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Showing papers by "Pierre-and-Marie-Curie University published in 2006"


Journal ArticleDOI
29 Sep 2006-Science
TL;DR: In situ analysis of tumor-infiltrating immune cells may be a valuable prognostic tool in the treatment of colorectal cancer and possibly other malignancies.
Abstract: The role of the adaptive immune response in controlling the growth and recurrence of human tumors has been controversial. We characterized the tumor-infiltrating immune cells in large cohorts of human colorectal cancers by gene expression profiling and in situ immunohistochemical staining. Collectively, the immunological data (the type, density, and location of immune cells within the tumor samples) were found to be a better predictor of patient survival than the histopathological methods currently used to stage colorectal cancer. The results were validated in two additional patient populations. These data support the hypothesis that the adaptive immune response influences the behavior of human tumors. In situ analysis of tumor-infiltrating immune cells may therefore be a valuable prognostic tool in the treatment of colorectal cancer and possibly other malignancies.

5,536 citations


Journal ArticleDOI
TL;DR: In this article, the authors compared the effect of clopidogrel and low-dose aspirin on the rate of myocardial infarction, stroke, or death from cardiovascular causes.
Abstract: Background Dual antiplatelet therapy with clopidogrel plus low-dose aspirin has not been studied in a broad population of patients at high risk for atherothrombotic events. Methods We randomly assigned 15,603 patients with either clinically evident cardiovascular disease or multiple risk factors to receive clopidogrel (75 mg per day) plus low-dose aspirin (75 to 162 mg per day) or placebo plus low-dose aspirin and followed them for a median of 28 months. The primary efficacy end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes. Results The rate of the primary efficacy end point was 6.8 percent with clopidogrel plus aspirin and 7.3 percent with placebo plus aspirin (relative risk, 0.93; 95 percent confidence interval, 0.83 to 1.05; P = 0.22). The respective rate of the principal secondary efficacy end point, which included hospitalizations for ischemic events, was 16.7 percent and 17.9 percent (relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.995; P = 0.04), and the rate of severe bleeding was 1.7 percent and 1.3 percent (relative risk, 1.25; 95 percent confidence interval, 0.97 to 1.61 percent; P = 0.09). The rate of the primary end point among patients with multiple risk factors was 6.6 percent with clopidogrel and 5.5 percent with placebo (relative risk, 1.2; 95 percent confidence interval, 0.91 to 1.59; P = 0.20) and the rate of death from cardiovascular causes also was higher with clopidogrel (3.9 percent vs. 2.2 percent, P = 0.01). In the subgroup with clinically evident atherothrombosis, the rate was 6.9 percent with clopidogrel and 7.9 percent with placebo (relative risk, 0.88; 95 percent confidence interval, 0.77 to 0.998; P = 0.046). Conclusions In this trial, there was a suggestion of benefit with clopidogrel treatment in patients with symptomatic atherothrombosis and a suggestion of harm in patients with multiple risk factors. Overall, clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infarction, stroke, or death from cardiovascular causes. (ClinicalTrials.gov number, NCT00050817.)

2,464 citations


Journal Article
TL;DR: It can be considered that obesity corresponds to a sub-clinical inflammatory condition that promotes the production of pro-inflammatory factors involved in the pathogenesis of insulin resistance, including leptin, TNF-alpha, IL-6 and resistin.
Abstract: It now appears that, in most obese patients, obesity is associated with a low-grade inflammation of white adipose tissue (WAT) resulting from chronic activation of the innate immune system and which can subsequently lead to insulin resistance, impaired glucose tolerance and even diabetes. WAT is the physiological site of energy storage as lipids. In addition, it has been more recently recognized as an active participant in numerous physiological and pathophysiological processes. In obesity, WAT is characterized by an increased production and secretion of a wide range of inflammatory molecules including TNF-alpha and interleukin-6 (IL-6), which may have local effects on WAT physiology but also systemic effects on other organs. Recent data indicate that obese WAT is infiltrated by macrophages, which may be a major source of locally-produced pro-inflammatory cytokines. Interestingly, weight loss is associated with a reduction in the macrophage infiltration of WAT and an improvement of the inflammatory profile of gene expression. Several factors derived not only from adipocytes but also from infiltrated macrophages probably contribute to the pathogenesis of insulin resistance. Most of them are overproduced during obesity, including leptin, TNF-alpha, IL-6 and resistin. Conversely, expression and plasma levels of adiponectin, an insulin-sensitising effector, are down-regulated during obesity. Leptin could modulate TNF-alpha production and macrophage activation. TNF-alpha is overproduced in adipose tissue of several rodent models of obesity and has an important role in the pathogenesis of insulin resistance in these species. However, its actual involvement in glucose metabolism disorders in humans remains controversial. IL-6 production by human adipose tissue increases during obesity. It may induce hepatic CRP synthesis and may promote the onset of cardiovascular complications. Both TNF-alpha and IL-6 can alter insulin sensitivity by triggering different key steps in the insulin signalling pathway. In rodents, resistin can induce insulin resistance, while its implication in the control of insulin sensitivity is still a matter of debate in humans. Adiponectin is highly expressed in WAT, and circulating adiponectin levels are decreased in subjects with obesity-related insulin resistance, type 2 diabetes and coronary heart disease. Adiponectin inhibits liver neoglucogenesis and promotes fatty acid oxidation in skeletal muscle. In addition, adiponectin counteracts the pro-inflammatory effects of TNF-alpha on the arterial wall and probably protects against the development of arteriosclerosis. In obesity, the pro-inflammatory effects of cytokines through intracellular signalling pathways involve the NF-kappaB and JNK systems. Genetic or pharmacological manipulations of these effectors of the inflammatory response have been shown to modulate insulin sensitivity in different animal models. In humans, it has been suggested that the improved glucose tolerance observed in the presence of thiazolidinediones or statins is likely related to their anti-inflammatory properties. Thus, it can be considered that obesity corresponds to a sub-clinical inflammatory condition that promotes the production of pro-inflammatory factors involved in the pathogenesis of insulin resistance.

