Showing papers by "University of Montpellier published in 2009"
TL;DR: The Large Area Telescope (Fermi/LAT) as mentioned in this paper is the primary instrument on the Fermi Gamma-ray Space Telescope, which is an imaging, wide field-of-view, high-energy gamma-ray telescope, covering the energy range from below 20 MeV to more than 300 GeV.
Abstract: (Abridged) The Large Area Telescope (Fermi/LAT, hereafter LAT), the primary instrument on the Fermi Gamma-ray Space Telescope (Fermi) mission, is an imaging, wide field-of-view, high-energy gamma-ray telescope, covering the energy range from below 20 MeV to more than 300 GeV. This paper describes the LAT, its pre-flight expected performance, and summarizes the key science objectives that will be addressed. On-orbit performance will be presented in detail in a subsequent paper. The LAT is a pair-conversion telescope with a precision tracker and calorimeter, each consisting of a 4x4 array of 16 modules, a segmented anticoincidence detector that covers the tracker array, and a programmable trigger and data acquisition system. Each tracker module has a vertical stack of 18 x,y tracking planes, including two layers (x and y) of single-sided silicon strip detectors and high-Z converter material (tungsten) per tray. Every calorimeter module has 96 CsI(Tl) crystals, arranged in an 8 layer hodoscopic configuration with a total depth of 8.6 radiation lengths. The aspect ratio of the tracker (height/width) is 0.4 allowing a large field-of-view (2.4 sr). Data obtained with the LAT are intended to (i) permit rapid notification of high-energy gamma-ray bursts (GRBs) and transients and facilitate monitoring of variable sources, (ii) yield an extensive catalog of several thousand high-energy sources obtained from an all-sky survey, (iii) measure spectra from 20 MeV to more than 50 GeV for several hundred sources, (iv) localize point sources to 0.3 - 2 arc minutes, (v) map and obtain spectra of extended sources such as SNRs, molecular clouds, and nearby galaxies, (vi) measure the diffuse isotropic gamma-ray background up to TeV energies, and (vii) explore the discovery space for dark matter.
3,666 citations
TL;DR: Human Splicing Finder is designed, a tool to predict the effects of mutations on splicing signals or to identify splicing motifs in any human sequence, and it is shown that the mutation effect was correctly predicted in almost all cases.
Abstract: Thousands of mutations are identified yearly. Although many directly affect protein expression, an increasing proportion of mutations is now believed to influence mRNA splicing. They mostly affect existing splice sites, but synonymous, non-synonymous or nonsense mutations can also create or disrupt splice sites or auxiliary cis-splicing sequences. To facilitate the analysis of the different mutations, we designed Human Splicing Finder (HSF), a tool to predict the effects of mutations on splicing signals or to identify splicing motifs in any human sequence. It contains all available matrices for auxiliary sequence prediction as well as new ones for binding sites of the 9G8 and Tra2-beta Serine-Arginine proteins and the hnRNP A1 ribonucleoprotein. We also developed new Position Weight Matrices to assess the strength of 5' and 3' splice sites and branch points. We evaluated HSF efficiency using a set of 83 intronic and 35 exonic mutations known to result in splicing defects. We showed that the mutation effect was correctly predicted in almost all cases. HSF could thus represent a valuable resource for research, diagnostic and therapeutic (e.g. therapeutic exon skipping) purposes as well as for global studies, such as the GEN2PHEN European Project or the Human Variome Project.
2,300 citations
TL;DR: In this paper, the authors present the results of 16 years of monitoring stellar orbits around the massive black hole in the center of the Milky Way, using high-resolution near-infrared techniques.
