443 research outputs found

    Isotope shifts of natural Sr+ measured by laser fluorescence in a sympathetically cooled Coulomb crystal

    Get PDF
    We measured by laser spectroscopy the isotope shifts between naturally-occurring even-isotopes of strontium ions for both the 5s\,\,^2S_{1/2}\to 5p\,\,^2P_{1/2} (violet) and the 4d\,\,^2D_{3/2}\to 5p\,\,^2P_{1/2} (infrared) dipole-allowed optical transitions. Fluorescence spectra were taken by simultaneous measurements on a two-component Coulomb crystal in a linear Paul trap containing 10310^3--10410^4 laser-cooled Sr+^+ ions. The isotope shifts are extracted from the experimental spectra by fitting the data with the analytical solution of the optical Bloch equations describing a three-level atom in interaction with two laser beams. This technique allowed us to increase the precision with respect to previously reported data obtained by optogalvanic spectroscopy or fast atomic-beam techniques. The results for the 5s\,\,^2S_{1/2}\to 5p\,\,^2P_{1/2} transition are Îœ88−Μ84=+378(4)\nu_{88}-\nu_{84}=+378(4) MHz and Îœ88−Μ86=+170(3)\nu_{88}-\nu_{86}=+170(3) MHz, in agreement with previously reported measurements. In the case of the previously unexplored 4d\,\,^2D_{3/2}\to 5p\,\,^2P_{1/2} transition we find Îœ88−Μ84=−828(4)\nu_{88}-\nu_{84}=-828(4) MHz and Îœ88−Μ86=−402(2)\nu_{88}-\nu_{86}=-402(2) MHz. These results provide more data for stringent tests of theoretical calculations of the isotope shifts of alkali-metal-like atoms. Moreover, they simplify the identification and the addressing of Sr+^+ isotopes for ion frequency standards or quantum-information-processing applications in the case of multi-isotope ion strings.Comment: 19 pages; 5 figures; accepted on Phys. Rev. A (http://pra.aps.org/

    Idiosyncratic features in tRNAs participating in bacterial cell wall synthesis

    Get PDF
    The FemXWv aminoacyl transferase of Weissella viridescens initiates the synthesis of the side chain of peptidoglycan precursors by transferring l-Ala from Ala-tRNAAla to UDP-MurNAc-pentadepsipeptide. FemXWv is an attractive target for the development of novel antibiotics, since the side chain is essential for the last cross-linking step of peptidoglycan synthesis. Here, we show that FemXWv is highly specific for incorporation of l-Ala in vivo based on extensive analysis of the structure of peptidoglycan. Comparison of various natural and in vitro-transcribed tRNAs indicated that the specificity of FemXWv depends mainly upon the sequence of the tRNA although additional specificity determinants may include post-transcriptional modifications and recognition of the esterified amino acid. Site-directed mutagenesis identified cytosines in the G1–C72 and G2–C71 base pairs of the acceptor stem as critical for FemXWv activity in agreement with modeling of tRNAAla in the catalytic cavity of the enzyme. In contrast, semi-synthesis of Ala-tRNAAla harboring nucleotide substitutions in the G3–U70 wobble base pair showed that this main identity determinant of alanyl-tRNA synthetase is non-essential for FemXWv. The different modes of recognition of the acceptor stem indicate that specific inhibition of FemXWv could be achieved by targeting the distal portion of tRNAAla for the design of substrate analogues

    Initial results from a hydroacoustic network to monitor submarine lava flows near Mayotte Island

    Get PDF
    In 2019, a new underwater volcano was discovered at 3500 m below sea level (b.s.l.), 50 km east of Mayotte Island in the northern part of the Mozambique Channel. In January 2021, the submarine eruption was still going on and the volcanic activity, along with the intense seismicity that accompanies this crisis, was monitored by the recently created REVOSIMA (MAyotte VOlcano and Seismic Monitoring) network. In this framework, four hydrophones were moored in the SOFAR channel in October 2020. Surrounding the volcano, they monitor sounds generated by the volcanic activity and the lava flows. The first year of hydroacoustic data evidenced many earthquakes, underwater landslides, large marine mammal calls, along with anthropogenic noise. Of particular interest are impulsive signals that we relate to steam bursts during lava flow emplacement. A preliminary analysis of these impulsive signals (ten days in a year, and only one day in full detail) reveals that lava emplacement was active when our monitoring started, but faded out during the first year of the experiment. A systematic and robust detection of these specific signals would hence contribute to monitor active submarine eruptions in the absence of seafloor deep-tow imaging or swath-bathymetry surveys of the active area

