237 research outputs found

    Institutional repositories provide an ideal medium for scholars to move beyond the journal article.

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    Reflecting on their experiences supporting the growth of Columbia University’s Academic Commons digital repository, Leyla Williams, Kathryn Pope, and Brian Luna Lucero make a clear case for why other institutional repositories should look to broaden the scope of the materials they house

    Methodological concerns in the study of personal epistemology : the effect of the directness, domain, and open versus closed-ended formats of questions eliciting epistemological assumptions.

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    The study of personal epistemology is concerned with people‟s beliefs or assumptions about the nature of knowledge and knowing, otherwise referred to as epistemological assumptions. As a relatively new field of enquiry, questions about the nature and scope of the construct and how best to investigate it have been tackled by many researchers although fundamental questions still remain. The current study explored the possible effects of three characterisations of questions aimed at eliciting epistemological assumptions on conclusions drawn about such assumptions in terms of their level of sophistication. The three characterisations explored were the level of directness with which questions targeted epistemological assumptions, the domain-specificity of the question, and whether the questions were open or closed-ended. A paper-and-pencil measure was designed to manipulate these variables, and the conclusions drawn about the assumptions of a sample of 30 postgraduate Psychology students were compared across the conditions to determine if there was any evidence for their influence. Comparison of results suggested that the characterisations do exert an influence and caution is raised regarding the validity of methodologies that have been, and continue to be, employed in the study of personal epistemology. The findings further lend support to particular conceptualisations of the construct, but at the same time also unearth additional questions about how epistemological beliefs are best construed and studied

    Les reincarnations de Carmen: La creation d\u27un mythe

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    Carmen, the title character of Prosper Mérimée’s 1845 novella, has taken on many lives in the creative world. Adaptations of her story have been produced over the past 150 years in operas, ballets, and films. With each new reincarnation of Carmen, her identities as a femme fatale, gypsy, and sorcerer have been altered in order to appeal to her audience. Carmen’s character changes with the audience, presented as relatable and desirable to each new generation. Each piece represents Carmen in a new light, and I explore what allows this character to be able to be altered time and time again but still remain uniquely identifiable. Her character is distinctly recognizable in each piece: Carmen is thus not merely a popular culture reference but rather a modern myth, comparable to Don Juan and Faust

    SNPPar: identifying convergent evolution and other homoplasies from microbial whole-genome alignments