Abstract: We present the results of 16 years of monitoring stellar orbits around the massive black hole in the center of the Milky Way, using high-resolution near-infrared techniques. This work refines our previous analysis mainly by greatly improving the definition of the coordinate system, which reaches a long-term astrometric accuracy of 300 μas, and by investigating in detail the individual systematic error contributions. The combination of a long-time baseline and the excellent astrometric accuracy of adaptive optics data allows us to determine orbits of 28 stars, including the star S2, which has completed a full revolution since our monitoring began. Our main results are: all stellar orbits are fit extremely well by a single-point-mass potential to within the astrometric uncertainties, which are now 6× better than in previous studies. The central object mass is , where the fractional statistical error of 1.5% is nearly independent from R 0, and the main uncertainty is due to the uncertainty in R 0. Our current best estimate for the distance to the Galactic center is R 0 = 8.33 ± 0.35 kpc. The dominant errors in this value are systematic. The mass scales with distance as (3.95 ± 0.06) × 106(R 0/8 kpc)2.19 M ☉. The orientations of orbital angular momenta for stars in the central arcsecond are random. We identify six of the stars with orbital solutions as late-type stars, and six early-type stars as members of the clockwise-rotating disk system, as was previously proposed. We constrain the extended dark mass enclosed between the pericenter and apocenter of S2 at less than 0.066, at the 99% confidence level, of the mass of Sgr A*. This is two orders of magnitudes larger than what one would expect from other theoretical and observational estimates.
1,787 citations
TL;DR: It is argued that mitochondrial DNA is not always clonal, far from neutrally evolving and certainly not clock‐like, questioning its relevance as a witness of recent species and population history and the great potential of accumulating mtDNA data for evolutionary and functional analysis of the mitochondrial genome.
Abstract: Over the last three decades, mitochondrial DNA has been the most popular marker of molecular diversity, for a combination of technical ease-of-use considerations, and supposed biological and evolutionary properties of clonality, near-neutrality and clock-like nature of its substitution rate. Reviewing recent literature on the subject, we argue that mitochondrial DNA is not always clonal, far from neutrally evolving and certainly not clock-like, questioning its relevance as a witness of recent species and population history. We critically evaluate the usage of mitochondrial DNA for species delineation and identification. Finally, we note the great potential of accumulating mtDNA data for evolutionary and functional analysis of the mitochondrial genome.
961 citations
TL;DR: This chapter focuses on phylogenetic tree estimation under the maximum likelihood (ML) principle, a software that implements recent ML phylogenetic methods and algorithms and illustrates the strengths and pitfalls of this program through the analysis of a real data set.
Abstract: Our understanding of the origins, the functions and/or the structures of biological sequences strongly depends on our ability to decipher the mechanisms of molecular evolution. These complex processes can be described through the comparison of homologous sequences in a phylogenetic framework. Moreover, phylogenetic inference provides sound statistical tools to exhibit the main features of molecular evolution from the analysis of actual sequences. This chapter focuses on phylogenetic tree estimation under the maximum likelihood (ML) principle. Phylogenies inferred under this probabilistic criterion are usually reliable and important biological hypotheses can be tested through the comparison of different models. Estimating ML phylogenies is computationally demanding, and careful examination of the results is warranted. This chapter focuses on PhyML, a software that implements recent ML phylogenetic methods and algorithms. We illustrate the strengths and pitfalls of this program through the analysis of a real data set. PhyML v3.0 is available from http://atgc.lirmm.fr/phyml.
779 citations
TL;DR: Preliminary data on the YSL family of transporters clearly argues in favour of its role in the long-distance transport of metals through and between vascular tissues to eventually support gametogenesis and embryo development.
707 citations
TL;DR: The Gamma-ray Burst Monitor and Large Area Telescope onboard the Fermi Observatory together record GRBs over a broad energy range spanning about 7 decades of gammaray energy, with the largest apparent energy release yet measured.
Abstract: Gamma-ray bursts (GRBs) are highly energetic explosions signaling the death of massive stars in distant galaxies. The Gamma-ray Burst Monitor and Large Area Telescope onboard the Fermi Observatory together record GRBs over a broad energy range spanning about 7 decades of gamma-ray energy. In September 2008, Fermi observed the exceptionally luminous GRB 080916C, with the largest apparent energy release yet measured. The high-energy gamma rays are observed to start later and persist longer than the lower energy photons. A simple spectral form fits the entire GRB spectrum, providing strong constraints on emission models. The known distance of the burst enables placing lower limits on the bulk Lorentz factor of the outflow and on the quantum gravity mass.
