2,649 research outputs found

    Visual BFI: an Exploratory Study for Image-based Personality Test

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    This paper positions and explores the topic of image-based personality test. Instead of responding to text-based questions, the subjects will be provided a set of "choose-your-favorite-image" visual questions. With the image options of each question belonging to the same concept, the subjects' personality traits are estimated by observing their preferences of images under several unique concepts. The solution to design such an image-based personality test consists of concept-question identification and image-option selection. We have presented a preliminary framework to regularize these two steps in this exploratory study. A demo version of the designed image-based personality test is available at http://www.visualbfi.org/. Subjective as well as objective evaluations have demonstrated the feasibility of image-based personality test in limited questions

    Evolution favors protein mutational robustness in sufficiently large populations

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    BACKGROUND: An important question is whether evolution favors properties such as mutational robustness or evolvability that do not directly benefit any individual, but can influence the course of future evolution. Functionally similar proteins can differ substantially in their robustness to mutations and capacity to evolve new functions, but it has remained unclear whether any of these differences might be due to evolutionary selection for these properties. RESULTS: Here we use laboratory experiments to demonstrate that evolution favors protein mutational robustness if the evolving population is sufficiently large. We neutrally evolve cytochrome P450 proteins under identical selection pressures and mutation rates in populations of different sizes, and show that proteins from the larger and thus more polymorphic population tend towards higher mutational robustness. Proteins from the larger population also evolve greater stability, a biophysical property that is known to enhance both mutational robustness and evolvability. The excess mutational robustness and stability is well described by existing mathematical theories, and can be quantitatively related to the way that the proteins occupy their neutral network. CONCLUSIONS: Our work is the first experimental demonstration of the general tendency of evolution to favor mutational robustness and protein stability in highly polymorphic populations. We suggest that this phenomenon may contribute to the mutational robustness and evolvability of viruses and bacteria that exist in large populations

    Gene variant effects across sodium channelopathies predict function and guide precision therapy

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    Pathogenic variants in the voltage-gated sodium channel gene family (SCNs) lead to early onset epilepsies, neurodevelopmental disorders, skeletal muscle channelopathies, peripheral neuropathies and cardiac arrhythmias. Disease-associated variants have diverse functional effects ranging from complete loss-of-function to marked gain-of-function. Therapeutic strategy is likely to depend on functional effect. Experimental studies offer important insights into channel function, but are resource intensive and only performed in a minority of cases. Given the evolutionarily conserved nature of the sodium channel genes we investigated whether similarities in biophysical properties between different voltage-gated sodium channels can predict function and inform precision treatment across sodium channelopathies. We performed a systematic literature search identifying functionally assessed variants in any of the nine voltage-gated sodium channel genes until 28 April 2021. We included missense variants that had been electrophysiologically characterised in mammalian cells in whole-cell patch-clamp recordings. We performed an alignment of linear protein sequences of all sodium channel genes and correlated variants by their overall functional effect on biophysical properties. Of 951 identified records, 437 sodium channel-variants met our inclusion criteria and were reviewed for functional properties. Of these, 141 variants were epilepsy-associated (SCN1/2/3/8A), 79 had a neuromuscular phenotype (SCN4/9/10/11A), 149 were associated with a cardiac phenotype (SCN5/10A) and 68 (16%) were considered benign. We detected 38 missense variant pairs with an identical disease-associated variant in a different sodium channel gene. 35 out of 38 of those pairs resulted in similar functional consequences indicating up to 92% biophysical agreement between corresponding sodium channel variants (odds ratio = 11.3; 95% CI = 2.8 to 66.9; P < 0.001). Pathogenic missense variants were clustered in specific functional domains, whereas population variants were significantly more frequent across non conserved domains (odds ratio = 18.6; 95% CI = 10.9 to 34.4; P < 0.001). Pore-loop regions were frequently associated with loss-of-function (LoF) variants, whereas inactivation sites were associated with gain-of-function (GoF; odds ratio = 42.1, 95% CI = 14.5 to 122.4; P < 0.001), whilst variants occurring in voltage-sensing regions comprised a range of gain- and loss-of-function effects. Our findings suggest that biophysical characterisation of variants in one SCN-gene can predict channel function across different SCN-genes where experimental data are not available. The collected data represent the first GoF versus LoF topological map of SCN proteins indicating shared patterns of biophysical effects aiding variant analysis and guiding precision therapy. We integrated our findings into a free online webtool to facilitate functional sodium channel gene variant interpretation (http://SCN-viewer.broadinstitute.org)

