiac repair. © 2014 Cold Spring Harbor Laboratory Press; All rights reserved.

Megdiche M.,University of Sfax | Perrin-Pellegrino C.,Aix - Marseille University | Gargouri M.,University of Sfax
Journal of Alloys and Compounds | Year: 2014

The SrNiP2O7 compound was prepared by a solid-state reaction method. Electrical properties and modulus analysis were studied using complex impedance spectroscopy in the frequency range 200 Hz-5 MHz and temperature range 609-728 K. The difference of the value of activation energy for the bulk obtained from analysis of equivalent circuit (0.88 eV) and modulus relaxation (0.77 eV) confirms that the transport is not due from a simple hopping mechanism. The AC conductivity is studied using the following equation: σac(ω)=σs1+τ2 ω2+σ © 2013 Elsevier B.V. All rights reserved.

French National Institute for Agricultural Research, French Institute of Petroleum, French National Center for Scientific Research and Aix - Marseille University | Date: 2013-09-10

The invention relates to a multi-enzymatic preparation containing the secretome of the CNCM I-4639 strain of Aspergillus japonicus. This secretome, which contains in particular cellulases and hemicellulases, can be used for the saccharification of lignocellulosic substrates, in particular in combination with the secretome of Trichoderma reesei.

This project aims to understand what kind of social identity change is going on within European societies. For policy-making, the analysis of social identity is highly valuable because the social identity moderates the impact of policies. And this is particularly true in times of crisis. In particular, the project aims: A) to verify whether the symbolic universes grounding the social identity has undergone a major change within European societies, as a consequence of the socio-economic crisis; B) to draw strategic and methodological implications for policy-making from point A. This project includes 4 core scientific work packages: a) Multilevel Analysis of the Symbolic Universes, aimed at mapping structurally and developmentally the systems of meaning (i.e. the symbolic universes) grounding the social identity; b) Case Studies for policies, aimed at see how different policies have been organized and how their impact might or might not have been moderated by the symbolic dynamics at stake; c) the results of this analysis will be transformed into abstract criteria, contextualised in 5 different European macro-Regions, discussed with stakeholders, opinions leaders, policy-makers and finally stored within the guidelines; d) finally, the guidelines will be validated in terms of pertinence, effectiveness and the feasibility criteria, through seminars with the policy makers, opinion leaders and stakeholders, belonging to national, European, international Agencies involved in the construction and implementation of policies. Also, focus groups will be organized in each cultural context in order to study the impact of context-specific criteria.

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2010.2.3.3-2 | Award Amount: 21.90M | Year: 2010

RNA virus infections kill millions of humans annually, largely due to the lack of suitable vaccines and drugs to control them. This problem is addressed in this FP7 call and in response a consortium of Europes and Asias leading molecular virologists, structural biologists, medicinal chemists and bioinformaticians has been brought together to generate a state-of-the-art drug discovery and design programme. The project aims to identify Small molecule Inhibitor Leads Versus Emerging and neglected RNA viruses (SILVER). It will focus its activities on selected medically important RNA viruses for which the development of drugs is considered essential (Dengue-, entero- and paramyxoviruses), whereas other relatively neglected and/or emerging RNA viruses will be explored to identify the most promising viral protein targets and antiviral compounds. A pipeline strategy has been developed to enable the inclusion in SILVER of viruses at all levels of existing knowledge. Targets for potential drugs include infectious virus, structurally characterised viral enzymes and other proteins. Leads for currently available antiviral drugs have been identified by screening compound libraries in virus-infected cell culture systems and in vitro assays using purified viral enzymes. Selective inhibitors of viral replication have also been (and are being) derived using detailed structural knowledge of viral proteins and structure-based drug design. Hits will be assayed using individual viral protein targets and replicative proteins in complex with viral RNA. The potential protective activity of the most potent inhibitors, that have a favourable (in vitro) ADME-tox profile, will be assessed in relevant infection models in animals. Licenses on promising compounds or compound classes will be presented to the interested pharmaceutical industry. The SILVER consortium will be well placed to play a major role in contributing to the international effort to develop strategies to improve world health.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.2.1-7 | Award Amount: 10.33M | Year: 2009

Mitochondrial dysfunction is a major hallmark of various neurodegenerative disorders including Alzheimers disease, Parkinsons disease, Huntingtons diseases or Amyotrophic Lateral Sclerosis (ALS). However linking mitochondrial dysfunction to the pathogenesis of some of these diseases still needs to be elucidated. Furthermore, in pathologies where this link is already established, the question remains whether specific targets or mechanisms involved in mitochondrial dysfunction will be amenable to therapeutic intervention. MitoTarget is an ambitious project aimed at providing solid data to better understand and exploit the circumstantial evidence linking mitochondrial dysfunction with neuronal dysfunction culminating in neurodegenerative disease. A 36 months translational research program will bring together a unique partnership between basic scientists, a seasoned team of clinical investigators and a SME that has identified a first-in-class compound, TRO19622, that targets mitochondria and has powerful neuroprotective and neuroregenerative activities. In parallel, and orchestrated by the SME that is the coordinator of the project, MitoTarget will bring together a more comprehensive insight into the mechanisms leading to mitochondrial impairments and establish their clinical relevance in a severe orphan neurodegenerative disease, ALS. If successful, it is expected that from this proof of principle a new class of therapeutic agents targeting the underlying mitochondrial dysfunction in neurons or their supporting cells will emerge. Results of the project have the potential to create a new paradigm for the drug discovery for neurodegenerative diseases.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2011.9.7 | Award Amount: 7.86M | Year: 2012

Future advancements in ICT domain are closely linked to the understanding about how multi-level complex systems function. Indeed, multi-level dependencies may amplify cascade failures or make more sudden the collapse of the entire system. Recent large-scale blackouts resulting from cascades in the power-grid coupled to the control communication system witness this point very clearly. A better understanding of multi-level systems is essential for future ICTs and for improving life quality and security in an increasingly interconnected and interdependent world. In this respect, complex networks science is particularly suitable for the many challenges that we face today, from critical infrastructures and communication systems, to techno-social and socio-economic networks.MULTIPLEX proposes a substantial paradigm shift for the development of a mathematical, computational and algorithmic framework for multi-level complex networks. Firstly, this will lead to a significant progress in the understanding and the prediction of complex multi-level systems. Secondly, it will enable a better control, and optimization of their dynamics. By combining mathematical analyses, modelling approaches and the use of massive heterogeneous data sets, we shall address several prominent aspects of multi-level complex networks, i.e. their topology, dynamical organization and evolution.

Agency: European Commission | Branch: FP7 | Program: CP-CSA-Infra | Phase: INFRA-2008-1.1.1 | Award Amount: 8.38M | Year: 2009

During the past 70 years or more, thousands of viruses have been isolated and partly characterised by experts working in different countries worldwide. These viruses potentially provide a unique and extremely valuable medical and educational resource for research and development to understand the basis of virus diseases, and to develop modern state of the art strategies for disease control. However, nowhere in the world has there been an attempt to coordinate these collections of viruses so that they can be authenticated, amplified under quality-controlled conditions, stored long-term, and disseminated worldwide to laboratories engaged in fundamental and/or applied research. Without carefully coordinated intervention, these valuable resources will be lost to science and medicine. The objective of this project is therefore to develop a readily accessible virus reference library at the European level through the creation of the European Virus Archive (EVA). Since it would create insurmountable problems to develop such a collection in a single laboratory, EVA will utilise the expertise and facilities of recognised centres of excellence in virology within Europe. EVA will also exploit the high international reputations of these centres to obtain viruses currently held outside Europe. The management structure of EVA will ensure the highest standards of quality assurance, security, traceability and dissemination for the benefit of science, medicine, education and global information. The EVA network will develop appropriate protocols for virus amplification, supported by sustainable long-term storage facilities. The resource will be available to all users who can demonstrate the appropriate biosecurity credentials. An associated technology transfer centre will develop products for diagnosis, research, therapeutic application, education, and training. The EVA consortium contains internationally recognised experts in all aspects of the proposal. EVA is therefore an exciting, ambitious and realisable concept that can work for the benefit of mankind.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: AAT.2012.6.3-1. | Award Amount: 792.52K | Year: 2013

The PEL-SKIN project aims to deliver a novel airfoil coating to improve the global aerodynamic performance and manoeuvrability of future air transport. We propose to investigate drag reduction from a prefabricated coating composed of a densely packed arrangement of flexible fibres that can be attached directly onto a wing or aerodynamic surface, in the region of separated flow. Inspired by the pop up of birds feathers in certain flight modes, the amelioration of aerodynamic performance via a Porous and ELastic (PEL) is based on the concept of reconfiguring/adapting to the separated flow, thereby directly changing the near-wall flow and the subsequent vortex shedding; which can lead to reduced form drag by decreasing the intensity and the size of the recirculation region. This concept of flow control is novel, more efficient than classical actuators, and can lead to significant increase in the aerodynamic performances. The objective of the project is to investigate the performance benefit this technology can deliver for flow at high Reynolds number, relevant for the next generation of aircrafts. The research will endeavour to deliver a clear physical understanding of the principle flow control mechanism and an accompanying numerical model of the phenomena, which shall be implemented and tested into industrial aerodynamics software tools; ready for more detailed downstream design work. Although this research is motivated from low to moderate Reynolds number flows, it is expected that the understanding of the physical mechanisms will pave the way to the development of breakthrough control strategies for separated flows at higher Reynolds-numbers for larger aircraft. The success of this project can thus be expected to deliver direct impact on the environment in long-term; where in the EU, it is currently estimated that 25% of CO2 emissions come from the aeronautical sector.

Agency: European Commission | Branch: FP7 | Program: CSA-SA | Phase: INCO.2011-6.2 | Award Amount: 911.17K | Year: 2012

The INCOMMET proposal is a response to the Call FP7-INCO-2011-6 but is also relevant to the EU objectives of the Environment Work Programme. The INCOMMET project, coordinated by the National Institute of Marine Sciences and Technologies (INSTM), the major public research institution in Tunisia in the field of oceanography and marine environments, and also involving the Universit dAix-Marseille (AMU, France) and the Zoological Station of Naples (SZN, Italy) aims at increasing research excellence and visibility of INSTM, and fostering its participation into ERA. INCOMMET is structured in 6 WP providing ideal conditions to achieve its goals. To reinforce the management capacity of INSTM with EU projects, a twinned management will be ensured by INSTM and the European Research Grant Unit of AMU. The consortium will make a scientific literature review on Mediterranean areas close to Tunisia and will undertake a SWOT analysis of INSTM. This will define training courses, workshops, twinnings and visits targeting INSTM staff, early stage researchers, PhD and master students to improve INSTM scientific and technological capacities. To enhance EU-INSTM cooperations and visibility and increase INSTMs participation in EU FP or related EU programmes, specific training will be provided by the EU Grant Unit of AMU to INSTM administrative staff and researchers. INCOMMET will elaborate a strategy to improve the internal and scientific structuring of INSTM and will conduct regional and national lobbying to increase the visibility of INSTM. INCOMMET will design an International Mixed Laboratory involving INSTM and its partners and elaborate a common EU research programme. The international scientific recognition of INSTM will be reinforced by strengthening communication and dissemination through a public website, production of leaflets, scientific DVDs, local conferences targeting socio-economic partners and stakeholders and a final international conference.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: INFRAIA-1-2014-2015 | Award Amount: 12.17M | Year: 2015

The overall objective will be to create and mobilise an International network of high calibre centres around a strong European group of institutes selected for their appropriate expertises, to collect, amplify, characterise, standardise, authenticate, distribute and track, mammalian and other exotic viruses. The network of EVAg laboratories including 25 institutions represents an extensive range of virological disciplines. The architecture of the consortium is based on the association of capacities accessible to the partners but also to any end-users through the EVAg web-based catalogue. This concept has been elaborated and tested for its efficiency during the successful EVA project (FP7). The project will integrate more facilities dedicated to high risk pathogen (HRP) manipulation (1 in EVA, 13 in EVAg) The access to products derived from those HRP will be enhanced and for instance the production of diagnostic reagents will be facilitated. The new project will also provide access to high containment biosafety facilities to carry out in vivo studies of infectious disease using natural or models hosts, to look at prophylactic or therapeutic control measures and to develop materials for the evaluation of diagnostic tests, meaning an extensive capacity to service and to training. EVAg will also link up with other network-based virus-associated programmes that exist globally. However, looking further ahead, EVAg is conceived ultimately to be an open entity aiming at developing synergies and complementarity capabilities in such a way as to offer an improved access to researchers. This project will generate the largest collection of mammalian viruses in the world and move beyond the current state-of-the-art to provide an increasingly valuable resource and service to the worlds scientific community, including government health departments, higher education institutes, industry and, through information systems, the general public.

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

Understanding the human brain is one of the greatest scientific challenges of our time. Such an understanding can provide profound insights into our humanity, leading to fundamentally new computing technologies, and transforming the diagnosis and treatment of brain disorders. Modern ICT brings this prospect within reach. The HBP Flagship Initiative (HBP) thus proposes a unique strategy that uses ICT to integrate neuroscience data from around the world, to develop a unified multi-level understanding of the brain and diseases, and ultimately to emulate its computational capabilities. The goal is to catalyze a global collaborative effort. During the HBPs first Specific Grant Agreement (SGA1), the HBP Core Project will outline the basis for building and operating a tightly integrated Research Infrastructure, providing HBP researchers and the scientific Community with unique resources and capabilities. Partnering Projects will enable independent research groups to expand the capabilities of the HBP Platforms, in order to use them to address otherwise intractable problems in neuroscience, computing and medicine in the future. In addition, collaborations with other national, European and international initiatives will create synergies, maximizing returns on research investment. SGA1 covers the detailed steps that will be taken to move the HBP closer to achieving its ambitious Flagship Objectives.

Agency: European Commission | Branch: FP7 | Program: CPCSA | Phase: INFRA-2010-1.2.3 | Award Amount: 2.76M | Year: 2010

The GISELA objective is to guarantee the long-term sustainability of the European Latin American e-Infrastructure and thus ensure the continuity and enhancement of the Virtual Research Communities (VRC) using it. The project will focus on:\n\tImplementing the Latin American Grid Initiative (LGI) sustainability model rooted on National Grid Initiatives (NGI) or Equivalent Domestic Grid Structures (EDGS), in association with CLARA and collaborating with EGI;\n\tProviding VRCs with the e-Infrastructure and Application-related Services required to improve the effectiveness of their research, addressing both:\no\tCurrent EELA-2 small User Communities;\no\tLarger VRCs through Specialised Support Centres (SSCs).\nThe GISELA mission is twofold:\n- Ensure the sustainability of the EU-LA e-Infrastructure\nThe sustainability of the EU part of the e-Infrastructure being cared of by EGI, GISELA will concentrate on its LA component. The tasks, at each level of the e-Infrastructure are:\n\tInstitution: Get all Services fully operational in the Resource Centre (RC);\n\tCountry: Implement all Grid Operation Centre (GOC) Services;\n\tContinent: Implement all Grid & Network Support Centres (GSC, NSC) Services;\n\tSupport a catchall GOC.\n- Support Virtual Research Communities\nThe support will encompass:\n\tUser Support:\no\tProvide access to the EU-LA Infrastructure to VOs represented in GISELA (HEP, Life Sciences, Earth Sciences, etc.);\no\tPublicise and support the GISELA e-Infrastructure and Application Services;\no\tCollaborate with VRCs or SSCs to the development of integrated services (e.g. gateways).\n\tTraining & Dissemination activities\no\tOrganisation of tutorials for single users and VRCs;\no\tCoordinate dissemination actions, workshops, Conferences;\no\tProduce dissemination material.\nGrid Services for VRCs will be provided by CLARA on the basis of a business plan using a Life Cycle Product Management (LCPM) approach.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: REV-INEQUAL-01-2016 | Award Amount: 2.11M | Year: 2016

Empirically informing a European theory of justice is a complex and challenging endeavour, however the emergence of current social crisis, and the resulting inequalities and unfairness, bring about the need to revise the premises that facilitate translation of the theory into concrete guidance to effective social policies and coherent programs and practices. To respond to this challenge, a trans-disciplinary Consortium has been organized to provide a comprehensive series of empirical data, in different ecological levels, in order to understand differences in perceptions of inequality. Through a case study on an extreme expression of inequality and unfairness - LONG-TERM HOMELESSNESS organized in a multi-method and convergent design, HOME_EU is focused on understanding: a) How much inequality do EU Citizens accept regarding Homelessness; b) How the people with a lived-experience of Homelessness (both present and past) perceive the opportunities, choices and capability gains with the services and the existing social policies; c) What strategies consider the service providers to be more effective in reversing Homelessness; d) How social policies and policy key stakeholders contribute to effectively reverse Homelessness; and e) Develop a generalizable indicator (correlating the different ecological levels of analysis) based on the data gathered by each partner country on the key elements of policy and program efficacy. We believe that with this journey into an extreme situation, we are able to generate translational knowledge about the ecology of long-term Homelessness and contribute towards the advancement of an empirically based EU theory & practice of justice as fairness.

Agency: European Commission | Branch: H2020 | Program: CSA | Phase: MSCA-NIGHT-2016 | Award Amount: 1.11M | Year: 2016

We are proposing ERNs for 2016 and 2017 in 12 French cities. Our consortium of 11 partners will organise afternoons for schoolchildren, events in the cities and, above all, evenings where 1000 researchers will meet up to 30,000 people a year. The general public will be able to meet a number of researchers directly and experience something memorable with them. Since 2006, we have acquired a solid knowhow in the art of interaction. In 2014-2015, we went one step further by including the public in the actual research experiments, thereby creating scientist-citizen cooperation. We will renew these experiences and go even further: we are encouraging the public and researchers to experience creative moments together! Several creative interactions will be set up, around the Ideas theme in 2016 and the Impossible? theme in 2017, to allow researchers and the public to interact. The evenings will be full of ideas, challenges, and encounters with diverse individuals. In this way, we will rally European researchers to get involved in each city. Specific strategies will be used (such as public radio recordings) to allow them to share their European experience. These moments of cooperation will without a doubt reinforce the mutual appreciation between researchers and citizens. Our communication strategy (attracting specific audiences through networking, web, partnerships with youth-oriented press, etc.) will be based on the slogan: General Creativity. This slogan denotes the interactive nature of the evening and gives us a chance to talk about the richness of European research. To this effect, and for the first time, Cdric Villani, an inspiring and renowned researcher, has accepted to be the ERNs patron. Lastly, we plan to renew the Great Participatory Experiment in 2017. In each city (and perhaps even Italy), the public will contribute to the same playful scientific experiment chosen in 2016 after a challenge involving all our research institutions.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2009.5.3 | Award Amount: 15.53M | Year: 2011

The airways diseases asthma and chronic obstructive pulmonary disease affect over 400 million people world-wide and cause considerable morbidity and mortality. Airways disease costs the European Union in excess of 56 billion per annum. Current therapies are inadequate and we do not have sufficient tools to predict disease progression or response to current or future therapies. Our consortium, Airway Disease PRedicting Outcomes through Patient Specific Computational Modelling (AirPROM), brings together the exisiting clinical consortia (EvA FP7, U-BIOPRED IMI and BTS Severe Asthma), and expertise in physiology, radiology, image analysis, bioengineering, data harmonization, data security and ethics, computational modeling and systems biology. We shall develop an integrated multi-scale model building upon existing models. This airway model will be comprised of an integrated micro-scale and macro-scale airway model informed and validated by omic data and ex vivo models at the genome-transcriptome-cell-tissue scale and by CT and functional MRI imaging coupled to detailed physiology at the tissue-organ scale utilising Europes largest airway disease cohort. Validation will be undertaken cross-sectionally, following interventions and after longitudinal follow-up to incorporate both spatial and temporal dimensions. AirPROM has a comprehensive data management platform and a well-developed ethico-legal framework. Critically, AirPROM has an extensive exploitation plan, involving at its inception and throughout its evolution those that will develop and use the technologies emerging from this project. AirPROM therefore will bridge the critical gaps in our clinical management of airways disease, by providing validated models to predict disease progression and response to treatment and the platform to translate these patient-specific tools, so as to pave the way to improved, personalised management of airways disease.

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2013.2.2.1-4 | Award Amount: 15.74M | Year: 2013

Epilepsy is a devastating condition affecting over 50 million people worldwide. This multidisciplinary project is focused on the process leading to epilepsy, epileptogenesis, in adults. Our main hypothesis is that there are combinations of various causes, acting in parallel and/or in succession, that lead to epileptogenesis and development of seizures. Our central premise and vision is that a combinatorial approach is necessary to identify appropriate biomarkers and develop effective antiepileptogenic therapeutics. The project will focus on identifying novel biomarkers and their combinations for epileptogenesis after potentially epileptogenic brain insults in clinically relevant animal models, such as traumatic brain injury (TBI) and status epilepticus (SE); explore multiple basic mechanisms of epileptogenesis and their mutual interactions related to cell degeneration, circuit reorganization, inflammatory processes, free radical formation, altered neurogenesis, BBB dysfunction, genetic and epigenetic alterations; and translating these findings towards the clinic by validating biomarkers identified from animal models in human post TBI brain tissue and blood samples, post-mortem brain tissue in individuals that died soon after SE, and human brain and blood samples from chronic epilepsy cases. The project will identify novel combinatorial biomarkers and novel disease-modifying combinatorial treatment strategies for epileptogenesis, create an Epilepsy Preclinical Biobank, and validate translational potential of results from animal models in human tissue. To adequately address the proposed goals, the project will develop technological breakthroughs, such as completely novel chemogenetic approaches, novel MRI techniques, novel multimodal organic recording devices for simultaneous recordings of EEG / cellular unit activity and biochemical measurements, novel bioluminescence for in vivo promoter activity analysis, and novel systems biology approaches.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2010-ITN | Award Amount: 4.98M | Year: 2011

Virus infections remain a major cause of disease, with dramatic costs in mortality, morbidity, and economic loss worldwide. There is an unmet need for potent antiviral drugs, in particular against viruses with a (\)RNA genome which include many important pathogens of humans and animals. Antiviral drug development requires a detailed understanding of virus replication and effective translation of this knowledge into drug discovery. Europe needs well-trained experts with multidisciplinary skills to advance this field. However, few, if any, European training institutes have the broad know-how required to provide such a comprehensive training programme. The EUVIRNA partnership aims to fill this gap with the proposed EUVIRNA training programme. The EUVIRNA partnership consists of six outstanding European academic partners and four industrial partners (one pharmaceutical R&D company and three SMEs), and an associated partner (SME specialized in education). All EUVIRNA partners are recognized leaders in their field, ensuring state-of-the-art training possibilities, and their skills are highly complementary. Three Visiting Researchers will complement the expertise of the partners. EUVIRNA aims to introduce 18 ESRs and 2 ERs to state-of-the-art knowledge and technology applied in molecular virology and antiviral therapy, with both local and network-wide training activities. Individual research projects, research training workshops and intersectoral secondments will be supplemented with complementary skills courses to improve career development and perspectives. The industrial partners are actively involved in the entire programme, and will furthermore organize a 1-week industry-oriented conference aimed at further bridging the gap between academia and industry. Thus, EUVIRNA offers talented researchers a multidisciplinary and intersectoral training programme and prepares them for a future leading role in European molecular virology research and antiviral dru

Aix - Marseille University, Assistance Publique Hopitaux De Marseille, French National Center for Scientific Research and French National Institute for Agricultural Research | Date: 2012-11-02

The present invention relates to a method for monitoring the tumor growth of an androgen-independent prostate cancer in a subject, by determining the amount of at least one adrenomedullin receptor and optionally adrenomedullin in a prostate cancer cell obtained from said subject. The present invention also relates to a pharmaceutical composition comprising an anti-adrenomedullin antagonist antibody and/or at least one anti-adrenomedullin receptor antagonist antibody for treating an androgen-independent prostate cancer.

Aix - Marseille University, French National Center for Scientific Research and University of Avignon | Date: 2015-03-11

A device for detecting radiation particles comprising at least one sensor for sensing radiation particles, capable of supplying an electrical pulse when it is traversed by at least one radiation particle, and at least one detection circuit comprising a voltage-controlled oscillator to which said electrical pulse originating from the sensor is supplied as the control voltage. The voltage-controlled oscillator is a ring oscillator.

Maumus F.,French National Institute for Agricultural Research | Epert A.,French National Institute for Agricultural Research | Nogue F.,French National Institute for Agricultural Research | Blanc G.,Aix - Marseille University
Nature Communications | Year: 2014

Nucleocytoplasmic large DNA viruses (NCLDVs) are eukaryotic viruses with large genomes (100 kb-2.5Mb), which include giant Mimivirus, Megavirus and Pandoravirus. NCLDVs are known to infect animals, protists and phytoplankton but were never described as pathogens of land plants. Here, we show that the bryophyte Physcomitrella patens and the lycophyte Selaginella moellendorffii have open reading frames (ORFs) with high phylogenetic affinities to NCLDV homologues. The P. patens genes are clustered in DNA stretches (up to 13 kb) containing up to 16 NCLDV-like ORFs. Molecular evolution analysis suggests that the NCLDV-like regions were acquired by horizontal gene transfer from distinct but closely related viruses that possibly define a new family of NCLDVs. Transcriptomics and DNA methylation data indicate that the NCLDV-like regions are transcriptionally inactive and are highly cytosine methylated through a mechanism not relying on small RNAs. Altogether, our data show that members of NCLDV have infected land plants. © 2014 Macmillan Publishers Limited. All rights reserved.

Agency: European Commission | Branch: FP7 | Program: MC-IRSES | Phase: FP7-PEOPLE-2010-IRSES | Award Amount: 577.10K | Year: 2011

Fundamental trends in the European Union and the world at large provide an increasingly important policy agenda for financing sustainable energy in terms of energy efficiency, innovation in energy exploitation and development of renewable resources. The long-range forecasts for investments and energy market are determined by highly interconnected environmental, geological and technological research despite scientific differences in modelling the scenarios and interpreting the data. The medium-range forecasts for investments and energy market largely depend on geopolitical considerations and internal pressure by public opinion and stakeholders. States, firms and other actors play their game within the current legal framework at the international, regional and national level. Accordingly, the proper policy design for the sustainable energy needs to be complemented by research on the legal, regulatory and geopolitical side. However, the characteristics of social sciences which drive their approach to such issues are determined by their fragmentation into sectoral domains and national traditions. It is commonly agreed that there are great benefits in overcoming the disciplinary divisions combining scientific, social and economic considerations in order to assess the policy impact of sustainable energy. The evaluation of the policies for sustainable energy investments requires to connect several national approaches on such topics, not only in Europe, where the fragmentation of social sciences into national traditions is a matter of fact. In turn, the global nature of the questions addressed by the project needs to be implemented through an IRSES programme in order to strengthen the research partnerships between European research organisations and research organisations from crucial world regions as far as European interests for energy matters are concerned.

Agency: European Commission | Branch: FP7 | Program: CPCSA | Phase: ICT-2013.9.9 | Award Amount: 72.73M | Year: 2013

Understanding the human brain is one of the greatest challenges facing 21st century science. If we can rise to the challenge, we can gain profound insights into what makes us human, develop new treatments for brain diseases and build revolutionary new computing technologies. Today, for the first time, modern ICT has brought these goals within sight. The goal of the Human Brain Project, part of the FET Flagship Programme, is to translate this vision into reality, using ICT as a catalyst for a global collaborative effort to understand the human brain and its diseases and ultimately to emulate its computational capabilities. The Human Brain Project will last ten years and will consist of a ramp-up phase (from month 1 to month 36) and subsequent operational phases.\nThis Grant Agreement covers the ramp-up phase. During this phase the strategic goals of the project will be to design, develop and deploy the first versions of six ICT platforms dedicated to Neuroinformatics, Brain Simulation, High Performance Computing, Medical Informatics, Neuromorphic Computing and Neurorobotics, and create a user community of research groups from within and outside the HBP, set up a European Institute for Theoretical Neuroscience, complete a set of pilot projects providing a first demonstration of the scientific value of the platforms and the Institute, develop the scientific and technological capabilities required by future versions of the platforms, implement a policy of Responsible Innovation, and a programme of transdisciplinary education, and develop a framework for collaboration that links the partners under strong scientific leadership and professional project management, providing a coherent European approach and ensuring effective alignment of regional, national and European research and programmes. The project work plan is organized in the form of thirteen subprojects, each dedicated to a specific area of activity.\nA significant part of the budget will be used for competitive calls to complement the collective skills of the Consortium with additional expertise.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2013.4.1 | Award Amount: 3.56M | Year: 2013

The overall goals of the SENSEI project are twofold. First, SENSEI will develop summarization/analytics technology to help users make sense of human conversation streams from diverse media channels. Second, SENSEI will design and evaluate its summarization technology in ecological environments, aiming to improve task performance and productivity of end-users.Conversational interaction is the most natural and persistent paradigm for business relations with end-customers or users. In contact centres millions of customer spoken conversations are handled daily. On social media platforms hundreds of millions of blog posts are delivered through generalist or proprietary platforms. In both cases, conversations have little impact on the intended target listeners due to the volume, velocity and diversity (media, style, social context) of the document streams (spoken conversations and blog posts). Most language analytics technology is limited in that it performs keyword search, which does not provide automatic descriptions of what happened, who said what, which opinions are held on what subject, in a coherent, readable and executable form. In the SENSEI project we plan to go beyond keyword search and sentence based analysis of conversations. We will design and adapt lightweight and large coverage linguistic models of semantic and discourse resources to learn a layered model of conversations. SENSEI will address the issue of multidimensional textual, spoken and metadata descriptors in terms of semantic, para-semantic and discourse structures. The combination of supervised and unsupervised learning techniques will support the scaling and adaptation of such computational models to the diversity of the conversation data. Automated generation of readable analytics documents (summaries) will support end-users in the context of large data analysis tasks. Summarization technology developed in SENSEI will be evaluated with respect to users productivity in the context of ecological scenarios, specifically, call centre and social media conversation analysis.

