103,642 research outputs found

    Instrumental Variables Estimation with Some Invalid Instruments and its Application to Mendelian Randomization

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    Instrumental variables have been widely used for estimating the causal effect between exposure and outcome. Conventional estimation methods require complete knowledge about all the instruments' validity; a valid instrument must not have a direct effect on the outcome and not be related to unmeasured confounders. Often, this is impractical as highlighted by Mendelian randomization studies where genetic markers are used as instruments and complete knowledge about instruments' validity is equivalent to complete knowledge about the involved genes' functions. In this paper, we propose a method for estimation of causal effects when this complete knowledge is absent. It is shown that causal effects are identified and can be estimated as long as less than 5050% of instruments are invalid, without knowing which of the instruments are invalid. We also introduce conditions for identification when the 50% threshold is violated. A fast penalized â„“1\ell_1 estimation method, called sisVIVE, is introduced for estimating the causal effect without knowing which instruments are valid, with theoretical guarantees on its performance. The proposed method is demonstrated on simulated data and a real Mendelian randomization study concerning the effect of body mass index on health-related quality of life index. An R package \emph{sisVIVE} is available online.Comment: 99 pages, 29 figures, 14 table

    Genome-Wide Studies of Histone Demethylation Catalysed by the Fission Yeast Homologues of Mammalian LSD1

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    In order to gain a more global view of the activity of histone demethylases, we report here genome-wide studies of the fission yeast SWIRM and polyamine oxidase (PAO) domain homologues of mammalian LSD1. Consistent with previous work we find that the two S. pombe proteins, which we name Swm1 and Swm2 (after SWIRM1 and SWIRM2), associate together in a complex. However, we find that this complex specifically demethylates lysine 9 in histone H3 (H3K9) and both up- and down-regulates expression of different groups of genes. Using chromatin-immunoprecipitation, to isolate fragments of chromatin containing either H3K4me2 or H3K9me2, and DNA microarray analysis (ChIP-chip), we have studied genome-wide changes in patterns of histone methylation, and their correlation with gene expression, upon deletion of the swm1+ gene. Using hyper-geometric probability comparisons we uncover genetic links between lysine-specific demethylases, the histone deacetylase Clr6, and the chromatin remodeller Hrp1. The data presented here demonstrate that in fission yeast the SWIRM/PAO domain proteins Swm1 and Swm2 are associated in complexes that can remove methyl groups from lysine 9 methylated histone H3. In vitro, we show that bacterially expressed Swm1 also possesses lysine 9 demethylase activity. In vivo, loss of Swm1 increases the global levels of both H3K9me2 and H3K4me2. A significant accumulation of H3K4me2 is observed at genes that are up-regulated in a swm1 deletion strain. In addition, H3K9me2 accumulates at some genes known to be direct Swm1/2 targets that are down-regulated in the swm1¿ strain. The in vivo data indicate that Swm1 acts in concert with the HDAC Clr6 and the chromatin remodeller Hrp1 to repress gene expression. In addition, our in vitro analyses suggest that the H3K9 demethylase activity requires an unidentified post-translational modification to allow it to act. Thus, our results highlight complex interactions between histone demethylase, deacetylase and chromatin remodelling activities in the regulation of gene expression

    Radiocarbon Date List XI: Radiocarbon Dates from Marine Sediment Cores of the Iceland, Greenland, and Northeast Canadian Arctic Shelves and Nares Strait

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    Radiocarbon Date List XI contains an annotated listing of 178 AMS radiocarbon dates on samples from marine (169 samples) and lake (9 samples) sediment cores. Marine sediment cores, from which the samples for dating were taken, were collected on the Greenland Shelf, Baffin Bay, and the Eastern Canadian Arctic shelf. About 80% of the marine samples for dating were collected on the SW to N Icelandic shelf. The lake sediment cores were collected in northwestern Iceland. For dating of the marine samples, we submitted molluscs (117 samples), benthic and planktic foraminifera (45 samples), plant macrofauna (3 samples), and one serpulid worm. For dating of the lake cores, we submitted wood (8 samples) and one peat sample. The Conventional Radiocarbon Ages range from 294±9114C yr BP to 34,600±640 14C yr BP. The dates have been used to address a variety of research questions. The dates constrain the timing of high northern latitude late Quaternary environmental fluctuations, which include glacier extent, sea level history, isostatic rebound, sediment input, and ocean circulation. The dates also allowed assessment of the accuracy of commonly used reservoir correction. The samples were submitted by INSTAAR and affiliated researchers