    Characteristics, management and outcome of a large necrotising otitis externa case series: need for standardised case definition

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    Background: Necrotising otitis externa (NOE) is a severe ear infection for which there are no established diagnostic or treatment guidelines. Objective: Describe clinical characteristics, management and outcomes for patients managed as NOE at a UK tertiary referral centre. Methods: Retrospective case series. Results: 58 (63%) patients were classified as definite NOE cases, 31 (34%) as probable and 3 (3%) as possible cases. Median duration of intravenous and oral antimicrobial therapy was 6.0 weeks (0.49-44.9). 6% of patients relapsed a median of 16.4 weeks (IQR 23-121) after stopping antimicrobials. 28% of cases had complex disease. These patients were older (p=0.042), had a longer duration of symptoms prior to imaging (p= 0.0001) and higher CRP at diagnosis (p=0.005). Despite longer courses of intravenous antimicrobials (23 days v 14 days; p=0.032), complex cases were more likely to relapse (p=0.016). Conclusion: A standardised case-definition of NOE is needed to optimise diagnosis, management and research

    Use of QSARs in international decision-making frameworks to predict health effects of chemical substances

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    This article is a review of the use of quantitative (and qualitative) structure-activity relationships (QSARs and SARs) by regulatory agencies and authorities to predict acute toxicity, mutagenicity, carcinogenicity, and other health effects. A number of SAR and QSAR applications, by regulatory agencies and authorities, are reviewed. These include the use of simple QSAR analyses, as well as the use of multivariate QSARs, and a number of different expert system approaches

    ALMA Observations of the Debris Disk of Solar Analogue Ï„ Ceti

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    We present 1.3 mm observations of the Sun-like star τ Ceti with the Atacama Large Millimeter/submillimeter Array that probe angular scales of (4 au). This first interferometric image of the τ Ceti system, which hosts both a debris disk and a possible multiplanet system, shows emission from a nearly face-on belt of cold dust with a position angle of surrounding an unresolved central source at the stellar position. To characterize this emission structure, we fit parametric models to the millimeter visibilities. The resulting best-fit model yields an inner belt edge of au, consistent with inferences from lower resolution, far-infrared Herschel observations. While the limited data at sufficiently short baselines preclude us from placing stronger constraints on the belt properties and its relation to the proposed five planet system, the observations do provide a strong lower limit on the fractional width of the belt, with 99% confidence. This fractional width is more similar to broad disks such as HD 107146 than narrow belts such as the Kuiper Belt and Fomalhaut. The unresolved central source has a higher flux density than the predicted flux of the stellar photosphere at 1.3 mm. Given previous measurements of an excess by a factor of ∼2 at 8.7 mm, this emission is likely due to a hot stellar chromosphere.ALMA is a partnership of ESO (representing its member states), NSF (USA), and NINS (Japan), together with NRC (Canada) and NSC and ASIAA (Taiwan) and KASI (Republic of Korea), in cooperation with the Republic of Chile. The Joint ALMA Observatory is operated by ESO, AUI/NRAO, and NAOJ. The National Radio Astronomy Observatory is a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc. M.A.M. acknowledges support from a National Science Foundation Graduate Research Fellowship (DGE1144152). S.M.L. gratefully acknowledges support from the NRC Canada Plaskett Fellowship. B.C.M. acknowledges support from a Natural Science and Engineering Research Council (NSERC) Discovery Accelerator Supplement grant. G.M.K. is supported by the Royal Society as a Royal Society University Research Fellow. M.B. acknowledges support from a FONDECYT Postdoctral Fellowship, project no. 3140479 and the Millennium Science Initiative (Chilean Ministry of Economy), through grant RC130007