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2010.2.3.3-1 | Award Amount: 16.37M | Year: 2011

To address the call for proposals Biology and control of vector-borne infections in Europe launched by the European Commission, we want to investigate the biological, ecological and epidemiological components of vector-borne diseases (VBD) introduction, emergence and spread, and to propose innovative tools for controlling them, building on the basis of acquired knowledge. We have selected the main groups of arthropod vectors involved in the transmission of vector-borne diseases in Europe: ticks, mosquitoes, sandflies, and biting midges (Culicoides). We have also selected the main diseases of actual or possible importance in human and veterinary public health. Rodents, insectivores and rodent-borne diseases have also been considered, both for their direct importance in public health, and for the major role of rodents and insectivores as reservoir hosts of many pathogens. We have put a strong focus on vector- and disease-quantitative modelling. The resulting predictive models will be used to assess climate or environmental change scenarios, as well as vector or disease control strategies. Human behaviour and risk perception are an important component of VBD introduction, emergence and spread. The consequences triggered by VBD for human and veterinary public health in Europe are just starting to emerge in public awareness. We will also account for this aspect of human and veterinary public health in our proposal. Finally, the set of innovative research methods, tools and results obtained during the project will be a step forward a generic approach of VBD in terms of disease monitoring and early warning systems, and will reinforce the general framework for an integrated pest and disease management system. For all these aspects, we will benefit from, and amplify the strong scientific results, capacity building, and research networks established by EDEN project on emerging, vector-borne diseases in a changing European environment.

Agency: European Commission | Branch: FP7 | Program: CP-CSA-Infra | Phase: INFRA-2010-1.1.29 | Award Amount: 8.13M | Year: 2011

VISIONAIR is a project of creation of a European infrastructure that should be a unique, visible and attractive entry towards high level visualisation facilities. These facilities must be open to the access of a wide set of research communities. By integrating existing facilities, it will create a world-class research infrastructure enabling to conduct frontier research. This integration will provide a significant attractiveness and visibility of the European Research Area. Current scientific challenges concern climate evolution, environmental risks, health, energy, etc. and require the management of more and more complex information. The development of information technologies, the increasing complexity of the information to be handled and analysed, along with the increasing capacities in scientific and engineering simulations, call for the development of increasingly powerful visualisation tools and methods. The Europe Research Area must be able to compete with other big Research Areas when addressing the previously defined challenges. By integrating visualisation facilities with the VISIONAIR project, ERA will be able to answer integrated challenges out of the scope of usually disseminated research teams. Both, physical access and virtual services, will be provided by the infrastructure. A full access to visualisation dedicated software will be organised, while physical access on high level platforms, will be partially (about 20% of global usage) open for other scientists for free on behalf of excellence of submitted projects. The partners of this project propose to build a common infrastructure that would grant access to high level visualisation facilities and resources to researchers. Indeed, researchers from Europe and from around the world will be welcome to carry out research projects using the visualisation facilities provided by the infrastructure. Visibility and attractiveness of ERA will be increased by the invitation of external projects.

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: KBBE-2007-3-2-06 | Award Amount: 8.10M | Year: 2009

The NEMO project provides novel efficient enzymes and microbes for 2nd generation bioethanol production. It generates through metabolic engineering and mutagenesis & screening approaches robust yeast strains that have a broad substrate range and can (co-)ferment C6 and C5 sugars to ethanol with high productivity (rate and yield), and that are significantly more stress tolerant, i.e. inhibitor, ethanol and thermotolerant than the current S.cerevisiae strains used in ethanol production. The NEMO project also identifies and improves enzymes for hydrolysis of biomasses relevant for Europe. Novel enzymes are identified and improved through various approaches, based on screening, broad comparative genomics analyses, and protein engineering. These efforts will generate more thermostable enzymes for high temperature hydrolysis, more efficient enzymes for hydrolysis of the resistant structures in lignocellulose such as crystalline cellulose and lignin-hemicellulose complexes, enzymes with reduced affinity on lignin, and efficient thermo and mesophilic enzyme mixtures that are optimised and tailor-made for the relevant biomasses for Europe and European industry. These novel biocatalysts are tested in an iterative manner in process relevant conditions, including also pilot-scale operations, which ensure that the novel enzymes and microbes will be superior in real process conditions. Furthermore, optimal enzyme, microbe and process regime combinations are identified, providing basis for the development of the most economic and ecoefficient overall processes. The impact of the NEMO project on 2nd generation bioethanol production is significant because it provides most realistic but widely applicable technologies that could be exploited broadly by European industry. Its impact goes also much beyond bioethanol because NEMO provides technology improvements that are directly applicable and crucial for efficient and economic production of also other biofuels and bulk chemicals.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: Health | Award Amount: 2.85M | Year: 2014

The ongoing Ebola outbreak in West Africa is the largest and deadliest the world has ever seen. In September 2014, the number of EBOV cases exceeded the total of all cases from previous known outbreaks. Further, this public health crisis shifted into a complex emergency, with significant, social, economic, humanitarian, political and security dimensions. Till date, no effective medicine has been proven to be effective against EBOV. As a result, it is immensely difficult to mitigate the current outbreak as well as prevent further outbreaks in this region. On Sept 4-5 2014, the WHO gathered expertise on experimental therapies and vaccines and their role in containing the Ebola outbreak in West Africa. During this consultation, experts identified several therapeutic and vaccine interventions that should be the focus of priority evaluation. Among these candidates is the existing antiviral drug Favipiravir, that has proven activity against many RNA viruses in vivo and in vitro including Ebola. Favipiravir is known to inhibit viral gene replication within infected cells to prevent propagation among which it inhibits viral gene replication within infected cells to prevent propagation. Hence, Favipiravir is currently aimed as a curative option in severe pandemic flue. Furthermore, there is currently enough stock of Favipiravir to even treat more than 20.000 patients, and the producer of Favipiravir, Toyoma Chemical/Fujifilm in Japan is willing to rapidly upscale the production of this drug. This drug has been extensively tested in humans and approved in Japan for treatment and prevention of influenza. The drug has shown an excellent safety profile in more than 2000 patients tested and no major adverse effect were reported. The current crisis requires both an immediate response to treat patients and prevent the further spread of the epidemic, as well as long term commitment in the complex sociocultural context. REACTION! will address both needs.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC1-PM-22-2016 | Award Amount: 15.59M | Year: 2016

ZIKAlliance is a multidisciplinary project with a global One Health approach, built: on a multi-centric network of clinical cohorts in the Caribbean, Central & South America; research sites in countries where the virus has been or is currently circulating (Africa, Asia, Polynesia) or at risk for emergence (Reunion Island); a strong network of European and Brazilian clinical & basic research institutions; and multiple interfaces with other scientific and public health programmes. ZIKAlliance will addrees three key objectives relating to (i) impact of Zika virus (ZIKV) infection during pregnancy and short & medium term effects on newborns, (ii) associated natural history of ZIKV infection in humans and their environment in the context of other circulating arboviruses and (iii) building the overall capacity for preparedness research for future epidemic threats in Latin America & the Caribbean. The project will take advantage of large standardised clinical cohorts of pregnant women and febrile patients in regions of Latin America and the Caribbean were the virus is circulating, expanding a preexisting network established by the IDAMS EU project. I will also benefit of a very strong expertise in basic and environmental sciences, with access to both field work and sophisticated technological infrastructures to characterise virus replication and physiopathology mechanisms. To meet its 3 key objectives, the scientific project has been organised in 9 work packages, with WP2/3 dedicated to clinical research (cohorts, clinical biology, epidemiology & modeling), WP3/4 to basic research (virology & antivirals, pathophysiology & animal models), WP5/6 to environmental research (animal reservoirs, vectors & vector control) , WP7/8 to social sciences & communication, and WP9 to management. The broad consortium set-up allow gathering the necessary expertise for an actual interdisciplinary approach, and operating in a range of countries with contrasting ZIKV epidemiological status.

Agency: European Commission | Branch: FP7 | Program: CSA-SA | Phase: SSH.2012.2.2-4 | Award Amount: 3.30M | Year: 2012

ECOPAS (European Consortium for Pacific Studies) is an innovative, ambitious multidisciplinary project designed to provide coordination and support to research and policy communities on issues connected to climate change and related processes in the Pacific Islands region, in order to define better options for sustainable development. The Pacific is notable for the discrepancy between the contribution of its small economies to global climate change, and the severity of climate change effects experienced by its peoples. Linkages between research networks and policy interfaces will contribute to more context-sensitive EU external action, and will set a future research agenda for social science and humanities in the Pacific. From an initial 3-year duration ECOPAS is the first-ever network to develop extensive, durable collaboration between European and Pacific scholarly institutions, as well as between research institutions and local, national and international political agencies. The project will have lasting effects on the ways in which research is undertaken in the social sciences and humanities and beyond in the Pacific, and on the efficacy of development efforts in and for the region. While the emphasis of ECOPAS is on developing a long-term strategy for SSH research on the Pacific, strong links are also forged with climate research in the natural sciences. Built on seven interrelated and complementary Work Packages, ECOPAS aims to define and strengthen the potential of European research in the Pacific by creating a platform and portal for knowledge exchanges, a long-term plan for capacity building, and a strategic plan for Pacific state and non-state involvement. ECOPAS is hosted by four recognized European university centres of excellence on Pacific research, in Norway, France, the United Kingdom and the Netherlands (Bergen BPS, Aix-Marseille CREDO, St. Andrews CPS and Nijmegen CPAS), and by two major Pacific institutions (University of the South Pacific, Fiji, and the National Research Institute, Papua New Guinea). While ECOPAS is coordinated from the University of Bergen, the projects seven interconnected Work Packages are directed by the participating centres, thus guaranteeing maximal efficiency and feasibility of work programme and deliverables. ECOPAS will grow to be the premier research network in the field of Pacific Studies, and will progressively involve additional associate researchers with strong track records and international visibility. During the projects stages, the collective networks of the six participant institutions throughout Europe, in the Anglophone and Francophone Pacific, and in North America will lead to near complete participation of the worlds community of Pacific scholars. A final outcome of the project will be the delivery to the European Commission of a comprehensive, forward-looking, long-term social sciences and humanities research policy agenda for the Pacific Islands region.

Ziegler J.C.,Aix - Marseille University | Perry C.,Swinburne University of Technology | Zorzi M.,University of Padua | Zorzi M.,IRCCS San Camillo Neurorehabilitation Hospital
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2014

The most influential theory of learning to read is based on the idea that children rely on phonological decoding skills to learn novel words. According to the self-teaching hypothesis, each successful decoding encounter with an unfamiliar word provides an opportunity to acquire word-specific orthographic information that is the foundation of skilled word recognition. Therefore, phonological decoding acts as a self-teaching mechanism or 'built-in teacher'. However, all previous connectionist models have learned the task of reading aloud through exposure to a very large corpus of spelling-sound pairs, where an 'external' teacher supplies the pronunciation of all words that should be learnt. Such a supervised training regimen is highly implausible. Here, we implement and test the developmentally plausible phonological decoding self-teaching hypothesis in the context of the connectionist dual process model. In a series of simulations, we provide a proof of concept that this mechanism works. The model was able to acquire word-specific orthographic representations for more than 25 000 words even though it started with only a small number of grapheme-phoneme correspondences. We then show how visual and phoneme deficits that are present at the outset of reading development can cause dyslexia in the course of reading development. © 2013 The Authors.

Agency: European Commission | Branch: FP7 | Program: CSA-CA | Phase: INCO-2007-1.2 | Award Amount: 4.94M | Year: 2008

The present Coordination Action aims at developing the objectives of the INCO-Net MPC action as described in the Call for proposals, to further enhance regional S&T dialogue in the Mediterranean Region and the complementarities with activities carried out by other European Policy instruments, notably the Union for the Mediterranean (UfM). These objectives are focused on creating a dialogue platform using the state of the art of the ICT technologies, which will enable the discussion between relevant stakeholders from both sides of the Mediterranean to improve the S&T cooperation by, among other means, connecting and facilitating the interaction between the dispersed S&T cooperation initiatives already existing supported by the Member States, the European Commission and other political bodies; addressing training activities to improve the quality of the participation and management of the partners of FP7 from the MPC; creating discussion platforms and organizing meetings to monitor and discuss the content of the Thematic priorities of FP7 in term of the common interest of the EU and MPC; creating an Observatory of the EU-MPC S&T cooperation, which will agree indicators for the monitoring of RTD cooperation activities; and creating networks of research institutions and technological transfer services from both sides of the Mediterranean, to support strategic collaboration and provide a reference element for the development of the Euro-Mediterranean Innovation Space. All these activities are aimed at providing a strong institutional basis for the EU-MPC S&T cooperation. Furthermore, the mentioned objectives will be complemented with other activities, notably the development toward the common appropriation of the results of MIRA to activities on Innovation, and profiting the identification of common scientific priorities that could be used as clustering glue (Research Driven Clusters) around Projects already approved by the UfM, where business development can be foreseen using the Research potential in both sides of the Mediterranean. Supporting the activities of the UfM Programs that need the identification and development of a Research agenda in support of its objectives, notably the Program Horizon 2020 and the strengthening of the industrial cooperation through the creation of the Euro-Mediterranean Innovation Space is as well scheduled. All these activities are aimed at providing a strong institutional basis for the UfM cooperation in RTD.

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

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

Agency: European Commission | Branch: FP7 | Program: CSA-CA | Phase: KBBE.2010.3.5-02 | Award Amount: 1.26M | Year: 2011

More than water scarcity, diseases and civil wars, Africa is also the least wealthy continent, in terms of economic and financial resources. These combined and tightly linked problems have led to a restricted range of choices, affordable for African countries, to deal particularly with the water issue, as a major topic. Polluted water treatment before use has been their almost unique solution to deal with a growing water scarcity. The treatment of water and elimination of pollutants, mainly pathogenic organisms, xenobiotics and heavy metals, although itself presents significant challenges, is crucial for human health and environmental considerations. However, most regions in developing countries cannot afford the costs of advanced and specialized systems. Numerous water cleaning methods are based in natural, plants or micro-organisms, biochemical processes. Biotechnology is a useful tool that is delivering improved products and process for environmental sustainability, and promises a range of benefits to manage the industrial WW economically and effectively around the world. Some biotechnological techniques are quite sophisticated but others are simple, cost effective and adapted to local conditions and resources of developing countries. These natural biological treatment systems include lagooning, land treatment, phytodepuration, or constructed wetlands systems. They can be applied as secondary or tertiary purification treatment, allowing the removal of pathogenic microorganisms and the degradation of the organic pollutants, so that waste water can be recycled for irrigation and domestic use and hence reduce the pressure on the hydric resources. Other biotechnological techniques to be taken into account within this proposal are biofiltration, membrane bioreactors and algae and other aquatic crops application for wastewater purification.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2011.9.7 | Award Amount: 2.46M | Year: 2012

Many complex systems are characterized by multi-level properties that make the study of their dynamics and of their emerging phenomena a daunting task. The huge amount of data available in modern sciences can be expected to support great progress in these studies, even though the nature of the data varies. Given that, it is crucial to extract as much as possible features from data, including qualitative (topological) ones. The goal of this project is to provide methods driven by the topology of data for describing the dynamics of multi-level complex systems. To this end the project will develop new mathematical and computational formalisms accounting for topological effects. To pursue these objectives the project brings together scientists from many diverse fields including as topology and geometry, statistical physics and information theory, computer science and biology. The proposed methods, obtained through concerted efforts, will cover different aspects of the science of complexity ranging from foundations, to simulations through modelling and analysis, and are expected to constitute the building blocks for a new generalized theory of complexity.

Agency: European Commission | Branch: FP7 | Program: CSA-SA | Phase: INCO.2011-6.2 | Award Amount: 612.18K | Year: 2012

The 30-month LEBIN project gives Lebanon the possibility to improve the research activities of their highest quality in the FP7 thematic priority Health, through twinning activities between one of the leading Lebanon scientific and educational organisations Saint-Joseph University, with their long term partner the Aix-Marseille University , located in Marseille (France). The S&T specialist (inno), an international S&T collaboration expert and experienced FP7 coach and trainer for the scientific organisations, will provide methodological, coaching and training support to the project. Berytech,a Lebanese business incubator, will provide input for alaytical work and health workshops. A coherent development strategy for USJ will be prepared, based on SWOT analysis and on the socio-economic analysis on a Lebanese, regional (Mediterranean) and European level. A joint research plan will be then agreed by the twinned partners and a plan for strengthening of collaboration research links between USJ and other EU research organisations will be set up and implemented. The objective of this proposal is to establish a framework of cooperation between USJ in Lebanon and AMU in France under the umbrella of FP7, INCO- ERA and to offer the USJ students, faculty members of this university and other educational institutions in neighbouring countries the possibility to perform research in adequate levels of HEALTH. This project aims to strengthen cooperation and research capacities of Lebanon prominent research centre, USJ, bringing them at the highest level. It will also include several main types of activities, thus forming a coherent plan for improving the USJ capacities in a number of fields relevant to the FP7 Thematic Priority HEALTH: Twinning activities Large-scale networking & brokerage activities Exchange of researchers and young specialists and organisation of joint events such as summer school and an international conference Training and coaching activit

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2011.2.3.3-1 | Award Amount: 15.16M | Year: 2011

The capacity of zoonotic RNA viruses to emerge as major agents of human disease can appear limitless. Current intervention strategies have demonstrated limited success. Rapid, innovative and effective solutions are needed to reduce the apparently accelerating process of zoonotic disease emergence. We will study the following zoonotic viruses with epidemic potential in Europe: influenza virus, hepatitis E virus, viruses of the Japanese encephalitis serocomplex and lyssaviruses. These diverse viruses arise from the main reservoirs and vectors of potentially emerging viral diseases and use the three major routes of transmission: respiratory, faecal-oral and vector borne. Inter-disciplinary studies will generate valuable data on patterns of crossing the species barrier, transmission and disease emergence, including ecological and anthropological factors which determine virus availability and opportunities for exposure and infection. We will unravel the complex biological interactions between the virus and the recipient hosts that drive the viral adaptation and elucidate the factors determining the ability of the viruses to spread to and between humans (including pandemic spread). Furthermore, immune mechanisms of protection and novel prevention strategies will be investigated. Data will be compiled in a unique and freely accessible data-sharing platform to build a framework for analysing the drivers of pathogen emergence. Modelling, building on the analysis of key data, will focus on the extent to which pathogen trajectories are predictable and will identify high-risk situations and environments. This will allow improvement of disease surveillance, control, preparedness and intervention. Training in leading European Universities, as well as exchanges of approaches and data sharing with national and international health organizations will strengthen European position in this global challenge.

News Article | December 23, 2015

Is string theory science? Physicists and cosmologists have been debating the question for the past decade. Now the community is looking to philosophy for help. Earlier this month, some of the feuding physicists met with philosophers of science at an unusual workshop aimed at addressing the accusation that branches of theoretical physics have become detached from the realities of experimental science. At stake is the integrity of the scientific method, as well as the reputation of science among the general public, say the workshop’s organizers. Held at the Ludwig Maximilian University of Munich in Germany on 7–9 December, the workshop came about as a result of an article in Nature a year ago, in which cosmologist George Ellis, of the University of Cape Town in South Africa, and astronomer Joseph Silk, of Johns Hopkins University in Baltimore, Maryland, lamented a “worrying turn” in theoretical physics (G. Ellis and J. Silk Nature 516, 321–323; 2014). “Faced with difficulties in applying fundamental theories to the observed Universe,” they wrote, some scientists argue that “if a theory is sufficiently elegant and explanatory, it need not be tested experimentally”. First among the topics discussed was testability. For a scientific theory to be considered valid, scientists often require that there be an experiment that could, in principle, rule the theory out — or ‘falsify’ it, as the philosopher of science Karl Popper put it in the 1930s. In their article, Ellis and Silk pointed out that in certain areas, some theoretical physicists had strayed from this guiding principle — even arguing for it to be relaxed. The duo cited string theory as the principal example. The theory replaces elementary particles with infinitesimally thin strings to reconcile the apparently incompatible theories that describe gravity and the quantum world. The strings are too tiny to detect using today’s technology — but some argue that string theory is worth pursuing whether or not experiments will ever be able to measure its effects, simply because it seems to be the ‘right’ solution to many quandaries. Silk and Ellis also called out another theory that seems to have abandoned ‘Popperism’: the concept of a multiverse, in which the Big Bang spawned many universes — most of which would be radically different fromour own. But in the opening talk at the workshop, David Gross, a theoretical physicist at the University of California, Santa Barbara, drew a distinction between the two theories. He classified string theory as testable “in principle” and thus perfectly scientific, because the strings are potentially detectable. Much more troubling, he says, are concepts such as the multiverse because the other universes that it postulates probably cannot be observed from our own, even in principle. “Just to argue that [string theory] is not science because it’s not testable at the moment is absurd,” says Gross, who shared a Nobel prize in 2004 for his work on the strong nuclear force, which is well tested in experiments, and has also made important contributions to string theory. Workshop attendee Carlo Rovelli, a theoretical physicist at Aix-Marseille University in France, agrees that just because string theory is not testable now does not mean that it is not worth theorists’ time. But the main target of Ellis and Silk’s piece were observations made by philosopher Richard Dawid of Ludwig Maximilian University in his book String Theory and the Scientific Method (Cambridge Univ. Press, 2013). Dawid wrote that string theorists had started to follow the principles of Bayesian statistics, which estimates the likelihood of a certain prediction being true on the basis of prior knowledge, and later revises that estimate as more knowledge is acquired. But, Dawid notes, physicists have begun to use purely theoretical factors, such as the internal consistency of a theory or the absence of credible alternatives, to update estimates, instead of basing those revisions on actual data. At the workshop, Gross, who has suggested that a lack of alternatives to string theory makes it more likely to be correct, sparred with Rovelli, who has worked for years on an alternative called loop quantum gravity. Rovelli flatly opposes the assumption that there are no viable alternatives. Ellis, meanwhile, rejects the idea that theoretical factors can improve odds. “My response to Bayesianism is: new evidence must be experimental evidence,” he says. Others flagged up separate issues surrounding the use of Bayesian statistics to bolster string theory. Sabine Hossenfelder, a physicist at the Frankfurt Institute for Advanced Studies in Germany, said that the theory’s popularity may have contributed to the impression that it is the only game in town. But string theory probably gained momentum for sociological reasons, she said: young researchers may have turned to it because the job prospects are better than in a lesser-known field, for example. Historian of science Helge Kragh of Aarhus University in Denmark drew on historical perspective. “Suggestions that we need ‘new methods of science’ have been made before, but attempts to replace empirical testability with some other criteria have always failed,” he said. But at least the problem is confined to just a few areas of physics, he added. “String theory and multiverse cosmology are but a very small part of what most physicists do.” That is cold comfort to Rovelli, who stressed the need for a clear distinction between scientific theories that are well established by experiments and those that are speculative. “It’s very bad when people stop you in the street and say, ‘Did you know that the world is made of strings and that there are parallel worlds?’.” At the end of the workshop, the feuding physicsts did not seem any closer to agreement. Dawid — who co-organized the event with Silk, Ellis and others — says that he does not expect people to change their positions in a fundamental way. But he hopes that exposure to other lines of reasoning might “result in slight rapprochement”. Ellis suggests that a more immersive format, such as a two-week summer school, might be more successful at producing a consensus.

News Article | March 4, 2016

Concrete is the world’s most widely used construction material, so abundant that its production is one of the leading sources of greenhouse gas emissions. Yet answers to some fundamental questions about the microscopic structure and behavior of this ubiquitous material have remained elusive. Concrete forms through the solidification of a mixture of water, gravel, sand, and cement powder. Is the resulting glue material — known as cement hydrate, or calcium silicate hydrate (CSH) — a continuous solid, like metal or stone, or is it an aggregate of small particles? As basic as that question is, it had never been definitively answered. In a paper published this week in the Proceedings of the National Academy of Sciences, a team of researchers at MIT, Georgetown University, and France’s CNRS (together with other universities in the U.S., France, and U.K.) say they have solved that riddle and identified key factors in the structure of CSH that could help researchers work out better formulations for producing more durable concrete. Roland Pellenq, a senior research scientist in MIT’s department of civil and environmental engineering, director of the MIT-CNRS lab 2 hosted by the MIT Energy Initiative, and a co-author of the new paper, says the work builds on previous research he conducted with others at the Concrete Sustainability Hub (CSHub) through a collaboration between MIT and the CNRS. “We did the first atomic-scale model” of the structure of concrete, he says, but questions still remained about the larger, mesoscale structure, on scales of a few hundred nanometers. The new work addresses some of those remaining uncertainties, he says. One key question was whether the solidified CSH material, which is composed of particles of many different sizes, should be considered a continuous matrix or an assembly of discrete particles. The answer turned out to be that it is a bit of both — the particle distribution is such that almost every space between grains is filled by yet smaller grains, to the point that it does approximate a continuous solid. “Those grains are in a very strong interaction at the mesoscale,” he says. “You can always find a smaller grain to fit in between” the larger grains, Pellenq says, and thus “you can see it as a continuous material.” But the grains within the CSH “are not able to get to equilibrium,” or a state of minimum energy, over length scales involving many grains, and this makes the material vulnerable to changes over time, he says. That can lead to “creep” of the solid concrete, and eventually cracking and degradation. “So both views are correct, in some sense,” he explains. The analysis of the structure of hardened concrete found that pores of different sizes play important roles in determining the material’s characteristics. While smaller, nanoscale pores had been previously studied, mesoscale pores, ranging from 15 to 20 nanometers on up, had been more difficult to study and not well-characterized, Pellenq says. These pore spaces can play a major role in determining how susceptible the material is to water that can enter the material and cause cracking, eventually leading to structural failure. (This cracking, perhaps surprisingly, has nothing to do with the expansion of the water when it freezes, however). The new mesoscale simulations are the first that can adequately match the sometimes conflicting and confusing results seen in experiments measuring the CSH texture, Pellenq says. The new simulations make it possible to match the values of key characteristics such as stiffness, elasticity, and hardness, which are seen in real concrete samples. That shows that the modeling is useful, he says, and might help guide research on developing improved formulas, for example ones that reduce the required amount of water in the initial mix with cement powder. It is the manufacturing of the cement powder, a process that requires cooking limestone (with clays) at very high temperatures, that makes concrete production one of the leading sources of human-caused greenhouse gas emissions. Fine-tuning the amount of water needed for a given application could also improve the material’s durability, the researchers found. The amount of water used in the original mixture can make a big difference in concrete’s longevity, even though most of that evaporates away during the setting process. While water is needed in order to make the slurry flow so that it can be poured in place, too much water leads to much bigger pore spaces and more loose, “fluffy” regions in the set concrete, the team found. Such regions might leave the material more vulnerable to later degradation, or could even be designed to improve its durability. “This is a quintessential step towards the provision of a seamless atom-to-structure understanding of concrete, with huge mid-term practical impact in terms of material design and optimization,” says Christian Hellmich, director of the Institute for Mechanics of Materials and Structures at the Vienna University of Technology, who was not involved in this research. He adds, “this research helps to promote concrete research as a cutting-edge scientific discipline, where the cooperation of engineers and physicists emerges as a driving force for the reunification of natural sciences across the often too-tightly set boundaries of sub-disciplines.” The first contributor of this work is MIT postdoc Katerina Ioannidou. The team also included other researchers at MIT; the University of California at Los Angeles; Newcastle University in the U.K.; and Sorbonne University, Aix-Marseille University, and CNRS, in France. The work was supported by Schlumberger, the French National Science Foundation (ANR) through the Labex ICoME2, and the CSHub at MIT.

Agency: European Commission | Branch: FP7 | Program: CPCSA | Phase: INFRA-2010-1.2.1 | Award Amount: 70.14M | Year: 2010

Scientific research is no longer conducted within national boundaries and is becoming increasing dependent on the large-scale analysis of data, generated from instruments or computer simulations housed in trans-national facilities, by using e Infrastructure (distributed computing and storage resources linked by high-performance networks).\nThe 48 month EGI-InSPIRE project will continue the transition to a sustainable pan-European e-Infrastructure started in EGEE-III. It will sustain support for Grids of high-performance and high-throughput computing resources, while seeking to integrate new Distributed Computing Infrastructures (DCIs), i.e. Clouds, SuperComputing, Desktop Grids, etc., as they are required by the European user community. It will establish a central coordinating organisation,, and support the staff throughout Europe necessary to integrate and interoperate individual national grid infrastructures. will provide a coordinating hub for European DCIs, working to bring existing technologies into a single integrated persistent production infrastructure for researchers within the European Research Area.\nEGI-InSPIRE will collect requirements and provide user-support for the current and new (e.g. ESFRI) users. Support will also be given for the current heavy users as they move their critical services and tools from a central support model to ones driven by their own individual communities. The project will define, verify and integrate within the Unified Middleware Distribution, the middleware from external providers needed to access the e-Infrastructure. The operational tools will be extended by the project to support a national operational deployment model, include new DCI technologies in the production infrastructure and the associated accounting information to help define EGIs future revenue model.

Agency: European Commission | Branch: FP7 | Program: CP-IP-SICA | Phase: OCEAN.2011-3 | Award Amount: 16.99M | Year: 2012

The overall scientific objectives of PERSEUS are to identify the interacting patterns of natural and human-derived pressures on the Mediterranean and Black Seas, assess their impact on marine ecosystems and, using the objectives and principles of the Marine Strategy Framework Directive as a vehicle, to design an effective and innovative research governance framework based on sound scientific knowledge. Well-coordinated scientific research and socio-economic analysis will be applied at a wide-ranging scale, from basin to coastal. The new knowledge will advance our understanding on the selection and application of the appropriate descriptors and indicators of the MSFD. New tools will be developed in order to evaluate the current environmental status, by way of combining monitoring and modelling capabilities and existing observational systems will be upgraded and extended. Moreover, PERSEUS will develop a concept of an innovative, small research vessel, aiming to serve as a scientific survey tool, in very shallow areas, where the currently available research vessels are inadequate. In view of reaching Good Environmental Status (GES), a scenario-based framework of adaptive policies and management schemes will be developed. Scenarios of a suitable time frame and spatial scope will be used to explore interactions between projected anthropogenic and natural pressures. A feasible and realistic adaptation policy framework will be defined and ranked in relation to vulnerable marine sectors/groups/regions in order to design management schemes for marine governance. Finally, the project will promote the principles and objectives outlined in the MSFD across the SES. Leading research Institutes and SMEs from EU Member States, Associated States, Associated Candidate countries, non-EU Mediterranean and Black Sea countries, will join forces in a coordinated manner, in order to address common environmental pressures, and ultimately, take action in the challenge of achieving GES.