2,034 citations


Journal ArticleDOI
TL;DR: A retrospective analysis is necessary for the understanding of fibrin technologies and the evaluation of the biochemical properties of 3 generations of surgical additives, respectively fibr in adhesives, concentrated platelet-rich plasma (cPRP) and PRF.
Abstract: Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates geared to simplified preparation without biochemical blood handling. In this initial article, we describe the conceptual and technical evolution from fibrin glues to platelet concentrates. This retrospective analysis is necessary for the understanding of fibrin technologies and the evaluation of the biochemical properties of 3 generations of surgical additives, respectively fibrin adhesives, concentrated platelet-rich plasma (cPRP) and PRF. Indeed, the 3-dimensional fibrin architecture is deeply dependent on artificial clinical polymerization processes, such as massive bovine thrombin addition. Currently, the slow polymerization during PRF preparation seems to generate a fibrin network very similar to the natural one. Such a network leads to a more efficient cell migration and proliferation and thus cicatrization.

1,295 citations


Journal ArticleDOI
10 Nov 2006-Science
TL;DR: The sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus is reported, a model for developmental and systems biology and yields insights into the evolution of deuterostomes.
Abstract: We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.

1,059 citations


Journal ArticleDOI
TL;DR: Initial analyses revealed that slow fibrin polymerization during PRF processing leads to the intrinsic incorporation of platelet cytokines and glycanic chains in the fibrIn meshes, which would imply that PRF, unlike the other platelet concentrates, would be able to progressively release cytokines during fibr in matrix remodeling; such a mechanism might explain the clinically observed healing properties of PRF.
Abstract: Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. In this second article, we investigate the platelet-associated features of this biomaterial. During PRF processing by centrifugation, platelets are activated and their massive degranulation implies a very significant cytokine release. Concentrated platelet-rich plasma platelet cytokines have already been quantified in many technologic configurations. To carry out a comparative study, we therefore undertook to quantify PDGF-BB, TGFβ-1, and IGF-I within PPP (platelet-poor plasma) supernatant and PRF clot exudate serum. These initial analyses revealed that slow fibrin polymerization during PRF processing leads to the intrinsic incorporation of platelet cytokines and glycanic chains in the fibrin meshes. This result would imply that PRF, unlike the other platelet concentrates, would be able to progressively release cytokines during fibrin matrix remodeling; such a mechanism might explain the clinically observed healing properties of PRF.

898 citations


Journal ArticleDOI
TL;DR: Investigation is made into the previously evaluated biology of PRF with the first established clinical results, to determine the potential fields of application for this biomaterial and to plan several future PRF applications, including plastic and bone surgery.
Abstract: Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. In this fourth article, investigation is made into the previously evaluated biology of PRF with the first established clinical results, to determine the potential fields of application for this biomaterial. The reasoning is structured around 4 fundamental events of cicatrization, namely, angiogenesis, immune control, circulating stem cells trapping, and wound-covering epithelialization. All of the known clinical applications of PRF highlight an accelerated tissue cicatrization due to the development of effective neovascularization, accelerated wound closing with fast cicatricial tissue remodelling, and nearly total absence of infectious events. This initial research therefore makes it possible to plan several future PRF applications, including plastic and bone surgery, provided that the real effects are evaluated both impartially and rigorously.

