1,611 research outputs found
Outcome-dependent effects of walking speed and age on quantitative and qualitative gait measures
Background: Walking speed predicts many clinical outcomes in old age. However, a comprehensive assessment of how walking speed affects accelerometer based quantitative and qualitive gait measures in younger and older adults is lacking. Research question: What is the relationship between walking speed and quantitative and qualitive gait outcomes in younger and older adults? Methods: Younger (n = 27, age: 21.6) and older participants (n = 27, age: 69.5) completed 340 steps on a treadmill at speeds of 0.70 to a maximum of 1.75 m·s-1. We used generalized additive mixed models to determine the relationship between walking speed and quantitative (stride length, stride time, stride frequency and their variability) and qualitive (stride regularity, stability, smoothness, symmetry, synchronization, predictability) gait measures extracted from trunk accelerations. Results: The type of relationship between walking speed and the majority of gait measures (quantitative and qualitative) was characterized as logarithmic, with more prominent speed-effects at speeds below 1.20 m·s−1. Changes in quantitative measures included shorter strides, longer stride times, and a lower stride frequency, with more variability at lower speeds independent of age. For qualitative measures, we found a decrease in gait symmetry, stability and regularity in all directions with decreasing speeds, a decrease in gait predictability (Vertical, V, anterior-posterior, AP) and stronger gait synchronization (AP-mediolateral, ML, AP-V), and direction dependent effects of gait smoothness, which decreased in V direction, but increased in AP and ML directions with decreasing speeds. We found outcome-dependent effects of age on the quantitative and qualitative gait measures, with either no differences between age-groups, age-related differences that existed regardless of speed, and age-related differences in the type of relationship with walking speed. Significance: The relationship between walking speed and quantitative and qualitative gait measures, and the effects of age on this relationship, depends on the type of gait measure studied
Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis
Completion of DNA replication needs to be ensured even when challenged with fork progression problems or DNA damage. PCNA and its modifications constitute a molecular switch to control distinct repair pathways. In yeast, SUMOylated PCNA (S-PCNA) recruits Srs2 to sites of replication where Srs2 can disrupt Rad51 filaments and prevent homologous recombination (HR). We report here an unexpected additional mechanism by which S-PCNA and Srs2 block the synthesis-dependent extension of a recombination intermediate, thus limiting its potentially hazardous resolution in association with a cross-over. This new Srs2 activity requires the SUMO interaction motif at its C-terminus, but neither its translocase activity nor its interaction with Rad51. Srs2 binding to S-PCNA dissociates Polδ and Polη from the repair synthesis machinery, thus revealing a novel regulatory mechanism controlling spontaneous genome rearrangements. Our results suggest that cycling cells use the Siz1-dependent SUMOylation of PCNA to limit the extension of repair synthesis during template switch or HR and attenuate reciprocal DNA strand exchanges to maintain genome stability. © 2013 European Molecular Biology Organization
Separation between coherent and turbulent fluctuations. What can we learn from the Empirical Mode Decomposition?
The performances of a new data processing technique, namely the Empirical
Mode Decomposition, are evaluated on a fully developed turbulent velocity
signal perturbed by a numerical forcing which mimics a long-period flapping.
First, we introduce a "resemblance" criterion to discriminate between the
polluted and the unpolluted modes extracted from the perturbed velocity signal
by means of the Empirical Mode Decomposition algorithm. A rejection procedure,
playing, somehow, the role of a high-pass filter, is then designed in order to
infer the original velocity signal from the perturbed one. The quality of this
recovering procedure is extensively evaluated in the case of a "mono-component"
perturbation (sine wave) by varying both the amplitude and the frequency of the
perturbation. An excellent agreement between the recovered and the reference
velocity signals is found, even though some discrepancies are observed when the
perturbation frequency overlaps the frequency range corresponding to the
energy-containing eddies as emphasized by both the energy spectrum and the
structure functions. Finally, our recovering procedure is successfully
performed on a time-dependent perturbation (linear chirp) covering a broad
range of frequencies.Comment: 23 pages, 13 figures, submitted to Experiments in Fluid
Observation of interstellar lithium in the low-metallicity Small Magellanic Cloud
The primordial abundances of light elements produced in the standard theory
of Big Bang nucleosynthesis (BBN) depend only on the cosmic ratio of baryons to
photons, a quantity inferred from observations of the microwave background. The
predicted primordial 7Li abundance is four times that measured in the
atmospheres of Galactic halo stars. This discrepancy could be caused by
modification of surface lithium abundances during the stars' lifetimes or by
physics beyond the Standard Model that affects early nucleosynthesis. The
lithium abundance of low-metallicity gas provides an alternative constraint on
the primordial abundance and cosmic evolution of lithium that is not
susceptible to the in situ modifications that may affect stellar atmospheres.