News Article | August 22, 2016

An MIT-led team has defined the nanoscale forces that control how particles pack together during the formation of cement “paste,” the material that holds together concrete and causes that ubiquitous construction material to be a major source of greenhouse gas emissions. By controlling those forces, the researchers will now be able to modify the microstructure of the hardened cement paste, reducing pores and other sources of weakness to make concrete stronger, stiffer, more fracture-resistant, and longer-lasting. Results from the researchers’ simulations explain experimental measurements that have confused observers for decades, and they may guide the way to other improvements, such as adding polymers to fill the pores and recycling waste concrete into a binder material, reducing the need to make new cement. Each year, the world produces 2.3 cubic yards of concrete for every person on earth, in the process generating more than 10 percent of all industrial carbon dioxide (CO ) emissions. New construction and repairs to existing infrastructure currently require vast amounts of concrete, and consumption is expected to escalate dramatically in the future. “To shelter all the people moving into cities in the next 30 years, we’ll have to build the equivalent of several hundred New York cities,” says Roland Pellenq, senior research scientist in the MIT Department of Civil and Environmental Engineering (CEE) and research director at France’s National Center for Scientific Research (CNRS). “There’s no material up to that task but concrete.” Recognizing the critical need for concrete, Pellenq and his colleague Franz-Josef Ulm, professor of CEE and director of the MIT Concrete Sustainability Hub (CSHub), have been working to reduce its environmental footprint. Their goal: to find ways to do more with less. “If we can make concrete stronger, we’ll need to use less of it in our structures,” says Ulm. “And if we can make it more durable, it’ll last longer before it needs to be replaced.” Surprisingly, while concrete has been a critical building material for 2,000 years, improvements have largely come from trial and error rather than rigorous research. As a result, the factors controlling how it forms and performs have remained poorly understood. “People always deemed what they saw under a microscope as being coincidence or evidence of the special nature of concrete,” says Ulm, who with Pellenq co-directs the joint MIT-CNRS laboratory called MultiScale Material Science for Energy and Environment, hosted at MIT by the MIT Energy Initiative (MITEI). “They didn’t go to the very small scale to see what holds it together — and without that knowledge, you can’t modify it.” Cement: the key to better concrete The problems with concrete — both environmental and structural — are linked to the substance that serves as its glue, namely, cement. Concrete is made by mixing together gravel, sand, water, and cement. The last two ingredients combine to make cement hydrate, the binder in the hardened concrete. But making the dry cement powder requires cooking limestone (typically with clay) at temperatures of 1,500 degrees Celsius for long enough to drive off the carbon in it. Between the high temperatures and the limestone decarbonization, the process of making cement powder for concrete is by itself responsible for almost 6 percent of all CO  emissions from industry worldwide. Structural problems can also be traced to the cement: When finished concrete cracks and crumbles, the failure inevitably begins within the cement hydrate that’s supposed to hold it together — and replacing that crumbling concrete will require making new cement and putting more CO  into the atmosphere. To improve concrete, then, the researchers had to address the cement hydrate — and they had to start with the basics: defining its fundamental structure through atomic-level analysis. In 2009, Pellenq, Ulm, and an international group of researchers associated with CSHub published the first description of cement hydrate’s three-dimensional molecular structure. Subsequently, they determined a new formula that yields cement hydrate particles in which the atoms occur in a specific configuration — a “sweet spot” — that increases particle strength by 50 percent. However, that nanoscale understanding doesn’t translate directly into macroscale characteristics. The strength and other key properties of cement hydrate actually depend on its structure at the “mesoscale” — specifically, on how nanoparticles have packed together over hundred-nanometer distances as the binder material forms. When dry cement powder dissolves in water, room-temperature chemical reactions occur, and nanoparticles of cement hydrate precipitate out. If the particles don’t pack tightly, the hardened cement will contain voids that are tens of nanometers in diameter — big enough to allow aggressive materials such as road salt to seep in. In addition, the individual cement hydrate particles continue to move around over time — at a tiny scale — and that movement can cause aging, cracking, and other types of degradation and failure. To understand the packing process, the researchers needed to define the precise physics that drives the formation of the cement hydrate microstructure — and that meant they had to understand the physical forces at work among the particles. Every particle in the system exerts forces on every other particle, and depending on how close together they are, the forces either pull them together or push them apart. The particles seek an organization that minimizes energy over length scales of many particles. But reaching that equilibrium state takes a long time. When the Romans made concrete 2,000 years ago, they used a binder that took many months to harden, so the particles in it had time to redistribute so as to relax the forces between them. But construction time is money, so today’s binder has been optimized to harden in a few hours. As a result, the concrete is solid long before the cement hydrate particles have relaxed, and when they do, the concrete sometimes shrinks and cracks. So while the Roman Colosseum and Pantheon are still standing, concrete that’s made today can fail in just a few years. Laboratory investigation of a process that can take place over decades isn’t practical, so the researchers turned to computer simulations. “Thanks to statistical physics and computational methods, we’re able to simulate this system moving toward the equilibrium state in a couple of hours,” says Ulm. Based on their understanding of interactions among atoms within a particle, the researchers — led by MITEI postdoc Katerina Ioannidou — defined the forces that control how particles space out relative to one another as cement hydrate forms. The result is an algorithm that mimics the precipitation process, particle by particle. By constantly tracking the forces among the particles already present, the algorithm calculates the most likely position for each new one — a position that will move the system toward equilibrium. It thus adds more and more particles of varying sizes until the space is filled and the precipitation process stops. Results from sample analyses appear in the first two diagrams in Figure 1 of the slideshow above. The width of each simulation box is just under 600 nanometers — about one-tenth the diameter of a human hair. The two analyses assume different packing fractions, that is, the total fraction of the simulation box occupied by particles. The packing fraction is 0.35 in the left-hand diagram and 0.52 in the center diagram. At the lower fraction, far more of the volume is made up of open pores, indicated by the white regions. The third diagram in Figure 1 is a sketch of the cement hydrate structure proposed in pioneering work by T.C. Powers in 1958. The similarity to the center figure is striking. The MIT results thus support Powers’ idea that the formation of mesoscale pores can be attributed to the use of excessive water during hydration — that is, more water than needed to dissolve and precipitate the cement hydrate. “Those pores are the fingerprint of the water you put into the mix in the first place,” says Pellenq. “Add too much water, and at the end you’ll have a cement paste that is too porous, and it will degrade faster over time.” To validate their model, the researchers performed experimental tests and parallel theoretical analyses to determine the stiffness and hardness (or strength) of cement hydrate samples. The laboratory measurements were taken using a technique called nanoindentation, which involves pushing a hard tip into a sample to determine the relationship between the applied load and the volume of deformed material beneath the indenter. The graphs in Figure 2 of the slideshow above show results from small-scale nanoindentation tests on three laboratory samples (small symbols) and from computations of those properties in a “sample” generated by the simulation (yellow squares). The graph on the left shows results for stiffness, the graph on the right results for hardness. In both cases, the X-axis indicates the packing fraction. The results from the simulations match the experimental results well. (The researchers note that at lower packing fractions, the material is too soggy to test experimentally — but the simulation can do the calculation anyway.) In another test, the team investigated experimental measurements of cement hydrate that have mystified researchers for decades. A standard way to determine the structure of a material is using small-angle neutron scattering (SANS). Send a beam of neutrons into a sample, and how they bounce back conveys information about the distribution of particles and pores and other features on length scales of a few hundred nanometers. SANS had been used on hardened cement paste for several decades, but the measurements always exhibited a regular pattern that experts in the field couldn’t explain. Some talked about fractal structures, while others proposed that concrete is simply unique. To investigate, the researchers compared SANS analyses of laboratory samples with corresponding scattering data calculated using their model. The experimental and theoretical results showed excellent agreement, once again validating their technique. In addition, the simulation elucidated the source of the past confusion: The unexplained patterns are caused by the rough edges at the boundary between the pores and the solid regions. “All of a sudden we could explain this signature, this mystery, but on a physics basis in a bottom-up fashion,” says Ulm. “That was a really big step.” “We now know that the microtexture of cement paste isn’t a given but is a consequence of an interplay of physical forces,” says Ulm. “And since we know those forces, we can modify them to control the microtexture and produce concrete with the characteristics we want.” The approach opens up a new field involving the design of cement-based materials from the bottom up to create a suite of products tailored to specific applications. The CSHub researchers are now exploring ways to apply their new techniques to all steps in the life cycle of concrete. For example, a promising beginning-of-life approach may be to add another ingredient — perhaps a polymer — to alter the particle-particle interactions and serve as filler for the pore spaces that now form in cement hydrate. The result would be a stronger, more durable concrete for construction and also a high-density, low-porosity cement that would perform well in a variety of applications. For instance, at today’s oil and natural gas wells, cement sheaths are generally placed around drilling pipes to keep gas from escaping. “A molecule of methane is 500 times smaller than the pores in today’s cement, so filling those voids would help seal the gas in,” says Pellenq. The ability to control the material’s microtexture could have other, less-expected impacts. For example, novel CSHub work has demonstrated that the fuel efficiency of vehicles is significantly affected by the interaction between tires and pavement. Simulations and experiments in the lab-scale setup shown in Figure 3 of the slideshow above suggest that making concrete surfaces stiffer could reduce vehicle fuel consumption by as much as 3 percent nationwide, saving energy and reducing emissions. Perhaps most striking is a concept for recycling spent concrete. Today, methods of recycling concrete generally involve cutting it up and using it in place of gravel in new concrete. But that approach doesn’t reduce the need to manufacture more cement. The researchers’ idea is to reproduce the cohesive forces they’ve identified in cement hydrate. “If the microtexture is just a consequence of the physical forces between nanometer-sized particles, then we should be able to grind old concrete into fine particles and compress them so that the same force field develops,” says Ulm. “We can make new binder without needing any new cement — a true recycling concept for concrete!” This research was supported by Schlumberger; France’s National Center for Scientific Research (through its Laboratory of Excellence Interdisciplinary Center on MultiScale Materials for Energy and Environment); and the Concrete Sustainability Hub at MIT. Schlumberger is a Sustaining Member of the MIT Energy Initiative. The research team also included other investigators at MIT; the University of California at Los Angeles; Newcastle University in the United Kingdom; and Sorbonne University, Aix-Marseille University, and the National Center for Scientific Research in France. This article appears in the Spring 2016 issue of Energy Futures, the magazine of the MIT Energy Initiative.

Descotes-Genon S.,University Paris - Sud | Knecht M.,Aix - Marseille University
European Physical Journal C | Year: 2012

Dispersive representations of the ππ scattering amplitudes and pion form factors, valid at two-loop accuracy in the low-energy expansion, are constructed in the presence of isospin-breaking effects induced by the difference between the charged and neutral pion masses. Analytical expressions for the corresponding phases of the scalar and vector pion form factors are computed. It is shown that each of these phases consists of the sum of a "universal" part and a form-factor dependent contribution. The first one is entirely determined in terms of the ππ scattering amplitudes alone, and reduces to the phase satisfying Watson's theorem in the isospin limit. The second one can be sizeable, although it vanishes in the same limit. The dependence of these isospin corrections with respect to the parameters of the subthreshold expansion of the ππ amplitude is studied, and an equivalent representation in terms of the S-wave scattering lengths is also briefly presented and discussed. In addition, partially analytical expressions for the two-loop form factors and ππ scattering amplitudes in the presence of isospin breaking are provided. © 2012 Springer-Verlag / Società Italiana di Fisica.

Natoli G.,Italian National Cancer Institute | Andrau J.-C.,Aix - Marseille University | Andrau J.-C.,French Institute of Health and Medical Research | Andrau J.-C.,French National Center for Scientific Research
Annual Review of Genetics | Year: 2012

Mammalian genomes are extensively transcribed outside the borders of protein-coding genes. Genome-wide studies recently demonstrated that cis-regulatory genomic elements implicated in transcriptional control, such as enhancers and locus-control regions, represent major sites of extragenic noncoding transcription. Enhancer-templated transcripts provide a quantitatively small contribution to the total amount of cellular nonribosomal RNA; nevertheless, the possibility that enhancer transcription and the resulting enhancer RNAs may, in some cases, have functional roles, rather than represent mere transcriptional noise at accessible genomic regions, is supported by an increasing amount of experimental data. In this article we review the current knowledge on enhancer transcription and its functional implications. © 2012 by Annual Reviews.

Fanciullino R.,La Conception University Hospital of Marseille | Ciccolini J.,Aix - Marseille University | Milano G.,Oncopharmacology Unit
Critical Reviews in Oncology/Hematology | Year: 2013

Improving the efficacy-toxicity balance of anticancer agents remains an ongoing challenge in oncology. Beside the ever-growing development of innovative drugs addressing newly discovered molecular targets, nanotechnologies provide today a promising and exciting strategy to achieve this goal. The idea of carrying active compounds to their respective targets so as to improve their efficacy while sparing healthy tissue and reducing side-effects is not new. However, this area of research is in constant rise, and benefits from the latest advances in the field of biopharmaceutics, medicinal chemistry and nanomedicine. In addition to anthracyclines already widely present as liposomal drugs on the shelves, a variety of anticancer drugs can be now encapsulated into different chemical of structures so as to enhance their specificity toward malignant cells, mainly through improved pharmacokinetics profiles. Indeed, the recent advances in chemistry allow now a wide variety of scaffolds to be used as drug-carriers, so as optimize the delivery of cytotoxics. Even more recently, conjugated-drugs such as nanoalbumin (Nab) conjugates have emerged as a new promising alternative to improve both anticancer drugs distribution in the body and efficacy/toxicity balance eventually. This review covers the achievements and current limits of nanoparticles in oncology, with a special focus on nab-paclitaxel as a paradigmatic drug for this new generation of conjugated entities. © 2013 Elsevier Ireland Ltd.

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

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

Issartel J.,Aix - Marseille University | Coiffard C.,Museum fur Naturkunde
Oecologia | Year: 2011

We have examined the extreme longevity displayed by trees in relation to a theory mainly developed in animals, namely, the controversial rate of living (ROL) theory of aging which proposes that longevity is negatively correlated to metabolic rate. Plant metabolism implies respiration and photosynthesis; both are susceptible to negatively impact longevity. The relationship between longevity and metabolism was studied in leaves and stems of several species with the aim of challenging the ROL theory in trees. Leaf and stem life spans were found to be highly correlated to metabolism (R2 = 0.97), and stems displayed a much lower metabolism than leaves. Analysis of covariance (ANCOVA), with metabolism as the covariate, revealed no difference between mean leaf and stem life spans, which would appear to conform to the expectations of the ROL theory. Consequently, the extremely high longevity of trees may be explained by the lower metabolism displayed by the stems. These results clearly reflect different energy allocation and energy expenditure rate strategies between leaves and stems, which may result in different senescence rates (and life spans) in these organs. They also suggest that, in contrast to animals, the ROL theory of aging may apply to woody plants at the organ level, thereby opening a promising new line of research to guide future studies on plant senescence. © 2010 Springer-Verlag.

Walasik W.,Aix - Marseille University | Walasik W.,Polytechnic University of Catalonia | Renversez G.,Aix - Marseille University
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2016

We present two complementary models to study stationary nonlinear solutions in one-dimensional plasmonic slot waveguides made of a finite-thickness nonlinear dielectric core surrounded by metal regions. The considered nonlinearity is of focusing Kerr type. In the first model, it is assumed that the nonlinear term depends only on the transverse component of the electric field and that the nonlinear refractive index change is small compared to the linear part of the refractive index. This first model allows us to describe analytically the field profiles in the whole waveguide using Jacobi elliptic special functions. It also provides a closed analytical formula for the nonlinear dispersion relation. In the second model, the full dependency of the Kerr nonlinearity on the electric-field components is taken into account and no assumption is required on the amplitude of the nonlinear term. The disadvantage of this approach is that the field profiles must be computed numerically. Nevertheless, analytical constraints are obtained to reduce the parameter space where the solutions of the nonlinear dispersion relations are sought. © 2016 American Physical Society.

Zamoum R.,Aix - Marseille University | Crepieux A.,Aix - Marseille University | Safi I.,University Paris - Sud
Physical Review B - Condensed Matter and Materials Physics | Year: 2012

We consider a one-channel coherent conductor with a good transmission embedded into an Ohmic environment, the impedance of which is equal to the quantum of resistance R q=h/e2 below the RC frequency. This choice is motivated by the mapping of this problem to a Tomonaga-Luttinger liquid with one impurity, the interaction parameter of which corresponds to the specific value K=1/2, allowing for a refermionization procedure. The "new" fermions have an energy-dependent transmission amplitude, which incorporates the strong correlation effects and yields the exact dc current and zero-frequency noise through expressions similar to those of the scattering approach. We recall and discuss these results for our present purpose. Then, we compute the finite-frequency differential conductance and the finite-frequency nonsymmetrized noise. Contrary to intuitive expectation, both can not be expressed within the scattering approach for the new fermions, even though they are still determined by the transmission amplitude. Even more, the finite-frequency conductance obeys an exact relation in terms of the dc current, which is similar to that derived perturbatively with respect to weak tunneling within the Tien-Gordon theory, and extended recently to arbitrary strongly interacting systems coupled eventually to an environment and/or with a fractional charge. We also show that the emission excess noise vanishes exactly above eV, even though the underlying Tomonaga-Luttinger liquid model corresponds to a many-body correlated system. Our results apply for all ranges of temperature, voltages, and frequencies below the RC frequency, and they allow us to explore fully the quantum regime. © 2012 American Physical Society.

Nishio M.,CHPI Institute | Umezawa Y.,Institute of Microbial Chemistry BIKAKEN Tokyo | Fantini J.,Aix - Marseille University | Weiss M.S.,Helmholtz Center Berlin | Chakrabarti P.,Bose Institute of India
Physical Chemistry Chemical Physics | Year: 2014

This is a sequel to the previous Perspective "The CH-π hydrogen bond in chemistry. Conformation, supramolecules, optical resolution and interactions involving carbohydrates", which featured in a PCCP themed issue on "Weak Hydrogen Bonds-Strong Effects?": Phys. Chem. Chem. Phys., 2011, 13, 13873-13900. Evidence that weak hydrogen bonds play an enormously important role in chemistry and biochemistry has now accumulated to an extent that the rigid classical concept of hydrogen bonds formulated by Pauling needs to be seriously revised and extended. The concept of a more generalized hydrogen bond definition is indispensable for understanding the folding mechanisms of proteins. The CH-π hydrogen bond, a weak molecular force occurring between a soft acid CH and a soft base π-electron system, among all is one of the most important and plays a functional role in defining the conformation and stability of 3D structures as well as in many molecular recognition events. This concept is also valuable in structure-based drug design efforts. Despite their frequent occurrence in organic molecules and bio-molecules, the importance of CH-π hydrogen bonds is still largely unknown to many chemists and biochemists. Here we present a review that deals with the evidence, nature, characteristics and consequences of the CH-π hydrogen bond in biological macromolecules (proteins, nucleic acids, lipids and polysaccharides). It is hoped that the present Perspective will show the importance of CH-π hydrogen bonds and stimulate interest in the interactions of biological macromolecules, one of the most fascinating fields in bioorganic chemistry. Implication of this concept is enormous and valuable in the scientific community. This journal is © the Partner Organisations 2014.

Soloshonok V.A.,University of the Basque Country | Soloshonok V.A.,Ikerbasque | Roussel C.,Aix - Marseille University | Kitagawa O.,Shibaura Institute of Technology | And 3 more authors.
Chemical Society Reviews | Year: 2012

This tutorial review describes the self-disproportionation of enantiomers (SDE) of chiral, non-racemic compounds, subjected to chromatography on an achiral stationary phase using an achiral eluent, which leads to the substantial enantiomeric enrichment and the corresponding depletion in different fractions, as compared to the enantiomeric composition of the starting material. The physicochemical background of SDE is a dynamic formation of homo- or heterochiral dimeric or oligomeric aggregates of different chromatographic behavior. This phenomenon is of a very general nature as the SDE has been reported for different classes of organic compounds bearing various functional groups and possessing diverse elements of chirality (central, axial and helical chirality). The literature data discussed in this review clearly suggest that SDE via achiral chromatography might be expected for any given chiral enantiomerically enriched compound. This presents two very important issues for organic chemists. First, chromatographic purification of reaction products can lead to erroneous determination of the stereochemical outcome of catalytic asymmetric reactions and second, achiral chromatography can be used as a new, nonconventional method for optical purifications. The latter has tremendous practical potential as the currently available techniques are limited to crystallization or chiral chromatography. However, a further systematic study of SDE is needed to develop understanding of this phenomenon and to design practical chromatographic separation techniques for optical purification of non-racemic mixtures by achiral-phase chromatography. © 2012 The Royal Society of Chemistry.

Manel S.,Aix - Marseille University | Manel S.,CIRAD - Agricultural Research for Development | Holderegger R.,Swiss Federal Institute of forest | Holderegger R.,ETH Zurich
Trends in Ecology and Evolution | Year: 2013

Landscape genetics is now ten years old. It has stimulated research into the effect of landscapes on evolutionary processes. This review describes the main topics that have contributed most significantly to the progress of landscape genetics, such as conceptual and methodological developments in spatial and temporal patterns of gene flow, seascape genetics, and landscape genomics. We then suggest perspectives for the future, investigating what the field will contribute to the assessment of global change and conservation in general and to the management of tropical and urban areas in particular. To address these urgent topics, future work in landscape genetics should focus on a better integration of neutral and adaptive genetic variation and their interplay with species distribution and the environment. © 2013 Elsevier Ltd.

Brochier-Armanet C.,Aix - Marseille University | Forterre P.,Institute Pasteur Paris | Forterre P.,University Paris - Sud | Gribaldo S.,Institute Pasteur Paris
Current Opinion in Microbiology | Year: 2011

Little more than 30 years since the discovery of the Archaea, over one hundred archaeal genome sequences are now publicly available, of which ~40% have been released in the last two years. Their analysis provides an increasingly complex picture of archaeal phylogeny and evolution with the proposal of new major phyla, such as the Thaumarchaeota, and important information on the evolution of key central cellular features such as cell division. Insights have been gained into the events and processes in archaeal evolution, with a number of additional and unexpected links to the Eukaryotes revealed. Taken together, these results predict that many more surprises will be found as new archaeal genomes are sequenced. © 2011 Elsevier Ltd.

Peeters D.,Max Planck Institute for Psycholinguistics | Dijkstra T.,Donders Institute for Brain | Grainger J.,Aix - Marseille University
Journal of Memory and Language | Year: 2013

Across the languages of a bilingual, translation equivalents can have the same orthographic form and shared meaning (e.g., TABLE in French and English). How such words, called orthographically identical cognates, are processed and represented in the bilingual brain is not well understood. In the present study, late French-English bilinguals processed such identical cognates and control words in an English lexical decision task. Both behavioral and electrophysiological data were collected. Reaction times to identical cognates were shorter than for non-cognate controls and depended on both English and French frequency. Cognates with a low English frequency showed a larger cognate advantage than those with a high English frequency. In addition, N400 amplitude was found to be sensitive to cognate status and both the English and French frequency of the cognate words. Theoretical consequences for the processing and representation of identical cognates are discussed. © 2013 Elsevier Inc.

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2012.2.1.1-1-B | Award Amount: 16.85M | Year: 2012

Neurodegenerative (ND) and neuromuscular (NM) disease is one of the most frequent classes of rare diseases, affecting life and mobility of 500,000 patients in Europe and millions of their caregivers, family members and employers. This NEUROMICS project brings together the leading research groups in Europe, five highly innovative SMEs and relevant oversea experts using the most sophisticated Omics technologies to revolutionize diagnostics and to develop pathomechanism-based treatment for ten major ND and NM diseases. Specifically we aim to: (i) use next generation WES to increase the number of known gene loci for the most heterogeneous disease groups from about 50% to 80%, (ii) increase patient cohorts by large scale genotyping by enriched gene variant panels and NGS of so far unclassified patients and subsequent phenotyping, (iii) develop biomarkers for clinical application with a strong emphasis on presymptomatic utility and cohort stratification, (iv) combine -omics approaches to better understand pathophysiology and identify therapeutic targets, (v) identify disease modifiers in disease subgroups cohorts with extreme age of onset (vi) develop targeted therapies (to groups or personalized) using antisense oligos and histone deacetylase inhibitors, translating the consortiums expertise in clinical development from ongoing trials toward other disease groups, notably the PolyQ diseases and other NMD. To warrant that advances affect a large fraction of patients we limited the selection to a number of major categories, some of which are in a promising stage of etiological and therapeutic research while some others are in great need of further classification. The efforts will be connected through a NEUROMICS platform for impact, communication and innovation that will provide tools and procedures for ensuring trial-readiness, WP performance, sustainability, interaction with the chosen Support IRDiRC and RD-Connect project and involvement of stakeholders in the NDD/NMD field.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2009.8.0 | Award Amount: 2.53M | Year: 2010

Algorithms in signal and image processing have reached an impressive level of sophistication and computing power still increases at an exponential rate. However, high-tech applications have an ever-increasing demand for even more efficient algorithms, even more powerful computers and new concepts for advancing applications.\nStarting from a recently discovered gap in the theory of uncertainty principles, this project aims at developing a framework for constructing problem adapted, ultra-efficient algorithms concerning (de-)coding and analyzing/synthesizing signals/images. We expect, that this will allow us to tackle complex applications in life sciences and ultra precise audio signal processing which presently cannot be solved appropriately with existing algorithms on existing computers.\nThe key for developing these algorithms is a representation of signals and images by function systems, which satisfy the following requirements:\n1.\tOptimal localization,\n2.\tEfficient discretization.\nThe theoretical foundation of this approach is based on the definition of suitable localization measures in generalized phase spaces and the construction of minimizing waveforms. These waveforms are then the basic building blocks in discretization schemes.\nWe expect that this approach allows us to shift the limits of the efficiency vs. precision paradigm considerably. The efficiency of an abstract algorithm has to be evaluated in connection with the computer hardware (parallelization, data exchange, storage) used. Accordingly, our proof of principle includes implementations of baseline algorithms as well as of advanced GPU implementations.\nAs final proof of principle we apply these methods for two challenging applications in audio signal design and life sciences (proteomics). The evaluation will be done by our industrial consortium partners together with our advisory board consisting of one SME, one world market leader and two internationally highly recognized scientific experts.

French Institute of Health, Medical Research, Aix - Marseille University and Institute Jean Paoli & Irene Calmettes | Date: 2015-12-09

The invention relates to antigen peptide derived from the Nectin4 and its use for preventing and treating cancer.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2012-ITN | Award Amount: 3.71M | Year: 2012

The overall objective of this project is the creation of an ITN network for the structured interdisciplinary training of researchers in advanced thin film photovoltaic (PV) technologies. The project proposes the development of new technologies compatible with the cost, efficiency, sustainability and mass production requirements that are needed to become a reliable and future alternative to conventional non renewable energy sources. With this objective in mind, the project will focus on the development of kesterite based solar cells. Kesterites are quaternary compounds with a crystalline structure very similar to that of chalcopyrites (CIGS: Cu(In,Ga)(S,Se)2). They have a strong potential for thin film low cost PV technologies, related to their direct bandgap and high optical absorption. In contrast with CIGS -where the potential for high mass production is compromised by the scarcity of In- they are constituted by abundant elements. For this, a consortium formed by research institutes, universities and companies with strongly complementary expertises has been formed. This includes groups that are leaders on the development of kesterite cells (Univ. Northumbria, HZB, Univ. Luxembourg) with groups with strong expertise on CIGS technologies (that are the parent technologies for kesterite solar cells) (EMPA, UU-ASC, NEXCIS, IREC, Free Univ. Berlin, Univ. dAix-Marseille, Autonomous Univ. Madrid). Free Univ. Berlin has also significant experience in the crystalline analysis of kesterites. Involvement of private companies (NEXCIS, Abengoa) devoted to the production and exploitation of PV technologies provides with complementary training aspects related to transferability of processes to industrial production and exploitation issues. All these aspects are relevant for the definition of a structured interdisciplinary training programme for the formation of high level researchers that will be required in Europe for the development of competitive PV technologies.

French National Center for Scientific Research, Aix - Marseille University and Assistance Publique Des Hopitaux De Marseille | Date: 2013-12-30

The present invention relates to a method of assessing proprioceptive status by calculating a proprioceptive score Sp from absolute and variable errors between target angles and angles estimated and joint motion detection by the person tested, and/or between measured time of perceived movement of the joint of the tested person these proprioceptive scores of a person being associated with an assessment date and then stored with a date so as to serve as a reference when said person is monitored or when there is a comparison of said person with at least another person. The present invention also concerns an apparatus for the proprioceptive assessment of at least one joint, this apparatus having two movable parts (8, 9) with drive means (12, 15) particular for the pivoting of the movable parts (8, 9), means of determining the pivot angle for each of the first and second parts (8, 9) also being provided. Applications are in the field of proprioceptive assessment by movement of a limb of a person.

French Institute of Health, Medical Research, Institute Jean Paoli & Irene Calmettes, Aix - Marseille University, University Claude Bernard Lyon 1 and Center Leon Berard | Date: 2016-05-26

The present invention provides antibodies directed against ICOS or a derivative thereof which neutralize ICOS engagement on Treg by inhibiting the fixation between ICOS and ICOS-L and abrogate proliferation of Treg induced by plasmacytoid dendritic cells. The present invention further provides antibodies directed against ICOS or a derivative thereof which induce IL-10 and IFN production, induce CD4+ T cells proliferation, reduce Tconv proliferation, and increase the immunosuppressive function of Treg.

