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Ecole Normale Superieure de Lyon, University of Lyon and French National Center for Scientific Research | Date: 2014-04-29

The invention concerns a new class of tubulin polymerisation inhibitors and their applications in research and medicine, notably in chemotherapy. The invention proposes new azoaryl derivatives of formula (I): as defined in Claim 1, which may be fully reversibly interconverted between non-tubulin-binding trans and tubulin-binding as isomeric forms, either by irradiation or spontaneously. The invention also concerns compounds with a azoaryl structure for use in studying the cytoskeleton and/or its associated processes, or in the treatment of a disease for which a tubulin polymerisation inhibition activity has a beneficial effect, wherein the compound is administered to the cell, organism or patient in need of such treatment in the trans form of the diazenyl bond, and where this trans form is inactive as regards a tubulin polymerisation inhibition effect, and where after photoisomerisation in vitro, in cellulo or in vivo to an azoaryl compound in its cis isomeric form of the diazenyl bond by the application of light, optionally with modification in vitro, in cellulo or in vivo of one or more substituents, the resultant cis form is active as regards a tubulin polymerisation inhibition effect.

Polytechnic University of Turin, INSA Lyon, Doceram Medical Ceramics Gmbh, University of Lyon and French National Center for Scientific Research | Date: 2015-02-13

A process is described, for producing zirconia-based multi-phasic ceramic composite materials, comprising the steps of: providing at least one ceramic suspension by dispersing at least one ceramic zirconia powder in at least one aqueous medium to obtain at least one matrix for such composite material; providing at least one aqueous solution containing one or more inorganic precursors and adding such aqueous solution to such ceramic suspension to surface modify such ceramic zirconia powder and obtain at least one additived suspension; quickly drying such additived suspension to obtain at least one additived powder; heat treating such additived powder to obtain at least one zirconia powder coated on its surface by second phases; and forming such zirconia powder coated on its surface by second phases.

Agency: Cordis | 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: Cordis | Branch: H2020 | Program: CSA | Phase: ISSI-5-2014 | Award Amount: 3.99M | Year: 2015

NUCLEUS develops, supports and implements inclusive and sustainable approaches to Responsible Research and Innovation within the governance and culture of research organisations in Europe. A major goal of the transdisciplinary project will be to stimulate research and innovation which continuously reflects and responds to societal needs. In order to achieve a multifaceted and cross-cultural New Understanding of Communication, Learning and Engagement in Universities and Scientific Institutions, 26 renowned institutions from 15 countries, among them leading representatives of 14 universities, will collaboratively identify, develop, implement and support inclusive and sustainable approaches to RRI. For a mutual learning and exchange process, the project will reach out beyond the European Research Area by including renowned scientific institutions in China, Russia and South Africa. Within a 4-year timeframe NUCLEUS will systematically uncover and analyse structural and cultural obstacles to RRI in scientific institutions. The partners will collaboratively develop innovative approaches to overcome these barriers. The project is expected to lead to an applicable RRI DNA, providing practical guidelines for higher education institutions and funding agencies across Europe and beyond. This DNA will form the basis for the NUCLEUS Living Network, an alliance to ensure sustainability of the approach beyond the project timeline. By offering new academic insights and practical recommendations derived from 30 RRI test beds, NUCLEUS will contribute to the debate on science policies both on a national and European level, including the future design of HORIZON 2020 and the European Research Area (ERA).

Agency: Cordis | Branch: H2020 | Program: CSA | Phase: SEAC-2-2014 | Award Amount: 1.50M | Year: 2015

The Enhancing Responsible Research and Innovation through Curricula in Higher Education (EnRRICH) project will build the capacity of staff in higher education to facilitate their students development of knowledge, skills and attitudes and competencies in responsible research and innovation, and respond to the research needs of society, particularly underserved civil society organisations (CSOs). It will do this by identifying, developing, testing, and disseminating resources, based on existing good practice and trials of new initiatives, to embed the five RRI keys in academic curricula across Europe, with specific reference to science and engineering. It will develop case studies which showcase examples for students, teachers, professional trainers and academic staff of HEIs. Through ongoing dialogue with academics, policymakers, and CSOs, EnRRICH will kick start debates at institutional, national and international levels to create awareness of, and enhance the policy context for, RRI in curricula and thereby produce more responsible and responsive graduates and researchers. These objectives will be achieved building on the Public Engagement with Research and Research Engagement with Society (PERARES) and RRI Tools projects. It will involve new partners as well as a core of established partners drawn from HEIs and CSOs, including from RRI tools. It will establish an advisory board drawn from relevant organisations to ensure the widest possible engagement and dissemination. Work packages will deal with project management, state of the art of good practices in introducing RRI into curriculum development, exchange and trialling of good practices at national, international and transdisciplinary levels, policy development, evaluation, dissemination and a conference. Deliverables will include case studies and policy papers, and materials and resources for academic staff to involve students in experiential learning about RRI, including projects in partnership with CSOs

Bouchet F.,University of Lyon | Venaille A.,Princeton University
Physics Reports | Year: 2012

