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  • 1
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    On the stationary distribution of iterative imputations (2014)
    Oxford University Press
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    Publikationsdatum: 2014-02-26
    Beschreibung: Iterative imputation, in which variables are imputed one at a time conditional on all the others, is a popular technique that can be convenient and flexible, as it replaces a potentially difficult multivariate modelling problem with relatively simple univariate regressions. In this paper, we begin to characterize the stationary distributions of iterative imputations and their statistical properties, accounting for the conditional models being iteratively estimated from data rather than being prespecified. When the families of conditional models are compatible, we provide sufficient conditions under which the imputation distribution converges in total variation to the posterior distribution of a Bayesian model. When the conditional models are incompatible but valid, we show that the combined imputation estimator is consistent.
    Print ISSN: 0006-3444
    Digitale ISSN: 1464-3510
    Thema: Biologie , Mathematik , Medizin
    Publiziert von Oxford University Press
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  • 2
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    Commentary: Physical activity and weight control (2014)
    Oxford University Press
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    Publikationsdatum: 2014-01-11
    Print ISSN: 0300-5771
    Digitale ISSN: 1464-3685
    Thema: Medizin
    Publiziert von Oxford University Press
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  • 3
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    Evidence for the thermal Sunyaev-Zel'dovich effect associated with quasar feedback (2016)
    Oxford University Press
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    Publikationsdatum: 2016-03-24
    Beschreibung: Using a radio-quiet subsample of the Sloan Digital Sky Survey spectroscopic quasar catalogue, spanning redshifts 0.5–3.5, we derive the mean millimetre and far-infrared quasar spectral energy distributions (SEDs) via a stacking analysis of Atacama Cosmology Telescope and Herschel -Spectral and Photometric Imaging REceiver data. We constrain the form of the far-infrared emission and find 3–4 evidence for the thermal Sunyaev–Zel'dovich (SZ) effect, characteristic of a hot ionized gas component with thermal energy (6.2 ± 1.7) x 10 60  erg. This amount of thermal energy is greater than expected assuming only hot gas in virial equilibrium with the dark matter haloes of (1–5) x 10 12 h –1 M that these systems are expected to occupy, though the highest quasar mass estimates found in the literature could explain a large fraction of this energy. Our measurements are consistent with quasars depositing up to $(14.5 \pm 3.3)\tau _8^{-1}$  per cent of their radiative energy into their circumgalactic environment if their typical period of quasar activity is 8 x 10 8 yr. For high quasar host masses, ~10 13 h –1 M , this percentage will be reduced. Furthermore, the uncertainty on this percentage is only statistical and additional systematic uncertainties enter at the 40 per cent level. The SEDs are dust dominated in all bands and we consider various models for dust emission. While sufficiently complex dust models can obviate the SZ effect, the SZ interpretation remains favoured at the 3–4 level for most models.
    Print ISSN: 0035-8711
    Digitale ISSN: 1365-2966
    Thema: Physik
    Publiziert von Oxford University Press
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  • 4
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    Foreground-induced biases in CMB polarimeter self-calibration (2016)
    Oxford University Press
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    Publikationsdatum: 2016-02-06
    Beschreibung: Precise polarization measurements of the cosmic microwave background (CMB) require accurate knowledge of the instrument orientation relative to the sky frame used to define the cosmological Stokes parameters. Suitable celestial calibration sources that could be used to measure the polarimeter orientation angle are limited, so current experiments commonly ‘self-calibrate.’ The self-calibration method exploits the theoretical fact that the EB and TB cross-spectra of the CMB vanish in the standard cosmological model, so any detected EB and TB signals must be due to systematic errors. However, this assumption neglects the fact that polarized Galactic foregrounds in a given portion of the sky may have non-zero EB and TB cross-spectra. If these foreground signals remain in the observations, then they will bias the self-calibrated telescope polarization angle and produce a spurious B -mode signal. In this paper, we estimate the foreground-induced bias for various instrument configurations and then expand the self-calibration formalism to account for polarized foreground signals. Assuming the EB correlation signal for dust is in the range constrained by angular power spectrum measurements from Planck at 353 GHz (scaled down to 150 GHz), then the bias is negligible for high angular resolution experiments, which have access to CMB-dominated high modes with which to self-calibrate. Low-resolution experiments observing particularly dusty sky patches can have a bias as large as 0 $_{.}^{\circ}$ 5. A miscalibration of this magnitude generates a spurious BB signal corresponding to a tensor-to-scalar ratio of approximately r  ~ 2  x  10 –3 , within the targeted range of planned experiments.
