1,300 research outputs found

    A New Place at the Table: Ancient Cadential Patterns for Modern Improvision and Aural Skills Training

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    Contemporary efforts to integrate improvisation practice into institutional music education are many and varied, but lack of improvisatory skill remains an ongoing problem, especially in classical music instruction. Drawing on artisanal training, in which a corpus of memorized repertoire becomes a stylistic knowledge base, source of cognitive schemata and raw material for creative variation, a useful set of historically-derived “standards” can be found in the three introductory cadences used in the Neapolitan conservatory partimento tradition (It. Cadenza Semplice, Cadenza Composta, Cadenza Doppia) of the seventeenth and eighteenth centuries. Referencing music cognition research, music theory sources and improvisation discourse, this paper argues that intervallic suspensions in these schemata (4-3, 7-6) can be seen as a simple demonstration of error perception and correction, a cognitive process that can be deployed to develop and strengthen both aural and creative skills. Integration of these cadences into beginner training also suggests a reassessment of the order of introduction of musical elements found in formal music instruction, which privileges the chord as a discrete entity, and relegates intervallic suspension, schemata and counterpoint to intermediate, advanced, or supplementary study. These cadences concisely synthesize and demonstrate contrapuntal interplay and voice leading between bass and treble voices, basic syncopation and rhythmic division, and the concept of dissonance/consonance within linear parameters as an integral aspect of musical form. A series of beginner to intermediate exercises for use in vocal and instrumental training are presented. The dissertation recommends that intervallic suspensions be given a renewed “place at the table,” once again taking their former role as primal examples of compositional structure and aesthetic possibility

    Repurposing Anti-Inflammasome NRTIs for Improving Insulin Sensitivity and Reducing Type 2 Diabetes Development

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    Innate immune signaling through the NLRP3 inflammasome is activated by multiple diabetes-related stressors, but whether targeting the inflammasome is beneficial for diabetes is still unclear. Nucleoside reverse-transcriptase inhibitors (NRTI), drugs approved to treat HIV-1 and hepatitis B infections, also block inflammasome activation. Here, we show, by analyzing five health insurance databases, that the adjusted risk of incident diabetes is 33% lower in patients with NRTI exposure among 128,861 patients with HIV-1 or hepatitis B (adjusted hazard ratio for NRTI exposure, 0.673; 95% confidence interval, 0.638 to 0.710; P \u3c 0.0001; 95% prediction interval, 0.618 to 0.734). Meanwhile, an NRTI, lamivudine, improves insulin sensitivity and reduces inflammasome activation in diabetic and insulin resistance-induced human cells, as well as in mice fed with high-fat chow; mechanistically, inflammasome-activating short interspersed nuclear element (SINE) transcripts are elevated, whereas SINE-catabolizing DICER1 is reduced, in diabetic cells and mice. These data suggest the possibility of repurposing an approved class of drugs for prevention of diabetes

    Rules for Growth: Promoting Innovation and Growth Through Legal Reform

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    The United States economy is struggling to recover from its worst economic downturn since the Great Depression. After several huge doses of conventional macroeconomic stimulus - deficit-spending and monetary stimulus - policymakers are understandably eager to find innovative no-cost ways of sustaining growth both in the short and long runs. In response to this challenge, the Kauffman Foundation convened a number of America’s leading legal scholars and social scientists during the summer of 2010 to present and discuss their ideas for changing legal rules and policies to promote innovation and accelerate U.S. economic growth. This meeting led to the publication of Rules for Growth: Promoting Innovation and Growth Through Legal Reform, a comprehensive and groundbreaking volume of essays prescribing a new set of growth-promoting policies for policymakers, legal scholars, economists, and business men and women. Some of the top Rules include: • Reforming U.S. immigration laws so that more high-skilled immigrants can launch businesses in the United States. • Improving university technology licensing practices so university-generated innovation is more quickly and efficiently commercialized. • Moving away from taxes on income that penalize risk-taking, innovation, and employment while shifting toward a more consumption-based tax system that encourages saving that funds investment. In addition, the research tax credit should be redesigned and made permanent. • Overhauling local zoning rules to facilitate the formation of innovative companies. • Urging judges to take a more expansive view of flexible business contracts that are increasingly used by innovative firms. • Urging antitrust enforcers and courts to define markets more in global terms to reflect contemporary realities, resist antitrust enforcement from countries with less sound antitrust regimes, and prohibit industry trade protection and subsidies. • Reforming the intellectual property system to allow for a post-grant opposition process and address the large patent application backlog by allowing applicants to pay for more rapid patent reviews. • Authorizing corporate entities to form digitally and use software as a means for setting out agreements and bylaws governing corporate activities. The collective essays in the book propose a new way of thinking about the legal system that should be of interest to policymakers and academic scholars alike. Moreover, the ideas presented here, if embodied in law, would augment a sustained increase in U.S. economic growth, improving living standards for U.S. residents and for many in the rest of the world

    SN 2022joj: A Peculiar Type Ia Supernova Possibly Driven by an Asymmetric Helium-shell Double Detonation