University of Bordeaux Segalen, Aix - Marseille University and University of Burgundy | Date: 2014-03-13

The invention relates to a method for preparing nanoparticles based on functional amphiphilic molecules or macromolecules, optionally in the presence of at least one colipide, enabling the encapsulation of therapeutic agents, especially anti-tumoral agents, and the use thereof for the transport and vectorization of therapeutic agents, especially anti-tumoral agents.

Aix - Marseille University and Assistance Publique Des Hopitaux De Marseille | Date: 2011-11-02

A simulator intended for learning tracheal intubation includes: an anatomic dummy element (1) reproducing at least one buccal cavity (2) provided with a tongue (4), with an epiglottis (7) and with the corresponding glossoepiglottic vallecula (8); a simulation system (15) capable of determining at least one physiological parameter of a patient subject to tracheal intubation; at least one force sensor (13) positioned on the dummy element at the glossoepiglottic vallecula so as to measure the force applied at this level by the blade (11) of a laryngoscope (12) handled by the operator; and transmission element (14) for providing the value of the measurement conducted with the force sensor at the input of the simulation system; wherein the simulation system is laid out for taking into account the value of the measurement conducted with the force sensor in order to determine the physiological parameter.

French Institute of Health, Medical Research, Aix - Marseille University, Institute Jean Paoli & Irene Calmettes and French National Center for Scientific Research | Date: 2014-06-05

The present invention concerns an oligonucleotide modified by substitution at the 3 or the 5 end by a moiety comprising at least one ketal functional group, wherein the ketal carbon of said ketal functional group bears two saturated or unsaturated, linear or branched, hydrocarbon chains comprising from 1 to 22 carbon atoms, and the use therefore as a medicament, in particular for use for treating cancer.

Institute Jean Paoli & Irene Calmettes, Aix - Marseille University and French National Center for Scientific Research | Date: 2014-02-21

Antagonist of the BTLA/HVEM interaction for use in therapy The present invention relates to an antagonist of the BTLA/HVEM interaction for use in therapy, wherein said antagonist increases the proliferation of V9V2 T cells.

Agency: European Commission | Branch: H2020 | Program: MSCA-RISE | Phase: MSCA-RISE-2016 | Award Amount: 711.00K | Year: 2017

Many dynamical processes in natural sciences are organized by invariant objects that behave in rather simple ways under time evolution, such as equilibria, periodic orbits, or higher-dimensional invariant surfaces. These objects and the invariant manifolds attached to them act as landmarks that organize the behavior of other trajectories and yield a qualitative description of the dynamics. By computing strategically chosen landmarks, one can obtain considerable information of the possible behaviors of the system. This strategy is particularly fruitful in Hamiltonian systems, in which a large number of invariant manifolds coexist. For example, it has been realized in recent years that Transition State theory, a framework first developed in chemistry and then applied to other fields of science, relies on the existence of invariant manifolds in phase space. These manifolds encode the essential dynamics of various reorganization processes. The objective of this RISE proposal is to build a multidisciplinary exchange programme around the determination of invariant dynamical objects which encompass applied mathematics, atomic and molecular physics, chemistry and celestial mechanics. The project aims at linking mathematicians, physicists and chemists to identify the universal mechanisms behind dynamical transition processes. The proposed collaborative project will be coordinated by the School of Mathematics of Loughborough University, and will involve the Department of Mathematics of the University of Barcelona, the Center for Theoretical Physics (CNRS / Aix Marseille University), the Physics Department of the Polytechnic University of Madrid, the Chemistry Department at the Universidad Autnoma of Madrid and the Physics Department at the University of Stuttgart. The third country partners are Georgia Institute of Technology, represented by the School of Mathematics and the School of Physics and Johns Hopkins University, represented by the School of Chemistry.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: OCEAN 2013.2 | Award Amount: 8.10M | Year: 2013

As stated by the marine research decision makers in Europe in the Ostend Declaration in 2010, a major challenge is to support the development of a truly integrated and sustainably funded European Ocean Observing System. This will be achieved with more long-term measurements of key parameters but is impaired by the costs and lack of reliability of ocean sensors in general. The NeXOS project aims to improve the temporal and spatial coverage, resolution and quality of marine observations through the development of cost-efficient innovative and interoperable in-situ sensors deployable from multiple platforms, and Web Services for key domains and applications. This will be achieved through the development of new, low-cost, compact and integrated sensors with multiple functionalities including the measurement of key parameters useful to a number of objectives, ranging from more precise monitoring and modelling of the marine environment to an improved assessment of fisheries. Seven new compact, cost-efficient sensors will be developed, based on optical and acoustics technologies, addressing a majority of descriptors identified by the Marine Strategy Framework Directive for Good Environmental Status. Two of the new sensors will specifically contribute to the Common Fisheries Policy with variables relevant for an Ecosystem Approach to Fisheries. All new sensors will respond to multiplatform integration, sensor and data interoperability, quality assurance and reliability requirements. These will be specified for each new sensor system. All new sensors will be calibrated, integrated on several types of platforms, scientifically validated and demonstrated. One of the main objectives of NeXOS will finally be to enhance the competitiveness of European SMEs in the ocean sensor market. To this end, sensor requirements and specifications will be assessed at an early phase of the project for market penetration.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: SPA.2013.2.1-01 | Award Amount: 3.10M | Year: 2013

VIALACTEA will bring to a common forum the major new-generation surveys of the Galactic Plane from 1um to the radio, both in thermal continuum and in atomic and molecular lines, from Europe-funded space missions and ground-based facilities, to engage one of the fundamental challenges in Galactic astronomy: to quantify Galaxy-wide the relationship between the physical agents responsible for the onset and the regulation of star formation in a spiral galaxy and the resulting Rate and Efficiency of star formation, and obtain a star formation recipe that will be a cornerstone to trace the star formation history of galaxies back to their formation. The new state-of-the-art Milky Way paradigm is offering today, for the first time, the possibility to deploy a coherent science analysis methodology that can be uniformly applied from the Galactic Center to the outskirts of the Galaxy. A homogeneous and inter-calibrated evolutionary classification of the cold and dense clumps hosting young forming clusters at a variety of evolutionary stages will allow to deliver a new 3D model of the Galaxy, mapping the essential critical parameters like column density thresholds, rate and efficiency of star formation in the Galaxy To make such an analysis possible in a timely and effective fashion, we will develop a suite of next-generation 3D-visualization tools that will integrate visual analytics, on-the-fly handling of multi-SED radiative transfer modeling and data mining/machine-learning technologies to incorporate the astronomers know-how into a set of supervised workflows with decision making capabilities. The focus on research and analysis of data obtained from European space missions in combination with data from Europe-funded ground facilities, will enable time-effective exploitation of steradiant-scale multi-wavelength Galactic Plane surveys through new 3D-based visual analytics frameworks, making VIALACTEAs objectives timely and totally relevant for FP7-SPACE-2013-1.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-1.4-1 | Award Amount: 7.86M | Year: 2008

Cancer is the second leading cause of death in European countries, and one of the most imminent health problems in the developed world. Innovative, so-called targeted therapies are urgently needed that aim specifically at cancer cells or to cells of the stroma that support tumor growth. The ultimate goal of a targeted therapy is to increase anti-tumor efficacy with lowest possible side effects. Rapid and efficient translation of basic scientific advances into reagents, and targeted molecular leads for preclinical and clinical research and development based on scientific rationales and state-of-the-art technologies, optimally requires an interdisciplinary, collaborative, team-oriented approach. EUCAAD represents a virtual research institute in Europe and consists of 9 research participants including 4 SMEs devoted to the discovery and evaluation of new antibodies for therapy of human cancers. The consortium consists of researchers from SMEs and scientific and clinical centres that have gained international acclaim in this area of research, many of who have worked together in previous EU funded applications e.g. ANGIOSTOP, EUCAPS, ESTDAB and ENACT. Within the consortium there is unique expertise regarding target discovery, target validation, antibody production and initiation of clinical trials. As part of its efforts to translate laboratory research into viable cancer therapies the individual partners has accumulated an extensive portfolio of intellectual property providing a competitive edge to this application. The focus of the grant is the development and evaluation of antibodies against new target structures on tumour cells and blood vessels supplying tumours which are responsible for tumour angiogenesis, progression and metastasis. Collectively, the activities of this consortium can improve the cancer treatment standards in Europe and provide economic benefit to European biotechnology and pharmaceutical research by providing novel immunopharmaceuticals.

Agency: European Commission | Branch: FP7 | Program: ERC-AG | Phase: ERC-AG-SH6 | Award Amount: 2.49M | Year: 2012

The Sasanian Empire (3rd-7th c. AD) stretched from Mesopotamia to the west of the Indian Subcontinent. A pilot study has shown that major frontier walls and geometrical fortifications, whose scale and sophistication surpasses those in contemporary Europe, date to the Sasanian era, as do grand urban foundations and canal systems. Yet, excavations and surveys of Sasanian monuments have been far and few between and have mostly employed conventional approaches. Publications amount to a fraction of those on Roman studies. Our interdisciplinary project will provide unique insights into one of the great powers of the age, but the one that is most poorly understood. It will achieve this by bringing together a broad range of complementary methods. Satellite images will be analysed to examine the Empires frontier zones. Key sites will be selected for geophysical survey, targeted excavation, scientific dating and systematic analysis of artefacts, faunal and botanical remains. Combining large-scale survey with small-scale case studies promises to provide unrivalled insights into military infrastructure, urbanisation and rural settlement intertwined phenomena, as agricultural surplus production enabled large-scale construction projects. Our in-depth study of Sasanian frontier territories promises to fill a major gap in our understanding of Late Antiquity and shed light on the reasons behind the longevity, economic and military dominance and dynamism of one of the largest empires of the ancient world, far beyond what has been achieved so far. The Empires capabilities challenge our traditional Eurocentric approach. While it is acknowledged that the later Caliphates military power and urban culture were unrivalled in Western Europe at the time, our project promises to show that some of these advances have their roots in the pre-Islamic era. Our project will open up new fields of research, and will have a major impact on archaeological studies and ancient and medieval history.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2009.8.8 | Award Amount: 12.10M | Year: 2011

The BrainScaleS project aims at understanding function and interaction of multiple spatial and temporal scales in brain information processing. The fundamentally new approach of BrainScaelS lies in the in-vivo biological experimentation and computational analysis. Spatial scales range from individual neurons over larger neuron populations to entire functional brain areas. Temporal scales range from milliseconds relevant for event based plasticity mechanisms to hours or days relevant for learning and development. In the project generic theoretical principles will be extracted to enable an artificial synthesis of cortical-like cognitive skills. Both, numerical simulations on petaflop supercomputers and a fundamentally different non-von Neumann hardware architecture will be employed for this purpose.Neurobiological data from the early perceptual visual and somatosensory systems will be combined with data from specifically targeted higher cortical areas. Functional databases as well as novel project-specific experimental tools and protocols will be developed and used.New theoretical concepts and methods will be developed for understanding the computational role of the complex multi-scale dynamics of neural systems in-vivo. Innovative in-vivo experiments will be carried out to guide this analytical understanding.Multiscale architectures will be synthesized into a non-von Neumann computing device realised in custom designed electronic hardware. The proposed Hybrid Multiscale Computing Facility (HMF) combines microscopic neuromorphic physical model circuits with numerically calculated mesoscopic and macroscopic functional units and a virtual environment providing sensory, decision-making and motor interfaces. The project also plans to employ petaflop supercomputing to obtain new insights into the specific properties of the different hardware architectures.A set of demonstration experiments will link multiscale analysis of biological systems with functionally and architecturally equivalent synthetic systems and offer the possibility for quantitative statements on the validity of theories bridging multiple scales. The demonstration experiments will also explore non-von Neumann computing outside the realm of brain-science.BrainScaelS will establish close links with the EU Brain-i-Nets and the Blue Brain project at the EPFL Lausanne. The consortium consists of a core group of 15 partners with 18 individual groups.Together with other projects and groups the BrainScaelS consortium plans to make important contributions to the preparation of a future FET flagship project. This project will address the understanding and exploitation of information processing in the human brain as one of the major intellectual challenges of humanity with vast potential applications.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.37M | Year: 2014

This ITN TRANSMIC project brings together a group of universities, think-tanks, institutes, practitioners and high-level officials that all share a long-term interest in migration policies and citizenship issues and who have extensive academic and/or practical expertise in this field. Their inter- and multi-disciplinary knowledge and experience is pooled with the main objective of improving the European and international career opportunities of young researchers by offering them a coherent academic training programme complemented with a professional skills training programme and by exposing them to experience on the work-floor through an internship at a think-tank, a consultancy or a law firm, all specialized in the issue of migration and citizenship issues. In addition the network will also be a catalyst for intensive cooperation and exchange of best practices amongst the participating partners and promote interaction and fertilization between academia, professional organizations, representatives of European institutions and member States as well as policy makers in various countries of research all around the globe with an interest in transnational migration and citizenship questions. Given the intensity of the cooperation, it is to be expected that the network will also provide a solid basis for cooperation and interaction beyond ITN. The focus of the research is the rapidly-evolving field of transnational migration and citizenship addressed from the perspective of circularity of rights and responsibilities. The in-depth and inter-/multi-disciplinary study of the concept of transnational migration, citizenship and related problems concerning the mobility of migrants from a comparative and rights-based perspective is extremely topical in the light of the current political and academic debates concerning circular migration, mobility partnerships, high- and low skilled migration. These debates are directly connected with the concepts and positions taken towards acquired rights, citizenship and nationality. These research issues also contribute to our broader understanding of the origins, evolution and effects of migration movements for the host as well as the home societies.

Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 3.05M | Year: 2015

Over 50 million people worldwide have epilepsy and 30% are resistant to our present therapies. Epilepsy, therefore, comprises a major burden to society and so there is a pressing need for new approaches to treatment. The brain extracellular matrix (ECM) plays a critical role in governing brain excitability and function. Although research into the role of the ECM in neuronal signalling and network function has advanced considerably in recent years, its full translational potential has yet to be realised. There is growing evidence for a major role of the ECM in epilepsy including the association between ECM protein mutations and epilepsy, changes in the ECM and associated proteins during the development of epilepsy and the strong association between the ECM and brain diseases associated with epilepsy including stroke, traumatic brain injury, neurodegeneration and autism. This proposal brings together considerable expertise from academic and industry partners in the biology of the ECM with experts in epilepsy research. This, therefore, represents a truly collaborative effort to determine not only the role of the ECM in the development of epilepsy but also novel approaches to treat and to prevent epilepsy. The academic partners will focus on specific research questions, whilst the industrial members will provide diagnostic, treatment and advanced research tools. The project has a strong translational theme and the combination of basic and translational science will be of great benefit for the training of young researchers. Trainees will be exposed to courses, workshops, joint research meetings and inter-laboratory visits. The focus of the training programme is on expanding knowledge and the application of such knowledge to address pertinent question relevant to the diagnosis, prognosis and treatment of epilepsy, so providing an ideal insight into translational neuroscience.

Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 3.96M | Year: 2015

NMR and MRI play unique roles in contemporary Science, from Physics, Chemistry and Biology, to clinical research and diagnosis. Despite its irreplaceable role, further progress in NMR and MRI is hampered by sensitivities that are much lower than those of alternatives such as mass-spec, or PET. The prospects of solving this problem by bigger machines are uncertain and of poor return, given the high maturity already achieved by NMR/MRI. This ETN challenges this status from an untapped perspective, combining NMR/MRI with nuclear hyperpolarization eliciting signals that surpass those currently available by up to 50,000x. Focus is placed on two particular approaches, dynamic nuclear polarization and para-hydrogen-driven polarization, exhibiting the highest potential for biophysical, metabolomic, pre-clinical and clinical research. To maximize these supersignals we assembled leading experts in the physics and engineering of magnetic resonance, in the synthetic chemistry essential for the success of these methods, in the uses of NMR to structural/cell biology, and in preclinical and clinical MRI applications. Guiding this assembling is the conception that only by teaming together key areas of expertise, can hyperpolarisations promises be realized. In addition to fostering synergies among experts from academia and industry, EUROPOL will provide frontier training for ESRs in all the topics underlying the advancement of MR. This will include advanced physics, new instruments and forms of exploiting NMR/MRIs hyperpolarisation, biophysical NMR, screening of healthy and diseased metabolomes, expanded portfolios of substrates to be targeted by in vivo MR, ancillary in cell and system biology explorations clarifying the nature of the metabolic phenomena, and in vivo hyperpolarisation strategies in MRI. This ETN is unparalleled in scope, breadth and potential for synergies.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-31-2014 | Award Amount: 2.65M | Year: 2015

FRESHER brings together ten research groups, including leaders in the management of large European Foresight projects and highly experienced health policy modelers, in an interdisciplinary team engaged in FoResight and Modelling for European Health policy and Regulation. The overall project objective is the representation of alternative futures where the detection of emerging health scenarios will be used to test future policies to effectively tackle the burden of non communicable diseases (NCDs). The project will produce quantitative estimates of the future global burden of NCDs in the EU and its impact on health care expenditures and delivery, population well-being, health and socio-economic inequalities, and potential changes in these impacts according to alternative health and non-health policy options. The added value of FRESHER lies in the fact that these estimates: - will not only be based on extrapolation of past health trends but also on foresight techniques (mapping of risk factors, horizon scanning and identification of key drivers for change, scenarios building) giving credit to the interdependencies of structural long-term trends in demography, gender relations, technological, economic, environmental, and societal factors at 2050. - will be produced through the development of an empirically-based micro-simulation model (starting from the Chronic Disease Policy Model of OECD), allowing to quantify the current and future health and economic impacts of NCDs and testing what if policy options according to alternative foresight scenarios, as well as potential new policies and policy combinations. FRESHER heavily relies on an interactive process with key stakeholders, at all stages of the project, in elaborating the framework, and giving inputs for the qualitative foresight scenarios and the quantitative micro-simulation model, and in deriving recommendations for future policies affecting population health and well-being.

Aix - Marseille University, French Institute of Health, Medical Research and Institute Jean Paoli & Irene Calmettes | Date: 2012-05-31

The invention relates to antigen peptide derived from the Nectin4 and its use for preventing and treating cancer.

French Institute of Health, Medical Research, Aix - Marseille University, Institute Jean Paoli & Irene Calmettes and French National Center for Scientific Research | Date: 2014-06-05

The present invention concerns an oligonucleotide modified by substitution at the 3 or the 5 end by a moiety comprising at least three saturated or unsaturated, linear or branched hydrocarbon chains comprising from 2 to 30 carbon atoms, and the use therefore as a medicament, in particular for use for treating cancer.

Institute Jean Paoli & Irene Calmettes, Aix - Marseille University, French Institute of Health, Medical Research, Center Leon Berard and University Claude Bernard Lyon 1 | Date: 2012-03-29

The present invention provides antibodies directed against ICOS or a derivative thereof which neutralize ICOS engagement on Treg by inhibiting the fixation between ICOS and ICOS-L and abrogate proliferation of Treg induced by plasmacytoid dendritic cells. The present invention further provides antibodies directed against ICOS or a derivative thereof which induce IL-10 and IFN production, induce CD4+ T cells proliferation, reduce Tconv proliferation, and increase the immunosuppressive function of Treg.

Aix - Marseille University, French National Center for Scientific Research and Primachip Sas | Date: 2010-12-15

The disclosure relates to an amplifier comprising a digital delta-sigma modulator, a quantifier receiving a signal supplied by a delta-sigma stage and supplying a quantified signal, and a power circuit supplying an output signal. The device comprises N state loops of a first type configured to send the output signal to adders of N delta-sigma stages of lower rank, each state loop of the first type comprising an analog low-pass filter for supplying a filtered output signal, and an analog to digital converter for supplying a digital filtered output signal.

French Institute of Health, Medical Research, Aix - Marseille University and Institute Jean Paoli & Irene Calmettes | Date: 2014-03-28

The present invention relates to methods and pharmaceutical compositions for treating breast cancers. In particular, the present invention relates to a method for predicting the survival of a patient suffering from a breast cancer comprising i) determining the expression level of Vangl2 in a tumor sample obtained from the patient, ii) comparing the expression level determined at step i) with a predetermined reference value and iii) providing a poor prognosis when the expression level determined at step i) is higher than the predetermined reference value. The present invention also relates to a method for treating a patient suffering from a breast cancer comprising the steps consisting of i) predicting the survival of the patient according to claim 1 and ii) administering the patient with an anti-Vangl2 antibody or an inhibitor of Vangl2 expression or an inhibitor of the Vangl2-p62 interaction when it is concluded that the patient has a poor prognosis at step i).

French Institute of Health, Medical Research, Aix - Marseille University, Institute Jean Paoli & Irene Calmettes and French National Center for Scientific Research | Date: 2013-05-24

The present invention relates to methods for selecting binders by phage display and masked selection. More particularly, the present invention relates to a method for selecting a plurality of binders specific for at least one relevant target comprising screening a phage binder library of binders against the relevant target in presence of a plurality of binders obtained from a library of binders directed against at least one irrelevant target and positively selecting the binders that are specific for the at least one relevant target.

Essilor, French National Center for Scientific Research and Aix - Marseille University | Date: 2014-08-07

A method of assisting visual exploration for individuals suffering from a retinal condition resulting in a scotoma and, more particularly, a method S for assisting visual exploration by such an individual of a digital image on a display device, the method including:recognizing, using shape recognition software, at least one object contained in an object area of the digital image,determining a blind area in the image, corresponding to a position of the scotoma in the field of vision of the user looking at the image,if the blind area and the object area are detected to be in close proximity to each other, applying image processing to the image consisting in highlighting the object area for the user.

Ortega H.G.,Glaxosmithkline | Liu M.C.,Johns Hopkins Asthma and Allergy Center | Pavord I.D.,University of Oxford | Brusselle G.G.,Ghent University | And 6 more authors.
New England Journal of Medicine | Year: 2014

Background: Some patients with severe asthma have frequent exacerbations associated with persistent eosinophilic inflammation despite continuous treatment with high-dose inhaled glucocorticoids with or without oral glucocorticoids. Methods: In this randomized, double-blind, double-dummy study, we assigned 576 patients with recurrent asthma exacerbations and evidence of eosinophilic inflammation despite high doses of inhaled glucocorticoids to one of three study groups. Patients were assigned to receive mepolizumab, a humanized monoclonal antibody against interleukin-5, which was administered as either a 75-mg intravenous dose or a 100-mg subcutaneous dose, or placebo every 4 weeks for 32 weeks. The primary outcome was the rate of exacerbations. Other outcomes included the forced expiratory volume in 1 second (FEV1) and scores on the St. George's Respiratory Questionnaire (SGRQ) and the 5-item Asthma Control Questionnaire (ACQ-5). Safety was also assessed. Results: The rate of exacerbations was reduced by 47% (95% confidence interval [CI], 29 to 61) among patients receiving intravenous mepolizumab and by 53% (95% CI, 37 to 65) among those receiving subcutaneous mepolizumab, as compared with those receiving placebo (P<0.001 for both comparisons). Exacerbations necessitating an emergency department visit or hospitalization were reduced by 32% in the group receiving intravenous mepolizumab and by 61% in the group receiving subcutaneous mepolizumab. At week 32, the mean increase from baseline in FEV1 was 100 ml greater in patients receiving intravenous mepolizumab than in those receiving placebo (P = 0.02) and 98 ml greater in patients receiving subcutaneous mepolizumab than in those receiving placebo (P=0.03). The improvement from baseline in the SGRQ score was 6.4 points and 7.0 points greater in the intravenous and subcutaneous mepolizumab groups, respectively, than in the placebo group (minimal clinically important change, 4 points), and the improvement in the ACQ-5 score was 0.42 points and 0.44 points greater in the two mepolizumab groups, respectively, than in the placebo group (minimal clinically important change, 0.5 points) (P<0.001 for all comparisons). The safety profile of mepolizumab was similar to that of placebo. Conclusions: Mepolizumab administered either intravenously or subcutaneously significantly reduced asthma exacerbations and was associated with improvements in markers of asthma control. Copyright © 2014 Massachusetts Medical Society.

Basel, Switzerland, Dec. 02, 2016 (GLOBE NEWSWIRE) -- Basel, Switzerland, December 02, 2016 - Basilea Pharmaceutica Ltd. (SIX: BSLN) announced today the expansion of its ongoing oncology drug candidate BAL101553 clinical phase 1/2a oral formulation study. The first patient has been dosed in an additional arm containing adult patients with recurrent or progressive glioblastoma (brain cancer) after prior radiotherapy with or without chemotherapy. Prof. Achim Kaufhold, Basilea's Chief Medical Officer, commented: "We are excited to explore BAL101553 in a separate glioblastoma study arm to our ongoing phase 1/2a clinical study. Glioblastoma is a cancer indication associated with high medical need. There are limited treatment options for glioblastoma patients due in part to the challenge of getting medication into the brain through the blood brain barrier. BAL101553 has been shown to enter the brain and has demonstrated anticancer activity with oral dosing in various preclinical models of glioblastoma, including models refractory to or with reduced sensitivity to standard therapies." In addition to the activity in glioblastoma tumor lines, BAL101553 was shown to have potent anticancer activity against glioblastoma stem-like cells in a pre-clinical model as reported in a recent publication co-authored by Basilea and the research group of Prof. Diane Braguer of Aix-Marseille University, France. Tumor stem-like cells contribute to glioblastoma regrowth as well as brain invasion, a phenomenon which also occurs in the pre-clinical model used. The publication further reported the observation that BAL101553 promoted the loss of stem-cell properties. These published data further support the potential of BAL101553 to target glioblastoma, a tumor often associated with poor prognosis for patients.1 Glioblastoma is the most common primary brain tumor and one of the most lethal types of cancer. The incidence of glioblastoma is approximately 3 patients per 100,000 in the United States.2 Median survival of about 15 months from diagnosis has been reported for adult glioblastoma patients receiving standard-of-care treatment,3 with a 5-year survival rate of 5%.2 The ongoing phase 1/2a study includes patients with advanced or recurrent solid tumors who have failed standard therapy or for whom no effective standard therapy was available. Phase 1 dose escalation to determine the maximum tolerated dose (MTD) of daily oral dosing is currently ongoing. A subsequent phase 2a extension of the study is planned to further evaluate the safety, tolerability and the pharmacokinetic profile of oral BAL101553 at the MTD, and to assess its anti-tumor activity. Furthermore, biomarkers are assessed in both the phase 1 and phase 2a parts of the study to determine their utility in identifying patients who are most likely to respond to treatment, including biomarkers with potential relevance to glioblastoma. Basilea's small molecule oncology drug candidate BAL101553 (the prodrug of BAL27862)4 is being developed as a potential therapy for diverse cancers. BAL101553 is currently undergoing clinical phase 1/2a evaluation (oral and continuous infusion) in patients with advanced solid tumors. In preclinical studies, the drug candidate demonstrated in-vitro and in-vivo activity against diverse treatment-resistant cancer models, including tumors refractory to conventional approved therapeutics and radiotherapy.5, 6, 7 BAL101553 efficiently distributes to the brain, with anticancer activity in glioblastoma (brain cancer) models.1, 8, 9 The active moiety BAL27862 binds the colchicine site of tubulin with distinct effects on microtubule organization,10 resulting in the formation of the "spindle assembly checkpoint" which promotes tumor cell death.11 Basilea Pharmaceutica Ltd. is a biopharmaceutical company developing products that address increasing resistance and non-response to current treatment options in the therapeutic areas of bacterial infections, fungal infections and cancer. The company uses the integrated research, development and commercial operations of its subsidiary Basilea Pharmaceutica International Ltd. to discover, develop and commercialize innovative pharmaceutical products to meet the medical needs of patients with serious and potentially life-threatening conditions. Basilea Pharmaceutica Ltd. is headquartered in Basel, Switzerland and listed on the SIX Swiss Exchange (SIX: BSLN). Additional information can be found at Basilea's website This communication expressly or implicitly contains certain forward-looking statements concerning Basilea Pharmaceutica Ltd. and its business. Such statements involve certain known and unknown risks, uncertainties and other factors, which could cause the actual results, financial condition, performance or achievements of Basilea Pharmaceutica Ltd. to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Basilea Pharmaceutica Ltd. is providing this communication as of this date and does not undertake to update any forward-looking statements contained herein as a result of new information, future events or otherwise. For further information, please contact: This press release can be downloaded from

Peltier G.,Aix - Marseille University | Aro E.-M.,University of Turku | Shikanai T.,Kyoto University
Annual Review of Plant Biology | Year: 2016

Oxygenic photosynthesis converts solar energy into chemical energy in the chloroplasts of plants and microalgae as well as in prokaryotic cyanobacteria using a complex machinery composed of two photosystems and both membrane-bound and soluble electron carriers. In addition to the major photosynthetic complexes photosystem II (PSII), cytochrome b6f, and photosystem I (PSI), chloroplasts also contain minor components, including a well-conserved type I NADH dehydrogenase (NDH-1) complex that functions in close relationship with photosynthesis and likewise originated from the endosymbiotic cyanobacterial ancestor. Some plants and many microalgal species have lost plastidial ndh genes and a functional NDH-1 complex during evolution, and studies have suggested that a plastidial type II NADH dehydrogenase (NDH-2) complex substitutes for the electron transport activity of NDH-1. However, although NDH-1 was initially thought to use NAD(P)H as an electron donor, recent research has demonstrated that both chloroplast and cyanobacterial NDH-1s oxidize reduced ferredoxin. We discuss more recent findings related to the biochemical composition and activity of NDH-1 and NDH-2 in relation to the physiology and regulation of photosynthesis, particularly focusing on their roles in cyclic electron flow around PSI, chlororespiration, and acclimation to changing environments. Copyright © 2016 by Annual Reviews. All rights reserved.

