69 research outputs found

    ProgGP: From GuitarPro Tablature Neural Generation To Progressive Metal Production

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    Recent work in the field of symbolic music generation has shown value in using a tokenization based on the GuitarPro format, a symbolic representation supporting guitar expressive attributes, as an input and output representation. We extend this work by fine-tuning a pre-trained Transformer model on ProgGP, a custom dataset of 173 progressive metal songs, for the purposes of creating compositions from that genre through a human-AI partnership. Our model is able to generate multiple guitar, bass guitar, drums, piano and orchestral parts. We examine the validity of the generated music using a mixed methods approach by combining quantitative analyses following a computational musicology paradigm and qualitative analyses following a practice-based research paradigm. Finally, we demonstrate the value of the model by using it as a tool to create a progressive metal song, fully produced and mixed by a human metal producer based on AI-generated music.Comment: Pre-print accepted for publication at CMMR202

    Evidence for large-scale gene-by-smoking interaction effects on pulmonary function

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    Background: Smoking is the strongest environmental risk factor for reduced pulmonary function. The genetic component of various pulmonary traits has also been demonstrated, and at least 26 loci have been reproducibly associated with either FEV1 (forced expiratory volume in 1 second) or FEV1/FVC (FEV1/forced vital capacity). Although the main effects of smoking and genetic loci are well established, the question of potential gene-by-smoking interaction effect remains unanswered. The aim of the present study was to assess, using a genetic risk score approach, whether the effect of these 26 loci on pulmonary function is influenced by smoking. Methods: We evaluated the interaction between smoking exposure, considered as either ever vs never or pack-years, and a 26-single nucleotide polymorphisms (SNPs) genetic risk score in relation to FEV1 or FEV1/FVC in 50 047 participants of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) and SpiroMeta consortia. Results: We identified an interaction (beta(int) = -0.036, 95% confidence interval, -0.040 to -0.032, P = 0.00057) between an unweighted 26 SNP genetic risk score and smoking status (ever/never) on the FEV1/FVC ratio. In interpreting this interaction, we showed that the genetic risk of falling below the FEV1/FVC threshold used to diagnose chronic obstructive pulmonary disease is higher among ever smokers than among never smokers. A replication analysis in two independent datasets, although not statistically significant, showed a similar trend in the interaction effect. Conclusions: This study highlights the benefit of using genetic risk scores for identifying interactions missed when studying individual SNPs and shows, for the first time, that persons with the highest genetic risk for low FEV1/FVC may be more susceptible to the deleterious effects of smoking.Peer reviewe

    Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations

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    Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 × 10−8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD

    Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function

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    Pulmonary function measures reflect respiratory health and predict mortality, and are used in the diagnosis of chronic obstructive pulmonary disease (COPD). We tested genome-wide association with the forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in 48,201 individuals of European ancestry, with follow-up of top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P<5×10−8) with pulmonary function, in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1, and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function

    A laboratory-numerical approach for modelling scale effects in dry granular slides

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    Granular slides are omnipresent in both natural and industrial contexts. Scale effects are changes in physical behaviour of a phenomenon at different geometric scales, such as between a laboratory experiment and a corresponding larger event observed in nature. These scale effects can be significant and can render models of small size inaccurate by underpredicting key characteristics such as ow velocity or runout distance. Although scale effects are highly relevant to granular slides due to the multiplicity of length and time scales in the flow, they are currently not well understood. A laboratory setup under Froude similarity has been developed, allowing dry granular slides to be investigated at a variety of scales, with a channel width configurable between 0.25-1.00 m. Maximum estimated grain Reynolds numbers, which quantify whether the drag force between a particle and the surrounding air act in a turbulent or viscous manner, are found in the range 102-103. A discrete element method (DEM) simulation has also been developed, validated against an axisymmetric column collapse and a granular slide experiment of Hutter and Koch (1995), before being used to model the present laboratory experiments and to examine a granular slide of significantly larger scale. This article discusses the details of this laboratory-numerical approach, with the main aim of examining scale effects related to the grain Reynolds number. Increasing dust formation with increasing scale may also exert influence on laboratory experiments. Overall, significant scale effects have been identified for characteristics such as ow velocity and runout distance in the physical experiments. While the numerical modelling shows good general agreement at the medium scale, it does not capture differences in behaviour seen at the smaller scale, highlighting the importance of physical models in capturing these scale effects

    Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets

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    Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97. A genetic risk score was associated with COPD susceptibility (odds ratio per 1 s.d. of the risk score (∼6 alleles) (95% confidence interval) = 1.24 (1.20-1.27), P = 5.05 × 10‾⁴⁹), and we observed a 3.7-fold difference in COPD risk between individuals in the highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in genes for development, elastic fibers and epigenetic regulation pathways. We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.This work was funded by a Medical Research Council (MRC) strategic award to M.D.T., I.P.H., D.S. and L.V.W. (MC_PC_12010). This research has been conducted using the UK Biobank Resource under application 648. This article presents independent research funded partially by the National Institute for Health Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the UK Department of Health. This research used the ALICE and SPECTRE High-Performance Computing Facilities at the University of Leicester. Additional acknowledgments and funding details can be found in the Supplementary Note
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