    Induced vertical disparity effects on local and global stereopsis

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    Purpose: Although significant amounts of vertical misalignment could have a noticeable effect on visual performance, there is no conclusive evidence about the effect of very small amount of vertical disparity on stereopsis and binocular vision. Hence, the aim of this study was to investigate the effects of induced vertical disparity on local and global stereopsis at near. Materials and Methods: Ninety participants wearing best-corrected refraction had local and global stereopsis tested with 0.5 and 1.0 prism diopter (Δ) vertical prism in front of their dominant and non-dominant eye in turn. This was compared to local and global stereopsis in the same subjects without vertical prism. Data were analyzed in SPSS.17 software using the independent samples T and the repeated measures ANOVA tests. Results: Induced vertical disparity decreases local and global stereopsis. This reduction is greater when vertical disparity is induced in front of the non-dominant eye and affects global more than local stereopsis. Repeated measures ANOVA showed differences in the mean stereopsis between the different measured states for local and global values. Local stereopsis thresholds were reduced by 10s of arc or less on average with 1.0Δ of induced vertical prism in front of either eye. However, global stereopsis thresholds were reduced by over 100s of arc by the same 1.0Δ of induced vertical prism. Conclusion: Induced vertical disparity affects global stereopsis thresholds by an order of magnitude (or a factor of 10) more than local stereopsis. Hence, using a test that measures global stereopsis such as the TNO is more sensitive to vertical misalignment than a test such as the Stereofly that measures local stereopsis. © 2014 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted

    A comparison of missing data methods for hypothesis tests of the treatment effect in substance abuse clinical trials: a Monte-Carlo simulation study

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    <p>Abstract</p> <p>Background</p> <p>Missing data due to attrition are rampant in substance abuse clinical trials. However, missing data are often ignored in the presentation of substance abuse clinical trials. This paper demonstrates missing data methods which may be used for hypothesis testing.</p> <p>Methods</p> <p>Methods involving stratifying and weighting individuals based on missing data pattern are shown to produce tests that are robust to missing data mechanisms in terms of Type I error and power. In this article, we describe several methods of combining data that may be used for testing hypotheses of the treatment effect. Furthermore, illustrations of each test's Type I error and power under different missing data percentages and mechanisms are quantified using a Monte-Carlo simulation study.</p> <p>Results</p> <p>Type I error rates were similar for each method, while powers depended on missing data assumptions. Specifically, power was greatest for the weighted, compared to un-weighted methods, especially for greater missing data percentages.</p> <p>Conclusion</p> <p>Results of this study as well as extant literature demonstrate the need for standards of design and analysis specific to substance abuse clinical trials. Given the known substantial attrition rates and concern for the missing data mechanism in substance abuse clinical trials, investigators need to incorporate missing data methods a priori. That is, missing data methods should be specified at the outset of the study and not after the data have been collected.</p

    TUIs vs. GUIs : comparing the learning potential with preschoolers

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    In an effort to better understand the learning potential of a tangible interface, we conducted a comparison study between a tangible and a traditional graphical user interface for teaching preschoolers (In Portugal, children enter preschool at the age of three and they attend it till entering school, normally at the age of six) about good oral hygiene. The study was carried with two groups of children aged 4 to 5 years. Questionnaires to parents, children’s drawings, and interviews were used for data collection and analysis and revealed important indicators about children’s change of attitude, involvement, and preferences for the interfaces. The questionnaires showed a remarkable change of attitude toward tooth brushing in the children that interacted with the tangible interface; particularly children’s motivation increased significantly. Children’s drawings were used to assess their degree of involvement with the interfaces. The drawings from the children that interacted with the tangible interface were very complete and detailed suggesting that the children felt actively involved with the experience. The results suggest that the tangible interface was capable of promoting a stronger and long-lasting involvement having a greater potential to engage children, therefore potentially promoting learning. Evaluation through drawing seems to be a promising method to work with preliterate children; however,it is advisable to use it together with other methods.Fundação para a Ciência e Tecnologia (FCT

    The Classification of T Dwarfs

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    We discuss methods for classifying T dwarfs based on spectral morphological features and indices. T dwarfs are brown dwarfs which exhibit methane absorption bands at 1.6 and 2.2 μm{\mu}m. Spectra at red optical (6300--10100 {\AA}) and near-infrared (1--2.5 μm{\mu}m) wavelengths are presented, and differences between objects are noted and discussed. Spectral indices useful for classification schemes are presented. We conclude that near-infrared spectral classification is generally preferable for these cool objects, with data sufficient to resolve the 1.17 and 1.25 μm{\mu}m K I doublets lines being most valuable. Spectral features sensitive to gravity are discussed, with the strength of the K-band peak used as an example. Such features may be used to derive a two-dimensional scheme based on temperature and mass, in analogy to the MK temperature and luminosity classes.Comment: 15 pages, 6 figures, conference proceedings for IAU Ultracool Dwarf Stars session, ed. I. Steele & H. Jone
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