Pavord I.D.,University of Leicester | Korn S.,Mainz University Hospital | Howarth P.,Southampton General Hospital | Bleecker E.R.,Center for Genomics and Personalized Medicine | And 4 more authors.
The Lancet | Year: 2012

Background Some patients with severe asthma have recurrent asthma exacerbations associated with eosinophilic airway infl ammation. Early studies suggest that inhibition of eosinophilic airway infl ammation with mepolizumab- a monoclonal antibody against interleukin 5-is associated with a reduced risk of exacerbations. We aimed to establish effi cacy, safety, and patient characteristics associated with the response to mepolizumab. Methods We undertook a multicentre, double-blind, placebo-controlled trial at 81 centres in 13 countries between Nov 9, 2009, and Dec 5, 2011. Eligible patients were aged 12-74 years, had a history of recurrent severe asthma exacerbations, and had signs of eosinophilic infl ammation. They were randomly assigned (in a 1:1:1:1 ratio) to receive one of three doses of intravenous mepolizumab (75 mg, 250 mg, or 750 mg) or matched placebo (100 mL 09% NaCl) with a central telephone-based system and computer-generated randomly permuted block schedule stratifi ed by whether treatment with oral corticosteroids was required. Patients received 13 infusions at 4-week intervals. The primary outcome was the rate of clinically signifi cant asthma exacerbations, which were defi ned as validated episodes of acute asthma requiring treatment with oral corticosteroids, admission, or a visit to an emergency department. Patients, clinicians, and data analysts were masked to treatment assignment. Analyses were by intention to treat. This trial is registered with, number NCT01000506. Findings 621 patients were randomised: 159 were assigned to placebo, 154 to 75 mg mepolizumab, 152 to 250 mg mepolizumab, and 156 to 750 mg mepolizumab. 776 exacerbations were deemed to be clinically signifi cant. The rate of clinically signifi cant exacerbations was 240 per patient per year in the placebo group, 124 in the 75 mg mepolizumab group (48% reduction, 95% CI 31-61%; p<00001), 146 in the 250 mg mepolizumab group (39% reduction, 19-54%; p=00005), and 115 in the 750 mg mepolizumab group (52% reduction, 36-64%; p<00001). Three patients died during the study, but the deaths were not deemed to be related to treatment. Interpretation Mepolizumab is an eff ective and well tolerated treatment that reduces the risk of asthma exacerbations in patients with severe eosinophilic asthma. Funding GlaxoSmithKline.

Erkosar B.,University Claude Bernard Lyon 1 | Storelli G.,University Claude Bernard Lyon 1 | Defaye A.,Aix - Marseille University | Leulier F.,University Claude Bernard Lyon 1
Cell Host and Microbe | Year: 2013

Given the complexity of the mammalian microbiota, there is a need for simple models to decipher the effector and regulatory mechanisms underlying host/microbiota mutualism. Approaches using Drosophila and its simple microbiota carry the potential to unravel the evolutionarily conserved mechanisms engaged in this association. Here, we review recent work carried out in this model, providing insights and exciting perspectives. © 2013 Elsevier Inc.

Rossi F.,Aix - Marseille University | Colaneri P.,Polytechnic of Milan | Shorten R.,National University of Ireland
IEEE Transactions on Automatic Control | Year: 2011

This technical note has been motivated by the need to assess the preservation of polyhedral Lyapunov functions for stable continuous-time linear systems under numerical discretization of the transition matrix. This problem arises when discretizing linear systems in such a manner as to preserve a certain type of stability of the discrete time approximation. Our main contribution is to show that a continuous-time system and its Padé discretization (of any order and sampling) always share at least one common piecewise linear (polyhedral) Lyapunov function. © 2011 IEEE.

Benedetti L.C.,Aix - Marseille University | Van Der Woerd J.,University of Strasbourg
Elements | Year: 2014

When the recurrence intervals of large earthquakes span several thousands of years, the dating of fault movements over long time intervals is essential for estimating the next event. Constraining the age of faulting, earthquake recurrence, or toppled rocks is especially important for determining if a fault is likely to break again soon. In recent years, cosmogenic nuclides have provided new insights into the dating of these ground movements. Approaches to gathering this information can be direct, such as dating fault surfaces with 36Cl, or indirect, such as dating fault-offset alluvial fans with 10Be or 26Al. New results from these methods are certain to better defi ne the tectonic and seismic hazards in areas with increasing population density.

Athanassoula E.,Aix - Marseille University | Machado R.E.G.,Aix - Marseille University | Machado R.E.G.,University of Sao Paulo | Rodionov S.A.,Aix - Marseille University | Rodionov S.A.,Saint Petersburg State University
Monthly Notices of the Royal Astronomical Society | Year: 2013

We follow the formation and evolution of bars in N-body simulations of disc galaxies with gas and/or a triaxial halo. We find that both the relative gas fraction and the halo shape play a major role in the formation and evolution of the bar. In gas-rich simulations, the disc stays near-axisymmetric much longer than in gas-poor ones, and, when the bar starts growing, it does so at a much slower rate. Because of these two effects combined, large-scale bars form much later in gas-rich than in gas-poor discs. This can explain the observation that bars are in place earlier in massive red disc galaxies than in blue spirals. We also find that the morphological characteristics in the bar region are strongly influenced by the gas fraction. In particular, the bar at the end of the simulation is much weaker in gas-rich cases. The quality of our simulations is such as to allow us to discuss the question of bar longevity because the resonances are well resolved and the number of gas particles is sufficient to describe the gas flow adequately. In no case did we find a bar which was destroyed. Halo triaxiality has a dual influence on bar strength. In the very early stages of the simulation it induces bar formation to start earlier. On the other hand, during the later, secular evolution phase, triaxial haloes lead to considerably less increase of the bar strength than spherical ones. The shape of the halo evolves considerably with time.We confirm previous results of gas-less simulations that find that the inner part of an initially spherical halo can become elongated and develop a halo bar. However we also show that, on the contrary, in gas-rich simulations, the inner parts of an initially triaxial halo can become rounder with time. The main body of initially triaxial haloes evolves towards sphericity, but in initially strongly triaxial cases it stops well short of becoming spherical. Part of the angular momentum absorbed by the halo generates considerable rotation of the halo particles that stay located relatively near the disc for long periods of time. Another part generates halo bulk rotation, which, contrary to that of the bar, increases with time but stays small. Thus, in our models there are two non-axisymmetric components rotating with different pattern speeds, namely the halo and the bar, so that the resulting dynamics have strong similarities to the dynamics of double bar systems. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.

Haggard H.M.,Aix - Marseille University | Haggard H.M.,Bard College | Rovelli C.,Aix - Marseille University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

We show that there is a classical metric satisfying the Einstein equations outside a finite spacetime region where matter collapses into a black hole and then emerges from a white hole. We compute this metric explicitly. We show how quantum theory determines the (long) time for the process to happen. A black hole can thus quantum tunnel into a white hole. For this to happen, quantum gravity should affect the metric also in a small region outside the horizon; we show that, contrary to what is commonly assumed, this is not forbidden by causality or by the semiclassical approximation, because quantum effects can pile up over a long time. This scenario alters radically the discussion on the black hole information puzzle. © 2015 American Physical Society.

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

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

Diacovich L.,Aix - Marseille University | Gorvel J.-P.,Aix - Marseille University | Gorvel J.-P.,Foundation FINOVI
Nature Reviews Microbiology | Year: 2010

The mammalian innate immune response provides a barrier against invading pathogens. Innate immune mechanisms are used by the host to respond to a range of bacterial pathogens in an acute and conserved fashion. Host cells express pattern recognition receptors that sense pathogen-associated molecular patterns. After detection, an arsenal of antimicrobial mechanisms is deployed to kill bacteria in infected cells. Innate immunity also stimulates antigen-specific responses mediated by the adaptive immune system. In response, pathogens manipulate host defence mechanisms to survive and eventually replicate. This Review focuses on the control of host innate immune responses by pathogenic intracellular bacteria. © 2010 Macmillan Publishers Limited. All rights reserved.

Battesti A.,U.S. National Cancer Institute | Battesti A.,Aix - Marseille University | Majdalani N.,U.S. National Cancer Institute | Gottesman S.,U.S. National Cancer Institute
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015

RpoS, the stationary phase/stress sigma factor of Escherichia coli, regulates a large cohort of genes important for the cell to deal with suboptimal conditions. Its level increases quickly in the cell in response to many stresses and returns to low levels when growth resumes. Increased RpoS results from increased translation and decreased RpoS degradation. Translation is positively regulated by small RNAs (sRNAs). Protein stability is positively regulated by anti-adaptors, which prevent the RssB adaptor-mediated degradation of RpoS by the ClpXP protease. Inactivation of aceE, a subunit of pyruvate dehydrogenase (PDH), was found to increase levels of RpoS by affecting both translation and protein degradation. The stabilization of RpoS in aceE mutants is dependent on increased transcription and translation of IraP and IraD, two known anti-adaptors. The aceE mutation also leads to a significant increase in rpoS translation. The sRNAs known to positively regulate RpoS are not responsible for the increased translation; sequences around the start codon are sufficient for the induction of translation. PDH synthesizes acetyl-CoA; acetate supplementation allows the cell to synthesize acetyl-CoA by an alternative, less favored pathway, in part dependent upon RpoS. Acetate addition suppressed the effects of the aceE mutant on induction of the anti-adaptors, RpoS stabilization, and rpoS translation. Thus, the bacterial cell responds to lowered levels of acetyl-CoA by inducing RpoS, allowing reprogramming of E. coli metabolism. © 2015, National Academy of Sciences. All rights reserved.

Theves C.,University of Strasbourg | Biagini P.,Aix - Marseille University | Crubezy E.,University of Strasbourg
Clinical Microbiology and Infection | Year: 2014

Smallpox is an infectious disease that is unique to humans, caused by a poxvirus. It is one of the most lethal of diseases; the virus variant Variola major has a mortality rate of 30%. People surviving this disease have life-long consequences, but also assured immunity. Historically, smallpox was recognized early in human populations. This led to prevention attempts-variolation, quarantine, and the isolation of infected subjects-until Jenner's discovery of the first steps of vaccination in the 18th century. After vaccination campaigns throughout the 19th and 20th centuries, the WHO declared the eradication of smallpox in 1980. With the development of microscopy techniques, the structural characterization of the virus began in the early 20th century. In 1990, the genomes of different smallpox viruses were determined; viruses could be classified in order to investigate their origin, diffusion, and evolution. To study the evolution and possible re-emergence of this viral pathogen, however, researchers can only use viral genomes collected during the 20th century. Cases of smallpox in ancient periods are sometimes well documented, so palaeomicrobiology and, more precisely, the study of ancient smallpox viral strains could be an exceptional opportunity. The analysis of poxvirus fragmented genomes could give new insights into the genetic evolution of the poxvirus. Recently, small fragments of the poxvirus genome were detected. With the genetic information obtained, a new phylogeny of smallpox virus was described. The interest in conducting studies on ancient strains is discussed, in order to explore the natural history of this disease. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: FETOPEN-01-2016-2017 | Award Amount: 4.58M | Year: 2017

M-Cube aims at changing the paradigm of High-Field MRI and Ultra High-Field antennas to offer a much better insight on the human body and enable earlier detection of diseases. Our main objective is to go beyond the limits of MRI clinical imaging and radically improve spatial and temporal resolutions. The clinical use of High-field MRI scanners is drastically limited due to the lack of homogeneity and to the Specific Absorption Rate (SAR) of the Radio Frequency (RF) fields associated with the magnetic resonance. The major way to tackle and solve these problems consists in increasing the number of active RF antennas, leading to complex and expensive solutions. M-Cube solution relies on innovative systems based upon passive metamaterial structures to avoid multiple active elements. These systems are expected to make High-Field MRI fully diagnostically relevant for physicians. To achieve these expectations, M-Cube consortium will develop a disruptive metamaterial antenna technology. This we will able us to tackle both the lack of homogeneity and SAR barriers. Metamaterials are composite structured manmade materials designed to produce effective properties unavailable in nature (e.g. negative optical index). They allow us to tailor electromagnetic waves at will. Thus, the scientifically ambitious idea is to develop antennas based on this unique ability for whole body coil. This technological breakthrough will be validated by preclinical and clinical tests with healthy volunteers. M-Cube gathers an interdisciplinary consortium composed of academic leaders in the field, eight universities, and two promising SMEs. Physicists, medical doctors and industrial actors will work closely all along the implementation of the project to guarantee the success this novel approach, a patient-centered solution which will pave the way for a more accurate diagnosis in the context of personalized medicine and will enable to detect a disease much earlier that is currently possible.

Aix - Marseille University, École Centrale Marseille, French National Center for Scientific Research and University Claude Bernard Lyon 1 | Date: 2014-05-20

The invention relates to a method suitable for detecting, capturing and/or selectively releasing chemical elements selected from poor metals, alkalines, alkaline earths, actinides and rare earths. Said method involves a molecular assembly formed by at least one amine, and at least one aldehyde and/or an imine and/or CO_(2), or an adduct formed by the contact between an amine and CO_(2), and at least one of said chemical elements. The invention also relates to a kit for implementing said method for detection, capture and/or release.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ENERGY.2010.10.2-1 | Award Amount: 3.64M | Year: 2011

In a solar cell that converts energy as efficient as the natural plant photosystems, electrons should travel over very short distances, through an extremely ordered structure free of traps. Guided by these principles that were worked out at WIS and CUNY, we want to synthesize many different peptides, and consecutively screen variants thereof for a putative diode function. When linked to light-harvesting building blocks, these should yield a novel type of solar cell that is based on biomimetic principles. To achieve these goals, UPC will chemically synthesize a panel of artificial building blocks that are designed to harvest light and/or tunnel electrons. When assembled into many different peptides, some of these constructs are expected to function as a diode, and, when linked to light-harvesting molecules, as a solar cell. Peptides will be embedded into a self-assembled monolayer of alkanethiols on individual gold pads of a computer chip, which will be designed and manufactured by IMS. Each individual peptide can be addressed by feeding in, and at the same time measuring, the amount of current flow in both directions through the gold pads of the individual pixels. A similar kind of screen should then detect a functional peptide-based solar cell. 10.000 Peptides per cm(\2) will be synthesized by a particle based combinatorial synthesis recently developed by KIT-G and PPP. These peptides will be transferred in the array format to the chip where they couple to the gold pads. Therein, peptides will be coupled through cysteine residues to the flat gold surface, where they are embedded into a membrane-like structure. We expect that our evolution inspired approach may open a novel route to very efficient, and very cheap solar cells. This is due to the small percolation distances, highly ordered modular peptide structures, the large number of generated peptides, the ability to easily combine and modify eventually found peptide-diodes, and the frugal material consumption.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2011.3.6 | Award Amount: 14.46M | Year: 2011

Organic photovoltaics (OPV) represent the newest generation of technologies in solar power generation, offering the benefits of flexibility, low weight and low cost enabling the development of new consumer nomadic applications and the long term perspective of easy deployment in Building Integrated Photo Voltaics (BIPV) and energy production farms. This is a key opportunity for the EU to further establish its innovation base in alternative energies.The current challenges reside in the combination to increase efficiencies to 8-10% (module level), increase expected lifetime up to 20 years and decrease production costs to 0.7 Eur/Wp, while taking into account the environmental impact and footprint.The key project objectives are to achieve:\tPrinted OPV with high efficiency architectures such as tandem cells and dedicated light management structures\tHigh performance photo active and passive (barrier) materials including process controlled morphology\tSolutions for cost effective flexible substrates, diffusion barriers and conductors\tDeep understanding of the device physics, elucidation of degradation mechanisms and estimate environmental impact of the main materials and processesThe project consortium combines industrial, institutional and academic support to make a significant impact at European and International level, especially on materials and processes while demonstrating their market-relevant implementations. The industrial project partners are well assembled along the supply chain of future OPV-based products, which is an important prerequisite for the creation of significant socio-economic impact of this proposal.

Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 3.82M | Year: 2015

Depletion of natural resources combined with the extending footprint of mankind has led to a shift in importance of research and development topics. In the 1970s and 1980s process yield was primarily targeted, but emphasis is now focussed on resource efficiency as a primary objective. Routes for resource efficiency have to be identified and implemented to provide a more environmental and resource-oriented technology in near future. MIGRATE is planned as an ETN, gathering top-level research and development capabilities from academia and industry as well as direct application possibilities with the focus set on thermal aspects of gas flows in microstructured systems. Within MIGRATE, a number of ESR projects will cover different aspects of enhanced heat transfer and thermal effects in gases, spanning from modelling of heat transfer processes and devices, development and characterization of sensors and measurement systems for heat transfer in gas flows as well as thermally driven micro gas separators to micro-scale devices for enhanced and efficient heat recovery in automotive, aeronautics and energy generation. This unique combination of university research, SME and world leading industrial stakeholders will contribute in a significant way to the increase of knowledge about micro scale gas flow heat transfer problems as well as to industrial applications of highly efficient miniaturized devices. A characteristic of MIGRATE is the high degree of applicability and the intense training. About 30% of the beneficiaries are from private sector. Thus, ESR projects will be developed in both directions, fundamental academic knowledge as well as direct application in industrial environment. The training of the ESRs is set in the same way to provide a broad variety of skills, reaching from classical academic research to IPR management and all-day-business in a company, being summarized under the aspect of resource efficiency and environmental-friendly technological approaches.

Agency: European Commission | Branch: FP7 | Program: CSA-SA | Phase: AAT-2007-7.0-07 | Award Amount: 663.73K | Year: 2007

The aim of the AEROCHINA2 Coordination Support Action (CSA) is to foster the cooperation between a number of industry, university and research organizations in the aeronautics sector in Europe and China in the field of multi-physics modelling, computer simulation and code validation, experimental testing and design methods for the solution of multi-physics problems of interest to the aeronautic sector. The spectrum multi-physical disciplines considered in AEROCHINA2 which are of interest of European and Chinese partners are Aerodynamics, Structures & Materials, Fluid Dynamics, Aeroacoustics, Active Flow Control and Aero Elasticity. The general strategic objectives of the project are three fold: 1) to identify areas of mutual RTD interest and the clarification of the skills, experiences and capabilities of the Chinese partners in the relevant technological areas of multi-physics analysis and design; 2) to develop concepts of collaboration in those areas between the European and Chinese partners in order to ensure a win-win situation; 3) prepare specific RTD activities that are mature for joint proposals for FP7. These AEROCHINA2 objectives correspond to a more long term preparation necessary for substantial and sustainable win-win cooperation in forthcoming FP7 calls.

Agency: European Commission | Branch: FP7 | Program: CSA-SA | Phase: INCO.2012-2.2 | Award Amount: 855.37K | Year: 2012

The EU and Morocco are fully engaged in a strong and deepen cooperation supported by a high level policy dialogue, and pertaining to multiple sectors including research and innovation. At the institutional level, the Association agreement (1996), the S&T agreement (2003), the European neighboring policy (2004), The new advanced status and the program called To succeed the advanced status has put emphasis on the consolidation of scientific and technological ties, and are supported by relevant implementation mechanisms and instruments. In May 2011, an institutional twinning program is launched to strengthen and bring closer the Moroccan research and innovation system to ERA. Morocco is highly devoted to reinforce and intensify the current bilateral initiatives and programs in the field of science and technology, aiming to the preparation and definition of joint activities targeting thematics of mutual interest, to improve oriented industry based on S&T cooperation between EU and Morocco, to set up joint collaboration and networking of technical platforms and research laboratories.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2009-2.4.4-1 | Award Amount: 7.54M | Year: 2009

The rapidly expanding knowledge of NMDs genetic diagnosis, pathogenesis and therapeutic possibilities has provided new targets for disease characterisation, early diagnosis, drug discovery and development as well as has raised many questions about how to translate this knowledge into clinical practice as (initial) clinical trials typically run for such a short time that clinical improvement can hardly be expected within that time frame. This militates for the discovery of surrogate endpoints for establishing the efficacy of clinical trials. The concept of biomarkers represents measurable bio-parameters able to flank the process of diagnosis, functional characterisation and therapy in NMDs. OMIC sciences (genomic, transcriptomics, proteomics) offer opportunities to identify biomarkers for finely defining and tuning the NMDs bases. This approach can make available non-invasive biomarkers, to be used for monitoring disease progression, prognosis and drugs response, therefore optimising the choice of appropriate and often personalised therapies. Validated biomarkers will increase therapy efficiency (meaning optimal dose of drug to get responders) and efficacy (responders vs non responders for example if we will identify genomic biomarkers linked to the lack of any therapeutic effect). In this case we could address a truly efficacious therapy (avoiding inefficacious treatment due to unfavourable genomic contexts). The new genomic and proteomic biomarkers discovered within BIO-NMD will be validated both in animal models and in human samples, before entering into a qualification process at the EMEA. The qualified biomarkers resulting from the BIO-NMD project will be ready for ongoing and further clinical trials for the patient benefit. This will increase the therapy efficacy and efficiency and also reduce adverse effects, with impact on patients quality of life with also economical relevance. The BIO-NMD consortium is led by the University of Ferrara, an internationally recognised university in the field of genomics of hereditary neuromuscular disorders. In addition the consortium is composed of 7 leading European academic partners bringing their expertise in all OMIC sciences as well as in bio-informatics and patient sample collection, 1 SME providing its skills in bio-informatics and 1 global company specialised in the development of patient samples screening.

INSA Lyon, French National Center for Scientific Research, University Claude Bernard Lyon 1 and Aix - Marseille University | Date: 2014-03-28

A device for the imaging of an object to be studied, combines: a prism made from a material with no losses (non-absorbent) for radiation in the microwave range; a sample holder on a front face of the prism for receiving the object to be studied; and a mobile emitting antenna on a rear face of the prism in order to emit radiation in the microwave range.

Aix - Marseille University, French National Center for Scientific Research, Bruker, Ecole Normale Superieure de Lyon, ETH Zurich and University Claude Bernard Lyon 1 | Date: 2014-04-15

The invention concerns a dinitroxide biradical compound, in which the two nitroxide units are held by a rigid linkage, of general formula (I) in whichA is a carbon, an ammonium or a phosphonium, each of A_(1 )to A6 is selected separately from the group comprising a single bond, O, N, N(O), S, S(O), SO2, C(O), a (C1-C4) alkyl chain, Z1 and Z2 are chosen from RI and R2 in combination, such that there is always, in the combination, at least one R2 group that needs to be substituted by an R3 group, RI is an H, a (C6-C18) aryl or a (C3-C18) heteroaryl, R2 a (C1-C17) alkyl chain, a (C1-C17) alkenyl chain, a (C1-C17) alkynyl chain, a (C4-C17) cycloalkyl, a (C4-C17) heterocycloalkyl, a (C6-C18) aryl, a (C3-C18) heteroaryl, R3 is a (C1-C17) alkyl chain, a (C1-C17) alkenyl chain, a (C1-C17) alkynyl chain, a (C4-C17) cycloalkyl, a (C4-C17) heterocycloalkyl, a (C6-C18) aryl, a (C3-C18) heteroaryl, an ether OR, an ester C(O)OR (in which R is any hydrocarbon radical), an azide, and in which, when Z1 and Z2 are combined together with the same carbon atom of the nitroxide ring to which they are bonded, they form a spirocycloalkyl or a spiroheterocycloalkyl substituted by R3.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: PEOPLE-2007-1-1-ITN | Award Amount: 3.94M | Year: 2008

Gas flows in microsystems are of great interest for various applications that touch almost every industrial field. This diversity is typified through the following examples: fluidic microactuators for active control of aerodynamic flows, vacuum generators for extracting biological samples, mass flow and temperature micro-sensors, pressure gauges, micro heat-exchangers for the cooling of electronic components or for chemical applications, micropumps and microsystems for mixing or separation for local gas analysis, mass spectrometers, vacuum and dosing valves. The main characteristic of gas microflows is their rarefaction, the level of which often requires a modelling both by continuous and molecular approaches. The role played by the interaction between the gas and the wall becomes essential and is generally badly known. Numerous models of boundary conditions are currently in confrontation and require an empirical adjustment strongly dependent on the micro manufacturing techniques. On the other hand, the experimental data are fragmentary and difficult to confront. Most of them do not address heat transfer and gas mixtures issues. The proposed network has been built from several existing collaborations within bilateral programmes, from scientific collaborations and national networks. However, there was no global coordination of the research efforts in the field of gas microflows at the European level. Thus, the two primary objectives of this ITN project are: (i) to structure research in Europe in the field of micro gas flows to improve global fundamental knowledge and enable technological applications to an industrial and commercial level; (ii) to train ESR and ER at a pan-European level, with the aim to providing both a global overview on problems linked to gas flow and heat transfer in microsystems, and advanced skills in specific domains of this research field.

Agency: European Commission | Branch: FP7 | Program: MC-IRSES | Phase: FP7-PEOPLE-2012-IRSES | Award Amount: 109.20K | Year: 2012

The theory of asymptotic behaviour of operator semigroups is a comparatively new field serving as a common denominator for many other areas of mathematics, such as for instance the theory of partial differential equations, complex analysis, harmonic analysis and topology. The primary interest in the study of asymptotic properties of strongly continuous operator semi-groups comes from the fact that such semigroups solve abstract Cauchy problems which are often models for various phenomena arising in natural sciences, engineering and economics. Knowledge of the asymptotics of semigroups allows one to determine the character of long-time evolution of these phenomena. Despite an obvious importance, the asymptotic theory of one-parameter strongly continuous operator semigroups was for a very long time a collection of scattered facts rather than an organized area of research. The interest increased in the 1980s and the theory has witnessed a dramatic development over the past thirty years. Still there is a number of notorious open problems that have been left open. These missing blocks prevent the theory from being complete, slow down the development of the theory and discourage specialists from related fields to engage into the theory. The goal of the project is to give new impetus to the theory of asymptotic behavior of operator semigroups. To this aim we plan to extend and unify various aspects of the asymptotic theory of operator semigroups: stability, hyperbolicity, rigidity, boundedness, relations to Fredholm property, to work out new methods and to solve several long-standing open problems thus giving the theory its final shape. We intend to create an international forum that enables and promotes a multi- and cross- disciplinary exchange of ideas, methods and tools under the common umbrella of asymptotic theory of operator semigroups. Thus we expect that, moreover, a wide range of modern analysis will benefit from the project.

A Europe-wide consortium of experimental biologists, biomathematicians, biostatisticians, computer scientists and clinical scientists will team up to approach cell death pathways in health and disease, placing particular emphasis on cancer and AIDS. The consortium will create a unique database integrating existing and accumulating knowledge on lethal signal transduction pathways leading to apoptosis or non-apoptotic (necrotic, autophagic, mitotic) cell death, perform data mining to integrate system-wide analyses on cell death (genome, epigenome, transcriptome, proteome, lipidome data), and use high-throughput methods (omics, CHiP-chip and genome-wide siRNA screens) for the experimental exploration of death pathways in human cell lines in vitro and in relevant disease models (in vitro in human cells and in vivo in mice and Drosophila). In addition, the consortium will establish mathematical models of lethal pathways to devise algorithms that predict apoptosis susceptibility and resistance, obtain data (genome, transcriptome, proteome, lipidome) on clinical samples (cancer cell lines, cancer tissues, serum, and blood samples) and perform biostatistical analyses on them in order to demonstrate the contribution of apoptotic process in human cancers and AIDS. Then, the consortium will integrate the knowledge into mathematical models for the optimal interpretation of clinical data, aiming at optimal diagnostic and prognostic performance as well as at the identification of possible therapeutic targets for the treatment of cancer and AIDS.

French National Center for Scientific Research, University of Maine, France and Aix - Marseille University | Date: 2013-07-26

The invention relates to a method for observing a sample under optical microscopy, in incoherent, unpolarised light, using a sample substrate including a contrast-amplifying layer having a complex index of refraction. The invention also relates to a method for detecting or metering at least one chemical or biological species using such a sample substrate.

Bruker, ETH Zurich, Aix - Marseille University, University Claude Bernard Lyon 1, French National Center for Scientific Research and Ecole Normale Superieure de Lyon | Date: 2012-06-08

Non aqueous solvents or mixtures for DNP NMR spectroscopy, method to prepare said solvents or mixtures and use of said solvents or mixtures The present invention concerns a method to determine the efficiency of a solvent to impregnate a sample material for use in a dynamic nuclear polarization (DNP) nuclear magnetic resonance (NMR) experiments, characterized in that the method comprising: selecting a non-aqueous solvent, providing a polarizing agent that is soluble in the non-aqueous solvent, dissolving the polarizing agent in the non-aqueous solvent, impregnating or dissolving the sample material with the non-aqueous solvent containing the polarizing agent, performing a solid state DNP NMR experiment on the impregnated sample material, determining a DNP enhancement factor of the DNP NMR experiment.