Here we report observations of interstellar 7Li in the low-metallicity gas of
the Small Magellanic Cloud, a nearby galaxy with a quarter the Sun's
metallicity. The present-day 7Li abundance of the Small Magellanic Cloud is
nearly equal to the BBN predictions, severely constraining the amount of
possible subsequent enrichment of the gas by stellar and cosmic-ray
nucleosynthesis. Our measurements can be reconciled with standard BBN with an
extremely fine-tuned depletion of stellar Li with metallicity. They are also
consistent with non-standard BBN.Comment: Published in Nature. Includes main text and Supplementary
Information. Replaced with final title and abstrac
Comparison of serious inhaler technique errors made by device-naïve patients using three different dry powder inhalers: a randomised, crossover, open-label study
Background: Serious inhaler technique errors can impair drug delivery to the lungs. This randomised, crossover, open-label study evaluated the proportion of patients making predefined serious errors with Pulmojet compared with Diskus and Turbohaler dry powder inhalers. Methods: Patients ≥18 years old with asthma and/or COPD who were current users of an inhaler but naïve to the study devices were assigned to inhaler technique assessment on Pulmojet and either Diskus or Turbohaler in a randomised order. Patients inhaled through empty devices after reading the patient information leaflet. If serious errors potentially affecting dose delivery were recorded, they repeated the inhalations after watching a training video. Inhaler technique was assessed by a trained nurse observer and an electronic inhalation profile recorder. Results: Baseline patient characteristics were similar between randomisation arms for the Pulmojet-Diskus (n = 277) and Pulmojet-Turbohaler (n = 144) comparisons. Non-inferiority in the proportions of patients recording no nurse-observed serious errors was demonstrated for both Pulmojet versus Diskus, and Pulmojet versus Turbohaler; therefore, superiority was tested. Patients were significantly less likely to make ≥1 nurse-observed serious errors using Pulmojet compared with Diskus (odds ratio, 0.31; 95 % CI, 0.19–0.51) or Pulmojet compared with Turbohaler (0.23; 0.12–0.44) after reading the patient information leaflet with additional video instruction, if required. Conclusions These results suggest Pulmojet is easier to learn to use correctly than the Turbohaler or Diskus for current inhaler users switching to a new dry powder inhaler
Definition of the σW regulon of Bacillus subtilis in the absence of stress
Bacteria employ extracytoplasmic function (ECF) sigma factors for their responses to environmental stresses. Despite intensive research, the molecular dissection of ECF sigma factor regulons has remained a major challenge due to overlaps in the ECF sigma factor-regulated genes and the stimuli that activate the different ECF sigma factors. Here we have employed tiling arrays to single out the ECF σW regulon of the Gram-positive bacterium Bacillus subtilis from the overlapping ECF σX, σY, and σM regulons. For this purpose, we profiled the transcriptome of a B. subtilis sigW mutant under non-stress conditions to select candidate genes that are strictly σW-regulated. Under these conditions, σW exhibits a basal level of activity. Subsequently, we verified the σW-dependency of candidate genes by comparing their transcript profiles to transcriptome data obtained with the parental B. subtilis strain 168 grown under 104 different conditions, including relevant stress conditions, such as salt shock. In addition, we investigated the transcriptomes of rasP or prsW mutant strains that lack the proteases involved in the degradation of the σW anti-sigma factor RsiW and subsequent activation of the σW-regulon. Taken together, our studies identify 89 genes as being strictly σW-regulated, including several genes for non-coding RNAs. The effects of rasP or prsW mutations on the expression of σW-dependent genes were relatively mild, which implies that σW-dependent transcription under non-stress conditions is not strictly related to RasP and PrsW. Lastly, we show that the pleiotropic phenotype of rasP mutant cells, which have defects in competence development, protein secretion and membrane protein production, is not mirrored in the transcript profile of these cells. This implies that RasP is not only important for transcriptional regulation via σW, but that this membrane protease also exerts other important post-transcriptional regulatory functions
Closed-loop separation control over a sharp edge ramp using Genetic Programming
We experimentally perform open and closed-loop control of a separating
turbulent boundary layer downstream from a sharp edge ramp. The turbulent
boundary layer just above the separation point has a Reynolds number
based on momentum thickness. The goal of the
control is to mitigate separation and early re-attachment. The forcing employs
a spanwise array of active vortex generators. The flow state is monitored with
skin-friction sensors downstream of the actuators. The feedback control law is
obtained using model-free genetic programming control (GPC) (Gautier et al.