897 citations


Journal ArticleDOI
02 Nov 2006-Nature
TL;DR: An experiment where a micromechanical resonator is used as a mirror in a very high-finesse optical cavity, and its displacements are monitored with unprecedented sensitivity, and a radiation-pressure-induced instability of the resonators is observed.
Abstract: Cooling of mechanical resonators is the focus of much research effort because of possible applications in ultra-high precision measurements such as gravitational wave detection. It is also of fundamental interest as using this technique it may be possible to observe a transition between classical and quantum behaviour of a mechanical system. Three groups report advances in this area. Gigan et al. and Arcizet et al. used radiation pressure to freeze out thermal vibrations of tiny mechanical microresonators, or micromirrors. In the right conditions, the mirrors cool from room temperature to about 10 K without outside influence. Once the technique is refined it should be possible to achieve further cooling and to observe the quantum ground state of a micromirror experimentally. In the third paper, Dustin Kleckner and Dirk Bouwmeester use optical feedback to cool a micromirror to sub-kelvin temperatures. A micromechanical resonator is used as a mirror in a very high-finesse optical cavity, and its displacements are monitored with unprecedented sensitivity. By detuning the laser frequency with respect to the cavity resonance, a drastic cooling of the microresonator by intracavity radiation pressure is observed, down to an effective temperature of 10 kelvin. Recent table-top optical interferometry experiments1,2 and advances in gravitational-wave detectors3 have demonstrated the capability of optical interferometry to detect displacements with high sensitivity. Operation at higher powers will be crucial for further sensitivity enhancement, but dynamical effects caused by radiation pressure on the interferometer mirrors must be taken into account, and the appearance of optomechanical instabilities may jeopardize the stable operation of the next generation of interferometers4,5,6. These instabilities7,8 are the result of a nonlinear coupling between the motion of the mirrors and the optical field, which modifies the effective dynamics of the mirror. Such ‘optical spring’ effects have already been demonstrated for the mechanical damping of an electromagnetic waveguide with a moving wall9, the resonance frequency of a specially designed flexure oscillator10, and the optomechanical instability of a silica microtoroidal resonator11. Here we present an experiment where a micromechanical resonator is used as a mirror in a very high-finesse optical cavity, and its displacements are monitored with unprecedented sensitivity. By detuning the laser frequency with respect to the cavity resonance, we have observed a drastic cooling of the microresonator by intracavity radiation pressure, down to an effective temperature of 10 kelvin. For opposite detuning, efficient heating is observed, as well as a radiation-pressure-induced instability of the resonator. Further experimental progress and cryogenic operation may lead to the experimental observation of the quantum ground state of a micromechanical resonator12,13,14, either by passive15 or active cooling techniques16,17,18.

890 citations


Journal ArticleDOI
TL;DR: The LMDZ4 general circulation model is the atmospheric component of the IPSL-CM4 coupled model which has been used to perform climate change simulations for the 4th IPCC assessment report.
Abstract: The LMDZ4 general circulation model is the atmospheric component of the IPSL–CM4 coupled model which has been used to perform climate change simulations for the 4th IPCC assessment report. The main aspects of the model climatology (forced by observed sea surface temperature) are documented here, as well as the major improvements with respect to the previous versions, which mainly come form the parametrization of tropical convection. A methodology is proposed to help analyse the sensitivity of the tropical Hadley–Walker circulation to the parametrization of cumulus convection and clouds. The tropical circulation is characterized using scalar potentials associated with the horizontal wind and horizontal transport of geopotential (the Laplacian of which is proportional to the total vertical momentum in the atmospheric column). The effect of parametrized physics is analysed in a regime sorted framework using the vertical velocity at 500 hPa as a proxy for large scale vertical motion. Compared to Tiedtke’s convection scheme, used in previous versions, the Emanuel’s scheme improves the representation of the Hadley–Walker circulation, with a relatively stronger and deeper large scale vertical ascent over tropical continents, and suppresses the marked patterns of concentrated rainfall over oceans. Thanks to the regime sorted analyses, these differences are attributed to intrinsic differences in the vertical distribution of convective heating, and to the lack of self-inhibition by precipitating downdraughts in Tiedtke’s parametrization. Both the convection and cloud schemes are shown to control the relative importance of large scale convection over land and ocean, an important point for the behaviour of the coupled model.

831 citations


Journal ArticleDOI
TL;DR: At diagnosis of Crohn's disease in a referral center, factors predictive of subsequent 5-year disabling course are an age below 40 years, the presence of perianal disease, and the initial requirement for steroids.