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    AbstractHomoplasic single nucleotide polymorphisms (SNPs) are considered important signatures of strong (positive) selective pressure, and hence of adaptive evolution for clinically relevant traits such as antibiotic resistance and virulence. Here we present a new tool, SNPPar, for efficient detection and analysis of homoplasic SNPs from large WGS datasets (&gt;1,000 isolates and/or &gt;100,000 SNPs). SNPPar takes as input a SNP alignment, tree and annotated reference genome, and uses a combination of simple monophyly tests and ancestral state reconstruction (ASR, via TreeTime) to assign mutation events to branches and identify homoplasies. Mutations are annotated at the level of codon and gene, to facilitate analysis of convergent evolution.Testing on simulated data (120Mycobacterium tuberculosisalignments representing local and global samples) showed SNPPar can detect homoplasic SNPs with very high sensitivity (zero false-positives in all tests) and high specificity (zero false-negatives in 89% of tests). SNPPar analysis of three empirically sampled datasets (E. anophelis, B. dolosaandM. tuberculosis) produced results that were in concordance with previous studies, in terms of both individual homoplasies and evidence of convergence at the codon and gene levels. SNPPar analysis of a simulated alignment of ∼64,000 genome-wide SNPs from 2000M. tuberculosisgenomes took ∼23 minutes and ∼2.6 GB of RAM to generate complete annotated results on a laptop. This analysis required ASR be conducted for only 1.25% of SNPs, and the ASR step took ∼23 seconds and 0.4 GB RAM.SNPPar automates the detection and annotation of homoplasic SNPs efficiently and accurately from large SNP alignments. As demonstrated by the examples included here, this information can be readily used to explore the role of homoplasy in parallel and/or convergent evolution at the level of nucleotide, codon and/or gene.Impact statementDNA sequences of bacterial pathogens are mutating all the time; most changes are deleterious or neutral, but sometimes a mutation leads to functional change that allows the pathogen to evade a potential threat. These random mutational changes (single nucleotide polymorphisms, or SNPs) are so very rarely beneficial, that when they do arise in parallel in distantly related isolates (known as homoplasic SNPs) this indicates that the change may be positively selected because it confers an adaptive advantage to the bacteria.Finding homoplasic SNPs in large sets of bacterial genomes is challenging as current tools require substantial time and computational resources to run. Here we present SNPPar, a software program to efficiently and accurately automate the detection and annotation of homoplasic SNPs from large whole-genome sequence data sets. We use simulated data to demonstrate accuracy of the program, and re-analyse published datasets using SNPPar to illustrate how the results can be used to gain insights into the evolution of antibiotic resistance and other traits.We envisage SNPPar will help facilitate the undertaking of long-term, real-time surveillance of bacterial pathogens, and their adaptive evolutionary response to interventions and control measures such as new drugs or vaccines.Data summaryThe authors confirm all supporting data, code and protocols have been provided within the article, through supplementary data files or other online sources as indicated in the article.New content generated for this paper is:SNPPar code is available fromhttps://github.com/d-j-e/SNPPar. The version described here is v1.0.A GitHub repository containing the full protocol, ‘in-house’ code and data used to carry out the validation and performance testing is available athttps://github.com/d-j-e/SNPPar_test. This repository includes all the simulated and real data sets used here.Data statementThe authors confirm all supporting data, code and protocols have been provided within the article, through supplementary data files or other online sources as indicated in the article.</jats:sec

    Information Transfer in Gonadotropin-Releasing Hormone (GnRH) Signaling:Extracellular Signal-Regulated Kinase (ERK)-Mediated Feedback Loops Control Hormone Sensing

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    Cell signaling pathways are noisy communication channels, and statistical measures derived from information theory can be used to quantify the information they transfer. Here we use single cell signaling measures to calculate mutual information as a measure of information transfer via gonadotropin-releasing hormone (GnRH) receptors (GnRHR) to extracellular signal-regulated kinase (ERK) or nuclear factor of activated T-cells (NFAT). This revealed mutual information values <1 bit, implying that individual GnRH-responsive cells cannot unambiguously differentiate even two equally probable input concentrations. Addressing possible mechanisms for mitigation of information loss, we focused on the ERK pathway and developed a stochastic activation model incorporating negative feedback and constitutive activity. Model simulations revealed interplay between fast (min) and slow (min-h) negative feedback loops with maximal information transfer at intermediate feedback levels. Consistent with this, experiments revealed that reducing negative feedback (by expressing catalytically inactive ERK2) and increasing negative feedback (by Egr1-driven expression of dual-specificity phosphatase 5 (DUSP5)) both reduced information transfer from GnRHR to ERK. It was also reduced by blocking protein synthesis (to prevent GnRH from increasing DUSP expression) but did not differ for different GnRHRs that do or do not undergo rapid homologous desensitization. Thus, the first statistical measures of information transfer via these receptors reveals that individual cells are unreliable sensors of GnRH concentration and that this reliability is maximal at intermediate levels of ERK-mediated negative feedback but is not influenced by receptor desensitization

    A refined, controlled 16S rRNA gene sequencing approach reveals limited detection of cerebrospinal fluid microbiota in children with bacterial meningitis