651 citations
Monterey Bay Aquarium Research Institute1, Washington University in St. Louis2, University of Washington3, Flanders Institute for Biotechnology4, United States Department of Energy5, J. Craig Venter Institute6, University of Miami7, Pierre-and-Marie-Curie University8, Stanford University9, University of Provence10, University of Arizona11, University of Oslo12, Australian National University13, Alfred Wegener Institute for Polar and Marine Research14, University of Iowa15, University of Perpignan16, Macquarie University17, University of Montpellier18, Erasmus University Rotterdam19
TL;DR: It is found that genomes from two isolates shared only 90% of their predicted genes, and divergence appears to have been facilitated by selection and acquisition processes that actively shape the repertoire of genes that are mutually exclusive between the two isolate differently than the core genes.
Abstract: Picoeukaryotes are a taxonomically diverse group of organisms less than 2 micrometers in diameter. Photosynthetic marine picoeukaryotes in the genus Micromonas thrive in ecosystems ranging from tropical to polar and could serve as sentinel organisms for biogeochemical fluxes of modern oceans during climate change. These broadly distributed primary producers belong to an anciently diverged sister clade to land plants. Although Micromonas isolates have high 18S ribosomal RNA gene identity, we found that genomes from two isolates shared only 90% of their predicted genes. Their independent evolutionary paths were emphasized by distinct riboswitch arrangements as well as the discovery of intronic repeat elements in one isolate, and in metagenomic data, but not in other genomes. Divergence appears to have been facilitated by selection and acquisition processes that actively shape the repertoire of genes that are mutually exclusive between the two isolates differently than the core genes. Analyses of the Micromonas genomes offer valuable insights into ecological differentiation and the dynamic nature of early plant evolution.
617 citations
TL;DR: The detection of emission up to ∼31 GeV from the distant and short GRB, and no evidence for the violation of Lorentz invariance is found, which disfavour quantum-gravity theories in which the quantum nature of space–time on a very small scale linearly alters the speed of light.
Abstract: A cornerstone of Einstein's special relativity is Lorentz invariance-the postulate that all observers measure exactly the same speed of light in vacuum, independent of photon-energy. While special relativity assumes that there is no fundamental length-scale associated with such invariance, there is a fundamental scale (the Planck scale, l(Planck) approximate to 1.62 x 10(-33) cm or E(Planck) = M(Planck)c(2) approximate to 1.22 x 10(19) GeV), at which quantum effects are expected to strongly affect the nature of space-time. There is great interest in the (not yet validated) idea that Lorentz invariance might break near the Planck scale. A key test of such violation of Lorentz invariance is a possible variation of photon speed with energy(1-7). Even a tiny variation in photon speed, when accumulated over cosmological light-travel times, may be revealed by observing sharp features in gamma-ray burst (GRB) light-curves(2). Here we report the detection of emission up to similar to 31GeV from the distant and short GRB090510. We find no evidence for the violation of Lorentz invariance, and place a lower limit of 1.2E(Planck) on the scale of a linear energy dependence (or an inverse wavelength dependence), subject to reasonable assumptions about the emission (equivalently we have an upper limit of l(Planck)/1.2 on the length scale of the effect). Our results disfavour quantum-gravity theories(3,6,7) in which the quantum nature of space-time on a very small scale linearly alters the speed of light.
586 citations
TL;DR: It was demonstrated that the charge-storage mechanism in manganese dioxide (MnO2)-based electrodes is mainly faradic rather than capacitive, and specific capacitances of MnO2 forms were strongly correlated with the corresponding ionic conductivities, which obviously rely on the microstructure.
Abstract: The charge-storage mechanism in manganese dioxide (MnO2)-based electrochemical supercapacitors was investigated and discussed toward prepared MnO2 microstructures. The preparation of a series of MnO2 allotropic phases was performed by following dedicated synthetic routes. The resulting compounds are classified into three groups depending on their crystal structures based on 1D channels, 2D layers, or 3D interconnected tunnels. The 1D group includes pyrolusite, ramsdellite, cryptomelane, Ni-doped todorokite (Ni-todorokite), and OMS-5. The 2D and 3D groups are composed of birnessite and spinel, respectively. The prepared MnO2 powders were characterized using X-ray diffraction, scanning electron microscopy, the Brunauer−Emmett−Teller technique, cyclic voltammetry (CV), and electrochemical impedance spectroscopy. The influence of the MnO2 microstructure on the electrochemical performance of MnO2-based electrodes is commented on through the specific surface area and the electronic and ionic conductivities. It ...