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    We present observations of SN 2022joj, a peculiar Type Ia supernova (SN Ia) discovered by the Zwicky Transient Facility (ZTF). SN 2022joj exhibits an unusually red gZTFrZTFg_\mathrm{ZTF}-r_\mathrm{ZTF} color at early times and a rapid blueward evolution afterwards. Around maximum brightness, SN 2022joj shows a high luminosity (MgZTF,max19.7M_{g_\mathrm{ZTF},\mathrm{max}}\simeq-19.7 mag), a blue broadband color (gZTFrZTF0.2g_\mathrm{ZTF}-r_\mathrm{ZTF}\simeq-0.2 mag), and shallow Si II absorption lines, consistent with those of overluminous, SN 1991T-like events. The maximum-light spectrum also shows prominent absorption around 4200 \r{A}, which resembles the Ti II features in subluminous, SN 1991bg-like events. Despite the blue optical-band colors, SN 2022joj exhibits extremely red ultraviolet - optical colors at maximum luminosity (uv1.6u-v\simeq1.6 mag and uvw1v4.0uvw1 - v\simeq4.0 mag), suggesting a suppression of flux between \sim2500--4000 \r{A}. Strong C II lines are also detected at peak. We show that these unusual spectroscopic properties are broadly consistent with the helium-shell double detonation of a sub-Chandrasekhar mass (M1MM\simeq1\mathrm{M_\odot}) carbon/oxygen (C/O) white dwarf (WD) from a relatively massive helium shell (Ms0.04M_s\simeq0.04--0.1M0.1\mathrm{M_\odot}), if observed along a line of sight roughly opposite to where the shell initially detonates. None of the existing models could quantitatively explain all the peculiarities observed in SN 2022joj. The low flux ratio of [Ni II] λ\lambda7378 to [Fe II] λ\lambda7155 emission in the late-time nebular spectra indicates a low yield of stable Ni isotopes, favoring a sub-Chandrasekhar mass progenitor. The significant blueshift measured in the [Fe II] λ\lambda7155 line is also consistent with an asymmetric chemical distribution in the ejecta, as is predicted in double-detonation models.Comment: 24 pages, 11 figures, 6 tables. Submitted to Ap

    The khmer software package: enabling efficient nucleotide sequence analysis

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    The khmer package is a freely available software library for working efficiently with fixed length DNA words, or k-mers. khmer provides implementations of a probabilistic k-mer counting data structure, a compressible De Bruijn graph representation, De Bruijn graph partitioning, and digital normalization. khmer is implemented in C++ and Python, and is freely available under the BSD license at https://github.com/dib-lab/khmer/

    The khmer software package: enabling efficient nucleotide sequence analysis [version 1; referees: 2 approved, 1 approved with reservations]

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    The khmer package is a freely available software library for working efficiently with fixed length DNA words, or k-mers. khmer provides implementations of a probabilistic k-mer counting data structure, a compressible De Bruijn graph representation, De Bruijn graph partitioning, and digital normalization. khmer is implemented in C++ and Python, and is freely available under the BSD license at https://github.com/dib-lab/khmer/

    Identification of functional elements and regulatory circuits by Drosophila modENCODE

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    To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation

    Event-based modelling in temporal lobe epilepsy demonstrates progressive atrophy from cross-sectional data

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    OBJECTIVE: Recent work has shown that people with common epilepsies have characteristic patterns of cortical thinning, and that these changes may be progressive over time. Leveraging a large multi-centre cross-sectional cohort, we investigated whether regional morphometric changes occur in a sequential manner, and whether these changes in people with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS) correlate with clinical features. METHODS: We extracted regional measures of cortical thickness, surface area and subcortical brain volumes from T1-weighted (T1W) MRI scans collected by the ENIGMA-Epilepsy consortium, comprising 804 people with MTLE-HS and 1,625 healthy controls from 25 centres. Features with a moderate case-control effect size (Cohen's d≥0.5) were used to train an Event-Based Model (EBM), which estimates a sequence of disease-specific biomarker changes from cross-sectional data and assigns a biomarker-based fine-grained disease stage to individual patients. We tested for associations between EBM disease stage and duration of epilepsy, age of onset and anti-seizure medicine (ASM) resistance. RESULTS: In MTLE-HS, decrease in ipsilateral hippocampal volume along with increased asymmetry in hippocampal volume was followed by reduced thickness in neocortical regions, reduction in ipsilateral thalamus volume and, finally, increase in ipsilateral lateral ventricle volume. EBM stage was correlated to duration of illness (Spearman's ρ=0.293, p=7.03x10-16 ), age of onset (ρ=-0.18, p=9.82x10-7 ) and ASM resistance (AUC=0.59, p=0.043, Mann-Whitney U test). However, associations were driven by cases assigned to EBM stage zero, which represents MTLE-HS with mild or non-detectable abnormality on T1W MRI. SIGNIFICANCE: From cross-sectional MRI, we reconstructed a disease progression model that highlights a sequence of MRI changes that aligns with previous longitudinal studies. This model could be used to stage MTLE-HS subjects in other cohorts and help establish connections between imaging-based progression staging and clinical features

    COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms.

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    Funder: Bundesministerium für Bildung und ForschungFunder: Bundesministerium für Bildung und Forschung (BMBF)We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective
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