508 research outputs found

    Read/Write Digital Libraries for Musicology

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    The Web and other digital technologies have democratised music creation, reception, and analysis, putting music in the hands, ears, and minds of billions of users. Music digital libraries typically focus on an essential subset of this deluge—commercial and academic publications, and historical materials—but neglect to incorporate contributions by scholars, performers, and enthusiasts, such as annotations or performed interpretations of these artifacts, despite their potential utility for many types of users. In this paper we consider means by which digital libraries for musicology may incorporate such contributions into their collections, adhering to principles of FAIR data management and respecting contributor rights as outlined in the EU’s General Data Protection Regulation. We present an overview of centralised and decentralised approaches to this problem, and propose hybrid solutions in which contributions reside in a) user-controlled personal online datastores, b) decentralised file storage, and c) are published and aggregated into digital library collections. We outline the implementation of these ideas using Solid, a Web decentralisation project building on W3C standard technologies to facilitate publication and control over Linked Data. We demonstrate the feasibility of this approach by implementing prototypes supporting two types of contribution: Web Annotations describing or analysing musical elements in score encodings and music recordings; and, music performances and associated metadata supporting performance analyses across many renditions of a given piece. Finally, we situate these ideas within a wider conception of enriched, decentralised, and interconnected online music repositories

    Environmental pH Affects Photoautotrophic Growth of Synechocystis sp. PCC 6803 Strains Carrying Mutations in the Lumenal Proteins of PSII.

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    Synechocystis sp. strain PCC 6803 grows photoautotrophically across a broad pH range, but wild-type cultures reach a higher density at elevated pH; however, photoheterotrophic growth is similar at high and neutral pH. A number of PSII mutants each lacking at least one lumenal extrinsic protein, and carrying a second PSII lumenal mutation, are able to grow photoautotrophically in BG-11 medium at pH 10.0, but not pH 7.5. We investigated the basis of this pH effect and observed no pH-specific change in variable fluorescence yield from PSII centers of the wild type or the pH-dependent ΔPsbO:ΔPsbU and ΔPsbV:ΔCyanoQ strains; however, 77 K fluorescence emission spectra indicated increased coupling of the phycobilisome (PBS) antenna at pH 10.0 in all mutants. DNA microarray data showed a cell-wide response to transfer from pH 10.0 to pH 7.5, including decreased mRNA levels of a number of oxidative stress-responsive transcripts. We hypothesize that this transcriptional response led to increased tolerance against reactive oxygen species and in particular singlet oxygen. This response enabled photoautotrophic growth of the PSII mutants at pH 10.0. This hypothesis was supported by increased resistance of all strains to rose bengal at pH 10.0 compared with pH 7.5

    Are multiple physical symptoms a poor prognostic factor or just a marker of depression severity?:Secondary analysis of the GenPod trial

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    AbstractBackgroundUsing data from the GenPod trial this study investigates: (i) if depressed individuals with multiple physical symptoms have a poorer response to antidepressants before and after adjustment for baseline Beck Depression Inventory II (BDI-II); and (ii) if reboxetine is more effective than citalopram in depression with multiple physical symptoms.MethodsLinear regression models were used to estimate differences in mean BDI-II score at 6 and 12 weeks.ResultsBefore adjusting for baseline BDI-II, the difference in mean BDI-II score between no and multiple physical symptoms was 4.5 (95% CI 1.87, 7.14) at 6 weeks, 4.51 (95% CI 1.60, 7.42) at 12 weeks. After adjustment for baseline BDI-II, there was no evidence of a difference in outcome according to physical symptoms with a difference in mean BDI-II of 2.17 (95% CI −0.39, 4.73) at 6 weeks and 2.43 (95% CI −0.46, 5.32) at 12 weeks. There was no evidence that reboxetine was more effective than citalopram in those with multiple physical symptoms at 6 (P=0.18) or 12 weeks (P=0.24).LimitationsDifferential non-adherence between treatment arms has the potential to bias estimates of treatment efficacy.ConclusionMultiple physical symptoms predict response to antidepressants, but not after adjustment for baseline depression severity. Physical symptoms could be a marker of severe depression rather than an independent prognostic factor and depression should be considered in patients with multiple physical symptoms. Treatment with reboxetine conferred no advantage over citalopram in those with physical symptoms, and it is less well tolerated

    Pre-main-sequence variability across the radiative-convective gap

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    Copyright © 2009 Royal Astronomical SocietyWe use I-band imaging to perform a variability survey of the 13-Myr-old cluster h Per. We find a significant fraction of the cluster members to be variable. Most importantly, we find that variable members lie almost entirely on the convective side of the gap in the cluster sequence between fully convective stars and those which have a radiative core. This result is consistent with a scenario in which the magnetic field changes topology when the star changes from being fully convective to one containing a radiative core. When the star is convective, the magnetic field appears dominated by large-scale structures, resulting in global-size spots that drive the observed variability. For those stars with radiative cores, we observe a marked absence of variability due to spots, which suggests a switch to a magnetic field dominated by smaller-scale structures, resulting in many smaller spots and thus less apparent variability. This implies that wide field variability surveys may only be sensitive to fully convective stars. On the one hand, this reduces the chances of picking out young groups (since the convective stars are the lower mass and therefore fainter objects), but conversely the absolute magnitude of the head of the convective sequence provides a straightforward measure of age for those groups which are discovered

