16,016 research outputs found

    Measures of genetic diversification in somatic tissues at bulk and single-cell resolution.

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    Intra-tissue genetic heterogeneity is universal to both healthy and cancerous tissues. It emerges from the stochastic accumulation of somatic mutations throughout development and homeostasis. By combining population genetics theory and genomic information, genetic heterogeneity can be exploited to infer tissue organization and dynamics in vivo. However, many basic quantities, for example the dynamics of tissue-specific stem cells remain difficult to quantify precisely. Here, we show that single-cell and bulk sequencing data inform on different aspects of the underlying stochastic processes. Bulk-derived variant allele frequency spectra (VAF) show transitions from growing to constant stem cell populations with age in samples of healthy esophagus epithelium. Single-cell mutational burden distributions allow a sample size independent measure of mutation and proliferation rates. Mutation rates in adult hematopietic stem cells are higher compared to inferences during development, suggesting additional proliferation-independent effects. Furthermore, single-cell derived VAF spectra contain information on the number of tissue-specific stem cells. In hematopiesis, we find approximately 2 Ă— 105 HSCs, if all stem cells divide symmetrically. However, the single-cell mutational burden distribution is over-dispersed compared to a model of Poisson distributed random mutations. A time-associated model of mutation accumulation with a constant rate alone cannot generate such a pattern. At least one additional source of stochasticity would be needed. Possible candidates for these processes may be occasional bursts of stem cell divisions, potentially in response to injury, or non-constant mutation rates either through environmental exposures or cell-intrinsic variation

    SOXE neofunctionalization and elaboration of the neural crest during chordate evolution

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    During chordate evolution, two genome-wide duplications facilitated acquisition of vertebrate traits, including emergence of neural crest cells (NCCs), in which neofunctionalization of the duplicated genes are thought to have facilitated development of craniofacial structures and the peripheral nervous system. How these duplicated genes evolve and acquire the ability to specify NC and their derivatives are largely unknown. Vertebrate SoxE paralogues, most notably Sox9/10, are essential for NC induction, delamination and lineage specification. In contrast, the basal chordate, amphioxus, has a single SoxE gene and lacks NC-like cells. Here, we test the hypothesis that duplication and divergence of an ancestral SoxE gene may have facilitated elaboration of NC lineages. By using an in vivo expression assay to compare effects of AmphiSoxE and vertebrate Sox9 on NC development, we demonstrate that all SOXE proteins possess similar DNA binding and homodimerization properties and can induce NCCs. However, AmphiSOXE is less efficient than SOX9 in transactivation activity and in the ability to preferentially promote glial over neuronal fate, a difference that lies within the combined properties of amino terminal and transactivation domains. We propose that acquisition of AmphiSoxE expression in the neural plate border led to NCC emergence while duplication and divergence produced advantageous mutations in vertebrate homologues, promoting elaboration of NC traits.published_or_final_versio

    Lorentz-Violating Supergravity

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    The standard forms of supersymmetry and supergravity are inextricably wedded to Lorentz invariance. Here a Lorentz-violating form of supergravity is proposed. The superpartners have exotic properties that are not possible in a theory with exact Lorentz symmetry and microcausality. For example, the bosonic sfermions have spin 1/2 and the fermionic gauginos have spin 1. The theory is based on a phenomenological action that is shown to follow from a simple microscopic and statistical picture.Comment: 15 pages; to be published in Proceedings of Beyond the Desert 2003 (Castle Ringberg, Tegernsee, Germany, 9-14 June 2003), edited by H. V. Klapdor-Kleingrothau

    ForestHash: Semantic Hashing With Shallow Random Forests and Tiny Convolutional Networks

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    Hash codes are efficient data representations for coping with the ever growing amounts of data. In this paper, we introduce a random forest semantic hashing scheme that embeds tiny convolutional neural networks (CNN) into shallow random forests, with near-optimal information-theoretic code aggregation among trees. We start with a simple hashing scheme, where random trees in a forest act as hashing functions by setting `1' for the visited tree leaf, and `0' for the rest. We show that traditional random forests fail to generate hashes that preserve the underlying similarity between the trees, rendering the random forests approach to hashing challenging. To address this, we propose to first randomly group arriving classes at each tree split node into two groups, obtaining a significantly simplified two-class classification problem, which can be handled using a light-weight CNN weak learner. Such random class grouping scheme enables code uniqueness by enforcing each class to share its code with different classes in different trees. A non-conventional low-rank loss is further adopted for the CNN weak learners to encourage code consistency by minimizing intra-class variations and maximizing inter-class distance for the two random class groups. Finally, we introduce an information-theoretic approach for aggregating codes of individual trees into a single hash code, producing a near-optimal unique hash for each class. The proposed approach significantly outperforms state-of-the-art hashing methods for image retrieval tasks on large-scale public datasets, while performing at the level of other state-of-the-art image classification techniques while utilizing a more compact and efficient scalable representation. This work proposes a principled and robust procedure to train and deploy in parallel an ensemble of light-weight CNNs, instead of simply going deeper.Comment: Accepted to ECCV 201

