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Large-scale annotation efforts typically involve several experts who may disagree with each other. We propose an approach for modeling disagreements among experts that allows providing each annotation with a confidence value (i.e., the posterior probability that it is correct). Our approach allows computing certainty-level for individual annotations, given annotator-specific parameters estimated from data. We developed two probabilistic models for performing this analysis, compared these models using computer simulation, and tested each model's actual performance, based on a large data set generated by human annotators specifically for this study. We show that even in the worst-case scenario, when all annotators disagree, our approach allows us to significantly increase the probability of choosing the correct annotation. Along with this publication we make publicly available a corpus of 10,000 sentences annotated according to several cardinal dimensions that we have introduced in earlier work. The 10,000 sentences were all 3-fold annotated by a group of eight experts, while a 1,000-sentence subset was further 5-fold annotated by five new experts. While the presented data represent a specialized curation task, our modeling approach is general; most data annotation studies could benefit from our methodology. 相似文献
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Atrial fibrillation (AF) remains the most common pathologic dysrhythmia in humans
with a prevalence of 1-2% of the total population and as high as 10% of the
elderly. AF is an independent risk marker for cardiovascular mortality and
morbidity, and given the increasing age of the population, represents an
increasing burden of disease. Although age and hypertension are known risk
factors for development of AF, the study of families with early onset AF
revealed mutations in genes coding for ion channels and other proteins involved
in electrotonic coupling as likely culprits for the pathology in select cases.
Recent investigations using Genome-Wide Association Studies have revealed
several single nucleotide polymorphisms (SNPs) that appear to be associated with
AF and have highlighted new genes in the proximity of the SNPs that may
potentially contribute to the development of the dysrhythmia. Here we review the
genetics of AF and discuss how application of GWAS and next generation
sequencing have advanced our knowledge of AF and further investigations may
yield novel therapeutic targets for the disease. 相似文献
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Getting In or Out: Early Segregation Between Importers and Exporters in the Evolution of ATP-Binding Cassette (ABC) Transporters 总被引:17,自引:0,他引:17
ATP-binding cassette (ABC) systems, also called traffic ATPases, are found in eukaryotes and prokaryotes and almost all participate
in the transport of a wide variety of molecules. ABC systems are characterized by a highly conserved ATPase module called
here the ABC module, involved in coupling transport to ATP hydrolysis. We have used the sequence of one of the first representatives
of bacterial ABC transporters, the MalK protein, to collect 250 closely related sequences from a nonredundant protein sequence
database. The sequences collected by this objective method are all known or putative ABC transporters. After having eliminated
short protein sequences and duplicates, the 197 remaining sequences were subjected to a phylogenetic analysis based on a mutational
similarity matrix. An unrooted tree for these modules was found to display two major branches, one grouping all collected
uptake systems and the other all collected export systems. This remarkable disposition strongly suggests that the divergence
between these two functionally different types of ABC systems occurred once in the history of these systems and probably before
the differentiation of prokaryotes and eukaryotes. We discuss the implications of this finding and we propose a model accounting
for the generation and the diversification of ABC systems.
