2,218 research outputs found

    Concert recording 2018-10-09

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    [Track 1]. Concerto. I. Andante II. Adagio III. Presto / Alessandro Marcello -- [Track 2]. Sonata for trumpet & piano. I. Allegro vivace II. Largo, allegro III. Presto con fuoco / Morten Lauridsen -- [Track 3]. Paths - In memoriam Witold Lutoslawski / Toru Takemitsu -- [Track 4]. Cententnial horizon. I. Aspen grove Interlude-Alpenglow II. Roaring Gunnison / Kevin McKee

    Adaptive Input and Parameter Estimation with Application to Engine Torque Estimation

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    This paper presents two estimation methods for systems with unknown time-varying input dynamics. By defining auxiliary filtered variables, an invariant manifold is derived and used to drive the input estimator with only one tuning parameter. Exponential error convergence to a small compact set around theorigin can be proved. Robustness against noise is studied and compared with two well-known schemes. Moreover, when the input dynamics to be estimated are parameterized in a quasilinear form with unknown parameters, the proposed idea is further investigated to estimate the associated unknowntime-varying parameters. The algorithms are tested by considering the torque estimation of internal combustion engines (ICEs). Comparative simulation results based on a benchmark engine simulation model show satisfactory transient androbustness performance

    Improved Semileptonic Form Factor Calculations in Lattice QCD

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    We investigate the computational efficiency of two stochastic based alternatives to the Sequential Propagator Method used in Lattice QCD calculations of heavy-light semileptonic form factors. In the first method, we replace the sequential propagator, which couples the calculation of two of the three propagators required for the calculation, with a stochastic propagator so that the calculations of all three propagators are independent. This method is more flexible than the Sequential Propagator Method but introduces stochastic noise. We study the noise to determine when this method becomes competitive with the Sequential Propagator Method, and find that for any practical calculation it is competitive with or superior to the Sequential Propagator Method. We also examine a second stochastic method, the so-called ``one-end trick", concluding it is relatively inefficient in this context. The investigation is carried out on two gauge field ensembles, using the non-perturbatively improved Wilson-Sheikholeslami-Wohlert action with N_f=2 mass-degenerate sea quarks. The two ensembles have similar lattice spacings but different sea quark masses. We use the first stochastic method to extract O(a){\mathcal O}(a)-improved, matched lattice results for the semileptonic form factors on the ensemble with lighter sea quarks, extracting f_+(0)

    Separating vascular and neuronal effects of age on fMRI BOLD signals.

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    Accurate identification of brain function is necessary to understand the neurobiology of cognitive ageing, and thereby promote well-being across the lifespan. A common tool used to investigate neurocognitive ageing is functional magnetic resonance imaging (fMRI). However, although fMRI data are often interpreted in terms of neuronal activity, the blood oxygenation level-dependent (BOLD) signal measured by fMRI includes contributions of both vascular and neuronal factors, which change differentially with age. While some studies investigate vascular ageing factors, the results of these studies are not well known within the field of neurocognitive ageing and therefore vascular confounds in neurocognitive fMRI studies are common. Despite over 10 000 BOLD-fMRI papers on ageing, fewer than 20 have applied techniques to correct for vascular effects. However, neurovascular ageing is not only a confound in fMRI, but an important feature in its own right, to be assessed alongside measures of neuronal ageing. We review current approaches to dissociate neuronal and vascular components of BOLD-fMRI of regional activity and functional connectivity. We highlight emerging evidence that vascular mechanisms in the brain do not simply control blood flow to support the metabolic needs of neurons, but form complex neurovascular interactions that influence neuronal function in health and disease. This article is part of the theme issue 'Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity'.This work is supported by the British Academy (PF160048), the Guarantors of Brain (G101149), the Wellcome Trust (103838), the Medical Research Council (SUAG/051 G101400; and SUAG/046 G101400), European Union’s Horizon 2020 (732592) and the Cambridge NIHR Biomedical Research Centre

    Single-nucleotide polymorphism-based genetic risk score and patient age at prostate cancer diagnosis

