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Showing papers by "Centre national de la recherche scientifique published in 2007"


01 Jan 2007
TL;DR: In this paper, the main definitions relating to dependability, a generic concept including a special case of such attributes as reliability, availability, safety, integrity, maintainability, etc.
Abstract: This paper gives the main definitions relating to dependability, a generic concept including a special case of such attributes as reliability, availability, safety, integrity, maintainability, etc. Security brings in concerns for confidentiality, in addition to availability and integrity. Basic definitions are given first. They are then commented upon, and supplemented by additional definitions, which address the threats to dependability and security (faults, errors, failures), their attributes, and the means for their achievement (fault prevention, fault tolerance, fault removal, fault forecasting). The aim is to explicate a set of general concepts, of relevance across a wide range of situations and, therefore, helping communication and cooperation among a number of scientific and technical communities, including ones that are concentrating on particular types of system, of system failures, or of causes of system failures.

4,335 citations


Journal ArticleDOI
01 May 2007-Oikos
TL;DR: An unambiguous definition of plant trait is given, with a particular emphasis on functional trait, and it is argued that this can be achieved by developing "integration functions" which can be grouped into functional response (community level) and effect (ecosystem level) algorithms.
Abstract: In its simplest definition, a trait is a surrogate of organismal performance, and this meaning of the term has been used by evolutionists for a long time. Over the last three decades, developments in community and ecosystem ecology have forced the concept of trait beyond these original boundaries, and trait-based approaches are now widely used in studies ranging from the level of organisms to that of ecosystems. Despite some attempts to fix the terminology, especially in plant ecology, there is currently a high degree of confusion in the use, not only of the term "trait" itself, but also in the underlying concepts it refers to. We therefore give an unambiguous definition of plant trait, with a particular emphasis on functional trait. A hierarchical perspective is proposed, extending the "performance paradigm" to plant ecology. "Functional traits" are defined as morpho-physiophenological traits which impact fitness indirectly via their effects on growth, reproduction and survival, the three components of individual performance. We finally present an integrative framework explaining how changes in trait values due to environmental variations are translated into organismal performance, and how these changes may influence processes at higher organizational levels. We argue that this can be achieved by developing "integration functions" which can be grouped into functional response (community level) and effect (ecosystem level) algorithms.

3,262 citations


Journal ArticleDOI
TL;DR: The current knowledge of the molecular mechanisms underlying Drosophila defense reactions together with strategies evolved by pathogens to evade them are reviewed.
Abstract: To combat infection, the fruit fly Drosophila melanogaster relies on multiple innate defense reactions, many of which are shared with higher organisms. These reactions include the use of physical barriers together with local and systemic immune responses. First, epithelia, such as those beneath the cuticle, in the alimentary tract, and in tracheae, act both as a physical barrier and local defense against pathogens by producing antimicrobial peptides and reactive oxygen species. Second, specialized hemocytes participate in phagocytosis and encapsulation of foreign intruders in the hemolymph. Finally, the fat body, a functional equivalent of the mammalian liver, produces humoral response molecules including antimicrobial peptides. Here we review our current knowledge of the molecular mechanisms underlying Drosophila defense reactions together with strategies evolved by pathogens to evade them.

2,884 citations


Journal ArticleDOI
TL;DR: A previously unrecognized pathway for the activation of tumor antigen–specific T-cell immunity that involves secretion of the high-mobility-group box 1 (HMGB1) alarmin protein by dying tumor cells and the action of HMGB1 on Toll-like receptor 4 (TLR4) expressed by dendritic cells (DCs) is described.
Abstract: Conventional cancer treatments rely on radiotherapy and chemotherapy. Such treatments supposedly mediate their effects via the direct elimination of tumor cells. Here we show that the success of some protocols for anticancer therapy depends on innate and adaptive antitumor immune responses. We describe in both mice and humans a previously unrecognized pathway for the activation of tumor antigen-specific T-cell immunity that involves secretion of the high-mobility-group box 1 (HMGB1) alarmin protein by dying tumor cells and the action of HMGB1 on Toll-like receptor 4 (TLR4) expressed by dendritic cells (DCs). During chemotherapy or radiotherapy, DCs require signaling through TLR4 and its adaptor MyD88 for efficient processing and cross-presentation of antigen from dying tumor cells. Patients with breast cancer who carry a TLR4 loss-of-function allele relapse more quickly after radiotherapy and chemotherapy than those carrying the normal TLR4 allele. These results delineate a clinically relevant immunoadjuvant pathway triggered by tumor cell death.