538 citations
TL;DR: A series of Cp*Ir catalysts are the most active known by over an order of magnitude for water oxidation with Ce(IV).
Abstract: A series of Cp*Ir catalysts are the most active known by over an order of magnitude for water oxidation with Ce(IV). DFT calculations support a Cp*Ir═O complex as an active species.
Felix Aharonian1, A. G. Akhperjanian1, Gisela Anton2, U. Barres de Almeida3 +165 more•Institutions (22)
TL;DR: In this article, the authors present a measurement of the cosmic-ray electron spectrum with H.E.S. starting at 340 GeV and show no indication of a structure in the electron spectrum, but rather a power-law spectrum with spectral index of 3.0 +- 0.1 (stat.) + − 0.3 (syst.) which steepens at about 1 TeV.
Abstract: The measurement of an excess in the cosmic-ray electron spectrum between 300 and 800 GeV by the ATIC experiment has - together with the PAMELA detection of a rise in the positron fraction up to 100 GeV - motivated many interpretations in terms of dark matter scenarios; alternative explanations assume a nearby electron source like a pulsar or supernova remnant. Here we present a measurement of the cosmic-ray electron spectrum with H.E.S.S. starting at 340 GeV. The H.E.S.S. data with their lower statistical errors show no indication of a structure in the electron spectrum, but rather a power-law spectrum with spectral index of 3.0 +- 0.1 (stat.) +- 0.3 (syst.) which steepens at about 1 TeV.
TL;DR: Well-studied examples that show how a disturbance of a fine-tuned balance of factors regulates splice site selection can cause human disease are discussed.
TL;DR: The LAT Bright AGN Sample (LBAS) as discussed by the authors contains two radio galaxies, namely Centaurus A and NGC 1275, and 104 blazars consisting of 57 flat spectrum radio quasars (FSRQs), 42 BL Lac objects, and 5 BLazars with uncertain classification.
Abstract: The first three months of sky-survey operation with the Fermi Gamma Ray Space Telescope (Fermi) Large Area Telescope (LAT) reveals 132 bright sources at |b|>10 deg with test statistic greater than 100 (corresponding to about 10 sigma). Two methods, based on the CGRaBS, CRATES and BZCat catalogs, indicate high-confidence associations of 106 of these sources with known AGNs. This sample is referred to as the LAT Bright AGN Sample (LBAS). It contains two radio galaxies, namely Centaurus A and NGC 1275, and 104 blazars consisting of 57 flat spectrum radio quasars (FSRQs), 42 BL Lac objects, and 5 blazars with uncertain classification. Four new blazars were discovered on the basis of the LAT detections. Remarkably, the LBAS includes 10 high-energy peaked BL Lacs (HBLs), sources which were so far hard to detect in the GeV range. Another 10 lower-confidence associations are found. Only thirty three of the sources, plus two at |b|>10 deg, were previously detected with EGRET, probably due to the variable nature of these sources. The analysis of the gamma-ray properties of the LBAS sources reveals that the average GeV spectra of BL Lac objects are significantly harder than the spectra of FSRQs. No significant correlation between radio and peak gamma-ray fluxes is observed. Blazar log N - log S and luminosity functions are constructed to investigate the evolution of the different blazar classes, with positive evolution indicated for FSRQs but none for BLLacs. The contribution of LAT-blazars to the total extragalactic gamma-ray intensity is estimated.
TL;DR: It is proposed that sarcoplasmic reticulum Ca2+ leak via RyR1 due to S-nitrosylation of the channel and calstabin-1 depletion contributes to muscle weakness in muscular dystrophy, and that preventing the RyR 1-mediated sarcoplASM Ca2+.