    The interest of gait markers in the identification of subgroups among fibromyalgia patients

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Fibromyalgia (FM) is a heterogeneous syndrome and its classification into subgroups calls for broad-based discussion. FM subgrouping, which aims to adapt treatment according to different subgroups, relies in part, on psychological and cognitive dysfunctions. Since motor control of gait is closely related to cognitive function, we hypothesized that gait markers could be of interest in the identification of FM patients' subgroups. This controlled study aimed at characterizing gait disorders in FM, and subgrouping FM patients according to gait markers such as stride frequency (SF), stride regularity (SR), and cranio-caudal power (CCP) which measures kinesia.</p> <p>Methods</p> <p>A multicentre, observational open trial enrolled patients with primary FM (44.1 ± 8.1 y), and matched controls (44.1 ± 7.3 y). Outcome measurements and gait analyses were available for 52 pairs. A 3-step statistical analysis was carried out. A preliminary single blind analysis using k-means cluster was performed as an initial validation of gait markers. Then in order to quantify FM patients according to psychometric and gait variables an open descriptive analysis comparing patients and controls were made, and correlations between gait variables and main outcomes were calculated. Finally using cluster analysis, we described subgroups for each gait variable and looked for significant differences in self-reported assessments.</p> <p>Results</p> <p>SF was the most discriminating gait variable (73% of patients and controls). SF, SR, and CCP were different between patients and controls. There was a non-significant association between SF, FIQ and physical components from Short-Form 36 (p = 0.06). SR was correlated to FIQ (p = 0.01) and catastrophizing (p = 0.05) while CCP was correlated to pain (p = 0.01). The SF cluster identified 3 subgroups with a particular one characterized by normal SF, low pain, high activity and hyperkinesia. The SR cluster identified 2 distinct subgroups: the one with a reduced SR was distinguished by high FIQ, poor coping and altered affective status.</p> <p>Conclusion</p> <p>Gait analysis may provide additional information in the identification of subgroups among fibromyalgia patients. Gait analysis provided relevant information about physical and cognitive status, and pain behavior. Further studies are needed to better understand gait analysis implications in FM.</p

    Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

    Get PDF
    Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, Îș-free light chain, ÎČ2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology

    Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease

    Get PDF
    Perivascular space (PVS) burden is an emerging, poorly understood, magnetic resonance imaging marker of cerebral small vessel disease, a leading cause of stroke and dementia. Genome-wide association studies in up to 40,095 participants (18 population-based cohorts, 66.3 ± 8.6 yr, 96.9% European ancestry) revealed 24 genome-wide significant PVS risk loci, mainly in the white matter. These were associated with white matter PVS already in young adults (N = 1,748; 22.1 ± 2.3 yr) and were enriched in early-onset leukodystrophy genes and genes expressed in fetal brain endothelial cells, suggesting early-life mechanisms. In total, 53% of white matter PVS risk loci showed nominally significant associations (27% after multiple-testing correction) in a Japanese population-based cohort (N = 2,862; 68.3 ± 5.3 yr). Mendelian randomization supported causal associations of high blood pressure with basal ganglia and hippocampal PVS, and of basal ganglia PVS and hippocampal PVS with stroke, accounting for blood pressure. Our findings provide insight into the biology of PVS and cerebral small vessel disease, pointing to pathways involving extracellular matrix, membrane transport and developmental processes, and the potential for genetically informed prioritization of drug targets.Etude de cohorte sur la santé des étudiantsStopping cognitive decline and dementia by fighting covert cerebral small vessel diseaseStudy on Environmental and GenomeWide predictors of early structural brain Alterations in Young student
    • 

    corecore