771 citations


Journal ArticleDOI
TL;DR: In this article, the potential of using the near-surface chlorophyll a concentration (Chla) as it can be derived from ocean color observation, to infer the column-integrated phytoplankton biomass, its vertical distribution, and ultimately the community composition.
Abstract: [1] The present study examines the potential of using the near-surface chlorophyll a concentration ([Chla]surf), as it can be derived from ocean color observation, to infer the column-integrated phytoplankton biomass, its vertical distribution, and ultimately the community composition. Within this context, a large High-Performance Liquid Chromatography (HPLC) pigment database was analyzed. It includes 2419 vertical pigment profiles, sampled in case 1 waters with various trophic states (0.03–6 mg Chla m � 3 ). The relationships between [Chla]surf and the chlorophyll a vertical distribution, as previously derived by Morel and Berthon (1989), are fully confirmed. This agreement makes it possible to go further and to examine if similar relationships between [Chla]surf and the phytoplankton assemblage composition along the vertical can be derived. Thanks to the detailed pigment composition, and use of specific pigment biomarkers, the contribution to the local chlorophyll a concentration of three phytoplankton groups can be assessed. With some cautions, these groups coincide with three size classes, i.e., microplankton, nanoplankton and picoplankton. Corroborating previous regional findings (e.g., large species dominate in eutrophic environments, whereas tiny phytoplankton prevail in oligotrophic zones), the present results lead to an empirical parameterization applicable to most oceanic waters. The predictive skill of this parameterization is satisfactorily tested on a separate data set. With such a tool, the vertical chlorophyll a profiles of each group can be inferred solely from the knowledge of [Chla]surf. By combining this tool with satellite ocean color data, it becomes possible to quantify on a global scale the phytoplankton biomass associated with each of the three algal assemblages.

Journal ArticleDOI
01 Dec 2006-Brain
TL;DR: A hybrid model of the anatomical and functional organization of the lateral SFG for WM is supported, according to which this region is involved in higher levels of WM processing but remains oriented towards spatial cognition, although the domain specificity is not exclusive and is overridden by an increase in executive demand, regardless of the domain being processed.
Abstract: The superior frontal gyrus (SFG) is thought to contribute to higher cognitive functions and particularly to working memory (WM), although the nature of its involvement remains a matter of debate. To resolve this issue, methodological tools such as lesion studies are needed to complement the functional imaging approach. We have conducted the first lesion study to investigate the role of the SFG in WM and address the following questions: do lesions of the SFG impair WM and, if so, what is the nature of the WM impairment? To answer these questions, we compared the performance of eight patients with a left prefrontal lesion restricted to the SFG with that of a group of 11 healthy control subjects and two groups of patients with focal brain lesions [prefrontal lesions sparing the SFG (n = 5) and right parietal lesions (n = 4)] in a series of WM tasks. The WM tasks (derived from the classical n-back paradigm) allowed us to study the impact of the SFG lesions on domain (verbal, spatial, face) and complexity (1-, 2- and 3-back) processing within WM. As expected, patients with a left SFG lesion exhibited a WM deficit when compared with all control groups, and the impairment increased with the complexity of the tasks. This complexity effect was significantly more marked for the spatial domain. Voxel-to-voxel mapping of each subject's performance showed that the lateral and posterior portion of the SFG (mostly Brodmann area 8, rostral to the frontal eye field) was the subregion that contributed the most to the WM impairment. These data led us to conclude that (i) the lateral and posterior portion of the left SFG is a key component of the neural network of WM; (ii) the participation of this region in WM is triggered by the highest level of executive processing; (iii) the left SFG is also involved in spatially oriented processing. Our findings support a hybrid model of the anatomical and functional organization of the lateral SFG for WM, according to which this region is involved in higher levels of WM processing (monitoring and manipulation) but remains oriented towards spatial cognition, although the domain specificity is not exclusive and is overridden by an increase in executive demand, regardless of the domain being processed. From a clinical perspective, this study provides new information on the impact of left SFG lesions on cognition that will be of use to neurologists and neurosurgeons.

Journal ArticleDOI
TL;DR: Initial analyses revealed that PRF could be an immune regulation node with inflammation retrocontrol abilities, which could explain the reduction of postoperative infections when PRF is used as surgical additive.
Abstract: Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. In this third article, we investigate the immune features of this biomaterial. During PRF processing, leucocytes could also secrete cytokines in reaction to the hemostatic and inflammatory phenomena artificially induced in the centrifuged tube. We therefore undertook to quantify 5 significant cell mediators within platelet poor plasma supernatant and PRF clot exudate serum: 3 proinflammatory cytokines (IL-1β, IL-6, and TNF-α), an antiinflammatory cytokine (IL-4), and a key growth promoter of angiogenesis (VEGF). Our data are correlated with that obtained in plasma (nonactivated blood) and in sera (activated blood). These initial analyses revealed that PRF could be an immune regulation node with inflammation retrocontrol abilities. This concept could explain the reduction of postoperative infections when PRF is used as surgical additive.