French National Center for Scientific Research, Aix - Marseille University and University of Strasbourg | Date: 2010-03-04

The present invention describes the use of a composition including or constituted by at least one element chosen from:

Cesium lead bromide perovskite nanocrystals are used to generate white light that can be used as both an efficient lighting source and for ultrafast data transfer. The growing demands for high-speed data communications (e.g., for the Internet) have greatly exceeded all predictions, and have thus greatly accelerated research and development activities for next-generation wireless communication systems.1, 2 As part of these efforts, visible light communication (VLC)—in which electromagnetic radiation at visible wavelengths (380–700nm) is used, rather than conventional radio frequency (RF) waves—has recently been proposed as a promising technology for enabling simultaneous energy-efficient illumination and high-speed data communication. Indeed, VLC has several advantages over conventional RF-based communication systems, including high security, fast speed, as well as an unregulated and uncrowded bandwidth. In a typical VLC system, LEDs or laser diodes (LDs) with phosphors (i.e., blue, green, and yellow/red color converters) are used in the transmitters to generate white light for solid-state light (SSL) and data communications.3, 4 There is, however, a phosphor-associated limitation in the modulation bandwidth of the VLC system. That is, the long excited-state lifetime (the time it takes to re-emit an absorbed photon) of conventional yttrium-aluminum-garnet (YAG)-based phosphors gives rise to a serious bottleneck in VLC applications.5 This phosphor-associated bandwidth thus limits VLC systems to about 10MHz and nullifies its key advantages over RF communication systems.4, 6 To overcome the drawback associated with conventional YAG phosphors, several alternative materials have been tested as color converters for VLC systems, including boron-dipyrromethene, poly[2-methoxy-5-(2'-ethylhexyloxy)-p-pheny-lene vinylene, and poly[2,5-bis(2',5'-bis(2”-ethylhexyloxy)phenyl)-p-phenylene vinylene (more commonly known as BODIPY, MEH-PPV, and BBEHP-PPV, respectively).7, 8 These other candidates, however, also suffer from relatively long excited-state lifetimes that also greatly limit their modulation bandwidth frequency and speed of data transmission. Developing an ideal color-converter phosphor material, with a short excited-state lifetime (i.e., fast light-intensity decay) and high efficiency (high brightness), therefore remains the major challenge for VLC and SSL applications. In recent years, perovskites have emerged as ‘magic’ materials for optoelectronic applications (e.g., photovoltaics and photodetectors). Moreover, recent studies have revealed that perovskite nanocrystals (NCs)—in the form of cesium lead bromide (CsPbBr )—have relatively high photoluminescence quantum yields (PLQYs) and short photoluminescence (PL) lifetimes.6, 9 In fact, this marriage of high PLQY and short PL lifetime is the essential requirement for ideal SSL and VLC color converters. In our work,6 we have therefore investigated the fast color-conversion behavior of CsPbBr perovskite NCs when they are used as a phosphor for white light transmission in an SSL-VLC dual-function system. Our perovskite NCs are inexpensive and relatively easy to prepare (i.e., in a toluene solution). In our study, we synthesized CsPbBr perovskite NCs that have a cubic shape and average dimensions of about 80nm (see Figure 1). We have also used time-resolved laser spectroscopy to study the excited-state dynamics of our NCs because this is the key characteristic for fast-response color-conversion materials. We measured a relatively short PL lifetime of about 7ns, which indicates that our materials outperform conventional phosphors (with PL lifetimes on the order of microseconds). Figure 1. Illustrations of the cesium lead bromide (CsPbBr ) perovskite nanocrystals (NCs). (a) High-resolution transmission microscopy image of the NCs. Photographic images of the NCs in a toluene solution are also shown, under (b) ambient light and (c) UV illumination. As part of our work we mixed our synthesized green-emitting perovksite NCs with a conventional red phosphor to attain white light. We excited the mixture with the use of an indium-gallium-nitride-based blue LD, and thus produced a warm white light. The corresponding chromaticity coordinates (0.38, 0.30) of this light are presented—within the International Commission on Illumination (CIE) 1931 color space—in Figure 2. We find that the converted light exhibits a correlated color temperature of 3236K, which mimics warm sunlight. The converted light also has a high color-rendering index of 89, which is better than white light produced from a yellow YAG phosphor alone. When the blue light excites an electron within the NCs, an electron-hole pair (known as an exciton) is formed. The small size of our NCs, however, means that the exciton energy levels are changed. This makes the electron more likely to recombine with its hole and emit a photon (in the green color regime). This result indicates that our high-quality perovskite NCs are a cost-effective color-converter option for laser-based indoor illumination. In addition, by varying the chemical composition of our perovskite NCs (e.g., by substituting different halides or metal ions), we can achieve flexible fine tuning of the color. Figure 2. White light generated from the CsPbBr perovskite NCs has chromacity (x, y) coordinates of 0.38, 0.30 in the International Commission of Illumination (CIE) 1931 color space, as well as a color-rendering index (CRI) of 89 and a correlated color temperature (CCT) of 3236K. Inset: Photograph of the white light generated from a mixture of green-emitting perovskite NC phosphor and a red-emitting nitride phosphor (collectively excited by blue laser light). We have also performed a small-signal frequency-response measurement to assess the modulation bandwidth of the white light that is generated from our CsPbBr -NC-based color converter. Although the conventional red-emitting phosphor that we use in the system only provides a limited bandwidth of about 12MHz, our additional use of the perovskites produces a greatly increased bandwidth of about 491MHz. Our new color converters can thus provide a bandwidth that is 40 times that of commercial phosphors. This is especially important in the current bandwidth-hungry era, when there is a continuous push for VLC systems that have ever-higher bit rates. In addition, high-speed LDs will eventually replace LEDs for the generation of white light in VLC systems. Our work therefore represents progress toward the development of NCs that convert high-energy photons from violet-blue LDs to red-yellow-green lights with ultrashort photon lifetimes. In the last part of our study, we demonstrated that our novel VLC system has a data transmission rate of 2Gb/s when we use a non-return-to-zero on-off keying modulation scheme. We also tested the corresponding bit error rate (BER) at the same time, to verify that an error-free communication link could be established. At data rates of 1, 1.5, and 2Gb/s, we thus obtained a BER of 1.2 × 10−7, 3.4 × 10−7, and 7.4 × 10−5, respectively, all of which easily pass the forward error-correction limit (with BER ≤ 3.8 × 10−3). In summary, we have synthesized CsPbBr perovskite NCs and have studied their use as a phosphor for white-light transmission. Our results indicate that these NCs have short photoluminescence lifetimes. In addition, the converted white light has a correlated color temperature similar to that of warm sunlight and a high color-rendering index. Moreover, our color converters have modulation bandwidths that are 40 times greater than those of conventional phosphors and we have demonstrated ultrafast data transfer rates. Our NC-based color converters thus present a new platform for next-generation SSL-VLC systems that offer simultaneous high-brightness lighting and Gb/s data transfer rates. In the near term, we plan to further improve the light-conversion yield of our nanocrystals, i.e., to produce near-ideal white light with a color-rendering index close to 100, while also being able to transmit data at bit rates of multi-gigabits per second. This work is supported by the King Abdullah University of Science and Technology and the King Abdulaziz City for Science and Technology (grant KACST TIC R2-FP-008). Division of Physical Sciences and Engineering King Abdullah University of Science and Technology (KAUST) Ibrahim Dursun is currently pursuing his PhD. He is working on a solution-processable hybrid perovskite for light-emissive applications. He previously obtained a master's in optics and photonics from Aix-Marseille University (France) and the Karlsruhe Institute of Technology (Germany) in 2013. He completed his undergraduate studies in physics at Izmir Institute of Technology (Turkey) in 2011. Osman Bakr is an associate professor of materials science and engineering. He has a BSc in materials science and engineering from the Massachusetts Institute of Technology (2003), as well as an MS and a PhD in applied physics from Harvard University (2009). His research group focuses on the study of hybrid organic–inorganic materials, particularly by advancing their synthesis and self-assembly for applications in photovoltaics and optoelectronics. Chao Shen and Boon S. Ooi Computer, Electrical, and Mathematical Sciences and Engineering KAUST Thuwal, Saudi Arabia Chao Shen received his BSc in materials physics from Fudan University, China, in 2011, and is currently a PhD candidate. His research interests include III-nitride laser diodes, superluminescent diodes, and micro-LEDs, as well as their applications for solid-state lighting, visible light communications, and photonic integrated circuits. Boon Ooi is a professor of electrical engineering. His research is focused on the development of gallium-nitride-based LEDs and lasers, as well as visible light communications. He is a fellow of SPIE. Division of Physical Sciences and EngineeringKing Abdullah University of Science and Technology (KAUST) 1. Y.-C. Chi, D.-H. Hsieh, C.-Y. Lin, H.-Y. Chen, C.-Y. Huang, J.-H. He, B. Ooi, et al., Phosphorus diffuser diverged blue laser diode for indoor lighting and communication, Sci. Rep. 5, p. 18690, 2015. 3. C. Shen, T. K. Ng, J. T. Leonard, A. Pourhashemi, S. Nakamura, S. P. DenBaars, J. S. Speck, A. Y. Alyamani, M. M. El-desouki, B. S. Ooi, High-brightness semipolar (2021) blue InGaN/GaN superluminescent diodes for droop-free solid-state lighting and visible-light communications, Opt. Lett. 41, p. 2608-2611, 2016. 4. C. Lee, C. Shen, H. M. Oubei, M. Cantore, B. Janjua, T. K. Ng, R. M. Farrell, et al., 2Gbit/s data transmission from an unfiltered laser-based phosphor-converted white lighting communication system, Opt. Express 23, p. 29779-29787, 2015. 6. I. Dursun, C. Shen, M. R. Parida, J. Pan, S. P. Sarmah, D. Priante, N. Alyami, et al., Perovskite nanocrystals as a color converter for visible light communication, ACS Photon. 3, p. 1150-1156, 2016. 7. M. T. Sajjad, P. P. Manousiadis, H. Chun, D. A. Vithanage, S. Rajbhandari, A. L. Kanibolotsky, G. Faulkner, et al., Novel fast color-converter for visible light communications using a blend of conjugated polymers, ACS Photon. 2, p. 194-199, 2015. 8. M. T. Sajjad, P. P. Manousiadis, C. Orofino, D. Cortizo-Lacalle, A. L. Kanibolotsky, S. Rajbhandari, D. Amarasinghe, et al., Fluorescent red-emitting BODIPY oligofluorene star-shaped molecules as a color converter material for visible light communications, Adv. Opt. Mater. 3, p. 536-540, 2015. 9. L. Protesescu, S. Yakunin, M. I. Bodnarchuk, F. Krieg, R. Caputo, C. H. Hendon, R. X. Yang, A. Walsh, M. V. Kovalenko, Nanocrystals of cesium lead halide perovskites (CsPbX , X = Cl, Br, and I): novel optoelectronic materials showing bright emission with wide color gamut, Nano Lett. 15, p. 3692-3696, 2015.

Martineau M.,University of Munster | Parpura V.,University of Alabama at Birmingham | Parpura V.,University of Rijeka | Mothet J.-P.,Aix - Marseille University
Frontiers in Synaptic Neuroscience | Year: 2014

Accumulating evidence during the last decade established that D-serine is a key signaling molecule utilized by neurons and astroglia in the mammalian central nervous system. D-serine is increasingly appreciated as the main physiological endogenous coagonist for synaptic NMDA receptors at central excitatory synapses; it is mandatory for long-term changes in synaptic strength, memory, learning, and social interactions. Alterations in the extracellular levels of D-serine leading to disrupted cell-cell signaling are a trademark of many chronic or acute neurological (i.e., Alzheimer disease, epilepsy, stroke) and psychiatric (i.e., schizophrenia) disorders, and are associated with addictive behavior (i.e., cocaine addiction). Indeed, fine tuning of the extracellular levels of D-serine, achieved by various molecular machineries and signaling pathways, is necessary for maintenance of accurate NMDA receptor functions. Here, we review the experimental data supporting the notion that astroglia and neurons use different pathways to regulate levels of extracellular D-serine. © 2014 Martineau, Parpura and Mothet.

Baffou G.,Aix - Marseille University | Quidant R.,ICFO - Institute of Photonic Sciences | Quidant R.,Catalan Institution for Research and Advanced Studies
Chemical Society Reviews | Year: 2014

Noble metal nanoparticles supporting plasmonic resonances behave as efficient nanosources of light, heat and energetic electrons. Owing to these properties, they offer a unique playground to trigger chemical reactions on the nanoscale. In this tutorial review, we discuss how nanoplasmonics can benefit chemistry and review the most recent developments in this new and fast growing field of research. © 2014 the Partner Organisations.

Vitte J.,Laboratoire Dimmunologie Hopital Of La Conception | Vitte J.,Aix - Marseille University
Molecular Immunology | Year: 2015

The most abundant prestored enzyme of human mast cell secretory granules is the serine-protease tryptase. In humans, there are four tryptase isoforms, but only two of them, namely the alpha and beta tryptases, are known as medically important. Low levels of continuous tryptase production as an immature monomer makes up the major part of the baseline serum tryptase levels, while transient release of mature tetrameric tryptase upon mast cell degranulation accounts for the anaphylactic rise of serum tryptase levels. Serum tryptase determination contributes to the diagnosis or monitoring of mast cell disorders including mast cell activation - induced anaphylaxis, mastocytosis and a number of myeloproliferative conditions with mast cell lineage involvement. Baseline serum tryptase levels are predictive of the severity risk in some allergic conditions. © 2014 Elsevier Ltd.

Leweke T.,Aix - Marseille University | Le Dizes S.,Aix - Marseille University | Williamson C.H.K.,Cornell University
Annual Review of Fluid Mechanics | Year: 2016

This article reviews the characteristics and behavior of counter-rotating and corotating vortex pairs, which are seemingly simple flow configurations yet immensely rich in phenomena. Since the reviews in this journal by Widnall (1975) and Spalart (1998), who studied the fundamental structure and dynamics of vortices and airplane trailing vortices, respectively, there have been many analytical, computational, and experimental studies of vortex pair flows. We discuss two-dimensional dynamics, including the merging of same-sign vortices and the interaction with the mutually induced strain, as well as three-dimensional displacement and core instabilities resulting from this interaction. Flows subject to combined instabilities are also considered, in particular the impingement of opposite-sign vortices on a ground plane. We emphasize the physical mechanisms responsible for the flow phenomena and clearly present the key results that are useful to the reader for predicting the dynamics and instabilities of parallel vortices. © Copyright 2016 by Annual Reviews. All rights reserved.

Grigor'yan A.,Bielefeld University | Nadirashvili N.,Aix - Marseille University
Archive for Rational Mechanics and Analysis | Year: 2015

We prove a certain upper bound for the number of negative eigenvalues of the Schrödinger operator H = −Δ − V in $${\mathbb{R}^{2}.}$$R2. © 2015, Springer-Verlag Berlin Heidelberg.

Bauchy M.,University of California at Los Angeles | Qomi M.J.A.,Massachusetts Institute of Technology | Bichara C.,Aix - Marseille University | Ulm F.-J.,Massachusetts Institute of Technology | And 2 more authors.
Physical Review Letters | Year: 2015

Understanding the composition dependence of the hardness in materials is of primary importance for infrastructures and handled devices. Stimulated by the need for stronger protective screens, topological constraint theory has recently been used to predict the hardness in glasses. Herein, we report that the concept of rigidity transition can be extended to a broader range of materials than just glass. We show that hardness depends linearly on the number of angular constraints, which, compared to radial interactions, constitute the weaker ones acting between the atoms. This leads to a predictive model for hardness, generally applicable to any crystalline or glassy material. © 2015 American Physical Society.

Rovelli C.,Aix - Marseille University | Rovelli C.,University of Toulon | Wilson-Ewing E.,Louisiana State University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2014

We point out that the relative Heisenberg uncertainty relations vanish for noncompact spaces in homogeneous loop quantum cosmology. As a consequence, for sharply peaked states quantum fluctuations in the scale factor never become important, even near the bounce point. This shows why quantum backreaction effects remain negligible and explains the surprising accuracy of the effective equations in describing the dynamics of sharply peaked wave packets. This also underlines the fact that minisuperspace models - where it is global variables that are quantized - do not capture the local quantum fluctuations of the geometry. © 2014 American Physical Society.

Doussin J.-F.,University Paris Est Creteil | Doussin J.-F.,University of Colorado at Boulder | Monod A.,Aix - Marseille University
Atmospheric Chemistry and Physics | Year: 2013

In the atmosphere, one important class of reactions occurs in the aqueous phase in which organic compounds are known to undergo oxidation towards a number of radicals, among which OH radicals are the most reactive oxidants. In 2008, Monod and Doussin have proposed a new structure-activity relationship (SAR) to calculate OH-oxidation rate constants in the aqueous phase. This estimation method is based on the group-additivity principle and was until now limited to alkanes, alcohols, acids, bases and related polyfunctional compounds. In this work, the initial SAR is extended to carbonyl compounds, including aldehydes, ketones, dicarbonyls, hydroxy carbonyls, acidic carbonyls, their conjugated bases, and the hydrated form of all these compounds. To do so, only five descriptors have been added and none of the previously attributed descriptors were modified. This extension leads now to a SAR which is based on a database of 102 distinct compounds for which 252 experimental kinetic rate constants have been gathered and reviewed. The efficiency of this updated SAR is such that 58% of the rate constants could be calculated within ±20% of the experimental data and 76% within ±40% (respectively 41 and 72% for the carbonyl compounds alone). © Author(s) 2013. Author(s) .

Donner J.S.,ICFO - Institute of Photonic Sciences | Thompson S.A.,ICFO - Institute of Photonic Sciences | Kreuzer M.P.,ICFO - Institute of Photonic Sciences | Baffou G.,Aix - Marseille University | And 2 more authors.
Nano Letters | Year: 2012

Heat is of fundamental importance in many cellular processes such as cell metabolism, cell division and gene expression.(1-3) Accurate and noninvasive monitoring of temperature changes in individual cells could thus help clarify intricate cellular processes and develop new applications in biology and medicine. Here we report the use of green fluorescent proteins (GFP) as thermal nanoprobes suited for intracellular temperature mapping. Temperature probing is achieved by monitoring the fluorescence polarization anisotropy of GFP. The method is tested on GFP-transfected HeLa and U-87 MG cancer cell lines where we monitored the heat delivery by photothermal heating of gold nanorods surrounding the cells. A spatial resolution of 300 nm and a temperature accuracy of about 0.4 °C are achieved. Benefiting from its full compatibility with widely used GFP-transfected cells, this approach provides a noninvasive tool for fundamental and applied research in areas ranging from molecular biology to therapeutic and diagnostic studies. © 2012 American Chemical Society.

Diogo R.,Howard University | Kelly R.G.,Aix - Marseille University | Christiaen L.,New York University | Levine M.,University of California at Berkeley | And 4 more authors.
Nature | Year: 2015

It has been more than 30 years since the publication of the new head hypothesis, which proposed that the vertebrate head is an evolutionary novelty resulting from the emergence of neural crest and cranial placodes. Neural crest generates the skull and associated connective tissues, whereas placodes produce sensory organs. However, neither crest nor placodes produce head muscles, which are a crucial component of the complex vertebrate head. We discuss emerging evidence for a surprising link between the evolution of head muscles and chambered hearts-both systems arise from a common pool of mesoderm progenitor cells within the cardiopharyngeal field of vertebrate embryos. We consider the origin of this field in non-vertebrate chordates and its evolution in vertebrates. © 2015 Macmillan Publishers Limited. All rights reserved.

Durand E.,Aix - Marseille University | Durand E.,CNRS Architecture and Functions of Biological Macromolecules Lab | Cambillau C.,Aix - Marseille University | Cascales E.,CNRS Architecture and Functions of Biological Macromolecules Lab | Journet L.,CNRS Architecture and Functions of Biological Macromolecules Lab
Trends in Microbiology | Year: 2014

The type VI secretion system (T6SS) is a macromolecular machine that delivers protein effectors into both prokaryotic and eukaryotic cells, therefore participating in interbacterial competition and virulence. The T6SS is functionally and structurally similar to the contractile bacteriophage cell puncturing device: the contraction of a sheath-like structure is believed to propel an inner tube terminated by a spike towards target cells, allowing the delivery of effectors. In this review, we summarize recent advances in the identification and characterization of T6SS effector proteins, highlighting the broad repertoire of enzymatic activities, and discuss recent findings relating to the secretion mechanisms. © 2014 Elsevier Ltd.

Donner J.S.,ICFO - Institute of Photonic Sciences | Baffou G.,ICFO - Institute of Photonic Sciences | Baffou G.,Aix - Marseille University | McCloskey D.,ICFO - Institute of Photonic Sciences | And 2 more authors.
ACS Nano | Year: 2011

We study the ability of a plasmonic structure under illumination to release heat and induce fluid convection at the nanoscale. We first introduce the unified formalism associated with this multidisciplinary problem combining optics, thermodynamics, and hydrodynamics. On this basis, numerical simulations were performed to compute the temperature field and velocity field evolutions of the surrounding fluid for a gold disk on glass while illuminated at its plasmon resonance. We show that the velocity amplitude of the surrounding fluid has a linear dependence on the structure temperature and a quadratic dependence on the structure size (for a given temperature). The fluid velocity remains negligible for single nanometer-sized plasmonic structures (<1 nm/s) due to a very low Reynolds number. However thermal-induced fluid convection can play a significant role when considering either micrometer-size structures or an assembly of nanostructures. © 2011 American Chemical Society.

Boubezoul A.,University Paris Est Creteil | Paris S.,Aix - Marseille University
Pattern Recognition | Year: 2012

Many data mining applications involve the task of building a model for predictive classification. The goal of this model is to classify data instances into classes or categories of the same type. The use of variables not related to the classes can reduce the accuracy and reliability of classification or prediction model. Superfluous variables can also increase the costs of building a model particularly on large datasets. The feature selection and hyper-parameters optimization problem can be solved by either an exhaustive search over all parameter values or an optimization procedure that explores only a finite subset of the possible values. The objective of this research is to simultaneously optimize the hyper-parameters and feature subset without degrading the generalization performances of the induction algorithm. We present a global optimization approach based on the use of Cross-Entropy Method to solve this kind of problem. © 2012 Elsevier Ltd.

Sarlegna F.R.,Aix - Marseille University | Mutha P.K.,Indian Institute of Technology Gandhinagar
Vision Research | Year: 2015

The continuously changing properties of our environment require constant monitoring of our actions and updating of our motor commands based on the task goals. Such updating relies upon our predictions about the sensory consequences of our movement commands, as well as sensory feedback received during movement execution. Here we focus on how visual information about target location is used to update and guide ongoing actions so that the task goal is successfully achieved. We review several studies that have manipulated vision of the target in a variety of ways, ranging from complete removal of visual target information to changes in visual target properties after movement onset to examine how such changes are accounted for during motor execution. We also examined the specific role of a critical neural structure, the parietal cortex, and argue that a fundamental challenge for the future is to understand how visual information about target location is integrated with other streams of information, during movement execution, to estimate the state of the body and the environment in order to ensure optimal motor performance. © 2014 The Authors.

Baffou G.,Aix - Marseille University | Quidant R.,ICFO - Institute of Photonic Sciences | Quidant R.,Catalan Institution for Research and Advanced Studies
Laser and Photonics Reviews | Year: 2013

Recent years have seen a growing interest in using metal nanostructures to control temperature on the nanoscale. Under illumination at its plasmonic resonance, a metal nanoparticle features enhanced light absorption, turning it into an ideal nano-source of heat, remotely controllable using light. Such a powerful and flexible photothermal scheme is the basis of thermo-plasmonics. Here, the recent progress of this emerging and fast-growing field is reviewed. First, the physics of heat generation in metal nanoparticles is described, under both continuous and pulsed illumination. The second part is dedicated to numerical and experimental methods that have been developed to further understand and engineer plasmonic-assisted heating processes on the nanoscale. Finally, some of the most recent applications based on the heat generated by gold nanoparticles are surveyed, namely photothermal cancer therapy, nano-surgery, drug delivery, photothermal imaging, protein tracking, photoacoustic imaging, nano-chemistry and optofluidics. Recent years have seen a growing interest in using metal nanostructures to control temperature on the nanoscale. Under illumination at its plasmonic resonance, a metal nanoparticle features enhanced light absorption, turning it into an ideal nano-source of heat, remotely controllable using light. Such a powerful and flexible photothermal scheme is the basis of thermo-plasmonics. Here, the recent progress of this emerging and fast-growing field is reviewed. First, the physics of heat generation in metal nanoparticles is described, under both continuous and pulsed illumination. The second part is dedicated to numerical and experimental methods that have been developed to further understand and engineer plasmonic-assisted heating processes on the nanoscale. Finally, some of the most recent applications based on the heat generated by gold nanoparticles are surveyed, namely photothermal cancer therapy, nano-surgery, drug delivery, photothermal imaging, protein tracking, photoacoustic imaging, nano-chemistry and optofluidics. © 2012 by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cascales E.,Aix - Marseille University | Cambillau C.,CNRS Architecture and Functions of Biological Macromolecules Lab
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2012

Type VI secretion systems (T6SSs) are transenvelope complexes specialized in the transport of proteins or domains directly into target cells. These systems are versatile as they can target either eukaryotic host cells and therefore modulate the bacteria-host interaction and pathogenesis or bacterial cells and therefore facilitate access to a specific niche. These molecular machines comprise at least 13 proteins. Although recent years have witnessed advances in the role and function of these secretion systems, little is known about how these complexes assemble in the cell envelope. Interestingly, the current information converges to the idea that T6SSs are composed of two subassemblies, one resembling the contractile bacteriophage tail, whereas the other subunits are embedded in the inner and outer membranes and anchor the bacteriophage-like structure to the cell envelope. In this review, we summarize recent structural information on individual T6SS components emphasizing the fact that T6SSs are composite systems, adapting subunits from various origins. ©2012 The Royal Society.

Lopez Lozano X.,University of Texas at San Antonio | Mottet C.,Aix - Marseille University | Weissker H.-Ch.,Aix - Marseille University | Weissker H.-Ch.,European Theoretical Spectroscopy Facility
Journal of Physical Chemistry C | Year: 2013

The optical response of Au-Ag bimetallic nanoalloys has been studied using pseudopotential time-dependent density-functional theory calculations. The structures included the magic-number icosahedral nanoparticles of 55 and 147 atoms, 37-atom pentagonal rods, and 20-atom tetrahedra. Our results show strong resonances for the pure Ag nanoparticles and strongly broadened spectra with many transitions for the pure gold structures, in qualitative agreement with available experiment and previous calculations. For bimetallic core-shell particles, the outer shell determines the overall character of the optical response; a single outer layer of Ag can produce an Ag-like resonance even in a gold-rich structure. The inclusion of a gold core within a silver shell leads to a distinct red-shift of the silver-like resonances as well as to some damping. The bimetallic nanoparticles are found to be very sensitive to the chemical configuration, the position of the atomic species in some cases outweighing the effect of changing composition. For randomly alloyed configurations of 147-atom nanoparticles, the spectra show a smooth transition between pure Ag and Au and are in good qualitative agreement with available experiment. © 2013 American Chemical Society.

Collinet C.,Aix - Marseille University | Rauzi M.,EMBL Heidelberg | Lenne P.-F.,Aix - Marseille University | Lecuit T.,Aix - Marseille University
Nature Cell Biology | Year: 2015

Convergence-extension is a widespread morphogenetic process driven by polarized cell intercalation. In the Drosophila germ band, epithelial intercalation comprises loss of junctions between anterior-posterior neighbours followed by growth of new junctions between dorsal-ventral neighbours. Much is known about how active stresses drive polarized junction shrinkage. However, it is unclear how tissue convergence-extension emerges from local junction remodelling and what the specific role, if any, of junction growth is. Here we report that tissue convergence and extension correlate mostly with new junction growth. Simulations and in vivo mechanical perturbations reveal that junction growth is due to local polarized stresses driven by medial actomyosin contractions. Moreover, we find that tissue-scale pulling forces at the boundary with the invaginating posterior midgut actively participate in tissue extension by orienting junction growth. Thus, tissue extension is akin to a polarized fluid flow that requires parallel and concerted local and tissue-scale forces to drive junction growth and cell-cell displacement. © 2015 Macmillan Publishers Limited.

Medie F.M.,Aix - Marseille University | Medie F.M.,CNRS Architecture and Functions of Biological Macromolecules Lab | Davies G.J.,University of York | Drancourt M.,Aix - Marseille University | Henrissat B.,CNRS Architecture and Functions of Biological Macromolecules Lab
Nature Reviews Microbiology | Year: 2012

Cellulolytic enzymes have been the subject of renewed interest owing to their potential role in the conversion of plant lignocellulose to sustainable biofuels. An analysis of ∼1,500 complete bacterial genomes, presented here, reveals that ∼40% of the genomes of sequenced bacteria encode at least one cellulase gene. Most of the bacteria that encode cellulases are soil and marine saprophytes, many of which encode a range of enzymes for cellulose hydrolysis and also for the breakdown of the other constituents of plant cell walls (hemicelluloses and pectins). Intriguingly, cellulases are present in organisms that are usually considered as non-saprophytic, such as Mycobacterium tuberculosis, Legionella pneumophila, Yersinia pestis and even Escherichia coli. We also discuss newly emerging roles of cellulases in such non-saprophytic organisms. © 2012 Macmillan Publishers Limited. All rights reserved.

Punj D.,Aix - Marseille University | Mivelle M.,ICFO - Institute of Photonic Sciences | Moparthi S.B.,Aix - Marseille University | Van Zanten T.S.,ICFO - Institute of Photonic Sciences | And 6 more authors.
Nature Nanotechnology | Year: 2013

Single-molecule fluorescence techniques are key for a number of applications, including DNA sequencing, molecular and cell biology and early diagnosis. Unfortunately, observation of single molecules by diffraction-limited optics is restricted to detection volumes in the femtolitre range and requires pico- or nanomolar concentrations, far below the micromolar range where most biological reactions occur. This limitation can be overcome using plasmonic nanostructures, which enable the confinement of light down to nanoscale volumes. Although these nanoantennas enhance fluorescence brightness, large background signals and/or unspecific binding to the metallic surface have hampered the detection of individual fluorescent molecules in solution at high concentrations. Here we introduce a novel 'antenna-in-box' platform that is based on a gap-antenna inside a nanoaperture. This design combines fluorescent signal enhancement and background screening, offering high single-molecule sensitivity (fluorescence enhancement up to 1,100-fold and microsecond transit times) at micromolar sample concentrations and zeptolitre-range detection volumes. The antenna-in-box device can be optimized for single-molecule fluorescence studies at physiologically relevant concentrations, as we demonstrate using various biomolecules. © 2013 Macmillan Publishers Limited. All rights reserved.