    Print ISSN: 0035-8711
    Digitale ISSN: 1365-2966
    Thema: Physik
    Publiziert von Oxford University Press
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  • 5
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    Cardiomyocyte ryanodine receptor degradation by chaperone-mediated autophagy (2013)
    Oxford University Press
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    Publikationsdatum: 2013-04-24
    Beschreibung: Time for primary review: 15 days Aims Chaperone-mediated autophagy (CMA) is a selective mechanism for the degradation of soluble cytosolic proteins bearing the sequence KFERQ. These proteins are targeted by chaperones and delivered to lysosomes where they are translocated into the lysosomal lumen and degraded via the lysosome-associated membrane protein type 2A (LAMP-2A). Mutations in LAMP2 that inhibit autophagy result in Danon disease characterized by hypertrophic cardiomyopathy. The ryanodine receptor type 2 (RyR2) plays a key role in cardiomyocyte excitation–contraction and its dysfunction can lead to cardiac failure. Whether RyR2 is degraded by CMA is unknown. Methods and results To induce CMA, cultured neonatal rat cardiomyocytes were treated with geldanamycin (GA) to promote protein degradation through this pathway. GA increased LAMP-2A levels together with its redistribution and colocalization with Hsc70 in the perinuclear region, changes indicative of CMA activation. The inhibition of lysosomes but not proteasomes prevented the loss of RyR2. The recovery of RyR2 content after incubation with GA by siRNA targeting LAMP-2A suggests that RyR2 is degraded via CMA. In silico analysis also revealed that the RyR2 sequence harbours six KFERQ motifs which are required for the recognition Hsc70 and its degradation via CMA. Our data suggest that presenilins are involved in RyR2 degradation by CMA. Conclusion These findings are consistent with a model in which oxidative damage of the RyR2 targets it for turnover by presenilins and CMA, which could lead to removal of damaged or leaky RyR2 channels.
    Print ISSN: 0008-6363
    Digitale ISSN: 1755-3245
    Thema: Medizin
    Publiziert von Oxford University Press
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  • 6
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    Delayed Puberty but Normal Fertility in Mice With Selective Deletion of Insulin Receptors From Kiss1 Cells (2013)
    Oxford University Press
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    Publikationsdatum: 2013-02-22
    Beschreibung: Pubertal onset only occurs in a favorable, anabolic hormonal environment. The neuropeptide kisspeptin, encoded by the Kiss1 gene, modifies GnRH neuronal activity to initiate puberty and maintain fertility, but the factors that regulate Kiss1 neurons and permit pubertal maturation remain to be clarified. The anabolic factor insulin may signal nutritional status to these neurons. To determine whether insulin sensing plays an important role in Kiss1 neuron function, we generated mice lacking insulin receptors in Kiss1 neurons (IR Kiss mice). IR Kiss females showed a delay in vaginal opening and in first estrus, whereas IR Kiss males also exhibited late sexual maturation. Correspondingly, LH levels in IR Kiss mice were reduced in early puberty in both sexes. Adult reproductive capacity, body weight, fat composition, food intake, and glucose regulation were comparable between the 2 groups. These data suggest that impaired insulin sensing by Kiss1 neurons delays the initiation of puberty but does not affect adult fertility. These studies provide insight into the mechanisms regulating pubertal timing in anabolic states.
    Print ISSN: 0013-7227
    Thema: Medizin
    Publiziert von Oxford University Press im Namen von The Endocrine Society.