Journal ArticleDOI
28 Apr 2006
TL;DR: This editorial proposes a technique that relies on the observation of the first five packets of a TCP connection to identify the application and opens a range of new possibilities for online traffic classification.
Abstract: The early detection of applications associated with TCP flows is an essential step for network security and traffic engineering. The classic way to identify flows, i.e. looking at port numbers, is not effective anymore. On the other hand, state-of-the-art techniques cannot determine the application before the end of the TCP flow. In this editorial, we propose a technique that relies on the observation of the first five packets of a TCP connection to identify the application. This result opens a range of new possibilities for online traffic classification.

Journal ArticleDOI
TL;DR: Sinus floor augmentation with FDBA and PRF leads to a reduction of healing time prior to implant placement, and histologic maturation of the test group appears to be identical to that of the control group after a period of 8 months.
Abstract: Objective Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. The use of platelet gel to improve bone regeneration is a recent technique in implantology. However, the biologic properties and real effects of such products remain controversial. In this article, we therefore attempt to evaluate the potential of PRF in combination with freeze-dried bone allograft (FDBA) (Phœnix; TBF, France) to enhance bone regeneration in sinus floor elevation. Study design Nine sinus floor augmentations were performed. In 6 sites, PRF was added to FDBA particles (test group), and in 3 sites FDBA without PRF was used (control group). Four months later for the test group and 8 months later for the control group, bone specimens were harvested from the augmented region during the implant insertion procedure. These specimens were treated for histologic analysis. Results Histologic evaluations reveal the presence of residual bone surrounded by newly formed bone and connective tissue. After 4 months of healing time, histologic maturation of the test group appears to be identical to that of the control group after a period of 8 months. Moreover, the quantities of newly formed bone were equivalent between the 2 protocols. Conclusions Sinus floor augmentation with FDBA and PRF leads to a reduction of healing time prior to implant placement. From a histologic point of view, this healing time could be reduced to 4 months, but large-scale studies are still necessary to validate these first results.

Journal ArticleDOI
Pietro Cortese, G. Dellacasa, Luciano Ramello, M. Sitta  +975 moreInstitutions (78)
TL;DR: The ALICE Collaboration as mentioned in this paper is a general-purpose heavy-ion experiment designed to study the physics of strongly interacting matter and the quark-gluon plasma in nucleus-nucleus collisions at the LHC.
Abstract: ALICE is a general-purpose heavy-ion experiment designed to study the physics of strongly interacting matter and the quark–gluon plasma in nucleus–nucleus collisions at the LHC. It currently involves more than 900 physicists and senior engineers, from both the nuclear and high-energy physics sectors, from over 90 institutions in about 30 countries.The ALICE detector is designed to cope with the highest particle multiplicities above those anticipated for Pb–Pb collisions (dNch/dy up to 8000) and it will be operational at the start-up of the LHC. In addition to heavy systems, the ALICE Collaboration will study collisions of lower-mass ions, which are a means of varying the energy density, and protons (both pp and pA), which primarily provide reference data for the nucleus–nucleus collisions. In addition, the pp data will allow for a number of genuine pp physics studies.The detailed design of the different detector systems has been laid down in a number of Technical Design Reports issued between mid-1998 and the end of 2004. The experiment is currently under construction and will be ready for data taking with both proton and heavy-ion beams at the start-up of the LHC.Since the comprehensive information on detector and physics performance was last published in the ALICE Technical Proposal in 1996, the detector, as well as simulation, reconstruction and analysis software have undergone significant development. The Physics Performance Report (PPR) provides an updated and comprehensive summary of the performance of the various ALICE subsystems, including updates to the Technical Design Reports, as appropriate.The PPR is divided into two volumes. Volume I, published in 2004 (CERN/LHCC 2003-049, ALICE Collaboration 2004 J. Phys. G: Nucl. Part. Phys. 30 1517–1763), contains in four chapters a short theoretical overview and an extensive reference list concerning the physics topics of interest to ALICE, the experimental conditions at the LHC, a short summary and update of the subsystem designs, and a description of the offline framework and Monte Carlo event generators.The present volume, Volume II, contains the majority of the information relevant to the physics performance in proton–proton, proton–nucleus, and nucleus–nucleus collisions. Following an introductory overview, Chapter 5 describes the combined detector performance and the event reconstruction procedures, based on detailed simulations of the individual subsystems. Chapter 6 describes the analysis and physics reach for a representative sample of physics observables, from global event characteristics to hard processes.