Cunha-Neto E.,University of Sao Paulo | Cunha-Neto E.,Institute for Investigation in Immunology Iii | Chevillard C.,Aix - Marseille University
Mediators of Inflammation | Year: 2014

Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America and affects ca. 10 million people worldwide. About 30% of Chagas disease patients develop chronic Chagas disease cardiomyopathy (CCC), a particularly lethal inflammatory cardiomyopathy that occurs decades after the initial infection, while most patients remain asymptomatic. Mortality rate is higher than that of noninflammatory cardiomyopathy. CCC heart lesions present a Th1 T-cell-rich myocarditis, with cardiomyocyte hypertrophy and prominent fibrosis. Data suggest that the myocarditis plays a major pathogenetic role in disease progression. Major unmet goals include the thorough understanding of disease pathogenesis and therapeutic targets and identification of prognostic genetic factors. Chagas disease thus remains a neglected disease, with no vaccines or antiparasitic drugs proven efficient in chronically infected adults, when most patients are diagnosed. Both familial aggregation of CCC cases and the fact that only 30% of infected patients develop CCC suggest there might be a genetic component to disease susceptibility. Moreover, previous case-control studies have identified some genes associated to human susceptibility to CCC. In this paper, we will review the immunopathogenesis and genetics of Chagas disease, highlighting studies that shed light on the differential progression of Chagas disease patients to CCC. © 2014 Edecio Cunha-Neto and Christophe Chevillard.

Habchi J.,Aix - Marseille University | Habchi J.,CNRS Architecture and Functions of Biological Macromolecules Lab | Tompa P.,Vrije Universiteit Brussel | Tompa P.,Hungarian Academy of Sciences | And 4 more authors.
Chemical Reviews | Year: 2014

Proteins are the major component of the living cell. They play crucial roles in the maintenance of life, and their dysfunctions are known to cause different pathologies. Simple amino acid propensities reflect some basic physical or sequence features. Such propensity-based predictors rely on simple statistics of amino acid propensity, on the physical/chemical features of amino acids, or on a preliminary concept on the physical background of disorder. Regions of missing electron density in the PDB are generally short, as long regions prevent crystallization. As such, short disorder is overrepresented in the database of disordered regions, and hence these predictors tend to perform better in predicting short disorder than long disorder. Predictors can also be classified based on the binary nature of the prediction. Examples of binary predictors are the CH plot and the cumulative distribution function (CDF) analysis.

Sharipov F.,Federal University of Paraná | Graur I.,Aix - Marseille University
Vacuum | Year: 2014

An approach to model a transient flow of rarefied gas through a long capillary based on numerical data for flow rate previously obtained from the linearized and stationary kinetic equation was proposed. As an example, non-steady flow through a long circular tube connecting two reservoirs is considered. Pressures in the reservoirs and flow rates in the inlet and outlet are obtained as a function of time. It is shown that the behaviors of these quantities vary by changing the gas rarefaction from the free-molecular regime to hydrodynamic one. The typical time to reach the equilibrium state is calculated. © 2013 Elsevier Ltd. All rights reserved.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.1.2-1 | Award Amount: 10.45M | Year: 2011

In the frame of this project it is proposed to define and build a bi-modal PET-US (Positron Emission Tomography and Ultrasound) endoscopic probe combining in a miniaturized system a fully digital, 200ps time resolution Time of Flight PET detector head (TOF-PET) coupled to a commercial ultrasound (US) assisted biopsy endoscope and to launch the first steps of clinical validation. The project addresses and combines several objectives of the topics Health 2010.1.2-1, such as novel multimodality imaging tools, including a single photon (quantum) counting PET detector head for the purpose of identifying and quantifying morphologic and functional markers and of developing new biomarkers of tumoral processes at the preclinical and clinical levels. Moreover the endoscopic approach, combined with an unprecedented PET timing resolution will allow more sensitive, more precise, lower radiation dose and less invasive imaging and intervention on small internal structures and lesions.

Agency: European Commission | Branch: FP7 | Program: MC-IRSES | Phase: FP7-PEOPLE-2013-IRSES | Award Amount: 129.20K | Year: 2014

Storms and hurricanes are a major natural hazard at international scales and significant risk to populations and offshore industry. Growing coastal populations and increased maritime activity make it of rising importance to understand the physical processes of small-scale air-sea interaction under very strong winds. These processes strongly affect the quality of strong storm forecasting. Crucially the existing methods of satellite remote sensing of wind over the sea surface cease to work in very strong winds. ASIST lays the basis for advances in modelling of air/sea interaction under stormy and hurricane conditions. ASIST unites 4 research teams (Keele University (UK), Mediterranean Institute of Oceanography (France), Heidelberg University (Germany) and the Institute for Applied Physics (Russia) to: strengthen existing research partnerships through staff exchange, networking and training activities, and address the key scientific issues related to development of novel and practical satellite based microwave technologies capable of monitoring very strong winds over sea. ASIST combines the unique wind-wave facilities at partners in the laboratory modelling of air-sea interactions. The wind-wave facility at the Institute for Applied Physics is the only one able to model hurricane strength winds and complements facilities in Marseille and Heidelberg. This 48 month programme involves a multi-disciplinary team in an integrated programme of experimental effort, supported by joint theoretical and modelling work. The specific outcomes include finding wind dependence of microwave cross-polarization cross-section for very high winds, identifying and quantifying the main physical mechanisms of heat and gas exchange between the atmosphere and oceans. Results will allow for significant advances in the accuracy of meteo- and climate modelling. ASIST will maximise benefits for early stage researchers (70% of the exchange) by heavy involvement in research and knowledge exchange

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-ITN-2008 | Award Amount: 2.34M | Year: 2009

EBRAMUS investigates an attractive, promising new research avenue at the intersection of neuroscience, the human sciences and new technologies: can music boost sensory, cognitive and motor development in normal and impaired children and adults? The project will assess this issue in an integrative way by combining behavioural, neurophysiological, neuropsychological and computational methods. Three research topics will cover both basic and clinical research using music in the rehabilitation of various patient populations and the elderly. The 1st topic focuses on the rehabilitation of auditory functions and language deficits, the 2nd focuses on the benefits of music for more general cognitive functions (learning, memory) and the 3d on timing behaviour and the use of music in motor rehabilitation. The overall project will increase our understanding of brain functioning and will have a tremendous impact on clinical and educational applications (developing new diagnostic tools, training and rehabilitation techniques, also leading to industrial developments) and for new music technology for the general public. EBRAMUS will foster strong links among partners at the forefront of this interdisciplinary research area. It provides an invaluable opportunity for young researches to gain state-of-the art knowledge in the field of cognitive neurosciences and interdisciplinary research by benefiting from exchanges within the network, from the offered training program (e.g., topical summer schools/workshops) and the projects good balance between basic research and clinical approaches. The training will ultimately increase students career opportunities, thanks to the networks academic and industrial partners. EBRAMUS partners present a strong network with common and complementary expertise, thus providing ideal multi-site and multidisciplinary training for young researchers and, more generally, providing the opportunity to considerably strengthen Europes position in the field.

Aix - Marseille University and Lascco Sa | Date: 2010-11-18

The present invention is directed to new compositions uses thereof and related methods for the treatment of a motoneuron disease or disorder. In particular, the invention relates to the new use of IFN antagonists or viral vectors, uses, compositions thereof and related methods for the treatment of motoneuron disease or disorder such as ALS.

Agency: European Commission | Branch: FP7 | Program: MC-IRSES | Phase: FP7-PEOPLE-2012-IRSES | Award Amount: 304.20K | Year: 2013

The NEUREN project is based on an interdisciplinary consortium of 14 laboratories from 4 EU countries (France, Italy, Spain, Poland), 3 industrialized countries (Australia, Canada, USA) and 3 Mediterranean countries (Egypt, Morocco, Lebanon). It covers a large scope of Neuroscience research topics from molecules to integrated physiology, associate basic, translational, and clinical research, from bench to bedside. EU institutions all share similar basic competences but they show significant complementarities to cover all aspects of Neuroscience. Third countries partners bring their own technical and conceptual expertise to build a consortium of excellence, taking advantage of previous collaborations to exploit existing complementary expertise and synergy between the partners. Given the complexity of neurobiological processes, and the broad range of methodological approaches, it is absolutely necessary to develop multi-sites integrated research projects. Therefore, 6 multi-sites projects have been elaborated, using staff exchange as a tool to develop research collaborations. Pain sensitization in the spinal cord (Bordeaux, Alexandria, Melbourne, Laval, Turin) Experimental models for neurological disorders (Turin, Marrakech, Alexandria, NY) Systems neurobiology of neurological disorders (Valence, Tetuan, Krakow, Melbourne) Cognitive impairment and neuronal dynamics (Marseille, Alexandria, Marrakech) Dysfunction of the prefrontal cortex and trait anxiety (Nice, Marrakech) Medical imaging of neurological disorders (Bordeaux, Laval, Beirut) Such consortium will highly support the current efforts to reach outstanding international research standards. It will contribute to develop poles of technical and scientific excellence that will become the reference for the South Mediterranean area. Northern institutions will fully benefit from this integration to further diversify their technical expertise and to aggregate powerful teams of well-trained researchers.

Agency: European Commission | Branch: FP7 | Program: MC-IRSES | Phase: FP7-PEOPLE-2012-IRSES | Award Amount: 588.00K | Year: 2013

Reflecting on the issues of EU-China relationships, aims at developing a new understanding of liberalism in its economic, political and social dimensions. It involves a comparative analysis of the cultural differences in its interpretation and of the political discrepancies in its enforcement, in particular with respect to economic, social and environmental rights in China and Europe in Modern times. It is a multidisciplinary project based on a comparative study of European and Chinese political philosophy and political economy, legal practice and philosophy of right. The project stands at the confluence of two major issues for the European Union, in terms of internal policies as well as external actions: 1/ the position and role of the European Union in the World and 2/ the present and future of Human Rights. The first issue, on liberal civil society and the various types of market-enhanced economies, brings concerns such as the World Trade Organization put forth recently when rebuking Chinas application to be reckoned as a market economy. It relates to the new partnerships that the European Union is building with China in the globalized World and in the aftermath of the sovereign debt crisis. Our project is comparative as it focuses both on relationships between the European Union and China in particular, and accommodates viewpoints from Chinas neighbors The second issue, involving the present enforcement and future potential implementation and/or revision of Human Rights concepts, is addressed by focusing principally on the political, legal and economic aspects of the concept of Liberalism, regarded as made of several traditions, from social liberalism to liberal theories of economics. The project thus aims at disclosing cultural and political differences in terms of interpretation and of enforcement of Liberalism in China. LIBEAC is geared towards finding useful criterion for EU decision-making and thus als means Liberalism for Action.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.1.1-1 | Award Amount: 9.36M | Year: 2011

Animal venoms are complex cocktails of peptides that have enormous potential as novel therapeutic leads. Replicating in vitro the diversity of venoms by generating large synthetic combinatorial peptide libraries will solve the challenge of working with limited amounts of natural products and permit high-throughput investigation of their pharmacology. A new investigation paradigm associating transcriptomics and proteomics is the only way to achieve this goal and to address the complexity of this unexplored 40,000,000 peptide resource. The vision of the VENOMICS project is to develop, integrate and implement cutting-edge and innovative technologies in a high-throughput approach to investigate the enormous structural and pharmacological diversity of venom peptides. We will use the largest venom and venom gland collection in the world to generate a comprehensive sequence database of bioactive peptides, and produce a 10,000 reticulated peptide bank to be used in drug discovery efforts and development of novel therapeutics. A 1000-fold improvement in throughput over the current situation (1 to 2 candidates generated per year) is reasonably foreseen. Implementation of the project will require both improvements and the integration of exisiting technologies in a high-throughput workflow comprising venom and tissue sourcing, mass spectrometry-based automated de novo peptide sequencing, transcriptomics of venom gland-derived RNA or cDNA/EST libraries, bioinformatics, implementation of a sequence database, and highly parallel synthetic or recombinant production including peptide refolding. The last step will be the validation of the approach in functional assays targeting specific pathologies. VENOMICS is a high-impact project with societal (new drugs against life threatening diseases), scientific and technological (filling the drug discovery pipeline), political (European leadership in the field) and economic (new opportunities for the biologics market) benefits.

Agency: European Commission | Branch: FP7 | Program: CSA-SA | Phase: INCO-2007-2.1 | Award Amount: 577.28K | Year: 2008

The M2ERA proposal builds on the success of the implementation of previous initiatives supported by the EC to increase awareness of research and collaboration activities between Morocco and the ERA. Furthermore, the present project will reinforce and complement the SSAs projects in which the Moroccan department of research has participated (Euromedanet, Food-N-CO, Idea-Ist, Promedaccess, MED7. The ERA-MED and MIRA project actually in progress will benefit from the synergies driven of sharing similar objectives. The M2ERA objective is to support, on a coordinated and efficient manner, the participation and involvement of the Moroccan R&D stakeholders in the ERA activities, mainly through the implementation of a sustainable structure for FPs promotion as thematic NCPs, information and awareness activities, partnership promotion by organisation and attendance of high-level events and improving the Moroccan environment to motivate researchers to involve European research projects. The project includes a qualitative and qualitative assessment of the S&T Moroccan EU cooperation in order to identify motivations, obstacles, and impact of this cooperation. The support of political dialogue in this project will help to identify priorities of collaboration, enhance the quality, quantity and visibility of future actions and set Links between existing S&T programs.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: SEC-2011.3.4-2 | Award Amount: 4.97M | Year: 2012

The research will develop a universal gas sensor using modular technologies to function as an artificial sniffer. It will detect a range of substances, including but not limited to people, drugs, explosives (including weapons) and CBRNe. The technology will complement trained sniffer dogs. The technology proposed is based on linear ion trap (LIT) mass spectrometry (MS). MS techniques have been increasingly deployed in security sniffing applications in the USA. MS is a non-intrusive high-resolution technique able to detect single atoms and complex molecules through their charged species (ions) or fragmentation pattern. The technique is capable of detecting a wide range of substances rapidly, with high accuracy and with a stand-off capability critically it is able to detect trace levels below parts per million. Once the MS fingerprint of a unknown substance is measured it can be compared online with a database of known substances enabling real-time rapid identification. Sniffles will develop a LIT MS based device with a larger mass range than other comparable MS techniques. Methods for miniaturisation and modularisation will be applied to allow reduced vacuum demand and upgradeability. Miniaturisation will be made possible through improved designs based on results from modelling, novel manufacturing techniques and improvements in the MS drive electronics and vacuum system. These advances will bring benefits including reduced acquisition/operating costs, greater mobility, user friendliness and flexibility. Sniffles has the potential to significantly impact on National Security and border control and enable exploitation of International Markets. Performance will be benchmarked against a state-of-the-art conventional MS system and security sniffer dogs within the context of a border security checkpoint. Sniffles aims to demonstrate an automated portable MS-based sniffer device, tested and evaluated for a range of security applications and markets by end-users.

Total Marketing Services Siege Social, French National Center for Scientific Research, Aix - Marseille University and Linstitut National Des Science Appliquees Insa | Date: 2014-04-09

Described herein are molecules, constructs and methods for the production and secretion of polypeptides of interest by host cells, preferably bacterial host cells, and more particularly gram positive bacteria. In particular, the present invention is related to a polynucleic acid encoding a fusion protein and to uses thereof for the secretion of heterologous or homologous polypeptides of interest by a bacterial host cell, preferably Clostridium bacteria. The present invention further relates to methods and constructs for the production and secretion of heterologous or homologous polypeptides of interest proteins by host cells using such polynucleic acids and fusion proteins.

News Article | September 13, 2016

MIT President L. Rafael Reif joined a high-level delegation of French officials at MIT on Friday to sign an agreement extending the research partnership behind MultiScale Material Science for Energy and Environment (MSE2), an international joint unit, or UMI (reflecting the French term “unité mixte internationale”), that has produced groundbreaking research into such complex materials as concrete and shale rocks. Reif signed the agreement with Alain Fuchs, president of the French National Center for Scientific Research (CNRS), and Yvon Berland, president of Aix-Marseille University, extending the collaboration for another seven years. The new pact also formalizes Aix-Marseille University’s role as a full partner in the UMI. “At MIT, our mission directs us to bring knowledge to bear on today’s challenges to make the world better. That’s a big aspiration. That obviously goes well beyond the capacity of one institution or one nation,” Reif said. “We take courage from knowing we face these challenges together.” Valéry Freland, France’s consul general in Boston, and Minh-Hà Pham, counselor for science and technology at the French embassy in Washington, were among the approximately 50 people who attended the ceremony in MIT’s Samberg Conference Center. “Congratulations on this French-American success story!” said France’s minister of state for higher education and research, Thierry Mandon, who spoke at the ceremony. Noting that France is working to bolster its higher education and research institutions, he said, “This is a perfect example of what we want to support.” More than 50 scholars work at the MSE2 lab, which hosts French researchers at MIT for years at a time. Going forward, MIT faculty and students will also have the opportunity to conduct research at a parallel lab centered at Aix-Marseille University: Centre Interdisciplinaire de Nanoscience de Marseille. “We are privileged to have really top students from France here, and we’re grateful Marseille is opening its doors to our students. We’re delighted,” said Bernd Widdig, director for international activities at MIT’s Office of the Provost. MSE2 was founded with support from the MIT Energy Initiative in 2012 to explore “bottom up” simulation and experimental verification of the properties of complex multiscale materials. Since that time, the joint lab has produced groundbreaking work — particularly in characterizing cement, the key component of concrete, the production of which accounts for 10 percent of carbon dioxide emissions worldwide. “Because of its ubiquitousness, [concrete] has an enormous environmental impact,” said Professor Franz-Josef Ulm, the George Macomber Professor of Civil and Environmental Engineering at MIT, who leads the lab along with Roland Pellenq, CNRS research director and an MIT senior research scientist, who emceed the day’s events. Ulm offered guests a brief summary of key MSE2 research, highlighting the lab’s recent discovery that cement has the structure of glass — a finding that will enable engineers to apply the field of glass physics to concrete science and potentially reduce the environmental footprint of the material. “UMI is driving progress in important areas of materials research,” Reif said. Speaking after the event, Pellenq said, “The UMI is the concrete expression of the will of merging engineering and science into a unified field where engineering solutions can be designed on sound fundamental scientific results. This is particularly important for complex materials such as concrete and shale rocks for which the span of complexity in texture and phenomena starts at the nanoscale. Altogether, this is an ambitious goal that encompasses education too; the UMI contributes to the annual Marseille Winterschool and the annual research workshop of the international network known as Groupement de Recherche International Multi-scale Materials Under the Nanoscope.” MIT’s partner signatories also offered remarks at the ceremony. Fuchs of CNRS thanked MIT for its collaboration and noted that the partnership succeeds because it relies on excellence. “This is the way things should be made at the international level,” he said. Berland of Aix-Marseille University in turn highlighted the lab’s interdisciplinary approach to multiscale research and noted that the UMI is successful because it integrates research with education and enlists resources from industry. “I am convinced that this project is an example to follow,” he said. Reif was similarly enthusiastic. “The UMI team has demonstrated a collaboration that is both strong and sustainable, and with today’s signing we know it will be enduring as well,” he said.

News Article | September 12, 2016

MIT President L. Rafael Reif joined a high-level delegation of French officials at MIT on Friday to sign an agreement extending the research partnership behind MultiScale Material Science for Energy and Environment (MSE2), an international joint unit, or UMI (reflecting the French term "unité mixte internationale"), that has produced groundbreaking research into such complex materials as concrete and shale rocks. Reif signed the agreement with Alain Fuchs, president of the French National Center for Scientific Research (CNRS), and Yvon Berland, president of Aix-Marseille University, extending the collaboration for another seven years. The new pact also formalizes Aix-Marseille University's role as a full partner in the UMI. "At MIT, our mission directs us to bring knowledge to bear on today's challenges to make the world better. That's a big aspiration. That obviously goes well beyond the capacity of one institution or one nation," Reif said. "We take courage from knowing we face these challenges together." Valéry Freland, France's consul general in Boston, and Minh-Hà Pham, counselor for science and technology at the French embassy in Washington, were among the approximately 50 people who attended the ceremony in MIT's Samberg Conference Center. "Congratulations on this French-American success story!" said France's minister of state for higher education and research, Thierry Mandon, who spoke at the ceremony. Noting that France is working to bolster its higher education and research institutions, he said, "This is a perfect example of what we want to support." More than 50 scholars work at the MSE2 lab, which hosts French researchers at MIT for years at a time. Going forward, MIT faculty and students will also have the opportunity to conduct research at a parallel lab centered at Aix-Marseille University: Centre Interdisciplinaire de Nanoscience de Marseille. "We are privileged to have really top students from France here, and we're grateful Marseille is opening its doors to our students. We're delighted," said Bernd Widdig, director for international activities at MIT's Office of the Provost. MSE2 was founded with support from the MIT Energy Initiative in 2012 to explore “bottom up” simulation and experimental verification of the properties of complex multiscale materials. Since that time, the joint lab has produced groundbreaking work — particularly in characterizing cement, the key component of concrete, the production of which accounts for 10 percent of carbon dioxide emissions worldwide. "Because of its ubiquitousness, [concrete] has an enormous environmental impact," said Professor Franz-Josef Ulm, the George Macomber Professor of Civil and Environmental Engineering at MIT, who leads the lab along with Roland Pellenq, CNRS research director and an MIT senior research scientist, who emceed the day's events. Ulm offered guests a brief summary of key MSE2 research, highlighting the lab's recent discovery that cement has the structure of glass — a finding that will enable engineers to apply the field of glass physics to concrete science and potentially reduce the environmental footprint of the material. "UMI is driving progress in important areas of materials research," Reif said. Speaking after the event, Pellenq said, "The UMI is the concrete expression of the will of merging engineering and science into a unified field where engineering solutions can be designed on sound fundamental scientific results. This is particularly important for complex materials such as concrete and shale rocks for which the span of complexity in texture and phenomena starts at the nanoscale. Altogether, this is an ambitious goal that encompasses education too; the UMI contributes to the annual Marseille Winterschool and the annual research workshop of the international network known as Groupement de Recherche International Multi-scale Materials Under the Nanoscope." MIT's partner signatories also offered remarks at the ceremony. Fuchs of CNRS thanked MIT for its collaboration and noted that the partnership succeeds because it relies on excellence. "This is the way things should be made at the international level," he said. Berland of Aix-Marseille University in turn highlighted the lab's interdisciplinary approach to multiscale research and noted that the UMI is successful because it integrates research with education and enlists resources from industry. "I am convinced that this project is an example to follow," he said. Reif was similarly enthusiastic. "The UMI team has demonstrated a collaboration that is both strong and sustainable, and with today's signing we know it will be enduring as well," he said.

Bourrely C.,Aix - Marseille University | Buccella F.,National Institute of Nuclear Physics, Italy | Soffer J.,Temple University
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2013

We consider W± gauge bosons production in connection with recent results from BNL-RHIC and FNAL-Tevatron and interesting predictions from the statistical parton distributions. They concern relevant aspects of the structure of the nucleon sea and the high-x region of the valence quark distributions. We also give predictions in view of future proton-neutron collisions experiments at BNL-RHIC. © 2013 Elsevier B.V.

Scott C.L.,Inflammation Research Center | Scott C.L.,Ghent University | Scott C.L.,University of Glasgow | Henri S.,Aix - Marseille University | And 3 more authors.
Immunological Reviews | Year: 2014

Tissues that are in direct contact with the outside world face particular immunological challenges. The intestine, the skin, and the lung possess important mononuclear phagocyte populations to deal with these challenges, but the cellular origin of these phagocytes is strikingly different from one subset to another, with some cells derived from embryonic precursors and some from bone marrow-derived circulating monocytes. Here, we review the current knowledge regarding the developmental pathways that control the differentiation of mononuclear phagocytes in these barrier tissues. We have also attempted to build a theoretical model that could explain the distinct cellular origin of mononuclear phagocytes in these tissues. © 2014 John Wiley & Sons A/S.

Eckard S.C.,University of Washington | Rice G.I.,University of Manchester | Fabre A.,Aix - Marseille University | Badens C.,Aix - Marseille University | And 5 more authors.
Nature Immunology | Year: 2014

Sensors of the innate immune system that detect intracellular nucleic acids must be regulated to prevent inappropriate activation by endogenous DNA and RNA. The exonuclease Trex1 regulates the DNA-sensing pathway by metabolizing potential DNA ligands that trigger it. However, an analogous mechanism for regulating the RIG-I-like receptors (RLRs) that detect RNA remains unknown. We found here that the SKIV2L RNA exosome potently limited the activation of RLRs. The unfolded protein response (UPR), which generated endogenous RLR ligands through the cleavage of cellular RNA by the endonuclease IRE-1, triggered the production of type I interferons in cells depleted of SKIV2L. Humans with deficiency in SKIV2L had a type I interferon signature in their peripheral blood. Our findings reveal a mechanism for the intracellular metabolism of immunostimulatory RNA, with implications for specific autoimmune disorders.

Guilliams M.,Inflammation Research Center | Guilliams M.,Ghent University | Malissen B.,Aix - Marseille University
Immunity | Year: 2016

In response to the comments by Lutz and colleagues to our recent preview of the paper from Helft and colleagues (Helft et al., 2015), we wish to respectfully point out that granulocyte-macrophage colony-stimulating factor (GM-CSF) bone-marrow (BM) cultures have indeed allowed conceptual advances essential for our current understanding of the immunobiology of myeloid cells. However, the study by Helft et al. emphasized that even by focusing on CD11c+MHC II+ cells, this model yields a mixed bag of myeloid cells that derive from both common dendritic cell (DC) precursors and common monocyte precursors and showed gene-expression profiles distantly mimicking those expressed by their in vivo counterparts. Given the complexity of the cells generated in GM-CSF BM cultures, we suggested that recently described Flt3L-based culture systems are better suited for the study of conventional DCs (cDCs) in vitro and the manufacture of cDC-based vaccines. In response to the comments by Lutz and colleagues to our recent preview of the paper from Helft and colleagues (Helft et al., 2015), we wish to respectfully point out that granulocyte-macrophage colony-stimulating factor (GM-CSF) bone-marrow (BM) cultures have indeed allowed conceptual advances essential for our current understanding of the immunobiology of myeloid cells. However, the study by Helft et al. emphasized that even by focusing on CD11c+MHC II+ cells, this model yields a mixed bag of myeloid cells that derive from both common dendritic cell (DC) precursors and common monocyte precursors and showed gene-expression profiles distantly mimicking those expressed by their in vivo counterparts. Given the complexity of the cells generated in GM-CSF BM cultures, we suggested that recently described Flt3L-based culture systems are better suited for the study of conventional DCs (cDCs) in vitro and the manufacture of cDC-based vaccines. © 2016 Elsevier Inc.

Piccoli B.,Rutgers University | Rossi F.,Aix - Marseille University
Archive for Rational Mechanics and Analysis | Year: 2014

In this article, we generalize the Wasserstein distance to measures with different masses. We study the properties of this distance. In particular, we show that it metrizes weak convergence for tight sequences. We use this generalized Wasserstein distance to study a transport equation with a source, in which both the vector field and the source depend on the measure itself. We prove the existence and uniqueness of the solution to the Cauchy problem when the vector field and the source are Lipschitzian with respect to the generalized Wasserstein distance. © 2013 Springer-Verlag Berlin Heidelberg.

De Padova P.,National Research Council Italy | Kubo O.,Japan International Center for Materials Nanoarchitectonics | Olivieri B.,National Research Council Italy | Quaresima C.,National Research Council Italy | And 4 more authors.
Nano Letters | Year: 2012

The synthesis of silicene, graphene-like silicon, has generated very strong interest. Here, we reveal the growth of high aspect ratio, perfectly straight, and aligned silicon nanoribbons, exhibiting pyramidal cross section. They are multistacks of silicene and show in angle-resolved photoemission cone-like dispersion of their φ and φ* bands, at the X̄ point of their one-dimensional Brillouin zone, with Fermi velocity of ∼1.3 × 10 6 m sec-1, which is very promising for potential applications. © 2012 American Chemical Society.

Weber A.A.-T.,University of Geneva | Weber A.A.-T.,Aix - Marseille University | Pawlowski J.,University of Geneva
PLoS ONE | Year: 2013

Protists are key players in microbial communities, yet our understanding of their role in ecosystem functioning is seriously impeded by difficulties in identification of protistan species and their quantification. Current microscopy-based methods used for determining the abundance of protists are tedious and often show a low taxonomic resolution. Recent development of next-generation sequencing technologies offered a very powerful tool for studying the richness of protistan communities. Still, the relationship between abundance of species and number of sequences remains subjected to various technical and biological biases. Here, we test the impact of some of these biological biases on sequence abundance of SSU rRNA gene in foraminifera. First, we quantified the rDNA copy number and rRNA expression level of three species of foraminifera by qPCR. Then, we prepared five mock communities with these species, two in equal proportions and three with one species ten times more abundant. The libraries of rDNA and cDNA of the mock communities were constructed, Sanger sequenced and the sequence abundance was calculated. The initial species proportions were compared to the raw sequence proportions as well as to the sequence abundance normalized by rDNA copy number and rRNA expression level per species. Our results showed that without normalization, all sequence data differed significantly from the initial proportions. After normalization, the congruence between the number of sequences and number of specimens was much better. We conclude that without normalization, species abundance determination based on sequence data was not possible because of the effect of biological biases. Nevertheless, by taking into account the variation of rDNA copy number and rRNA expression level we were able to infer species abundance, suggesting that our approach can be successful in controlled conditions. © 2013 Weber, Pawlowski.

Leimkuhler S.,University of Potsdam | Iobbi-Nivol C.,Aix - Marseille University
FEMS Microbiology Reviews | Year: 2015

Molybdoenzymes are widespread in eukaryotic and prokaryotic organisms where they play crucial functions in detoxification reactions in the metabolism of humans and bacteria, in nitrate assimilation in plants and in anaerobic respiration in bacteria. To be fully active, these enzymes require complex molybdenum-containing cofactors, which are inserted into the apoenzymes after folding. For almost all the bacterial molybdoenzymes, molybdenum cofactor insertion requires the involvement of specific chaperones. In this review, an overview on the molybdenum cofactor biosynthetic pathway is given together with the role of specific chaperones dedicated for molybdenum cofactor insertion and maturation. Many bacteria are involved in geochemical cycles on earth and therefore have an environmental impact. The roles of molybdoenzymes in bioremediation and for environmental applications are presented. © FEMS 2015.