    The Human Mitochondrial Transcriptome

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    SummaryThe human mitochondrial genome comprises a distinct genetic system transcribed as precursor polycistronic transcripts that are subsequently cleaved to generate individual mRNAs, tRNAs, and rRNAs. Here, we provide a comprehensive analysis of the human mitochondrial transcriptome across multiple cell lines and tissues. Using directional deep sequencing and parallel analysis of RNA ends, we demonstrate wide variation in mitochondrial transcript abundance and precisely resolve transcript processing and maturation events. We identify previously undescribed transcripts, including small RNAs, and observe the enrichment of several nuclear RNAs in mitochondria. Using high-throughput in vivo DNaseI footprinting, we establish the global profile of DNA-binding protein occupancy across the mitochondrial genome at single-nucleotide resolution, revealing regulatory features at mitochondrial transcription initiation sites and functional insights into disease-associated variants. This integrated analysis of the mitochondrial transcriptome reveals unexpected complexity in the regulation, expression, and processing of mitochondrial RNA and provides a resource for future studies of mitochondrial function (accessed at http://mitochondria.matticklab.com)

    The feasibility and acceptability of self-testing for proteinuria during pregnancy: A mixed methods approach.

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    OBJECTIVE: To investigate feasibility and acceptability of self-testing for proteinuria during pregnancy. STUDY DESIGN: Mixed methods approach which included: an accuracy study where pregnant women (n = 100) and healthcare professionals (n = 96) tested seven synthetic protein samples and completed a questionnaire, a feasibility study where pregnant women who were self-monitoring their blood pressure were asked to self-test for proteinuria (n = 30), and an online questionnaire about women's experiences of self-testing (n = 200). MAIN OUTCOME MEASURES: Sensitivity and specificity of testing and questionnaire results. RESULTS: There were no significant differences in the accuracy of synthetic sample testing by pregnant women (sensitivity 0.81 (95% confidence intervals (CI) 0.78-0.85), specificity 0.93 (95% CI 0.91-0.95)) and healthcare professionals: (sensitivity 0.83 (95% CI 0.79-0.86), specificity 0.92 (95% CI 0.90-0.94)). Automated readers had significantly better sensitivity (0.94 (0.91-0.97) (p ≤ .001 in each case), but worse specificity 0.78 (0.69-0.85). Similar results were gained using self-tested urine samples compared to staff-testing using a reference standard of laboratory urine protein-creatinine ratio (uPCR). Women who completed the online survey with experience of self-testing (n = 39, 20%) generally found it easy, and with support from healthcare professionals felt it improved involvement in their care and reduced anxiety. CONCLUSIONS: Self-testing for proteinuria by pregnant women had similar accuracy to healthcare professional testing and was acceptable to both groups. Self-testing of urine combined with self-monitoring of blood pressure could provide a useful adjunct to clinic-based surveillance for the detection of pre-eclampsia. Such novel strategies warrant further research

    Evaluation of Pyridoacridine Alkaloids in a Zebrafish Phenotypic Assay

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    Three new minor components, the pyridoacridine alkaloids 1-hydroxy-deoxyamphimedine (1), 3-hydroxy-deoxyamphimedine (2), debromopetrosamine (3), and three known compounds, amphimedine (4), neoamphimedine (5) and deoxyamphimedine (6), have been isolated from the sponge Xestospongia cf. carbonaria, collected in Palau. Structures were assigned on the basis of extensive 1D and 2D NMR studies as well as analysis by HRESIMS. Compounds 1–6 were evaluated in a zebrafish phenotype-based assay. Amphimedine (4) was the only compound that caused a phenotype in zebrafish embryos at 30 μM. No phenotype other than death was observed for compounds 1–3, 5, 6

    Genome-wide discovery of human splicing branchpoints

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    During the splicing reaction, the 59 intron end is joined to the branchpoint nucleotide, selecting the next exon to incorporate into the mature RNA and forming an intron lariat, which is excised. Despite a critical role in gene splicing, the locations and features of human splicing branchpoints are largely unknown. We use exoribonuclease digestion and targeted RNA-sequencing to enrich for sequences that traverse the lariat junction, by split and inverted alignment, reveal the branchpoint. We identify 59,359 high-confidence human branchpoints in >10,000 genes, providing a first map of splicing branchpoints in the human genome. Branchpoints are predominantly adenosine, highly conserved, and closely distributed to the 3 ′ splice site. Analysis of human branchpoints reveals numerous novel features, including distinct features of branchpoints for alternatively spliced exons and a family of conserved sequence motifs overlapping branchpoints we term B-boxes, which exhibit maximal nucleotide diversity while maintaining interactions with the keto-rich U2 snRNA. Different B-box motifs exhibit divergent usage in vertebrate lineages and associate with other splicing elements and distinct intron-exon architectures, suggesting integration within a broader regulatory splicing code. Lastly, although branchpoints are refractory to common mutational processes and genetic variation, mutations occurring at branchpoint nucleotides are enriched for disease associations
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