112 research outputs found

    Model-based automatic generation of grasping regions

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    The problem of automatically generating stable regions for a robotic end effector on a target object, given a model of the end effector and the object is discussed. In order to generate grasping regions, an initial valid grasp transformation from the end effector to the object is obtained based on form closure requirements, and appropriate rotational and translational symmetries are associated with that transformation in order to construct a valid, continuous grasping region. The main result of this algorithm is a list of specific, valid grasp transformations of the end effector to the target object, and the appropriate combinations of translational and rotational symmetries associated with each specific transformation in order to produce a continuous grasp region

    Assessing chemistry schemes and constraints in air quality models used to predict ozone in London against the detailed Master Chemical Mechanism

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    Air pollution is the environmental factor with the greatest impact on human health in Europe. Understanding the key processes driving air quality across the relevant spatial scales, especially during pollution exceedances and episodes, is essential to provide effective predictions for both policymakers and the public. It is particularly important for policy regulators to understand the drivers of local air quality that can be regulated by national policies versus the contribution from regional pollution transported from mainland Europe or elsewhere. One of the main objectives of the Coupled Urban and Regional processes: Effects on AIR quality (CUREAIR) project is to determine local and regional contributions to ozone events. A detailed zero-dimensional (0-D) box model run with the Master Chemical Mechanism (MCMv3.2) is used as the benchmark model against which the less explicit chemistry mechanisms of the Generic Reaction Set (GRS) and the Common Representative Intermediates (CRIv2-R5) schemes are evaluated. GRS and CRI are used by the Atmospheric Dispersion Modelling System (ADMS-Urban) and the regional chemistry transport model EMEP4UK, respectively. The MCM model uses a near-explicit chemical scheme for the oxidation of volatile organic compounds (VOCs) and is constrained to observations of VOCs, NOx, CO, HONO (nitrous acid), photolysis frequencies and meteorological parameters measured during the ClearfLo (Clean Air for London) campaign. The sensitivity of the less explicit chemistry schemes to different model inputs has been investigated: Constraining GRS to the total VOC observed during ClearfLo as opposed to VOC derived from ADMS-Urban dispersion calculations, including emissions and background concentrations, led to a significant increase (674% during winter) in modelled ozone. The inclusion of HONO chemistry in this mechanism, particularly during wintertime when other radical sources are limited, led to substantial increases in the ozone levels predicted (223%). When the GRS and CRIv2-R5 schemes are run with the equivalent model constraints to the MCM, they are able to reproduce the level of ozone predicted by the near-explicit MCM to within 40% and 20% respectively for the majority of the time. An exception to this trend was observed during pollution episodes experienced in the summer, when anticyclonic conditions favoured increased temperatures and elevated O3. The in situ O3 predicted by the MCM was heavily influenced by biogenic VOCs during these conditions and the low GRS [O3] : MCM [O3] ratio (and low CRIv2-R5 [O3] : MCM [O3] ratio) demonstrates that these less explicit schemes under-represent the full O3 creation potential of these VOCs. To fully assess the influence of the in situ O3 generated from local emissions versus O3 generated upwind of London and advected in, the time since emission (and, hence, how far the real atmosphere is from steady state) must be determined. From estimates of the mean transport time determined from the NOx : NOy ratio observed at North Kensington during the summer and comparison of the O3 predicted by the MCM model after this time, ∼60% of the median observed [O3] could be generated from local emissions. During the warmer conditions experienced during the easterly flows, however, the observed [O3] may be even more heavily influenced by London's emissions

    The breakthrough listen search for intelligent life: a wideband data recorder system for the Robert C. Byrd green bank telescope

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    The Breakthrough Listen Initiative is undertaking a comprehensive search for radio and optical signatures from extraterrestrial civilizations. An integral component of the project is the design and implementation of wide-bandwidth data recorder and signal processing systems. The capabilities of these systems, particularly at radio frequencies, directly determine survey speed; further, given a fixed observing time and spectral coverage, they determine sensitivity as well. Here, we detail the Breakthrough Listen wide-bandwidth data recording system deployed at the 100-m aperture Robert C. Byrd Green Bank Telescope. The system digitizes up to 6 GHz of bandwidth at 8 bits for both polarizations, storing the resultant 24 GB/s of data to disk. This system is among the highest data rate baseband recording systems in use in radio astronomy. A future system expansion will double recording capacity, to achieve a total Nyquist bandwidth of 12 GHz in two polarizations. In this paper, we present details of the system architecture, along with salient configuration and disk-write optimizations used to achieve high-throughput data capture on commodity compute servers and consumer-class hard disk drives