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    Advances in both laboratory and computational components of high-throughput 16S amplicon sequencing (16S HTS) have markedly increased its sensitivity and specificity. Additionally, these refinements have better delineated the limits of sensitivity, and contributions of contamination to these limits, for 16S HTS that are particularly relevant for samples with low bacterial loads, such as human cerebrospinal fluid (CSF). The objectives of this work were to (i) optimize the performance of 16S HTS in CSF samples with low bacterial loads by defining and addressing potential sources of error, and (ii) perform refined 16S HTS on CSF samples from children diagnosed with bacterial meningitis and compare results with those from microbiological cultures. Several bench and computational approaches were taken to address potential sources of error for low bacterial load samples. We compared DNA yields and sequencing results after applying three different DNA extraction approaches to an artificially constructed mock-bacterial community. We also compared two postsequencing computational contaminant removal strategies, decontam R and full contaminant sequence removal. All three extraction techniques followed by decontam R yielded similar results for the mock community. We then applied these methods to 22 CSF samples from children diagnosed with meningitis, which has low bacterial loads relative to other clinical infection samples. The refined 16S HTS pipelines identified the cultured bacterial genus as the dominant organism for only 3 of these samples. We found that all three DNA extraction techniques followed by decontam R generated similar DNA yields for mock communities at the low bacterial loads representative of CSF samples. However, the limits of detection imposed by reagent contaminants and methodologic bias precluded the accurate detection of bacteria in CSF from children with culture-confirmed meningitis using these approaches, despite rigorous controls and sophisticated computational approaches. Although we did not find current DNA-based diagnostics to be useful for pediatric meningitis samples, the utility of these methods for CSF shunt infection remains undefined. Future advances in sample processing methods to minimize or eliminate contamination will be required to improve the sensitivity and specificity of these methods for pediatric meningitis

    Molecular characterization of microbiota in cerebrospinal fluid from patients with CSF shunt infections using whole genome amplification followed by shotgun sequencing

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    Understanding the etiology of cerebrospinal fluid (CSF) shunt infections and reinfections requires detailed characterization of associated microorganisms. Traditionally, identification of bacteria present in the CSF has relied on culture methods, but recent studies have used high throughput sequencing of 16S rRNA genes. Here we evaluated the method of shotgun DNA sequencing for its potential to provide additional genomic information. CSF samples were collected from 3 patients near the beginning and end of each of 2 infection episodes. Extracted total DNA was sequenced by: (1) whole genome amplification followed by shotgun sequencing (WGA) and (2) high-throughput sequencing of the 16S rRNA V4 region (16S). Taxonomic assignments of sequences from WGA and 16S were compared with one another and with conventional microbiological cultures. While classification of bacteria was consistent among the 3 approaches, WGA provided additional insights into sample microbiological composition, such as showing relative abundances of microbial versus human DNA, identifying samples of questionable quality, and detecting significant viral load in some samples. One sample yielded sufficient non-human reads to allow assembly of a high-qualit

    Early Agriculture in the Maya Lowlands

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    Wetland research in northern Belize provides the earliest evidence for development of agriculture in the Maya Lowlands. Pollen data confirm the introduction of maize and manioc before 3000 B.C. Dramatic deforestation, beginning ca. 2500 B.C. and intensifying in wetland environments ca. 1500-1300 B.C., marks an expansion of agriculture, which occurred in the context of a mixed foraging economy. By 1000 B.C. a rise in groundwater levels led farmers to construct drainage ditches coeval with the emergence of Maya complex society ca. 1000-400 B.C. Field manipulations often involved minor modifications of natural hummocks. Canal systems are not as extensive in northern Belize as previously reported, nor is there evidence of artificially raised planting platforms. By the Classic period, wetland fields were flooded and mostly abandoned

    Interventions for the well-being of healthcare workers during a pandemic or other crisis : scoping review

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    Funding This study was supported by Chief Scientist Office of Scotland, grant number COV/ABN/20/06. Acknowledgements The authors thank Vicki Cormie, librarian at University of St Andrews, for advice on conducting scoping reviews.Peer reviewedPublisher PD
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