2015). The resulting flow is assessed using the momentum coefficient, pressure
distribution and skin friction over the ramp and stereo PIV. The PIV yields
vector field statistics, e.g. shear layer growth, the backflow area and vortex
region. GPC is benchmarked against the best periodic forcing. While open-loop
control achieves separation reduction by locking-on the shedding mode, GPC
gives rise to similar benefits by accelerating the shear layer growth.
Moreover, GPC uses less actuation energy.Comment: 24 pages, 24 figures, submitted to Experiments in Fluid
A Vast Thin Plane of Co-rotating Dwarf Galaxies Orbiting the Andromeda Galaxy
Dwarf satellite galaxies are thought to be the remnants of the population of
primordial structures that coalesced to form giant galaxies like the Milky Way.
An early analysis noted that dwarf galaxies may not be isotropically
distributed around our Galaxy, as several are correlated with streams of HI
emission, and possibly form co-planar groups. These suspicions are supported by
recent analyses, and it has been claimed that the apparently planar
distribution of satellites is not predicted within standard cosmology, and
cannot simply represent a memory of past coherent accretion. However, other
studies dispute this conclusion. Here we report the existence (99.998%
significance) of a planar sub-group of satellites in the Andromeda galaxy,
comprising approximately 50% of the population. The structure is vast: at least
400 kpc in diameter, but also extremely thin, with a perpendicular scatter
<14.1 kpc (99% confidence). Radial velocity measurements reveal that the
satellites in this structure have the same sense of rotation about their host.
This finding shows conclusively that substantial numbers of dwarf satellite
galaxies share the same dynamical orbital properties and direction of angular
momentum, a new insight for our understanding of the origin of these most dark
matter dominated of galaxies. Intriguingly, the plane we identify is
approximately aligned with the pole of the Milky Way's disk and is co-planar
with the Milky Way to Andromeda position vector. The existence of such
extensive coherent kinematic structures within the halos of massive galaxies is
a fact that must be explained within the framework of galaxy formation and
cosmology.Comment: Published in the 3rd Jan 2013 issue of Nature. 19 pages, 4 figures, 1
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The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis
Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P = 1.34×10<sup>−8</sup>, OR = 1.22, CI 95% = 1.14–1.30; rs2004640: P = 4.60×10<sup>−7</sup>, OR = 0.84, CI 95% = 0.78–0.90; rs10488631: P = 7.53×10<sup>−20</sup>, OR = 1.63, CI 95% = 1.47–1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P = 9.04×10<sup>−22</sup>, OR = 1.75, CI 95% = 1.56–1.97) better explained the observed association (likelihood P-value = 1.48×10<sup>−4</sup>), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that this association is not sub-phenotype-specific
The remnants of galaxy formation from a panoramic survey of the region around M31
In hierarchical cosmological models, galaxies grow in mass through the
continual accretion of smaller ones. The tidal disruption of these systems is
expected to result in loosely bound stars surrounding the galaxy, at distances
that reach times the radius of the central disk. The number,
luminosity and morphology of the relics of this process provide significant
clues to galaxy formation history, but obtaining a comprehensive survey of
these components is difficult because of their intrinsic faintness and vast
extent. Here we report a panoramic survey of the Andromeda galaxy (M31). We
detect stars and coherent structures that are almost certainly remnants of
dwarf galaxies destroyed by the tidal field of M31. An improved census of their
surviving counterparts implies that three-quarters of M31's satellites brighter
than await discovery. The brightest companion, Triangulum (M33), is
surrounded by a stellar structure that provides persuasive evidence for a
recent encounter with M31. This panorama of galaxy structure directly confirms
the basic tenets of the hierarchical galaxy formation model and reveals the
shared history of M31 and M33 in the unceasing build-up of galaxies.Comment: Published in Nature. Supplementary movie available at
https://www.astrosci.ca/users/alan/PANDAS/Latest%20news%3A%20movie%20of%20orbit.htm
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