    Long-term influence of normal variation in neonatal characteristics on human brain development

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    It is now recognized that a number of cognitive, behavioral, and mental health outcomes across the lifespan can be traced to fetal development. Although the direct mediation is unknown, the substantial variance in fetal growth, most commonly indexed by birth weight, may affect lifespan brain development. We investigated effects of normal variance in birth weight on MRI-derived measures of brain development in 628 healthy children, adolescents, and young adults in the large-scale multicenter Pediatric Imaging, Neurocognition, and Genetics study. This heterogeneous sample was recruited through geographically dispersed sites in the United States. The influence of birth weight on cortical thickness, surface area, and striatal and total brain volumes was investigated, controlling for variance in age, sex, household income, and genetic ancestry factors. Birth weight was found to exert robust positive effects on regional cortical surface area in multiple regions as well as total brain and caudate volumes. These effects were continuous across birth weight ranges and ages and were not confined to subsets of the sample. The findings show that (i) aspects of later child and adolescent brain development are influenced at birth and (ii) relatively small differences in birth weight across groups and conditions typically compared in neuropsychiatric research (e.g., Attention Deficit Hyperactivity Disorder, schizophrenia, and personality disorders) may influence group differences observed in brain parameters of interest at a later stage in life. These findings should serve to increase our attention to early influences

    Genome-Wide Association of Bipolar Disorder Suggests an Enrichment of Replicable Associations in Regions near Genes

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    Although a highly heritable and disabling disease, bipolar disorder's (BD) genetic variants have been challenging to identify. We present new genotype data for 1,190 cases and 401 controls and perform a genome-wide association study including additional samples for a total of 2,191 cases and 1,434 controls. We do not detect genome-wide significant associations for individual loci; however, across all SNPs, we show an association between the power to detect effects calculated from a previous genome-wide association study and evidence for replication (P = 1.5×10−7). To demonstrate that this result is not likely to be a false positive, we analyze replication rates in a large meta-analysis of height and show that, in a large enough study, associations replicate as a function of power, approaching a linear relationship. Within BD, SNPs near exons exhibit a greater probability of replication, supporting an enrichment of reproducible associations near functional regions of genes. These results indicate that there is likely common genetic variation associated with BD near exons (±10 kb) that could be identified in larger studies and, further, provide a framework for assessing the potential for replication when combining results from multiple studies

    Disease-Toxicant Interactions in Manganese Exposed Huntington Disease Mice: Early Changes in Striatal Neuron Morphology and Dopamine Metabolism

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    YAC128 Huntington's disease (HD) transgenic mice accumulate less manganese (Mn) in the striatum relative to wild-type (WT) littermates. We hypothesized that Mn and mutant Huntingtin (HTT) would exhibit gene-environment interactions at the level of neurochemistry and neuronal morphology. Twelve-week-old WT and YAC128 mice were exposed to MnCl2-4H2O (50 mg/kg) on days 0, 3 and 6. Striatal medium spiny neuron (MSN) morphology, as well as levels of dopamine (DA) and its metabolites (which are known to be sensitive to Mn-exposure), were analyzed at 13 weeks (7 days from initial exposure) and 16 weeks (28 days from initial exposure). No genotype-dependent differences in MSN morphology were apparent at 13 weeks. But at 16 weeks, a genotype effect was observed in YAC128 mice, manifested by an absence of the wild-type age-dependent increase in dendritic length and branching complexity. In addition, genotype-exposure interaction effects were observed for dendritic complexity measures as a function of distance from the soma, where only YAC128 mice were sensitive to Mn exposure. Furthermore, striatal DA levels were unaltered at 13 weeks by genotype or Mn exposure, but at 16 weeks, both Mn exposure and the HD genotype were associated with quantitatively similar reductions in DA and its metabolites. Interestingly, Mn exposure of YAC128 mice did not further decrease DA or its metabolites versus YAC128 vehicle exposed or Mn exposed WT mice. Taken together, these results demonstrate Mn-HD disease-toxicant interactions at the onset of striatal dendritic neuropathology in YAC128 mice. Our results identify the earliest pathological change in striatum of YAC128 mice as being between 13 to 16 weeks. Finally, we show that mutant HTT suppresses some Mn-dependent changes, such as decreased DA levels, while it exacerbates others, such as dendritic pathology

    A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

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    Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

    American Gut: an Open Platform for Citizen Science Microbiome Research

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    McDonald D, Hyde E, Debelius JW, et al. American Gut: an Open Platform for Citizen Science Microbiome Research. mSystems. 2018;3(3):e00031-18

    Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

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    Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders
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