Iobbi-Nivol C.,Aix - Marseille University | Leimkuhler S.,University of Potsdam
Biochimica et Biophysica Acta - Bioenergetics | Year: 2013

Molybdenum cofactor (Moco) biosynthesis is an ancient, ubiquitous, and highly conserved pathway leading to the biochemical activation of molybdenum. Moco is the essential component of a group of redox enzymes, which are diverse in terms of their phylogenetic distribution and their architectures, both at the overall level and in their catalytic geometry. A wide variety of transformations are catalyzed by these enzymes at carbon, sulfur and nitrogen atoms, which include the transfer of an oxo group or two electrons to or from the substrate. More than 50 molybdoenzymes were identified in bacteria to date. In molybdoenzymes Mo is coordinated to a dithiolene group on the 6-alkyl side chain of a pterin called molybdopterin (MPT). The biosynthesis of Moco can be divided into four general steps in bacteria: 1) formation of the cyclic pyranopterin monophosphate, 2) formation of MPT, 3) insertion of molybdenum into molybdopterin to form Moco, and 4) additional modification of Moco with the attachment of GMP or CMP to the phosphate group of MPT, forming the dinucleotide variant of Moco. This review will focus on molybdoenzymes, the biosynthesis of Moco, and its incorporation into specific target proteins focusing on Escherichia coli. This article is part of a Special Issue entitled: Metals in Bioenergetics and Biomimetics Systems. © 2012 Elsevier B.V. All rights reserved.

Grainger J.,Aix - Marseille University | Tydgat I.,Ghent University | Issele J.,Ghent University
Journal of Experimental Psychology: Human Perception and Performance | Year: 2010

Five experiments examined crowding effects with letter and symbol stimuli. Experiments 1 through 3 compared 2-alternative forced-choice (2AFC) identification accuracy for isolated targets presented left and right of fixation with targets flanked either by 2 other items of the same category or a single item situated to the right or left of targets. Interference from flankers (crowding) was significantly stronger for symbols than letters. Single flankers generated performance similar to the isolated targets when the stimuli were letters but closer to the 2-flanker condition when the stimuli were symbols. Experiment 4 confirmed this pattern using a partial-report bar probe procedure. Experiment 5 showed that another measure of crowding, critical spacing, was greater for symbols than for letters. The results support the hypothesis that letter-string processing involves a specialized system developed to limit the spatial extent of crowding for letters in words. © 2010 American Psychological Association.

Ege M.J.,Ludwig Maximilians University of Munich | Mayer M.,TU Munich | Normand A.-C.,University of Franche Comte | Genuneit J.,University of Ulm | And 5 more authors.
New England Journal of Medicine | Year: 2011

Background: Children who grow up in environments that afford them a wide range of microbial exposures, such as traditional farms, are protected from childhood asthma and atopy. In previous studies, markers of microbial exposure have been inversely related to these conditions. Methods: In two cross-sectional studies, we compared children living on farms with those in a reference group with respect to the prevalence of asthma and atopy and to the diversity of microbial exposure. In one study - PARSIFAL (Prevention of Allergy - Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle) - samples of mattress dust were screened for bacterial DNA with the use of single-strand conformation polymorphism (SSCP) analyses to detect environmental bacteria that cannot be measured by means of culture techniques. In the other study - GABRIELA (Multidisciplinary Study to Identify the Genetic and Environmental Causes of Asthma in the European Community [GABRIEL] Advanced Study) - samples of settled dust from children's rooms were evaluated for bacterial and fungal taxa with the use of culture techniques. Results: In both studies, children who lived on farms had lower prevalences of asthma and atopy and were exposed to a greater variety of environmental microorganisms than the children in the reference group. In turn, diversity of microbial exposure was inversely related to the risk of asthma (odds ratio for PARSIFAL, 0.62; 95% confidence interval [CI], 0.44 to 0.89; odds ratio for GABRIELA, 0.86; 95% CI, 0.75 to 0.99). In addition, the presence of certain more circumscribed exposures was also inversely related to the risk of asthma; this included exposure to species in the fungal taxon eurotium (adjusted odds ratio, 0.37; 95% CI, 0.18 to 0.76) and to a variety of bacterial species, including Listeria monocytogenes, bacillus species, corynebacterium species, and others (adjusted odds ratio, 0.57; 95% CI, 0.38 to 0.86). Conclusions: Children living on farms were exposed to a wider range of microbes than were children in the reference group, and this exposure explains a substantial fraction of the inverse relation between asthma and growing up on a farm. (Funded by the Deutsche Forschungsgemeinschaft and the European Commission.) Copyright © 2011 Massachusetts Medical Society.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.1.4-1 | Award Amount: 7.89M | Year: 2013

Hearing impairment is the most frequent human sensory deficit and is mainly caused by the irreversible loss of neurosensory cells in the cochlea. The lack of human otic cell models represents a significant roadblock that has hampered the development of drug-based or cell-based therapies for the treatment of hearing loss. In a collaborative effort under this proposal we wish to devise approaches to generate human otic progenitors and differentiated otic cells from different human stem cell sources. We have devised guidance protocols for mouse and human embryonic and reprogrammed stem cells toward inner ear cell types that make use of principles of early germ layer formation and otic induction. A limitation is the efficacy of otic progenitor cell generation. Purification techniques for human otic progenitors from ES/iPS cell sources and in addition from native human otic tissues from fetal and adult stages will will serve the dual purpose for one to enable the development of novel bioassays for drug screens, as well as generating cells with decreased tumorigenicity for cell transplantation studies in in vivo animal models. New hit compounds identified from screening efforts will be tested and validated further in established organ culture models. The identification of relevant candidate compounds will be further developed as lead drug candidates in noise and ototoxic drug induced in vivo models. The scope of this stem cell technology development requires a collaborative team effort, with groups that have substantial combined experience in human ES/iPS cell work, inner ear stem cell biology, high-throughput assay development, and in translating research findings into the clinic as well as into the biotechnology realm. Within the consortium there exists an established translational route from bench to bedside for the commercial development of human otic stem cell derived technology towards inner ear medical applications aiming at the restoration of hearing function.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: CULT-COOP-08-2016 | Award Amount: 2.64M | Year: 2016

iMARECULTURE is focusing in raising European identity awareness using maritime and underwater cultural interaction and exchange in Mediterranean sea. Commercial ship routes joining Europe with other cultures are vivid examples of cultural interaction, while shipwrecks and submerged sites, unreachable to wide public are excellent samples that can benefit from immersive technologies, augmented and virtual reality. iMARECULTURE will bring inherently unreachable underwater cultural heritage within digital reach of the wide public using virtual visits and immersive technologies. Apart from reusing existing 3D data of underwater shipwrecks and sites, with respect to ethics, rights and licensing, to provide a personalized dry visit to a museum visitor or augmented reality to the diver, it also emphasizes on developing pre- and after- encounter of the digital visitor. The former one is implemented exploiting geospatial enabled technologies for developing a serious game of sailing over ancient Mediterranean and the latter for an underwater shipwreck excavation game. Both games are realized thought social media, in order to facilitate information exchange among users. iMARECULTURE supports dry visits by providing immersive experience through VR Cave and 3D info kiosks on museums or through the web. Additionally aims to significantly enhance the experience of the diver, visitor or scholar, using underwater augmented reality in a tablet and an underwater housing. iMARECULTURE is composed by universities and SMEs with experience in diverse underwater projects, existing digital libraries, and people many of which are divers themselves.

Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 3.85M | Year: 2015

Viral infections are a major cause of disease, mortality and economic losses worldwide. Antiviral therapy is an essential instrument to control virus infections. At present, however, licensed antiviral drugs have been developed only against a limited number of viruses (e.g. HIV, HCV, influenza, herpesviruses). There is a clear and unmet need for antiviral drugs to treat infections with other important human pathogens. Europe needs well-trained experts with multidisciplinary skills to advance the antiviral drug development field. However, few, if any, European universities or research institutes have the ability to deliver an intersectoral training programme that covers the broad spectrum of disciplines important for antiviral drug development. The ANTIVIRALS partnership has been established to fill this gap. It consists of six outstanding European academic partners and four industrial partners (two large R&D companies, of which one is specialized in antiviral drug discovery and development, and two SMEs), and two partner organisations (incl. one SME specialised in education). All partners are leaders in their field, ensuring state-of-the-art training possibilities, and their skills are highly complementary. ANTIVIRALS aims to introduce 15 ESRs to state-of-the-art knowledge and technology applied in antiviral drug development through both local and network-wide training activities. Individual research projects, research training workshops and intersectoral secondments will be supplemented with complementary skills courses and dissemination activities to improve career development and perspectives. The industrial partners are actively involved in the entire programme and will organize an industry-oriented conference aimed at further bridging the gap between academia and industry. Thus, ANTIVIRALS offers talented researchers a multidisciplinary and intersectoral training programme and prepares them for a future leading role in antiviral drug development in Europe.

Thales Alenia, Aix - Marseille University, French National Center for Space Studies and French National Center for Scientific Research | Date: 2012-09-14

Optical devices can comprise a deformable mirror and a system for deforming said mirror. A deformation system comprises a first mechanical structure comprising a first surround, one or more electromechanical actuators attached to the first mechanical structure, a second mechanical structure comprising a substantially planar bottom and a second surround, both deformable, the bottom being attached to the first surround, the second surround being attached to the surround of the mirror, a rigid stud being attached to the bottom, substantially planar and centred on the bottom, the electromechanical actuator or actuators exerting predetermined forces or bending moments on the stud so as to generate a particular distribution of the bending moments on the surround of the mirror, deforming it according to a geometrical form representative or of one or more predetermined geometrical aberrations.

Fontolan L.,University of Geneva | Morillon B.,Columbia University | Liegeois-Chauvel C.,Aix - Marseille University | Giraud A.-L.,University of Geneva
Nature Communications | Year: 2014

The fact that feed-forward and top-down propagation of sensory information use distinct frequency bands is an appealing assumption for which evidence remains scarce. Here we obtain human depth recordings from two auditory cortical regions in both hemispheres, while subjects listen to sentences, and show that information travels in each direction using separate frequency channels. Bottom-up and top-down propagation dominates in γ- and δ-β (<40 Hz) bands, respectively. The predominance of low frequencies for top-down information transfer is confirmed by cross-regional frequency coupling, which indicates that the power of γ-activity in A1 is modulated by the phase of δ-β activity sampled from association auditory cortex (AAC). This cross-regional coupling effect is absent in the opposite direction. Finally, we show that information transfer does not proceed continuously but by time windows where bottom-up or top-down processing alternatively dominates. These findings suggest that the brain uses both frequency- and time-division multiplexing to optimize directional information transfer. © 2014 Macmillan Publishers Limited. All rights reserved.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-4.2-1 | Award Amount: 2.58M | Year: 2009

Cancer chemotherapy has a key role in the successful treatment of a number of childhood cancers. Nevertheless, at least 20% of patients are not cured by current therapies and a significant number experience debilitating toxicities. Given the high cure rates and potential life-span of survivors of childhood cancer, it is particularly important to minimize the impact of potential chronic toxicities. For several of the most widely-used drugs, little is known about their pharmacokinetics and metabolism in children, particularly very young children (<3 years). There are many examples where such knowledge has been used to optimize the use of chemotherapeutic drugs, both to avoid toxicity and to maximize the therapeutic effect. The need for further research to investigate these drugs in children is acknowledged in the Priority List for Studies into Paediatric Medicinal Products, issued by the EMEA. Doxorubicin is on this list and is one of the most important drugs used in the treatment of childhood cancers. Several national groups have been successful in studying the pharmacology of drugs used in paediatric oncology. However, in order to recruit sufficient patient numbers for meaningful studies it is necessary to establish a wider group, bringing together the successful elements of established national organizations. The EPOC group combines leading pharmacologists, paediatric oncologists, regulatory organizations and a management structure which will successfully deliver data of appropriate quality on which to base future clinical use of this drug and to meet the demands of the EMEA priority list. Such data will form the basis of future applications for Paediatric Usage Marketing Authorization for doxorubicin. The overall aim of the consortium is to provide data that will guide the optimal use of this drug in the clinic, and also meet the regulatory requirements of the EMA.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: Health | Award Amount: 3.04M | Year: 2014

The objective of this proposal is to urgently determine the efficacy, safety and feasibility of convalescent whole blood (CWB) and convalescent plasma (CP) therapy, as a treatment for patients with Ebola Viral Disease (EVD) to reduce the case fatality rate in the present EVD epidemic in West Africa. The trial will take place in three consecutive phases; i) initial phase to initiate harmonized standard supportive care (SC), ii) evaluation of CWB iii) evaluation of CP. Supportive care (SC) including intravenous hydration and shock management will be standardised and made available to all patients. Day 14 mortality will be used to determine primary outcome. Survival for patients treated with CWB \ SC or CP \ SC will be compared to SC alone using a non-randomised open-label design. Based on available figures, a 20% decrease in the case fatality rate will be considered proof of clinical efficacy. Internationally agreed stands of ethics and human rights will be applied for the duration of the trial. Written consent will be requested from patients and/or guardians of patients. Every consideration will be given to the safely of health-care workers involved in the trial, including their consent to be involved and adequate training and psycho-emotional support. Given the study context, community communication will be prioritized. We propose a unique partnership of academics, clinical trial units, non-governmental organizations, international research networks, international and local actors to conduct a clinical trial according to the highest standards attainable in the current context. If found to be effective, this intervention can be scaled-up relatively rapidly as the trial will provide the information required to mobilize local partners, with major public health implications.

Agency: European Commission | Branch: FP7 | Program: JTI-CP-FCH | Phase: SP1-JTI-FCH-3.3 | Award Amount: 2.68M | Year: 2010

The present proposal aims at the development of SPG&CHP systems based on Polymeric Electrolyte Membrane Fuel Cell Hydrogen (PEMFCH). A drawback in the state-of-the-art systems is the too low operating temperatures (70-80C) of PEMFCHs for cogeneration purposes. Operating temperatures above 100C would have several advantages including easier warm water distribution in buildings, reduced anode poisoning due to carbon monoxide impurities in the fuel and improved fuel oxidation kinetics. A PEMFCH operating in the temperature range of 100-130C is highly desirable and could be decisive for the development of SPG&CHP systems based on PEMFCHs. The main objective of the present project is to give a clear demonstration that long-life SPG&CHP systems based on PEMFCHs operating above 100C can now be developed on the basis of recent knowledge on the degradation mechanisms of ionomeric membranes and on innovative synthetic approaches recently disclosed by some participants of this project. Main research tasks: (1) Develop long life (longer 40000 hrs) perfluoro sulfonic acid membranes and sulfonated aromatic polymer membranes operating at 100-130C with current density of at least 4000A/m2; (2) Create new long-life catalytic electrodes and MEAs working in the above temperature range; (3) Perform accelerated ageing tests and long-term single cell tests to understand degradation mechanisms, to make lifetime predictions and to give input to objectives 1 and 2; (4) Develop a prototype of a modular SPG&CHP system based on multi-PEMFCHs realized with the new long-life MEAs; (5) Benchmarking the single-cell and the modular prototype performance at temperatures above 100C against the best literature results. The project will benefit from the synergy arising from the know-how of leading research groups of universities and research institutes as well as from the technical knowledge and expertise of industries and utility companies involved in fuel cell development and testing.

Riello A.,Aix - Marseille University | Riello A.,University of Toulon
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

We calculate the most divergent contribution to the nondegenerate sector of the self-energy (or "melonic") graph in the context of the Lorentzian Engle-Pereira-Rovelli-Livine and Freidel-Krasnov spin foam model of quantum gravity. We find that such a contribution is logarithmically divergent in the cutoff over the SU(2) representation spins when one chooses the face amplitude guaranteeing the face-splitting invariance of the foam. We also find that the dependence on the boundary data is different from that of the bare propagator. This fact has its origin in the noncommutativity of the Engle-Pereira-Rovelli- Livine and Freidel-Krasnov Yγ map with the projector onto SL(2,C)-invariant states. In the course of the paper, we discuss in detail the approximations used during the calculations, their geometrical interpretation, and the physical consequences of our result. © 2013 American Physical Society.

Rovelli C.,Aix - Marseille University | Rovelli C.,University of Toulon
Classical and Quantum Gravity | Year: 2015

Disavowed by one of its fathers, ill-defined, never empirically tested, the Wheeler-DeWitt equation has nevertheless had a powerful influence on fundamental physics. A well-deserved one. © 2015 IOP Publishing Ltd.

Perez A.,Aix - Marseille University | Perez A.,University of Toulon
Classical and Quantum Gravity | Year: 2015

In an approach to quantum gravity where space-time arises from coarse graining of fundamentally discrete structures, black hole formation and subsequent evaporation can be described by a unitary evolution without the problems encountered by the standard remnant scenario or the schemes where information is assumed to come out with the radiation during evaporation (firewalls and complementarity). The final state is purified by correlations with the fundamental pre-geometric structures (in the sense of Wheeler), which are available in such approaches, and, like defects in the underlying space-time weave, can carry zero energy. © 2015 IOP Publishing Ltd.

Moutin T.,Aix - Marseille University | Van Wambeke F.,Aix - Marseille University | Prieur L.,University Pierre and Marie Curie
Biogeosciences | Year: 2012

The overall goal of the BOUM (Biogeochemistry from the Oligotrophic to the Ultraoligotrophic Mediterranean) experiment was to obtain a better representation of the interactions between planktonic organisms and the cycle of biogenic elements in the Mediterranean Sea (MS), in the context of global climate change and, more particularly, on the role of the ocean in carbon sequestration through biological processes. The BOUM experiment was organized around three main objectives: (1) to give a longitudinal description of the biogeochemistry and the biological diversity of the MS during the strongest stratified period, (2) to study processes at the centre of three anticyclonic eddies, and (3) to obtain a representation of the main biogeochemical fluxes and the dynamics of the planktonic trophic network. The international BOUM cruise took place between 16 June and 20 July 2008, involved 32 scientists on board, and covered around 3000 km in the MS from the south of Cyprus to Marseilles (France). This paper describes in detail the objectives of the BOUM experiment, the implementation plan of the cruise before giving an introduction of the 25 other papers published in this special issue. ©2012 Author(s).

Kravets V.G.,University of Manchester | Schedin F.,University of Manchester | Jalil R.,University of Manchester | Britnell L.,University of Manchester | And 7 more authors.
Nature Materials | Year: 2013

The non-trivial behaviour of phase is crucial for many important physical phenomena, such as, for example, the Aharonov-Bohm effect and the Berry phase. By manipulating the phase of light one can create 'twisted' photons, vortex knots and dislocations which has led to the emergence of the field of singular optics relying on abrupt phase changes. Here we demonstrate the feasibility of singular visible-light nano-optics which exploits the benefits of both plasmonic field enhancement and the peculiarities of the phase of light. We show that properly designed plasmonic metamaterials exhibit topologically protected zero reflection yielding to sharp phase changes nearby, which can be employed to radically improve the sensitivity of detectors based on plasmon resonances. By using reversible hydrogenation of graphene and binding of streptavidin-biotin, we demonstrate an areal mass sensitivity at a level of fg mm -2 and detection of individual biomolecules, respectively. Our proof-of-concept results offer a route towards simple and scalable single-molecule label-free biosensing technologies. © 2013 Macmillan Publishers Limited. All rights reserved.

Garron M.-L.,Aix - Marseille University | Garron M.-L.,French National Center for Scientific Research | Cygler M.,University of Saskatchewan
Current Opinion in Structural Biology | Year: 2014

In the past several years progress has been made in the field of structure and function of polysaccharide lyases (PLs). The number of classified polysaccharide lyase families has increased to 23 and more detailed analysis has allowed the identification of more closely related subfamilies, leading to stronger correlation between each subfamily and a unique substrate. The number of as yet unclassified polysaccharide lyases has also increased and we expect that sequencing projects will allow many of these unclassified sequences to emerge as new families. The progress in structural analysis of PLs has led to having at least one representative structure for each of the families and for two unclassified enzymes. The newly determined structures have folds observed previously in other PL families and their catalytic mechanisms follow either metal-assisted or Tyr/His mechanisms characteristic for other PL enzymes. Comparison of PLs with glycoside hydrolases (GHs) shows several folds common to both classes but only for the β-helix fold is there strong indication of divergent evolution from a common ancestor. Analysis of bacterial genomes identified gene clusters containing multiple polysaccharide cleaving enzymes, the Polysaccharides Utilization Loci (PULs), and their gene complement suggests that they are organized to process completely a specific polysaccharide. © 2014.

Faranda D.,French National Center for Scientific Research | Vaienti S.,Aix - Marseille University | Vaienti S.,University of Toulon
Geophysical Research Letters | Year: 2013

In this paper, we analyze several instrumental records of temperatures at different locations by using new techniques originally developed for the analysis of extreme values of dynamical systems. We show that they have the same recurrence time statistics as a chaotic dynamical system perturbed with dynamical noise and by instrument errors. The technique provides a criterion to discriminate whether the recurrence of a certain temperature belongs to the normal variability or can be considered as a genuine extreme event with respect to a specific timescale fixed as parameter. The method gives a self-consistent estimation of the convergence of the statistics of recurrences toward the theoretical extreme value laws. Key Points The method distinguishes between real extremes and natural climate variability The method presents a built-in test of convergence The method is easy to be implemented and fast ©2013. American Geophysical Union. All Rights Reserved.

Rovelli C.,Aix - Marseille University | Rovelli C.,University of Toulon
Foundations of Physics | Year: 2014

The world appears to be well described by gauge theories; why? I suggest that gauge is more than mathematical redundancy. Gauge-dependent quantities can not be predicted, but there is a sense in which they can be measured. They describe "handles" though which systems couple: they represent real relational structures to which the experimentalist has access in measurement by supplying one of the relata in the measurement procedure itself. This observation leads to a physical interpretation for the ubiquity of gauge: it is a consequence of a relational structure of physical quantities. © 2013 Springer Science+Business Media New York.

Barrau A.,CNRS Laboratory of Subatomic Physics & Cosmology | Rovelli C.,Aix - Marseille University | Rovelli C.,University of Toulon
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2014

It is possible that black holes hide a core of Planckian density, sustained by quantum-gravitational pressure. As a black hole evaporates, the core remembers the initial mass and the final explosion occurs at macroscopic scale. We investigate possible phenomenological consequences of this idea. Under several rough assumptions, we estimate that up to several short gamma-ray bursts per day, around 10 MeV, with isotropic distribution, can be expected coming from a region of a few hundred light years around us. © 2014 The Authors.

Dumur F.,Aix - Marseille University | Goubard F.,Cergy-Pontoise University
New Journal of Chemistry | Year: 2014

During the past decade, organic electronics has attracted a great deal of interest due to its applicability in a wide range of applications and high potential for commercial success. These applications notably range from organic light emitting diodes (OLEDs) to organic photovoltaics (OPVs) and sensors. Organic diodes undoubtedly have the potential to redefine many present day lighting solutions if performances and device stability are significantly improved. In these different applications, materials which combine in one molecule a balanced hole and electron transport are currently under intensive research as these materials can ensure an effective exciton recombination or dissociation within the active layer. Over the years, several basic structures have received the attention of researchers for the design of these appealing materials, namely triphenylamines (TPA) and oxadiazoles (OXD) that can respectively act as the hole-transporting and electron-transporting moieties in these ambipolar materials. This review aims at reporting the different OXD-TPA hybrids that have been synthesized to date and to develop a systematic understanding of the structure-property-performance relationships. This journal is © the Partner Organisations 2014.

Masoero E.,Massachusetts Institute of Technology | Del Gado E.,ETH Zurich | Pellenq R.J.-M.,Massachusetts Institute of Technology | Pellenq R.J.-M.,Aix - Marseille University | And 2 more authors.
Physical Review Letters | Year: 2012

Cement setting and cohesion are governed by the precipitation and growth of calcium-silicate-hydrate, through a complex evolution of microstructure. A colloidal model to describe nucleation, packing, and rigidity of calcium-silicate-hydrate aggregates is proposed. Polydispersity and particle size dependent cohesion strength combine to produce a spectrum of packing fractions and of corresponding elastic properties that can be tested against nanoindentation experiments. Implications regarding plastic deformations and reconciling current structural characterizations are discussed. © 2012 American Physical Society.

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.

Rovelli C.,Aix - Marseille University | Rovelli C.,University of Toulon | Vidotto F.,Radboud University Nijmegen
Physical Review Letters | Year: 2013

A simple argument indicates that covariant loop gravity (spin foam theory) predicts a maximal acceleration and hence forbids the development of curvature singularities. This supports the results obtained for cosmology and black holes using canonical methods. © 2013 American Physical Society.

Wilson-Ewing E.,Aix - Marseille University | Wilson-Ewing E.,University of Toulon
Journal of Cosmology and Astroparticle Physics | Year: 2013

In the matter bounce scenario, a dust-dominated contracting space-time generates scale-invariant perturbations that, assuming a nonsingular bouncing cosmology, propagate to the expanding branch and set appropriate initial conditions for the radiation-dominated era. Since this scenario depends on the presence of a bounce, it seems appropriate to consider it in the context of loop quantum cosmology where a bouncing universe naturally arises. For a pressureless collapsing universe in loop quantum cosmology, the predicted power spectrum of the scalar perturbations after the bounce is scale-invariant and the tensor to scalar ratio is negligibly small. A slight red tilt can be given to the scale-invariance of the scalar perturbations by a scalar field whose equation of state is P = -ρ, where is a small positive number. Then, the power spectrum for tensor perturbations is also almost scale-invariant with the same red tilt as the scalar perturbations, and the tensor to scalar ratio is expected to be r 9 × 10-4. Finally, for the predicted amplitude of the scalar perturbations to agree with observations, the critical density in loop quantum cosmology must be of the order ρc ∼ 10 -9ρPl. © 2013 IOP Publishing Ltd and Sissa Medialab srl.

Goubard F.,Cergy-Pontoise University | Dumur F.,Aix - Marseille University
RSC Advances | Year: 2015

Truxene (10,15-dihydro-5H-diindeno[1,2-a;1′,2′-c]fluorene), which is a heptacyclic polyarene structure, has attracted a great deal of interest due to its exceptional solubility, high thermal stability and ease with which it may be modified. Over the years and thanks to the advances in the synthesis of truxene derivatives, the scope of applications of this attractive building block, initially limited to synthesis and photoluminescence, has nowadays been extended to organic electronics. This review aims at highlighting the benefits brought by the introduction of this rigid star-shaped molecule in different materials. Perspectives for this highly appealing molecule in future research will also be put forth. © The Royal Society of Chemistry 2015.

Havaux M.,French Atomic Energy Commission | Havaux M.,French National Center for Scientific Research | Havaux M.,Aix - Marseille University
Plant Journal | Year: 2014

Carotenoids are known to play important roles in plants as antioxidants, accessory light-harvesting pigments, and attractants for pollinators and seed dispersers. A new function for carotenoids has recently emerged, which relates to the response of plants to environmental stresses. Reactive oxygen species, especially singlet oxygen, produced in the chloroplasts under stress conditions, can oxidize carotenoids leading to a variety of oxidized products, including aldehydes, ketones, endoperoxides and lactones. Some of those carotenoid derivatives, such as volatile β-cyclocitral, derived from the oxidation of β-carotene, are reactive electrophile species that are bioactive and can induce changes in gene expression leading to acclimation to stress conditions. This review summarizes the current knowledge on the non-enzymatic oxidation of carotenoids, the bioactivity of the resulting cleavage compounds and their functions as stress signals in plants. © 2013 The Author The Plant Journal © 2013 John Wiley & Sons Ltd.

Fraysse F.,French National Center for Scientific Research | Pokrovsky O.S.,French National Center for Scientific Research | Meunier J.-D.,Aix - Marseille University
Geochimica et Cosmochimica Acta | Year: 2010

Quantification of silicon and calcium recycling by plants is hampered by the lack of physico-chemical data on reactivity of plant litter in soil environments. We applied a laboratory experimental approach for determining the silica and calcium release rates from litter of typical temperate and boreal plants: pine (Pinus laricio), birch (Betula pubescens), larch (Larix gmelinii), elm (Ulmus laevis Pall.), tree fern (Dicksonia squarrosa), and horsetail (Equisetum arvense) in 0.01 M NaCl solutions, pH of 2-10 and temperature equals to 5, 25 and 40 °C. Open system, mixed-flow reactors equipped with dialysis compartment and batch reactors were used. Comparative measurements were performed on intact larch needles and samples grounded during different time, sterilized or not and with addition or not of sodium azide in order to account for the effect of surface to mass ratio and possible microbiological activity on the litter dissolution rates. Litter degradation results suggest that the silica release rate is independent on dissolved organic carbon release (cell breakdown) which implies the presence of phytoliths in a pure "inorganic" pool not complexed with organic matter. Calcium and DOC are released at the very first stage of litter dissolution while Si concentration increases gradually suggesting the presence of Ca and Si in two different pools. The dry-weight normalized dissolution rate at circum-neutral pH range (approx. 1-10 μmol/gDW/day) is 2 orders of magnitude higher than the rates of Si release from common soil minerals (kaolinite, smectite, illite). Minimal Ca release rates evaluated from batch and mixed-flow reactors are comparable with those of most reactive soil minerals such as calcite and apatite, and several orders of magnitude higher than the dissolution rates of major rock-forming silicates (feldspars, pyroxenes). The activation energy for Si liberation from plant litter is approx. 50 kJ/mol which is comparable with that of surface-controlled mineral dissolutions. It is shown that the Si release rate from the above-ground forest biomass is capable of producing the Si concentrations observed in soil solutions of surficial horizons and contribute significantly to the Si flux from the soil to the river. © 2009 Elsevier Ltd. All rights reserved.

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