    Exploiting Polyhedral Symmetries in Social Choice

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    A large amount of literature in social choice theory deals with quantifying the probability of certain election outcomes. One way of computing the probability of a specific voting situation under the Impartial Anonymous Culture assumption is via counting integral points in polyhedra. Here, Ehrhart theory can help, but unfortunately the dimension and complexity of the involved polyhedra grows rapidly with the number of candidates. However, if we exploit available polyhedral symmetries, some computations become possible that previously were infeasible. We show this in three well known examples: Condorcet's paradox, Condorcet efficiency of plurality voting and in Plurality voting vs Plurality Runoff.Comment: 14 pages; with minor improvements; to be published in Social Choice and Welfar

    Consenting to health record linkage: evidence from a multi-purpose longitudinal survey of a general population

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    Background: The British Household Panel Survey (BHPS) is the first long-running UK longitudinal survey with a non-medical focus and a sample covering the whole age range to have asked for permission to link to a range of administrative health records. This study determines whether informed consent led to selection bias and reflects on the value of the BHPS linked with health records for epidemiological research. Methods. Multivariate logistical regression is used, with whether the respondent gave consent to data linkage or not as the dependent variable. Independent variables were entered as four blocks; (i) a set of standard demographics likely to be found in most health registration data, (ii) a broader set of socio-economic characteristics, (iii) a set of indicators of health conditions and (iv) information about the use of health services. Results: Participants aged 16-24, males and those living in England were more likely to consent. Consent is not biased with respect to socio-economic characteristics or health. Recent users of GP services are underrepresented among consenters. Conclusions: Whilst data could only be linked for a minority of BHPS participants, the BHPS offers a great range of information on people's life histories, their attitudes and behaviours making it an invaluable source for epidemiological research. © 2012 Knies et al; licensee BioMed Central Ltd

    Learning Free-Form Deformations for 3D Object Reconstruction

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    Representing 3D shape in deep learning frameworks in an accurate, efficient and compact manner still remains an open challenge. Most existing work addresses this issue by employing voxel-based representations. While these approaches benefit greatly from advances in computer vision by generalizing 2D convolutions to the 3D setting, they also have several considerable drawbacks. The computational complexity of voxel-encodings grows cubically with the resolution thus limiting such representations to low-resolution 3D reconstruction. In an attempt to solve this problem, point cloud representations have been proposed. Although point clouds are more efficient than voxel representations as they only cover surfaces rather than volumes, they do not encode detailed geometric information about relationships between points. In this paper we propose a method to learn free-form deformations (FFD) for the task of 3D reconstruction from a single image. By learning to deform points sampled from a high-quality mesh, our trained model can be used to produce arbitrarily dense point clouds or meshes with fine-grained geometry. We evaluate our proposed framework on both synthetic and real-world data and achieve state-of-the-art results on point-cloud and volumetric metrics. Additionally, we qualitatively demonstrate its applicability to label transferring for 3D semantic segmentation.Comment: 16 pages, 7 figures, 3 table

    Associations Between Parenting Styles and Perceived Child Effortful Control Within Chinese Families in the United States, the United Kingdom, and Taiwan

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    The current study examined the associations between parentally perceived child effortful control (EC) and the parenting styles of 122 Chinese mothers (36 first-generation Chinese immigrants in the United Kingdom, 40 first-generation Chinese immigrants in the United States, and 46 Taiwanese mothers) of 5- to 7-year-old (M age = 5.82 years, SD = .805; 68 boys and 54 girls) children. The findings showed significant cultural group differences in mothers’ reported authoritarian parenting style. Significant associations also emerged between mothers’ reports of their children’s EC and some parenting dimensions, although there were no cultural group differences in perceived child EC. Different patterns of associations between perceived child EC and parenting styles in these three groups also demonstrated heterogeneity within the Chinese population, and highlighted the need to consider differences between original and receiving societies when seeking to understand parenting and child development in different immigrant groups
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