2,666 citations


Journal ArticleDOI
Sabeeha S. Merchant1, Simon E. Prochnik2, Olivier Vallon3, Elizabeth H. Harris4, Steven J. Karpowicz1, George B. Witman5, Astrid Terry2, Asaf Salamov2, Lillian K. Fritz-Laylin6, Laurence Maréchal-Drouard7, Wallace F. Marshall8, Liang-Hu Qu9, David R. Nelson10, Anton A. Sanderfoot11, Martin H. Spalding12, Vladimir V. Kapitonov13, Qinghu Ren, Patrick J. Ferris14, Erika Lindquist2, Harris Shapiro2, Susan Lucas2, Jane Grimwood15, Jeremy Schmutz15, Pierre Cardol3, Pierre Cardol16, Heriberto Cerutti17, Guillaume Chanfreau1, Chun-Long Chen9, Valérie Cognat7, Martin T. Croft18, Rachel M. Dent6, Susan K. Dutcher19, Emilio Fernández20, Hideya Fukuzawa21, David González-Ballester22, Diego González-Halphen23, Armin Hallmann, Marc Hanikenne16, Michael Hippler24, William Inwood6, Kamel Jabbari25, Ming Kalanon26, Richard Kuras3, Paul A. Lefebvre11, Stéphane D. Lemaire27, Alexey V. Lobanov17, Martin Lohr28, Andrea L Manuell29, Iris Meier30, Laurens Mets31, Maria Mittag32, Telsa M. Mittelmeier33, James V. Moroney34, Jeffrey L. Moseley22, Carolyn A. Napoli33, Aurora M. Nedelcu35, Krishna K. Niyogi6, Sergey V. Novoselov17, Ian T. Paulsen, Greg Pazour5, Saul Purton36, Jean-Philippe Ral7, Diego Mauricio Riaño-Pachón37, Wayne R. Riekhof, Linda A. Rymarquis38, Michael Schroda, David B. Stern39, James G. Umen14, Robert D. Willows40, Nedra F. Wilson41, Sara L. Zimmer39, Jens Allmer42, Janneke Balk18, Katerina Bisova43, Chong-Jian Chen9, Marek Eliáš44, Karla C Gendler33, Charles R. Hauser45, Mary Rose Lamb46, Heidi K. Ledford6, Joanne C. Long1, Jun Minagawa47, M. Dudley Page1, Junmin Pan48, Wirulda Pootakham22, Sanja Roje49, Annkatrin Rose50, Eric Stahlberg30, Aimee M. Terauchi1, Pinfen Yang51, Steven G. Ball7, Chris Bowler25, Carol L. Dieckmann33, Vadim N. Gladyshev17, Pamela J. Green38, Richard A. Jorgensen33, Stephen P. Mayfield29, Bernd Mueller-Roeber37, Sathish Rajamani30, Richard T. Sayre30, Peter Brokstein2, Inna Dubchak2, David Goodstein2, Leila Hornick2, Y. Wayne Huang2, Jinal Jhaveri2, Yigong Luo2, Diego Martinez2, Wing Chi Abby Ngau2, Bobby Otillar2, Alexander Poliakov2, Aaron Porter2, Lukasz Szajkowski2, Gregory Werner2, Kemin Zhou2, Igor V. Grigoriev2, Daniel S. Rokhsar6, Daniel S. Rokhsar2, Arthur R. Grossman22 
University of California, Los Angeles1, United States Department of Energy2, University of Paris3, Duke University4, University of Massachusetts Medical School5, University of California, Berkeley6, Centre national de la recherche scientifique7, University of California, San Francisco8, Sun Yat-sen University9, University of Tennessee Health Science Center10, University of Minnesota11, Iowa State University12, Genetic Information Research Institute13, Salk Institute for Biological Studies14, Stanford University15, University of Liège16, University of Nebraska–Lincoln17, University of Cambridge18, Washington University in St. Louis19, University of Córdoba (Spain)20, Kyoto University21, Carnegie Institution for Science22, National Autonomous University of Mexico23, University of Münster24, École Normale Supérieure25, University of Melbourne26, University of Paris-Sud27, University of Mainz28, Scripps Research Institute29, Ohio State University30, University of Chicago31, University of Jena32, University of Arizona33, Louisiana State University34, University of New Brunswick35, University College London36, University of Potsdam37, Delaware Biotechnology Institute38, Boyce Thompson Institute for Plant Research39, Macquarie University40, Oklahoma State University Center for Health Sciences41, İzmir University of Economics42, Academy of Sciences of the Czech Republic43, Charles University in Prague44, St. Edward's University45, University of Puget Sound46, Hokkaido University47, Tsinghua University48, Washington State University49, Appalachian State University50, Marquette University51
12 Oct 2007-Science
TL;DR: Analyses of the Chlamydomonas genome advance the understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella.
Abstract: Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the approximately 120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella.