Abstract: Duchenne muscular dystrophy is characterized by progressive muscle weakness and early death resulting from dystrophin deficiency. Loss of dystrophin results in disruption of a large dystrophin glycoprotein complex, leading to pathological calcium (Ca2+)-dependent signals that damage muscle cells. We have identified a structural and functional defect in the ryanodine receptor (RyR1), a sarcoplasmic reticulum Ca2+ release channel, in the mdx mouse model of muscular dystrophy that contributes to altered Ca2+ homeostasis in dystrophic muscles. RyR1 isolated from mdx skeletal muscle showed an age-dependent increase in S-nitrosylation coincident with dystrophic changes in the muscle. RyR1 S-nitrosylation depleted the channel complex of FKBP12 (also known as calstabin-1, for calcium channel stabilizing binding protein), resulting in 'leaky' channels. Preventing calstabin-1 depletion from RyR1 with S107, a compound that binds the RyR1 channel and enhances the binding affinity of calstabin-1 to the nitrosylated channel, inhibited sarcoplasmic reticulum Ca2+ leak, reduced biochemical and histological evidence of muscle damage, improved muscle function and increased exercise performance in mdx mice. On the basis of these findings, we propose that sarcoplasmic reticulum Ca2+ leak via RyR1 due to S-nitrosylation of the channel and calstabin-1 depletion contributes to muscle weakness in muscular dystrophy, and that preventing the RyR1-mediated sarcoplasmic reticulum Ca2+ leak may provide a new therapeutic approach.
TL;DR: In this article, the authors presented the initial results for energies above 100 MeV for the 205 most significant (statistical significance greater than 10-sigma) gamma-ray sources in early-mission data.
Abstract: Following its launch in June 2008, the Fermi Gamma-ray Space Telescope (Fermi) began a sky survey in August. The Large Area Telescope (LAT) on Fermi in 3 months produced a deeper and better-resolved map of the gamma-ray sky than any previous space mission. We present here initial results for energies above 100 MeV for the 205 most significant (statistical significance greater than 10-sigma) gamma-ray sources in these data. These are the best-characterized and best-localized gamma-ray sources in the early-mission data.
TL;DR: In this article, the Gamma-ray Burst Monitor (GBM) and Large Area Telescope (LAT) instruments on-board the Fermi observatory were used to observe the long gamma-ray burst, GRB 090902B.
Abstract: We report on the observation of the bright, long gamma-ray burst (GRB), GRB 090902B, by the Gamma-ray Burst Monitor (GBM) and Large Area Telescope (LAT) instruments on-board the Fermi observatory. ...
TL;DR: Data indicate that Top1 prevents replication fork collapse by suppressing the formation of R-loops in an ASF/SF2-dependent manner, and proposes that interference between replication and transcription represents a major source of spontaneous replication stress, which could drive genomic instability during the early stages of tumorigenesis.
Abstract: Topoisomerase I (Top1) is a key enzyme acting at the interface between DNA replication, transcription and mRNA maturation. Here, we show that Top1 suppresses genomic instability in mammalian cells by preventing conflicts between transcription and DNA replication. Using DNA combing and ChIP-on-chip, we found that Top1-deficient cells accumulate stalled replication forks and chromosome breaks in S phase and that breaks occur preferentially at gene-rich regions of the genome. Strikingly, these phenotypes were suppressed by preventing the formation of RNA-DNA hybrids (R-loops) during transcription. Moreover, these defects could be mimicked by depletion of the splicing factor ASF/SF2, which interacts functionally with Top1. Taken together, these data indicate that Top1 prevents replication fork collapse by suppressing the formation of R-loops in an ASF/SF2-dependent manner. We propose that interference between replication and transcription represents a major source of spontaneous replication stress, which could drive genomic instability during early stages of tumorigenesis.
TL;DR: The requirements for identifying additional specific growth Factors and evaluating the optimal combination of cells, growth factors and scaffolds that is able to respond to the functional demand placed upon cartilage tissue replacement in clinics are discussed.
TL;DR: In this article, a well-balanced numerical scheme for simulating frictional shallow flows over complex domains involving wetting and drying is presented, in a finite volume Godunov-type framework, a set of pre-balanced shallow water equations derived by considering pressure balancing.
University of Cambridge1, Monash University2, Centre national de la recherche scientifique3, University of Bonn4, Harish-Chandra Research Institute5, University of Paris6, University of Turin7, Center for Theoretical Studies, University of Miami8, KEK9, University of Barcelona10, Spanish National Research Council11, University of Montpellier12, Stanford University13, CERN14, University of Edinburgh15, Fermilab16, ETH Zurich17, University of Southampton18, University of Zaragoza19, University of Würzburg20, Moscow State University21, Durham University22, Sapienza University of Rome23, Paul Scherrer Institute24
TL;DR: Extensions of the conventions of the first SLHA are proposed to include various generalisations: the minimal supersymmetric standard model with violation of CP, R-parity, and flavour, as well as the simplest next-to-minimal model.