    Gray’s revised Reinforcement Sensitivity Theory in relation to Attention-Deficit/Hyperactivity and Tourette-like behaviors in the general population

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    Attention-Deficit/Hyperactivity Disorder (ADHD) and Tourette Syndrome (TS) present as distinct conditions clinically; however, they show comorbidity and inhibitory control deficits have been proposed to underlie both. The role of reinforcement sensitivity in ADHD has been studied previously, but no study has addressed this in relation to TS-like behaviors in the general population. The present study examined these associations within the remit of the revised Reinforcement Sensitivity Theory (rRST). One hundred and thirty-eight participants completed psychometric measures of the rRST, and self-report checklists for ADHD- and TS-like behaviors

    On the correlation structure of microstructure noise in theory and practice

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    We argue for incorporating the financial economics of market microstructure into the financial econometrics of asset return volatility estimation. In particular, we use market microstructure theory to derive the cross-correlation function between latent returns and market microstructure noise, which feature prominently in the recent volatility literature. The cross-correlation at zero displacement is typically negative, and cross-correlations at nonzero displacements are positive and decay geometrically. If market makers are sufficiently risk averse, however, the cross-correlation pattern is inverted. Our results are useful for assessing the validity of the frequently-assumed independence of latent price and microstructure noise, for explaining observed cross-correlation patterns, for predicting as-yet undiscovered patterns, and for making informed conjectures as to improved volatility estimation methods

    Representations of sources and data: working with exceptions to hierarchy in historical documents

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    Joint Learning of Correlated Sequence Labelling Tasks Using Bidirectional Recurrent Neural Networks

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    The stream of words produced by Automatic Speech Recognition (ASR) systems is typically devoid of punctuations and formatting. Most natural language processing applications expect segmented and well-formatted texts as input, which is not available in ASR output. This paper proposes a novel technique of jointly modeling multiple correlated tasks such as punctuation and capitalization using bidirectional recurrent neural networks, which leads to improved performance for each of these tasks. This method could be extended for joint modeling of any other correlated sequence labeling tasks.Comment: Accepted in Interspeech 201

    The Calibration of Mid-Infrared Star Formation Rate Indicators

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    With the goal of investigating the degree to which the mid-infrared emission traces the star formation rate (SFR), we analyze Spitzer 8 um and 24 um data of star-forming regions in a sample of 33 nearby galaxies with available HST/NICMOS images in the Paschen-alpha (1.8756 um) emission line. The galaxies are drawn from the Spitzer Infrared Nearby Galaxies Survey (SINGS) sample, and cover a range of morphologies and a factor ~10 in oxygen abundance. Published data on local low-metallicity starburst galaxies and Luminous Infrared Galaxies are also included in the analysis. Both the stellar-continuum-subtracted 8 um emission and the 24 um emission correlate with the extinction-corrected Pa-alpha line emission, although neither relationship is linear. Simple models of stellar populations and dust extinction and emission are able to reproduce the observed non-linear trend of the 24 um emission versus number of ionizing photons, including the modest deficiency of 24 um emission in the low metallicity regions, which results from a combination of decreasing dust opacity and dust temperature at low luminosities. Conversely, the trend of the 8 um emission as a function of the number of ionizing photons is not well reproduced by the same models. The 8 um emission is contributed, in larger measure than the 24 um emission, by dust heated by non-ionizing stellar populations, in agreement with previous findings. Two SFR calibrations, one using the 24 um emission and the other using a combination of the 24 um and H-alpha luminosities (Kennicutt et al. 2007), are presented. No calibration is presented for the 8 um emission, because of its significant dependence on both metallicity and environment. The calibrations presented here should be directly applicable to systems dominated by on-going star formation.Comment: 67 pages, 15 figures, accepted for publication on the Astrophysical Journal; replacement contains: correction to equation 8; important tweaks to equation 9; various typos correcte
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