2,554 citations


Journal ArticleDOI
TL;DR: F(ST) estimation from corrected genotype frequencies performed well when restricted to visible allele sizes, and the use of the genetic distance of Cavalli-Sforza and Edwards (1967) corrected by the conventional method gave better estimates than those obtained without correction.
Abstract: Microsatellite null alleles are commonly encountered in population genetics studies, yet little is known about their impact on the estimation of population differentiation. Computer simulations based on the coalescent were used to investigate the evolutionary dynamics of null alleles, their impact on F(ST) and genetic distances, and the efficiency of estimators of null allele frequency. Further, we explored how the existing method for correcting genotype data for null alleles performed in estimating F(ST) and genetic distances, and we compared this method with a new method proposed here (for F(ST) only). Null alleles were likely to be encountered in populations with a large effective size, with an unusually high mutation rate in the flanking regions, and that have diverged from the population from which the cloned allele state was drawn and the primers designed. When populations were significantly differentiated, F(ST) and genetic distances were overestimated in the presence of null alleles. Frequency of null alleles was estimated precisely with the algorithm presented in Dempster et al. (1977). The conventional method for correcting genotype data for null alleles did not provide an accurate estimate of F(ST) and genetic distances. However, the use of the genetic distance of Cavalli-Sforza and Edwards (1967) corrected by the conventional method gave better estimates than those obtained without correction. F(ST) estimation from corrected genotype frequencies performed well when restricted to visible allele sizes. Both the proposed method and the traditional correction method have been implemented in a program that is available free of charge at http://www.montpellier.inra.fr/URLB/. We used 2 published microsatellite data sets based on original and redesigned pairs of primers to empirically confirm our simulation results.

2,470 citations


Journal ArticleDOI
TL;DR: The authors are starting to see a new paradigm where magnetization dynamics and charge currents act on each other in nanostructured artificial materials, allowing faster, low-energy operations: spin electronics is on its way.
Abstract: Electrons have a charge and a spin, but until recently these were considered separately. In classical electronics, charges are moved by electric fields to transmit information and are stored in a capacitor to save it. In magnetic recording, magnetic fields have been used to read or write the information stored on the magnetization, which 'measures' the local orientation of spins in ferromagnets. The picture started to change in 1988, when the discovery of giant magnetoresistance opened the way to efficient control of charge transport through magnetization. The recent expansion of hard-disk recording owes much to this development. We are starting to see a new paradigm where magnetization dynamics and charge currents act on each other in nanostructured artificial materials. Ultimately, 'spin currents' could even replace charge currents for the transfer and treatment of information, allowing faster, low-energy operations: spin electronics is on its way.

2,191 citations


Journal ArticleDOI
04 Jan 2007-Nature
TL;DR: The presence of tiny holes in an opaque metal film leads to a wide variety of unexpected optical properties such as strongly enhanced transmission of light through the holes and wavelength filtering, which are now known to be due to the interaction of the light with electronic resonances in the surface of the metal film.
Abstract: The presence of tiny holes in an opaque metal film, with sizes smaller than the wavelength of incident light, leads to a wide variety of unexpected optical properties such as strongly enhanced transmission of light through the holes and wavelength filtering. These intriguing effects are now known to be due to the interaction of the light with electronic resonances in the surface of the metal film, and they can be controlled by adjusting the size and geometry of the holes. This knowledge is opening up exciting new opportunities in applications ranging from subwavelength optics and optoelectronics to chemical sensing and biophysics.