TL;DR: Only HIV-1 M evolved a fully functional Vpu following the three independent cross-species transmissions that resulted in HIV- 1 groups M, N, and O, which may explain why group M viruses are almost entirely responsible for the global HIV/AIDS pandemic.
TL;DR: It is demonstrated that IL-17 alone or in combination with B cell–activating factor controlled the survival and proliferation of human B cells and their differentiation into immunoglobulin-secreting cells.
Abstract: Studies have suggested involvement of interleukin 17 (IL-17) in autoimmune diseases, although its effect on B cell biology has not been clearly established. Here we demonstrate that IL-17 alone or in combination with B cell-activating factor controlled the survival and proliferation of human B cells and their differentiation into immunoglobulin-secreting cells. This effect was mediated mainly through the nuclear factor-kappaB-regulated transcription factor Twist-1. In support of the relevance of our observations and the potential involvement of IL-17 in B cell biology, we found that the serum of patients with systemic lupus erythematosus had higher concentrations of IL-17 than did the serum of healthy people and that IL-17 abundance correlated with the disease severity of systemic lupus erythematosus.
TL;DR: It is proposed that tetraspanins tightly regulate transient interactions between a variety of molecules and as such favour the efficient assembly of specialized structures upon proper stimulation.
Abstract: Despite high expression levels at the plasma membrane or in intracellular vesicles, tetraspanins remain among the most mysterious transmembrane molecules 20 years after their discovery. Several genetic studies in mammals and invertebrates have demonstrated key physiological roles for some of these tetraspanins, in particular in the immune response, sperm-egg fusion, photoreceptor function and the normal function of certain epithelia. Other studies have highlighted their ability to modulate cell migration and metastasis formation. Their role in the propagation of infectious agents has drawn recent attention, with evidence for HIV budding in tetraspanin-enriched plasma membrane domains. Infection of hepatocytic cells by two major pathogens, the hepatitis C virus and the malaria parasite, also requires the tetraspanin CD81. The function of tetraspanins is thought to be linked to their ability to associate with one another and a wealth of other integral proteins, thereby building up an interacting network or 'tetraspanin web'. On the basis of the biochemical dissection of the tetraspanin web and recent analysis of the dynamics of some of its constituents, we propose that tetraspanins tightly regulate transient interactions between a variety of molecules and as such favour the efficient assembly of specialized structures upon proper stimulation.
TL;DR: In this article, a set of four reactive flow-through experiments at temperature T = 100 degrees C and total pressure P = 12 MPa was performed in limestone reservoir samples, with various ranging from 0.7 to 10 MPa, showing non-uniform dissolution features associated with transport-controlled mass transfer, while reaction-controlled uniform dissolution is observed for P-CO2 = 2.5 MPa.
TL;DR: The body of results shows that the coadsorption of CO(2) and CH(4) leads to a similar breathing of MIL-53(Cr) as with pureCO(2), but increasing the CH( 4) content progressively decreases the transformation of LP to NP, which seems to be excluded from the NP form.
Abstract: The present study attempts to understand the use of the flexible porous chromium terephthalate Cr(OH)(O2C−C6H4−CO2) denoted MIL-53(Cr) (MIL = Material from Institut Lavoisier) for the separation of mixtures of CO2 and CH4 at ambient temperature. The coadsorption of CO2 and CH4 was studied by a variety of different techniques. In situ synchrotron X-ray Powder Diffraction allowed study of the breathing of the solid upon adsorption of the gas mixtures and simultaneously measured Raman spectra yielded an estimation of the adsorbed quantities of CO2 and CH4, as well as a quantification of the fraction of the narrow pore (NP) and the large pore (LP) form of MIL-53. Quantitative coadsorption data were then measured by gravimetry and by breakthrough curves. In addition, computer simulation was performed to calculate the composition of the adsorbed phase in comparison with experimental equilibrium isotherms and breakthrough results. The body of results shows that the coadsorption of CO2 and CH4 leads to a similar ...