Journal ArticleDOI
21 Sep 2006-Nature
TL;DR: It is shown that the high-redshift supernova SNLS-03D3bb has an exceptionally high luminosity and low kinetic energy that both imply a super-Chandrasekhar-mass progenitor, which may provide an explanation for the observed trend that overluminous type Ia supernovae occur only in ‘young’ environments.
Abstract: The acceleration of the expansion of the universe, and theneed for Dark Energy, were inferred from the observations of Type Iasupernovae (SNe Ia) 1;2. There is consensus that SNeIa are thermonuclearexplosions that destroy carbon-oxygen white dwarf stars that accretematter from a companion star3, although the nature of this companionremains uncertain. SNe Ia are thought to be reliable distance indicatorsbecause they have a standard amount of fuel and a uniform trigger theyare predicted to explode when the mass of the white dwarf nears theChandrasekhar mass 4 - 1.4 solar masses. Here we show that the highredshift supernova SNLS-03D3bb has an exceptionally high luminosity andlow kinetic energy that both imply a super-Chandrasekhar mass progenitor.Super-Chandrasekhar mass SNeIa shouldpreferentially occur in a youngstellar population, so this may provide an explanation for the observedtrend that overluminous SNe Ia only occur in young environments5;6. Sincethis supernova does not obey the relations that allow them to becalibrated as standard candles, and since no counterparts have been foundat low redshift, future cosmology studies will have to considercontamination from such events.

Journal ArticleDOI
TL;DR: Human MYH11 gene mutations provide the first example of a direct change in a specific SMC protein leading to an inherited arterial disease.
Abstract: We have recently described two kindreds presenting thoracic aortic aneurysm and/or aortic dissection (TAAD) and patent ductus arteriosus (PDA) and mapped the disease locus to 16p12.2-p13.13 (ref. 3). We now demonstrate that the disease is caused by mutations in the MYH11 gene affecting the C-terminal coiled-coil region of the smooth muscle myosin heavy chain, a specific contractile protein of smooth muscle cells (SMC). All individuals bearing the heterozygous mutations, even if asymptomatic, showed marked aortic stiffness. Examination of pathological aortas showed large areas of medial degeneration with very low SMC content. Abnormal immunological recognition of SM-MHC and the colocalization of wild-type and mutant rod proteins in SMC, in conjunction with differences in their coimmunoprecipitation capacities, strongly suggest a dominant-negative effect. Human MYH11 gene mutations provide the first example of a direct change in a specific SMC protein leading to an inherited arterial disease.

Journal ArticleDOI
TL;DR: In this paper, the authors show that Type Ia supernovae are formed within both very young and old stellar populations, with observed rates that depend on the stellar mass and mean star formation rates (SFRs) of their host galaxies.
Abstract: We show that Type Ia supernovae (SNe Ia) are formed within both very young and old stellar populations, with observed rates that depend on the stellar mass and mean star formation rates (SFRs) of their host galaxies. Models in which the SN Ia rate depends solely on host galaxy stellar mass are ruled out with >99% confidence. Our analysis is based on 100 spectroscopically confirmed SNe Ia, plus 24 photometrically classified events, all from the Supernova Legacy Survey (SNLS) and distributed over 0.2 < z < 0.75. We estimate stellar masses and SFRs for the SN Ia host galaxies by fitting their broadband spectral energy distributions with the galaxy spectral synthesis code PEGASE.2. We show that the SN Ia rate per unit mass is proportional to the specific SFR of the parent galaxies—more vigorously star-forming galaxies host more SNe Ia per unit stellar mass, broadly equivalent to the trend of increasing SN Ia rate in later type galaxies seen in the local universe. Following earlier suggestions for a simple "two-component" model approximating the SN Ia rate, we find bivariate linear dependencies of the SN Ia rate on both the stellar masses and the mean SFRs of the host systems. We find that the SN Ia rate can be well represented as the sum of 5.3 ± 1.1 × 10 to the -14 SNe yr to the -1 M(.)to the -1 and 3.9 ± 0.7 × 10 to the -4 SNe yr to the -1 (M(.) yr to the -1)to the -1 of star formation. We also demonstrate a dependence of distant SN Ia light-curve shapes on star formation in the host galaxy, similar to trends observed locally. Passive galaxies, with no star formation, preferentially host faster declining/dimmer SNe Ia, while brighter events are found in systems with ongoing star formation.