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    Importance: Few studies have evaluated the association between a single-nucleotide polymorphism-based genetic risk score (GRS) and patient age at prostate cancer (PCa) diagnosis. Objectives: To test the association between a GRS and patient age at PCa diagnosis and to compare the performance of a GRS with that of family history (FH) in PCa risk stratification. Design, Setting, and Participants: A cohort study of 3225 white men was conducted as a secondary analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) chemoprevention trial, a 4-year, randomized, double-blind, placebo-controlled multicenter study conducted from March 2003 to April 2009 to evaluate the safety and efficacy of dutasteride in reducing PCa events. Participants were confirmed to be cancer free by prostate biopsy (6-12 cores) within 6 months prior to the study and underwent 10 core biopsies every 2 years per protocol. The dates for performing data analysis were from July 2016 to October 2019. Interventions: A well-established, population-standardized GRS was calculated for each participant based on 110 known PCa risk-associated single-nucleotide polymorphisms, which is a relative risk compared with the general population. Men were classified into 3 GRS risk groups based on predetermined cutoff values: low (\u3c0.50), average (0.50-1.49), and high (≥1.50). Main Outcomes and Measures: Prostate cancer diagnosis-free survival among men of different risk groups. Results: Among 3225 men (median age, 63 years [interquartile range, 58-67 years]) in the study, 683 (21%) were classified as low risk, 1937 (60%) as average risk, and 605 (19%) as high risk based on GRS alone. In comparison, 2789 (86%) were classified as low or average risk and 436 (14%) as high risk based on FH alone. Men in higher GRS risk groups had a PCa diagnosis-free survival rate that was worse than that of those in the lower GRS risk group (χ2 = 53.3; P \u3c .001 for trend) and in participants with a negative FH of PCa (χ2 = 45.5; P \u3c .001 for trend). Combining GRS and FH further stratified overall genetic risk, indicating that 957 men (30%) were at high genetic risk (either high GRS or positive FH), 1667 men (52%) were at average genetic risk (average GRS and negative FH), and 601 men (19%) were at low genetic risk (low GRS and negative FH). The median PCa diagnosis-free survival was 74 years (95% CI, 73-75 years) for men at high genetic risk, 77 years (95% CI, 75 to \u3e80 years) for men at average genetic risk, and more than 80 years (95% CI, \u3e80 to \u3e80 years) for men at low genetic risk. In contrast, the median PCa diagnosis-free survival was 73 years (95% CI, 71-76 years) for men with a positive FH and 77 years (95% CI, 76-79 years) for men with a negative FH. Conclusions and Relevance: This study suggests that a GRS is significantly associated with patient age at PCa diagnosis. Combining FH and GRS may better stratify inherited risk than FH alone for developing personalized PCa screening strategies

    Two \u3ci\u3eMagnaporthe\u3c/i\u3e appressoria-specific (MAS) proteins, MoMas3 and MoMas5, are required for suppressing host innate immunity and promoting biotrophic growth in rice cells

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    In the devastating rice blast fungus Magnaporthe oryzae, six Magnaporthe appressoria-specific (MAS) proteins are encoded by MoGAS1, MoGAS2 and MoMAS3–MoMAS6. MoGAS1 and MoGAS2 were previously characterized as M. oryzae virulence factors; however, the roles of the other four genes are unknown. Here, we found that, although the loss of any MAS gene did not affect appressorial formation or vegetative growth, ΔMomas3 and ΔMomas5 mutant strains (but not the others) were reduced in virulence on susceptible CO-39 rice seedlings. Focusing on ΔMomas3 and ΔMomas5 mutant strains, we found that they could penetrate host leaf surfaces and fill the first infected rice cell but did not spread readily to neighbouring cells, suggesting they were impaired for biotrophic growth. Live-cell imaging of fluorescently labelled MoMas3 and MoMas5 proteins showed that during biotrophy, MoMas3 localized to the apoplastic compartment formed between fungal invasive hyphae and the plant-derived extra-invasive hyphal membrane while MoMas5 localized to the appressoria and the penetration peg. The loss of either MoMAS3 or MoMAS5 resulted in the accumulation of reactive oxygen species (ROS) in infected rice cells, resulting in the triggering of plant defences that inhibited mutant growth in planta. ΔMomas3 a nd ΔMomas5 biotrophic growth could be remediated by inhibiting host NADPH oxidases and suppressing ROS accumulation. Thus, MoMas3 and MoMas5 are novel virulence factors involved in suppressing host plant innate immunity to promote biotrophic growth

    Age Differentiation within Gray Matter, White Matter, and between Memory and White Matter in an Adult Life Span Cohort.

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    It is well established that brain structures and cognitive functions change across the life span. A long-standing hypothesis called "age differentiation" additionally posits that the relations between cognitive functions also change with age. To date, however, evidence for age-related differentiation is mixed, and no study has examined differentiation of the relationship between brain and cognition. Here we use multigroup structural equation models (SEMs) and SEM trees to study differences within and between brain and cognition across the adult life span (18-88 years) in a large (N > 646, closely matched across sexes), population-derived sample of healthy human adults from the Cambridge Centre for Ageing and Neuroscience (www.cam-can.org). After factor analyses of gray matter volume (from T1- and T2-weighted MRI) and white matter organization (fractional anisotropy from diffusion-weighted MRI), we found evidence for the differentiation of gray and white matter, such that the covariance between brain factors decreased with age. However, we found no evidence for age differentiation among fluid intelligence, language, and memory, suggesting a relatively stable covariance pattern among cognitive factors. Finally, we observed a specific pattern of age differentiation between brain and cognitive factors, such that a white matter factor, which loaded most strongly on the hippocampal cingulum, became less correlated with memory performance in later life. These patterns are compatible with the reorganization of cognitive functions in the face of neural decline, and/or with the emergence of specific subpopulations in old age.SIGNIFICANCE STATEMENT The theory of age differentiation posits age-related changes in the relationships among cognitive domains, either weakening (differentiation) or strengthening (dedifferentiation), but evidence for this hypothesis is mixed. Using age-varying covariance models in a large cross-sectional adult life span sample, we found age-related reductions in the covariance among both brain measures (neural differentiation), but no covariance change among cognitive factors of fluid intelligence, language, and memory. We also observed evidence of uncoupling (differentiation) between a white matter factor and cognitive factors in older age, most strongly for memory. Together, our findings support age-related differentiation as a complex, multifaceted pattern that differs for brain and cognition, and discuss several mechanisms that might explain the changing relationship between brain and cognition
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