Received: 23 February 1997 / Accepted: 7 April 1998 相似文献
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The potential of exosomes to treat central nervous system (CNS) pathologies has been recently demonstrated. These studies make way for a complete new field that aims to exploit the natural characteristics of these vesicles, considered for a long time as side products of physiological cellular pathways. Recently, however, the biological significance of exosomes has been evaluated and exosomes can now be viewed upon as new relevant functional entities for development of novel therapeutic strategies. In this review, we aim to summarize the state-of-the-art role of exosomes in the CNS and to speculate about possible future therapeutic applications of exosomes. In particular, we will speculate about the use of these vesicles as a substitute of cell-based therapies for the treatment of brain damage and review the potential of exosomes as drug delivery vehicles for the CNS. 相似文献
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Kolesnik Matvey V. Fedorova Iana Karneyeva Karyna A. Artamonova Daria N. Severinov Konstantin V. 《Biochemistry. Biokhimii?a》2021,86(10):1301-1314
Biochemistry (Moscow) - The emergence and persistence of selfish genetic elements is an intrinsic feature of all living systems. Cellular organisms have evolved a plethora of elaborate defense... 相似文献
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Objective: Body fatness is partly under hypothalamic control with effector limbs, which include the endocrine system and the autonomic nervous system (ANS). In previous studies we have shown, in both obese and never‐obese subjects, that weight increase leads to increased sympathetic and decreased parasympathetic activity, whereas weight decrease leads to decreased sympathetic and increased parasympathetic activity. We now report on the involvement of such ANS mechanisms in the action of anti‐obesity drugs, independent of change in weight. Research Methods and Procedures: Normal weight males (ages 22 to 38 years) were fed a solid food diet, carefully measured to maintain body weight, for at least 2 weeks, as inpatients at the Rockefeller University General Clinical Research Center. In a single‐blind, placebo/drug/placebo design, eight subjects received dexfenfluramine, seven phentermine (PHE), and seven sibutramine (SIB). ANS measures of parasympathetic and sympathetic activity included: determination of amount of parasympathetic control (PC) and sympathetic control (SC) of heart period (interbeat interval), using sequential pharmacological blockade by intravenous administration of atropine and esmolol. These autonomic controls of heart period are used to estimate the overall level of parasympathetic and sympathetic activities. Norepinephrine, dopamine, and epinephrine levels in 24‐hour urine collections were measured and also resting metabolic rate (RMR). Results: Sufficient food intake maintained constant body weight in all groups. PHE and SIB produced significant increases in SC but no change in PC or in RMR. In contrast, dexfenfluramine produced marked decreases in SC, PC, and RMR. For all three drugs, the effects on urine catecholamines directly paralleled changes in cardiac measures of SC. Discussion: ANS responses to PHE and SIB were anticipated. The large, and unanticipated, response to dexfenfluramine suggests further study to determine whether there could be any relation of these ANS changes to the adverse cardiovascular effects of treatment with dexfenfluramine. 相似文献
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Context
Because positive biomedical observations are more often published than those reporting no effect, initial observations are often refuted or attenuated by subsequent studies.Objective
To determine whether newspapers preferentially report on initial findings and whether they also report on subsequent studies.Methods
We focused on attention deficit hyperactivity disorder (ADHD). Using Factiva and PubMed databases, we identified 47 scientific publications on ADHD published in the 1990s and soon echoed by 347 newspapers articles. We selected the ten most echoed publications and collected all their relevant subsequent studies until 2011. We checked whether findings reported in each “top 10” publication were consistent with previous and subsequent observations. We also compared the newspaper coverage of the “top 10” publications to that of their related scientific studies.Results
Seven of the “top 10” publications were initial studies and the conclusions in six of them were either refuted or strongly attenuated subsequently. The seventh was not confirmed or refuted, but its main conclusion appears unlikely. Among the three “top 10” that were not initial studies, two were confirmed subsequently and the third was attenuated. The newspaper coverage of the “top 10” publications (223 articles) was much larger than that of the 67 related studies (57 articles). Moreover, only one of the latter newspaper articles reported that the corresponding “top 10” finding had been attenuated. The average impact factor of the scientific journals publishing studies echoed by newspapers (17.1 n = 56) was higher (p<0.0001) than that corresponding to related publications that were not echoed (6.4 n = 56).Conclusion
Because newspapers preferentially echo initial ADHD findings appearing in prominent journals, they report on uncertain findings that are often refuted or attenuated by subsequent studies. If this media reporting bias generalizes to health sciences, it represents a major cause of distortion in health science communication. 相似文献16.
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Glickman MH 《Seminars in cell & developmental biology》2000,11(3):149-158
By far the best understood role of the proteasome is to remove ubiquitin-conjugated proteins from eukaryotric cells by hydrolysing them into small peptides of varying lengths. These include both misfolded/abnormal proteins, as well as 'normal' proteins that need to be rapidly removed for regulatory purposes. However, the proteasome is also present in numerous prokaryotic organisms, while ubiquitin, and the ubiquitin conjugating system, are not. The eukaryotic proteasome has been adapted to degrading proteins in a ubiquitin-dependent fashion by the addition of regulatory factors that assemble in different layers onto the proteolytic core of the proteasome, and by increasing the diversity of the core subunits as well. In addition to hydrolysing ubiquitinated proteins into amino acids, the proteasome can also proteolyse selected non-ubiquitinated proteins, process proteins, and possibly refold misfolded proteins. This review will focus on the different proteasome functions, and how these are used in the multiple regulatory roles the proteasome plays in eukaryotic cells. 相似文献
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