Journal ArticleDOI
TL;DR: In this article, the stellar atmospheric parameters (effective temperature, surface gravity, overall metallicity), radial velocities, individual abundances, and distances determined for 425,561 stars, which constitute the fourth public data release of the RAdial Velocity Experiment (RAVE).
Abstract: We present the stellar atmospheric parameters (effective temperature, surface gravity, overall metallicity), radial velocities, individual abundances, and distances determined for 425,561 stars, which constitute the fourth public data release of the RAdial Velocity Experiment (RAVE). The stellar atmospheric parameters are computed using a new pipeline, based on the algorithms of MATISSE and DEGAS. The spectral degeneracies and the Two Micron All Sky Survey photometric information are now better taken into consideration, improving the parameter determination compared to the previous RAVE data releases. The individual abundances for six elements (magnesium, aluminum, silicon, titanium, iron, and nickel) are also given, based on a special-purpose pipeline that is also improved compared to that available for the RAVE DR3 and Chemical DR1 data releases. Together with photometric information and proper motions, these data can be retrieved from the RAVE collaboration Web site and the Vizier database.

Journal ArticleDOI
09 Aug 2006-JAMA
TL;DR: This large-scale collaborative analysis demonstrates that SNCA REP1 allele-length variability is associated with an increased risk of Parkinson disease.
Abstract: ContextIdentification and replication of susceptibility genes for Parkinson disease at the population level have been hampered by small studies with potential biases. α-Synuclein (SNCA) has been one of the most promising susceptibility genes, but large-scale studies have been lacking.ObjectiveTo determine whether allele-length variability in the dinucleotide repeat sequence (REP1) of the SNCA gene promoter is associated with Parkinson disease susceptibility, whether SNCA promoter haplotypes are associated with Parkinson disease, and whether REP1 variability modifies age at onset.Design, Setting, and ParticipantsWe performed a collaborative analysis of individual-level data on SNCA REP1 and flanking markers in patients with Parkinson disease and controls. Study site recruitment, data collection, and analyses were performed between April 5, 2004, and December 31, 2005. Eighteen participating sites of a global genetics consortium provided clinical data. Genotyping was performed for SNCA REP1, −770, and −116 markers at individual sites; however, each site also provided 20 DNA samples for regenotyping centrally.Main Outcome MeasuresMeasures included estimations of Hardy-Weinberg equilibrium in controls; a test of heterogeneity; analyses for association of single variants or haplotypes; and survival analyses for age at onset.ResultsOf the 18 sites, 11 met stringent criteria for concordance with Hardy-Weinberg equilibrium and low genotyping error rate. These 11 sites provided complete data for 2692 cases and 2652 controls. There was no heterogeneity across studies (P>.60). The SNCA REP1 alleles differed in frequency for cases and controls (P<.001). Genotypes defined by the 263 base-pair allele were associated with Parkinson disease (odds ratio, 1.43; 95% confidence interval, 1.22-1.69; P<.001 for trend). Multilocus haplotypes differed in frequency for cases and controls (global score statistic, P<.001). Two-loci haplotypes were associated with Parkinson disease only when they included REP1 as one of the loci. However, genotypes defined by REP1 alleles did not modify age at onset (P = .55).ConclusionThis large-scale collaborative analysis demonstrates that SNCA REP1 allele-length variability is associated with an increased risk of Parkinson disease.

Journal ArticleDOI
TL;DR: The purpose of the present paper is to provide some examples of the knowledge that is available in the field of obesity genetics, and also the new strategies being developed that are aimed at studying the relative contribution of numerous genes to obesity and their responses to environmental changes.

Journal ArticleDOI
TL;DR: In the proposed framework, Bayesian analysis makes it possible to estimate and test the partial statistical dependencies between regions without any prior model on the underlying functional interactions and demonstrates the interest of this approach on real data.

Journal ArticleDOI
TL;DR: This paper analyzes these new methods for symmetric positive definite problems and shows their relation to other modern domain decomposition methods like the new Finite Element Tearing and Interconnect (FETI) variants.
Abstract: Optimized Schwarz methods are a new class of Schwarz methods with greatly enhanced convergence properties. They converge uniformly faster than classical Schwarz methods and their convergence rates dare asymptotically much better than the convergence rates of classical Schwarz methods if the overlap is of the order of the mesh parameter, which is often the case in practical applications. They achieve this performance by using new transmission conditions between subdomains which greatly enhance the information exchange between subdomains and are motivated by the physics of the underlying problem. We analyze in this paper these new methods for symmetric positive definite problems and show their relation to other modern domain decomposition methods like the new Finite Element Tearing and Interconnect (FETI) variants.

Journal ArticleDOI
TL;DR: Au catalysts with different metallic particle sizes and supported on silica, alumina, titania, zirconia, ceria, and niobia were prepared, and the reduced catalysts were characterized by EXAFS spectroscopy.