2,009 citations



Journal ArticleDOI
TL;DR: Recent advances in several fields that have enabled scaling between species responses to recent climatic changes and shifts in ecosystem productivity are discussed, with implications for global carbon cycling.
Abstract: Plants are finely tuned to the seasonality of their environment, and shifts in the timing of plant activity (i.e. phenology) provide some of the most compelling evidence that species and ecosystems are being influenced by global environmental change. Researchers across disciplines have observed shifting phenology at multiple scales, including earlier spring flowering in individual plants and an earlier spring green-up' of the land surface revealed in satellite images. Experimental and modeling approaches have sought to identify the mechanisms causing these shifts, as well as to make predictions regarding the consequences. Here, we discuss recent advances in several fields that have enabled scaling between species responses to recent climatic changes and shifts in ecosystem productivity, with implications for global carbon cycling.

1,863 citations


Journal ArticleDOI
10 Aug 2007-Science
TL;DR: It is suggested that the interplay between obliquity and precession accounts for the variable intensity of interglacial periods in ice core records.
Abstract: A high-resolution deuterium profile is now available along the entire European Project for Ice Coring in Antarctica Dome C ice core, extending this climate record back to marine isotope stage 20.2, ∼800,000 years ago. Experiments performed with an atmospheric general circulation model including water isotopes support its temperature interpretation. We assessed the general correspondence between Dansgaard-Oeschger events and their smoothed Antarctic counterparts for this Dome C record, which reveals the presence of such features with similar amplitudes during previous glacial periods. We suggest that the interplay between obliquity and precession accounts for the variable intensity of interglacial periods in ice core records.

Journal ArticleDOI
TL;DR: A user friendly program for X-ray fluorescence analysis has been developed at the European Synchrotron Radiation Facility as mentioned in this paper, which allows interactive as well as batch processing of large data sets.

Journal ArticleDOI
TL;DR: Supramolecular chemistry considers chemical objects and systems capable of responding to external solicitations by modification of their constitution through component exchange or reorganisation, and opens the way towards an adaptive and evolutive chemistry, a further step towards the chemistry of complex matter.
Abstract: Supramolecular chemistry has developed over the last forty years as chemistry beyond the molecule. Starting with the investigation of the basis of molecular recognition, it has explored the implementation of molecular information in the programming of chemical systems towards self-organisation processes, that may occur either on the basis of design or with selection of their components. Supramolecular entities are by nature constitutionally dynamic by virtue of the lability of non-covalent interactions. Importing such features into molecular chemistry, through the introduction of reversible bonds into molecules, leads to the emergence of a constitutional dynamic chemistry, covering both the molecular and supramolecular levels. It considers chemical objects and systems capable of responding to external solicitations by modification of their constitution through component exchange or reorganisation. It thus opens the way towards an adaptive and evolutive chemistry, a further step towards the chemistry of complex matter.

Journal ArticleDOI
TL;DR: In this article, the authors present the physical bases underlying the definition of a sorption isotherm, different empirical or mechanistic models, and details several experimental methods to acquire a sink.

Journal ArticleDOI
23 Feb 2007-Cell
TL;DR: Polycomb group (PcG) and trithorax group (trxG) proteins are critical regulators of numerous developmental genes and recent work suggests that PcG-mediated gene silencing involves noncoding RNAs and the RNAi machinery.

Journal ArticleDOI
10 Aug 2007-Cell
TL;DR: The proteins required for viRNA production as well as several key downstream components of the antiviral immunity pathway have been identified in plants, flies, and worms, illuminating an ongoing molecular arms race that likely impacts the evolution of both viral and host genomes.

Journal ArticleDOI
Wolfgang Ackermann1, G. Asova, Valeri Ayvazyan2, A. Azima2  +154 moreInstitutions (16)
TL;DR: In this paper, the performance of a free-electron laser operating at a wavelength of 13.7 nm where unprecedented peak and average powers for a coherent extreme-ultraviolet radiation source have been measured.
Abstract: We report results on the performance of a free-electron laser operating at a wavelength of 13.7 nm where unprecedented peak and average powers for a coherent extreme-ultraviolet radiation source have been measured. In the saturation regime, the peak energy approached 170 J for individual pulses, and the average energy per pulse reached 70 J. The pulse duration was in the region of 10 fs, and peak powers of 10 GW were achieved. At a pulse repetition frequency of 700 pulses per second, the average extreme-ultraviolet power reached 20 mW. The output beam also contained a significant contribution from odd harmonics of approximately 0.6% and 0.03% for the 3rd (4.6 nm) and the 5th (2.75 nm) harmonics, respectively. At 2.75 nm the 5th harmonic of the radiation reaches deep into the water window, a wavelength range that is crucially important for the investigation of biological samples.

