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The intricate details of how proteins bind to proteins, DNA, and RNA are crucial for the understanding of almost all biological processes. Disease-causing sequence variants often affect binding residues. Here, we described a new, comprehensive system of in silico methods that take only protein sequence as input to predict binding of protein to DNA, RNA, and other proteins. Firstly, we needed to develop several new methods to predict whether or not proteins bind (per-protein prediction). Secondly, we developed independent methods that predict which residues bind (per-residue). Not requiring three-dimensional information, the system can predict the actual binding residue. The system combined homology-based inference with machine learning and motif-based profile-kernel approaches with word-based (ProtVec) solutions to machine learning protein level predictions. This achieved an overall non-exclusive three-state accuracy of 77% ± 1% (±one standard error) corresponding to a 1.8 fold improvement over random (best classification for protein-protein with F1 = 91 ± 0.8%). Standard neural networks for per-residue binding residue predictions appeared best for DNA-binding (Q2 = 81 ± 0.9%) followed by RNA-binding (Q2 = 80 ± 1%) and worst for protein-protein binding (Q2 = 69 ± 0.8%). The new method, dubbed ProNA2020, is available as code through github (https://github.com/Rostlab/ProNA2020.git) and through PredictProtein (www.predictprotein.org)., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Our purpose, by modification of standard bedside tilt-testing, was to search for lesser known but important initial orthostatic hypotension (IOH), occurring transiently within the first 30 seconds of standing, heretofore only detectable with sophisticated continuous photoplethysmographic monitoring systems, not readily available in most medical facilities. In screened outpatients over 60 years of age, supine blood pressure (BP) parameters were recorded. To achieve readiness for immediate BP after standing, the cuff was re-inflated prior to standing, rather than after. Immediate, 1-, and 3-minute standing BPs were recorded. One hundred fifteen patients were studied (mean age, 71.1 years; 50.5% male). Eighteen (15.6%) had OH, of whom 14 (12.1%) had classical OH, and four (3.5%) had IOH. Early standing BP detection time was 20.1 ± 5.3 seconds. Immediate transient physiologic systolic BP decline was detected in non-OH (-8.8 ± 9.9 mm Hg; P < .0001). In contrast to classical OH (with lesser but persistent orthostatic BP decrements), IOH patients had immediate mean orthostatic systolic/diastolic BP change of -32.8 (±13.8) mm Hg/-14.0 (±8.5) mm Hg (P < .02), with recovery back to baseline by 1 minute. Two of the four IOH patients had pre-syncopal symptoms. For the first time, using standard inflation-deflation BP equipment, immediate transient standing physiologic BP decrement and IOH were demonstrated. This preliminary study confirms proof of principle that manual BP cuff inflation prior to standing may be useful and practical in diagnosing IOH, and may stimulate direct comparative studies with continuous monitoring systems., (Copyright © 2015 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

In the application of saturation transfer difference (STD) experiments to the study of protein-ligand interactions, the relaxation of the ligand is one of the major influences on the experimentally observed STD factors, making interpretation of these difficult when attempting to define a group epitope map (GEM). In this paper, we describe a simplification of the relaxation matrix that may be applied under specified experimental conditions, which results in a simplified equation reflecting the directly transferred magnetisation rate from the protein onto the ligand, defined as the summation over the whole protein of the protein-ligand cross-relaxation multiplied by with the fractional saturation of the protein protons. In this, the relaxation of the ligand is accounted for implicitly by inclusion of the experimentally determined longitudinal relaxation rates. The conditions under which this "group epitope mapping considering relaxation of the ligand" (GEM-CRL) can be applied were tested on a theoretical model system, which demonstrated only minor deviations from that predicted by the full relaxation matrix calculations (CORCEMA-ST) [7]. Furthermore, CORCEMA-ST calculations of two protein-saccharide complexes (Jacalin and TreR) with known crystal structures were performed and compared with experimental GEM-CRL data. It could be shown that the GEM-CRL methodology is superior to the classical group epitope mapping approach currently used for defining ligand-protein proximities. GEM-CRL is also useful for the interpretation of CORCEMA-ST results, because the transferred magnetisation rate provides an additional parameter for the comparison between measured and calculated values. The independence of this parameter from the above mentioned factors can thereby enhance the value of CORCEMA-ST calculations., (Copyright (c) 2009 Elsevier Inc. All rights reserved.)

Objective: To examine whether explanatory illustrations can improve older adults' comprehension of written health information., Methods: Six short health-related texts were selected from websites and pamphlets. Young and older adults were randomly assigned to read health-related texts alone or texts accompanied by explanatory illustrations. Eye movements were recorded while reading. Word recognition, text comprehension, and comprehension of the illustrations were assessed after reading., Results: Older adults performed as well as or better than young adults on the word recognition and text comprehension measures. However, older adults performed less well than young adults on the illustration comprehension measures. Analysis of readers' eye movements showed that older adults spent more time reading illustration-related phrases and fixating on the illustrations than did young adults, yet had poorer comprehension of the illustrations., Conclusion: Older adults might not benefit from text illustrations because illustrations can be difficult to integrate with the text., Practice Implications: Health practitioners should not assume that illustrations will increase older adults' comprehension of health information.

Sentence processing in Alzheimer's disease (AD) has been found to be influenced by several grammatical and extragrammatical factors, including phrase structure and verb-argument relations, number of propositions/verbs, and processing resource capacity. This study examines the effects of these variables on sentence production in AD. Normal control and AD subjects were asked to repeat six types of sentences varying along the above dimensions of complexity. Subjects' processing resource capacity was measured using several verbal working memory tests. AD subjects' sentence-repetition performance was impaired compared to the normal control group. Significant effects were observed for branching direction of phrase structure, canonicity of verb-argument relations, and serial position of errors. Sentence-repetition performance significantly correlated with working memory scores. The findings are interpreted within a resource capacity theory of sentence processing., (Copyright 2000 Academic Press.)