National Institute on Drug Abuse1, Université de Montréal2, Duke University3, Icahn School of Medicine at Mount Sinai4, University of Montpellier5, Karolinska Institutet6, University of Toronto7, Columbia University8, University of Würzburg9, Indiana University10, University of Glasgow11, University of Western Australia12, Medical University of Graz13, University of Barcelona14
TL;DR: This commentary considers research questions underlying the proposed nomenclature, with recommendations for receptor heteromer identification in native tissues and their use as targets for drug development.
Abstract: Receptor heteromers constitute a new area of research that is reshaping our thinking about biochemistry, cell biology, pharmacology and drug discovery. In this commentary, we recommend clear definitions that should facilitate both information exchange and research on this growing class of transmembrane signal transduction units and their complex properties. We also consider research questions underlying the proposed nomenclature, with recommendations for receptor heteromer identification in native tissues and their use as targets for drug development.
TL;DR: In this paper, the dynamics of kinetically constrained models of glass formers were investigated by analyzing the statistics of trajectories of the dynamics, or histories, using large deviation function methods, and it was shown that these models exhibit a first-order dynamical transition between active and inactive dynamical phases.
Abstract: We investigate the dynamics of kinetically constrained models of glass formers by analysing the statistics of trajectories of the dynamics, or histories, using large deviation function methods. We show that, in general, these models exhibit a first-order dynamical transition between active and inactive dynamical phases. We argue that the dynamical heterogeneities displayed by these systems are a manifestation of dynamical first-order phase coexistence. In particular, we calculate dynamical large deviation functions, both analytically and numerically, for the Fredrickson–Andersen model, the East model, and constrained lattice gas models. We also show how large deviation functions can be obtained from a Landau-like theory for dynamical fluctuations. We discuss possibilities for similar dynamical phase-coexistence behaviour in other systems with heterogeneous dynamics.
TL;DR: Elderly people taking anticholinergic drugs were at increased risk for cognitive decline and dementia and doctors should carefully consider prescription of anticholergic drugs in elderly people, especially in the very elderly and in persons at high genetic risk for Cognitive disorder.
Abstract: BACKGROUND: Despite the high intake of medications with anticholinergic properties by community-dwelling elderly persons, the effects on cognitive decline and dementia have rarely been evaluated. METHODS: Participants were 4128 women and 2784 men 65 years or older from a population-based cohort recruited from 3 French cities. Cognitive performance, clinical diagnosis of dementia, and anticholinergic use were evaluated at baseline and 2 and 4 years later. RESULTS: A total of 7.5% of the participants reported anticholinergic drug use at baseline. Multivariate-adjusted logistic regression indicated that women reporting use of anticholinergic drugs at baseline showed greater decline over 4 years in verbal fluency scores (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.11-1.79) and in global cognitive functioning (OR, 1.22; 95% CI, 0.96-1.55) than women not using anticholinergic drugs. In men, an association was found with decline in visual memory (OR, 1.63; 95% CI, 1.08-2.47) and to a lesser extent in executive function (OR, 1.47; 95% CI, 0.89-2.44). Notable interactions were observed in women between anticholinergic use and age, apolipoprotein E, or hormone therapy. A 1.4- to 2-fold higher risk of cognitive decline was observed for those who continuously used anticholinergic drugs but not for those who had discontinued use. The risk of incident dementia over the 4-year follow-up period was also increased in continuous users (hazard ratio [HR], 1.65; 95% CI, 1.00-2.73) but not in those who discontinued the use of anticholinergic drugs (HR, 1.28; 95% CI, 0.59-2.76). CONCLUSIONS: Elderly people taking anticholinergic drugs were at increased risk for cognitive decline and dementia. Discontinuing anticholinergic treatment was associated with a decreased risk. Physicians should carefully consider prescription of anticholinergic drugs in elderly people, especially in the very elderly and in persons at high genetic risk for cognitive disorder.
TL;DR: It is shown that exercising the hemiparetic hand and wrist is essential in all stages of a stroke rehabilitation program and new data stemming from neurosciences suggest that ipsilesional corticospinal excitability should be a priority.