Journal ArticleDOI
15 Jun 2007-Cell
TL;DR: The data reveal that BBS may be caused by defects in vesicular transport to the cilium, and a complex composed of seven highly conserved BBS proteins is identified, the BBSome, which localizes to nonmembranous centriolar satellites in the cytoplasm but also to the membrane of the cILium.

Journal ArticleDOI
TL;DR: The large-pore iron(III) carboxylate MIL-100(Fe) with a zeotype architecture has been isolated under hydrothermal conditions, its structure solved from synchrotron X-ray powder diffraction data, while Friedel-Crafts benzylation catalytic tests indicate a high activity and selectivity for MIL- 100(Fe).

Journal ArticleDOI
TL;DR: In this paper, a set of coupled ocean-atmosphere simulations using state-of-the-art climate models is presented for the Last Glacial Maximum and the Mid-Holocene through the second phase of the Paleoclimate Modeling Intercomparison Project (PMIP2).
Abstract: . A set of coupled ocean-atmosphere simulations using state of the art climate models is now available for the Last Glacial Maximum and the Mid-Holocene through the second phase of the Paleoclimate Modeling Intercomparison Project (PMIP2). This study presents the large-scale features of the simulated climates and compares the new model results to those of the atmospheric models from the first phase of the PMIP, for which sea surface temperature was prescribed or computed using simple slab ocean formulations. We consider the large-scale features of the climate change, pointing out some of the major differences between the different sets of experiments. We show in particular that systematic differences between PMIP1 and PMIP2 simulations are due to the interactive ocean, such as the amplification of the African monsoon at the Mid-Holocene or the change in precipitation in mid-latitudes at the LGM. Also the PMIP2 simulations are in general in better agreement with data than PMIP1 simulations.

Journal ArticleDOI
TL;DR: A range of developmental phenomena can be explained by the regulation of cell surface tension, and the framework that emerges from diverse disciplines such as cell biology, physics and developmental biology points to adhesion and cortical actin networks as regulators ofcell surface mechanics.
Abstract: Many signalling pathways have been shown to control cell shape and cell surface mechanics. Recent insights from diverse disciplines point to adhesion and cortical tension as regulators of cell shape and provide insights into how cell shape controls tissue geometry. Embryonic morphogenesis requires the execution of complex mechanisms that regulate the local behaviour of groups of cells. The orchestration of such mechanisms has been mainly deciphered through the identification of conserved families of signalling pathways that spatially and temporally control cell behaviour. However, how this information is processed to control cell shape and cell dynamics is an open area of investigation. The framework that emerges from diverse disciplines such as cell biology, physics and developmental biology points to adhesion and cortical actin networks as regulators of cell surface mechanics. In this context, a range of developmental phenomena can be explained by the regulation of cell surface tension.

Journal ArticleDOI
TL;DR: A critical overview is provided on how understanding of the physiological and molecular controls of N assimilation under varying environmental conditions in crops has been improved through the use of combined approaches, mainly based on whole-plant physiology, quantitative genetics, and forward and reverse genetics approaches.
Abstract: In this review, recent developments and future prospects of obtaining a better understanding of the regulation of nitrogen use efficiency in the main crop species cultivated in the world are presented. In these crops, an increased knowledge of the regulatory mechanisms controlling plant nitrogen economy is vital for improving nitrogen use efficiency and for reducing excessive input of fertilizers, while maintaining an acceptable yield. Using plants grown under agronomic conditions at low and high nitrogen fertilization regimes, it is now possible to develop whole-plant physiological studies combined with gene, protein, and metabolite profiling to build up a comprehensive picture depicting the different steps of nitrogen uptake, assimilation, and recycling to the final deposition in the seed. A critical overview is provided on how understanding of the physiological and molecular controls of N assimilation under varying environmental conditions in crops has been improved through the use of combined approaches, mainly based on whole-plant physiology, quantitative genetics, and forward and reverse genetics approaches. Current knowledge and prospects for future agronomic development and application for breeding crops adapted to lower fertilizer input are explored, taking into account the world economic and environmental constraints in the next century.