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  • 7
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    MP-T: improving membrane protein alignment for structure prediction (2012)
    Oxford University Press
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    Publikationsdatum: 2012-12-21
    Beschreibung: Motivation: Membrane proteins are clinically relevant, yet their crystal structures are rare. Models of membrane proteins are typically built from template structures with low sequence identity to the target sequence, using a sequence-structure alignment as a blueprint. This alignment is usually made with programs designed for use on soluble proteins. Biological membranes have layers of varying hydrophobicity, and membrane proteins have different amino-acid substitution preferences from their soluble counterparts. Here we include these factors into an alignment method to improve alignments and consequently improve membrane protein models. Results: We developed Membrane Protein Threader (MP-T), a sequence-structure alignment tool for membrane proteins based on multiple sequence alignment. Alignment accuracy is tested against seven other alignment methods over 165 non-redundant alignments of membrane proteins. MP-T produces more accurate alignments than all other methods tested ( F M from +0.9 to +5.5%). Alignments generated by MP-T also lead to significantly better models than those of the best alternative alignment tool (one-fourth of models see an increase in GDT_TS of ≥4%). Availability: All source code, alignments and models are available at http://www.stats.ox.ac.uk/proteins/resources Contact: deane@stats.ox.ac.uk Supplementary information : Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Digitale ISSN: 1460-2059
    Thema: Biologie , Informatik , Medizin
    Publiziert von Oxford University Press
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  • 8
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    Memoir: template-based structure prediction for membrane proteins (2013)
    Oxford University Press
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    Publikationsdatum: 2013-06-23
    Beschreibung: Membrane proteins are estimated to be the targets of 50% of drugs that are currently in development, yet we have few membrane protein crystal structures. As a result, for a membrane protein of interest, the much-needed structural information usually comes from a homology model. Current homology modelling software is optimized for globular proteins, and ignores the constraints that the membrane is known to place on protein structure. Our Memoir server produces homology models using alignment and coordinate generation software that has been designed specifically for transmembrane proteins. Memoir is easy to use, with the only inputs being a structural template and the sequence that is to be modelled. We provide a video tutorial and a guide to assessing model quality. Supporting data aid manual refinement of the models. These data include a set of alternative conformations for each modelled loop, and a multiple sequence alignment that incorporates the query and template. Memoir works with both α-helical and β-barrel types of membrane proteins and is freely available at http://opig.stats.ox.ac.uk/webapps/memoir .
    Print ISSN: 0305-1048
    Digitale ISSN: 1362-4962
    Thema: Biologie
    Publiziert von Oxford University Press
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  • 9
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    General model for diffusive growth of nanostructures (2015)
    Oxford University Press
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    Publikationsdatum: 2015-03-21
    Beschreibung: The physical properties of carbon nanotubes are known to be strongly dependent on both their radius and length. If nanotubes are to be mass produced for a wide variety of different applications, it is important that techniques are developed to reliably grow a large number of nanotubes with specific dimensions. Although there has been less research into the possible applications of different-sized fullerenes, as well as more unusual nanostructures like nanocones, it is to be expected that the dimensions of any nanostructure will be an important factor in many applications. For this reason, we need to understand how nanostructures can be forced to grow, or shrink, to any prescribed size. Here we model the diffusive growth of a general nanostructure using the classical diffusion equation coupled with a moving boundary condition that describes the growing surface of the nanostructure. The moving boundary condition plays the role of a Stefan moving boundary condition and describes a moving 2D surface with constant atomic surface density. We illustrate the model with reference to growing fullerenes, nanotubes and nanocones.
    Print ISSN: 0272-4960
    Digitale ISSN: 1464-3634
    Thema: Mathematik
    Publiziert von Oxford University Press
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  • 10
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    Cohort Profile: Mysore Parthenon Birth Cohort (2015)
    Oxford University Press
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    Publikationsdatum: 2015-02-26
    Beschreibung: The Mysore Parthenon Birth Cohort was established to examine the long-term effects of maternal glucose tolerance and nutritional status on cardiovascular disease risk factors in the offspring. During 1997–98, 830 of 1233 women recruited from the antenatal clinics of the Holdsworth Memorial Hospital (HMH), Mysore, India, underwent an oral glucose tolerance test. Of these, 667 women delivered live babies at HMH. Four babies with major congenital anomalies were excluded, and the remaining 663 were included for further follow-up. The babies had detailed anthropometry at birth and at 6–12-monthly intervals subsequently. Detailed cardiovascular investigations were done at ages 5, 9.5 and 13.5 years in the children, and in the parents at the 5-year and 9.5-year follow-ups. This ongoing study provides extensive data on serial anthropometry and body composition, physiological and biochemical measures, dietary intake, nutritional status, physical activity measures, stress reactivity measures and cognitive function, and socio-demographic parameters for the offspring. Data on anthropometry, cardiovascular risk factors and nutritional status are available for mothers during pregnancy. Anthropometry and risk factor measures are available for both parents at follow-up.
    Print ISSN: 0300-5771
    Digitale ISSN: 1464-3685
    Thema: Medizin
    Publiziert von Oxford University Press
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