Proceedings ArticleDOI
25 Oct 2006
TL;DR: A new publicly-availabletraceroute is provided, called Paris traceroute, which controls packet header contents to obtain a more precise picture of the actual routes that packets follow, and to suggest possible causes for others.
Abstract: Traceroute is widely used, from the diagnosis of network problems to the assemblage of internet maps. However, there are a few serious problems with this tool, in particular due to the presence of load balancing routers in the network. This paper describes a number of anomalies that arise in nearly all traceroute-based measurements. We categorize them as "loops", "cycles", and "diamonds". We provide a new publicly-available traceroute, called Paris traceroute, which controls packet header contents to obtain a more precise picture of the actual routes that packets follow. This new tool allows us to find conclusive explanations for some of the anomalies, and to suggest possible causes for others.

Journal ArticleDOI
V. M. Abazov1, Brad Abbott2, M. Abolins3, Bobby Samir Acharya4  +814 moreInstitutions (74)
TL;DR: The D0 experiment enjoyed a very successful data-collection run at the Fermilab Tevatron collider between 1992 and 1996 as discussed by the authors, and the detector has been upgraded to take advantage of improvements to the Tevoton and to enhance its physics capabilities.
Abstract: The D0 experiment enjoyed a very successful data-collection run at the Fermilab Tevatron collider between 1992 and 1996. Since then, the detector has been upgraded to take advantage of improvements to the Tevatron and to enhance its physics capabilities. We describe the new elements of the detector, including the silicon microstrip tracker, central fiber tracker, solenoidal magnet, preshower detectors, forward muon detector, and forward proton detector. The uranium/liquid-argon calorimeters and central muon detector, remaining from Run I, are discussed briefly. We also present the associated electronics, triggering, and data acquisition systems, along with the design and implementation of software specific to D0.

Journal ArticleDOI
TL;DR: In this article, the authors comprehensively reviewed the kinetics and mechanism of dithiobenzoate-mediated Reversible Addition-Fragmentation Chain Transfer (RAFT) polymerizations, which exhibit nonideal kinetic behavior, such as induction periods and rate retardation.
Abstract: Investigations into the kinetics and mechanism of dithiobenzoate-mediated Reversible Addition-Fragmentation Chain Transfer (RAFT) polymerizations, which exhibit nonideal kinetic behavior, such as induction periods and rate retardation, are comprehensively reviewed. The appreciable uncertainty in the rate coefficients associated with the RAFT equilibrium is discussed and methods for obtaining RAFT-specific rate coefficients are detailed. In addition, mechanistic studies are presented, which target the elucidation of the fundamental cause of rate retarding effects. The experimental and theoretical data existing in the literature are critically evaluated and apparent discrepancies between the results of different studies into the kinetics of RAFT polymerizations are discussed. Finally, recommendations for further work are given. (c) 2006 Wiley Periodicals, Inc.

Journal ArticleDOI
TL;DR: Functional and expression analyses have revealed that At NCED6 and AtNCED9 are required for ABA biosynthesis during seed development, and demonstrate that ABA synthesized in both the endosperm and the embryo participates in the hormonal balance that controls seed dormancy and germination.
Abstract: Summary The cleavage of 9-cis-epoxycarotenoids to xanthoxin, catalyzed by 9-cis-epoxycarotenoid dioxygenases, is considered to be the key regulatory step of abscisic acid (ABA) biosynthesis. In Arabidopsis, genes for these enzymes form a multigene family with nine members, only five of which are thought to be involved in ABA production. In contrast to the prominent function of AtNCED3 in stress responses, the physiological and developmental role of the other 9-cis-epoxycarotenoid dioxygenases (NCEDs) remain unknown. Our functional and expression analyses have revealed that AtNCED6 and AtNCED9 are required for ABA biosynthesis during seed development. Reverse genetic analysis showed that ABA levels were reduced in Atnced6 and Atnced9 mutant seeds. In addition, transgenic plants overexpressing the AtNCED6 gene overproduced ABA. In accordance with mutant phenotypes, both AtNCED6 and AtNCED9 exhibited seed-specific expression. Detailed cytological studies were carried out, either by using transcriptional fusions of the promoter with GUS and GFP reporter genes, or by in situ hybridization. Expression of AtNCED6 was observed exclusively in the endosperm during seed development, that of AtNCED9 in both embryo and endosperm at mid-development. In addition to reduced ABA levels, Atnced6 and Atnced9 mutant seeds were also resistant to paclobutrazol, a gibberellin biosynthesis inhibitor. Although seeds of single mutants were still dormant, reduced dormancy was observed in the Atnced6 Atnced9 double-mutant seeds. These demonstrate that ABA synthesized in both the endosperm and the embryo participates in the hormonal balance that controls seed dormancy and germination.