The theoretical study of the self-organization of two-dimensional and geophysical turbulent flows is addressed based on statistical mechanics methods. This review is a self-contained presentation of classical and recent works on this subject; from the statistical mechanics basis of the theory up to applications to Jupiter's troposphere and ocean vortices and jets. Emphasize has been placed on examples with available analytical treatment in order to favor better understanding of the physics and dynamics.After a brief presentation of the 2D Euler and quasi-geostrophic equations, the specificity of two-dimensional and geophysical turbulence is emphasized. The equilibrium microcanonical measure is built from the Liouville theorem. Important statistical mechanics concepts (large deviations and mean field approach) and thermodynamic concepts (ensemble inequivalence and negative heat capacity) are briefly explained and described.On this theoretical basis, we predict the output of the long time evolution of complex turbulent flows as statistical equilibria. This is applied to make quantitative models of two-dimensional turbulence, the Great Red Spot and other Jovian vortices, ocean jets like the Gulf-Stream, and ocean vortices. A detailed comparison between these statistical equilibria and real flow observations is provided.We also present recent results for non-equilibrium situations, for the studies of either the relaxation towards equilibrium or non-equilibrium steady states. In this last case, forces and dissipation are in a statistical balance; fluxes of conserved quantity characterize the system and microcanonical or other equilibrium measures no longer describe the system. © 2012 Elsevier B.V.

Bachelard-Cascales E.,University of Lyon
Stem cells (Dayton, Ohio) | Year: 2010

The major components of the mammary ductal tree are an inner layer of luminal cells, an outer layer of myoepithelial cells, and a basement membrane that separates the ducts from the underlying stroma. Cells in the outer layer express CD10, a zinc-dependent metalloprotease that regulates the growth of the ductal tree during mammary gland development. To define the steps in the human mammary lineage at which CD10 acts, we have developed an in vitro assay for human mammary lineage progression. We show that sorting for CD10 and EpCAM cleanly separates progenitors from differentiated luminal cells and that the CD10-high EpCAM-low population is enriched for early common progenitor and mammosphere-forming cells. We also show that sorting for CD10 enriches sphere-forming cells from other tissue types, suggesting that it may provide a simple tool to identify stem or progenitor populations in tissues for which lineage studies are not currently possible. We demonstrate that the protease activity of CD10 and the adhesion function of beta1-integrin are required to prevent differentiation of mammary progenitors. Taken together, our data suggest that integrin-mediated contact with the basement membrane and cleavage of signaling factors by CD10 are key elements in the niche that maintains the progenitor and stem cell pools in the mammary lineage.

Ricard-Blum S.,University of Lyon
Cold Spring Harbor perspectives in biology | Year: 2011

Collagens are the most abundant proteins in mammals. The collagen family comprises 28 members that contain at least one triple-helical domain. Collagens are deposited in the extracellular matrix where most of them form supramolecular assemblies. Four collagens are type II membrane proteins that also exist in a soluble form released from the cell surface by shedding. Collagens play structural roles and contribute to mechanical properties, organization, and shape of tissues. They interact with cells via several receptor families and regulate their proliferation, migration, and differentiation. Some collagens have a restricted tissue distribution and hence specific biological functions.

Pao W.,Vanderbilt Ingram Cancer Center | Girard N.,University of Lyon
The Lancet Oncology | Year: 2011

Treatment decisions for patients with lung cancer have historically been based on tumour histology. Some understanding of the molecular composition of tumours has led to the development of targeted agents, for which initial findings are promising. Clearer understanding of mutations in relevant genes and their effects on cancer cell proliferation and survival, is, therefore, of substantial interest. We review current knowledge about molecular subsets in non-small-cell lung cancer that have been identified as potentially having clinical relevance to targeted therapies. Since mutations in EGFR and KRAS have been extensively reviewed elsewhere, here, we discuss subsets defined by so-called driver mutations in ALK, HER2 (also known as ERBB2), BRAF, PIK3CA, AKT1, MAP2K1, and MET. The adoption of treatment tailored according to the genetic make-up of individual tumours would involve a paradigm shift, but might lead to substantial therapeutic improvements. © 2011 Elsevier Ltd.

Garnero P.,University of Lyon
Bone | Year: 2014

Over the last 15. years several biological markers of bone turnover have been developed with increased specificity and sensitivity. In osteoporosis clinical studies, the IOF and IFCC organizations have recently recommended the measurements of serum type I collagen N-propeptide (PINP) and the crosslinked C-terminal telopeptide (serum CTX) as markers of bone formation and bone resorption, respectively. However these markers have some limitations including a lack of specificity for bone tissue, their inability to reflect osteocyte activity or periosteal apposition. In addition they do not allow the investigation of bone tissue quality an important determinant of skeletal fragility. To address these limitations, new developments in markers of bone metabolism have been recently achieved. These include assays for periostin, a matricellular protein preferentially localized in the periosteal tissue, sphingosine 1-phosphate, a lipid mediator which acts mainly on osteoclastogenesis and the osteocyte factors such as sclerostin and FGF-23. Recent studies have shown an association between the circulating levels of these biological markers and fracture risk in postmenopausal women or elderly men, although data require confirmation in additional prospective studies. Finally, recent studies suggest that the measurements of circulating microRNAs may represent a novel class of early biological markers in osteoporosis. It is foreseen that with the use of genomics and proteomics, new markers will be developed to ultimately improve the management of patients with osteoporosis. © 2014 Elsevier Inc.

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