Journal ArticleDOI
TL;DR: A seeded-growth approach is reported to the synthesis of asymmetric core-shell CdSe/CdS nanorods with regular shapes and narrow distributions of rod diameters and lengths, the latter being easily tunable up to 150 nm.
Abstract: Key limitations of the colloidal semiconductor nanorods that have been reported so far are a significant distribution of lengths and diameters as well as the presence of irregular shapes produced by the current synthetic routes and, finally, the poor ability to fabricate large areas of oriented nanorod arrays. Here, we report a seeded-growth approach to the synthesis of asymmetric core−shell CdSe/CdS nanorods with regular shapes and narrow distributions of rod diameters and lengths, the latter being easily tunable up to 150 nm. These rods are highly fluorescent and show linearly polarized emission, whereby the emission energy depends mainly on the core diameter. We demonstrate their lateral alignment as well as their vertical self-alignment on substrates up to areas of several square micrometers.

Journal ArticleDOI
TL;DR: A novel autophagy‐stimulatory function of BH3‐only proteins beyond their established role as apoptosis inducers is revealed and is revealed by competitively disrupting the interaction between Beclin‐1 and B cl‐2 or Bcl‐XL.
Abstract: The anti-apoptotic proteins Bcl-2 and Bcl-XL bind and inhibit Beclin-1, an essential mediator of autophagy. Here, we demonstrate that this interaction involves a BH3 domain within Beclin-1 (residues 114–123). The physical interaction between Beclin-1 and Bcl-XL is lost when the BH3 domain of Beclin-1 or the BH3 receptor domain of Bcl-XL is mutated. Mutation of the BH3 domain of Beclin-1 or of the BH3 receptor domain of Bcl-XL abolishes the Bcl-XL-mediated inhibition of autophagy triggered by Beclin-1. The pharmacological BH3 mimetic ABT737 competitively inhibits the interaction between Beclin-1 and Bcl-2/Bcl-XL, antagonizes autophagy inhibition by Bcl-2/Bcl-XL and hence stimulates autophagy. Knockout or knockdown of the BH3-only protein Bad reduces starvation-induced autophagy, whereas Bad overexpression induces autophagy in human cells. Gain-of-function mutation of the sole BH3-only protein from Caenorhabditis elegans, EGL-1, induces autophagy, while deletion of EGL-1 compromises starvation-induced autophagy. These results reveal a novel autophagy-stimulatory function of BH3-only proteins beyond their established role as apoptosis inducers. BH3-only proteins and pharmacological BH3 mimetics induce autophagy by competitively disrupting the interaction between Beclin-1 and Bcl-2 or Bcl-XL.

Journal ArticleDOI
TL;DR: The goal is to offer a molecular and clinical perspective that will enable IFNs or their TLR agonist inducers to reach their full clinical potential.
Abstract: The family of interferon (IFN) proteins has now more than reached the potential envisioned by early discovering virologists: IFNs are not only antivirals with a spectrum of clinical effectiveness against both RNA and DNA viruses, but are also the prototypic biological response modifiers for oncology, and show effectiveness in suppressing manifestations of multiple sclerosis. Studies of IFNs have resulted in fundamental insights into cellular signalling mechanisms, gene transcription and innate and acquired immunity. Further elucidation of the multitude of IFN-induced genes, as well as drug development strategies targeting IFN production via the activation of the Toll-like receptors (TLRs), will almost certainly lead to newer and more efficacious therapeutics. Our goal is to offer a molecular and clinical perspective that will enable IFNs or their TLR agonist inducers to reach their full clinical potential.

Journal ArticleDOI
14 Sep 2007-Science
TL;DR: Human TLR3 appears to be redundant in host defense to most microbes but is vital for natural immunity to HSV-1 in the CNS, which suggests that neurotropic viruses have contributed to the evolutionary maintenance ofTLR3.
Abstract: Some Toll and Toll-like receptors (TLRs) provide immunity to experimental infections in animal models, but their contribution to host defense in natural ecosystems is unknown. We report a dominant-negative TLR3 allele in otherwise healthy children with herpes simplex virus 1 (HSV-1) encephalitis. TLR3 is expressed in the central nervous system (CNS), where it is required to control HSV-1, which spreads from the epithelium to the CNS via cranial nerves. TLR3 is also expressed in epithelial and dendritic cells, which apparently use TLR3-independent pathways to prevent further dissemination of HSV-1 and to provide resistance to other pathogens in TLR3-deficient patients. Human TLR3 appears to be redundant in host defense to most microbes but is vital for natural immunity to HSV-1 in the CNS, which suggests that neurotropic viruses have contributed to the evolutionary maintenance of TLR3.

Journal ArticleDOI
TL;DR: Various types of functionalized carbon nanotubes (f-CNTs) exhibit a capacity to be taken up by a wide range of cells and can intracellularly traffic through different cellular barriers.
Abstract: The development of nanomaterials for biomedical and biotechnological applications is an area of research that holds great promise and intense interest1, and carbon-based nanostructures in particular, such as carbon nanotubes (CNTs), are attracting an increasing level of attention2,3. One of the key advantages that CNTs offer is the possibility of effectively crossing biological barriers, which would allow their use in the delivery of therapeutically active molecules. Our laboratories have been investigating the use of CNTs in biomedical applications, and in particular as nanovectors for therapeutic agent delivery4,5,6,7,8. The interaction between cells and CNTs is a critical issue that will determine any future biological application of such structures. Here we show that various types of functionalized carbon nanotubes (f-CNTs) exhibit a capacity to be taken up by a wide range of cells and can intracellularly traffic through different cellular barriers.

Journal ArticleDOI
TL;DR: The zCOSMOS-bright survey as discussed by the authors is a large-redshift survey that is being undertaken in the CosMOS field using 600 hr of observation with the VIMOS spectrograph on the 8 m VLT.
Abstract: zCOSMOS is a large-redshift survey that is being undertaken in the COSMOS field using 600 hr of observation with the VIMOS spectrograph on the 8 m VLT. The survey is designed to characterize the environments of COSMOS galaxies from the 100 kpc scales of galaxy groups up to the 100 Mpc scale of the cosmic web and to produce diagnostic information on galaxies and active galactic nuclei. The zCOSMOS survey consists of two parts: (1) zCOSMOSbright, a magnitude-limited I-band I_(AB) < 22.5 sample of about 20,000 galaxies with 0.1 < z < 1.2 covering the whole 1.7 deg^2 COSMOS ACS field, for which the survey parameters at z ~ 0.7 are designed to be directly comparable to those of the 2dFGRS at z ~ 0.1; and (2) zCOSMOS-deep, a survey of approximately 10,000 galaxies selected through color-selection criteria to have 1.4 < z < 3.0, within the central 1 deg^2. This paper describes the survey design and the construction of the target catalogs and briefly outlines the observational program and the data pipeline. In the first observing season, spectra of 1303 zCOSMOS-bright targets and 977 zCOSMOS-deep targets have been obtained. These are briefly analyzed to demonstrate the characteristics that may be expected from zCOSMOS, and particularly zCOSMOS-bright, when it is finally completed between 2008 and 2009. The power of combining spectroscopic and photometric redshifts is demonstrated, especially in correctly identifying the emission line in single-line spectra and in determining which of the less reliable spectroscopic redshifts are correct and which are incorrect. These techniques bring the overall success rate in the zCOSMOS-bright so far to almost 90% and to above 97% in the 0.5 < z < 0.8 redshift range. Our zCOSMOS-deep spectra demonstrate the power of our selection techniques to isolate high-redshift galaxies at 1.4 < z < 3.0 and of VIMOS to measure their redshifts using ultraviolet absorption lines.

Journal ArticleDOI
TL;DR: Within a range of stiffness spanning that of soft tissues, fibroblasts tune their internal stiffness to match that of their substrate, and modulation of cellular stiffness by the rigidity of the environment may be a mechanism used to direct cell migration and wound repair.

Journal ArticleDOI
TL;DR: In this article, the authors explain the significance of a political sociology approach to public policy instruments in accounting for processes of public policy change, since it reveals a (fairly explicit) theorization of the relationship between the governing and the governed.
Abstract: Public policy instrumentation and its choice of tools and modes of operation are treated either as a kind of evidence (governing means making regulations, taxing, entering into contracts, communicating, etc.) or as if the questions it raises (the properties of instruments, justifications for choosing them, their applicability, etc.) are part of a rationality of methods without any autonomous meaning. This paper aims to explain the significance of a political sociology approach to public policy instruments in accounting for processes of public policy change: (1) public policy instrumentation is a major issue in public policy, since it reveals a (fairly explicit) theorization of the relationship between the governing and the governed: every instrument constitutes a condensed form of knowledge about social control and ways of exercising it; and (2) instruments at work are not neutral devices: they produce specific effects, independently of the objective pursued (the aims ascribed to them), which structure public policy according to their own logic.