Disentanglement in a GAN for Unconditional Speech Synthesis

Can we develop a model that can synthesize realistic speech directly from a latent space, without explicit conditioning? Despite several efforts over the last decade, previous adversarial and diffusion-based approaches still struggle to achieve this, even on small-vocabulary datasets. To address this, we propose AudioStyleGAN (ASGAN) -- a generative adversarial network for unconditional speech synthesis tailored to learn a disentangled latent space. Building upon the StyleGAN family of image synthesis models, ASGAN maps sampled noise to a disentangled latent vector which is then mapped to a sequence of audio features so that signal aliasing is suppressed at every layer. To successfully train ASGAN, we introduce a number of new techniques, including a modification to adaptive discriminator augmentation which probabilistically skips discriminator updates. We apply it on the small-vocabulary Google Speech Commands digits dataset, where it achieves state-of-the-art results in unconditional speech synthesis. It is also substantially faster than existing top-performing diffusion models. We confirm that ASGAN's latent space is disentangled: we demonstrate how simple linear operations in the space can be used to perform several tasks unseen during training. Specifically, we perform evaluations in voice conversion, speech enhancement, speaker verification, and keyword classification. Our work indicates that GANs are still highly competitive in the unconditional speech synthesis landscape, and that disentangled latent spaces can be used to aid generalization to unseen tasks. Code, models, samples: https://github.com/RF5/simple-asgan/Comment: 12 pages, 5 tables, 4 figures. Submitted to IEEE TASLP. arXiv admin note: substantial text overlap with arXiv:2210.0527

Voice Conversion With Just Nearest Neighbors

Any-to-any voice conversion aims to transform source speech into a target voice with just a few examples of the target speaker as a reference. Recent methods produce convincing conversions, but at the cost of increased complexity -- making results difficult to reproduce and build on. Instead, we keep it simple. We propose k-nearest neighbors voice conversion (kNN-VC): a straightforward yet effective method for any-to-any conversion. First, we extract self-supervised representations of the source and reference speech. To convert to the target speaker, we replace each frame of the source representation with its nearest neighbor in the reference. Finally, a pretrained vocoder synthesizes audio from the converted representation. Objective and subjective evaluations show that kNN-VC improves speaker similarity with similar intelligibility scores to existing methods. Code, samples, trained models: https://bshall.github.io/knn-vcComment: 5 page, 1 table, 2 figures. Accepted at Interspeech 202

Phosphorus mobilizing consortium Mammoth P enhances plant growth

Global agricultural productivity may be constrained by the finite and limited supply of phosphorus (P), adding to the challenges in meeting the projected needs of a growing human population in the coming decades. In addition, when P fertilizers are added to soils, they can become bound to soils resulting in low fertilizer efficiency. However, P-mobilizing bacteria could potentially liberate soil-bound P, resulting in a higher plant P uptake and increased yield. Bacteria can mobilize P through several mechanisms, suggesting that consortia of P-bacteria may be more effective than single species. Species diversity can have a synergistic, or non-additive, effect on ecosystem functioning ("the whole is more than the sum of its parts") but rarely is the microbial community structure intentionally managed to improve plant nutrient uptake. We investigated whether inoculation of soils with a four-species bacterial community developed to mobilize soil P could increase plant productivity. In wheat and turf trials, we found that Mammoth P was able to deliver yields equivalent to those achieved using conventional fertilizer applications. Herbs and fruits showed that the combination of fertilizer with Mammoth P significantly increased productivity -in some cases productivity doubled. Metabolites produced by the Mammoth P consortium led to increased yields in some cases, suggesting that microbial products (produced in the absence of plants) played a role in enhancing plant productivity. Results from these trials indicate substantial potential of Mammoth P to enhance P supply to plants, improving P fertilizer use-efficiency and increasing agricultural productivity. 19 Agricultural productivity may be constrained in the 21 st Century by the finite supply of global a 20 phosphorus (P), adding to the challenges in meeting the projected needs of a growing human population 21 in the coming decades. In addition, when P fertilizers are added to soils, they can become bound to soils 22 resulting in low fertilizer efficiency. However, bacteria have the ability to mobilize soil bound P through 23 several mechanisms potentially resulting in a higher plant P uptake and increased yield. Furthermore, 24 species diversity can have a synergistic effect on ecosystem functioning ("the whole is more than the sum 25 of its parts") suggesting that bacterial communities, or consortia, may be more effective than single 26 species. However, in agriculture management practices, rarely is the soil microbial community structure 27 effectively manipulated to improve plant nutrient uptake. We investigated whether inoculation of soils 28 with a bacterial consortium developed to mobilize soil P named Mammoth P could increase plant 29 productivity. In turf, herbs and fruits, we showed that the combination of conventional inorganic fertilizer 30 combined with Mammoth P increased productivity up to twofold compared to the fertilizer treatments 31 without the Mammoth P inoculant. In wheat trials, we found that Mammoth P by itself was able to deliver 32 yields equivalent to those achieved with conventional inorganic fertilizer applications. The metabolites 33 produced by the consortium in Mammoth P likely played a role in enhancing plant productivity. Results 34 from this study indicate the substantial potential of Mammoth P to enhance P supply to plants, improving 35 P fertilizer use-efficiency and increasing agricultural productivity. 3

Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy

OBJECTIVE To expand the clinical phenotype of autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) due to mutations in the dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene. METHODS Patients with a phenotype suggestive of a motor, non-length-dependent neuronopathy predominantly affecting the lower limbs were identified at participating neuromuscular centers and referred for targeted sequencing of DYNC1H1. RESULTS We report a cohort of 30 cases of SMA-LED from 16 families, carrying mutations in the tail and motor domains of DYNC1H1, including 10 novel mutations. These patients are characterized by congenital or childhood-onset lower limb wasting and weakness frequently associated with cognitive impairment. The clinical severity is variable, ranging from generalized arthrogryposis and inability to ambulate to exclusive and mild lower limb weakness. In many individuals with cognitive impairment (9/30 had cognitive impairment) who underwent brain MRI, there was an underlying structural malformation resulting in polymicrogyric appearance. The lower limb muscle MRI shows a distinctive pattern suggestive of denervation characterized by sparing and relative hypertrophy of the adductor longus and semitendinosus muscles at the thigh level, and diffuse involvement with relative sparing of the anterior-medial muscles at the calf level. Proximal muscle histopathology did not always show classic neurogenic features. CONCLUSION Our report expands the clinical spectrum of DYNC1H1-related SMA-LED to include generalized arthrogryposis. In addition, we report that the neurogenic peripheral pathology and the CNS neuronal migration defects are often associated, reinforcing the importance of DYNC1H1 in both central and peripheral neuronal functions

Comparative toxicity of pesticides and environmental contaminants in bees: are honey bees a useful proxy for wild bee species?

Threats to wild and managed insect pollinators in Europe are cause for both ecological and socio-economic concern. Multiple anthropogenic pressures may be exacerbating pollinator declines. One key pressure is exposure to chemicals including pesticides and other contaminants. Historically the honey bee (Apis mellifera spp.) has been used as an ‘indicator’ species for ‘standard’ ecotoxicological testing but it has been suggested that it is not always a good proxy for other types of eusocial and solitary bees because of species differences in autecology and sensitivity to various stressors. We developed a common toxicity test system to conduct acute and chronic exposures of up to 240 h of similar doses of seven chemicals, targeting different metabolic pathways, on three bee species (Apis mellifera spp., Bombus terrestris and Osmia bicornis). We compared the relative sensitivity between species in terms of potency between the chemicals and the influence of exposure time on toxicity. While there were significant interspecific differences that varied through time, overall the magnitude of these differences (in terms of treatment effect ratios) was generally comparable ( 25 fold within test). These are rarely considered in standard regulatory testing but may have severe environmental consequences, especially when coupled with the likelihood of differential species exposures in the wild. These insights indicate that further work is required to understand how differences in toxicokinetics vary between species and mixtures of chemicals

Comparing bee species responses to chemical mixtures: common response patterns?

Pollinators in agricultural landscapes can be exposed to mixtures of pesticides and environmental pollutants. Existing mixture toxicity modelling approaches, such as the models of concentration addition and independent action and the mechanistic DEBtox framework have been previously shown as valuable tools for understanding and ultimately predicting joint toxicity. Here we apply these mixture models to investigate the potential to interpret the effects of semi-chronic binary mixture exposure for three bee species: Apis mellifera, Bombus terrestris and Osmia bicornis within potentiation and mixture toxicity experiments. In the potentiation studies, the effect of the insecticide dimethoate with added propiconazole fungicide and neonicotinoid insecticide clothianidin with added tau-fluvalinate pyrethroid acaricide showed no difference in toxicity compared to the single chemical alone. Clothianidin toxicity showed a small scale, but temporally conserved increase in exposure conducted in the presence of propiconazole, particularly for B. terrestris and O. bicornis, the latter showing a near three-fold increase in clothianidin toxicity in the presence of propiconazole. In the mixture toxicity studies, the dominant response patterns were of additivity, however, binary mixtures of clothianidin and dimethoate in A. mellifera, B. terrestris and male O. bicornis there was evidence of a predominant antagonistic interaction. Given the ubiquitous nature of exposures to multiple chemicals, there is an urgent need to consider mixture effects in pollinator risk assessments. Our analyses suggest that current models, particularly those that utilise time-series data, such as DEBtox, can be used to identify additivity as the dominant response pattern and also those examples of interactions, even when small-scale, that may need to be taken into account during risk assessment

Atmospheric conditions during the Arctic Clouds in Summer Experiment (ACSE): Contrasting open-water and sea-ice surfaces during melt and freeze-up seasons

The Arctic Clouds in Summer Experiment (ACSE) was conducted during summer and early autumn 2014, providing a detailed view of the seasonal transition from ice melt into freeze-up. Measurements were taken over both ice-free and ice-covered surfaces near the ice edge, offering insight into the role of the surface state in shaping the atmospheric conditions. The initiation of the autumn freeze-up was related to a change in air mass, rather than to changes in solar radiation alone; the lower atmosphere cooled abruptly, leading to a surface heat loss. During melt season, strong surface inversions persisted over the ice, while elevated inversions were more frequent over open water. These differences disappeared during autumn freeze-up, when elevated inversions persisted over both ice-free and ice-covered conditions. These results are in contrast to previous studies that found a well-mixed boundary layer persisting in summer and an increased frequency of surface-based inversions in autumn, suggesting that knowledge derived from measurements taken within the pan-Arctic area and on the central ice pack does not necessarily apply closer to the ice edge. This study offers an insight into the atmospheric processes that occur during a crucial period of the year; understanding and accurately modeling these processes is essential for the improvement of ice-extent predictions and future Arctic climate projections

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value &lt; 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p &lt; 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression.</p

A review of the dodo and its ecosystem: insights from a vertebrate concentration Lagerstätte in Mauritius

The dodo Raphus cucullatus Linnaeus, an extinct and flightless, giant pigeon endemic to Mauritius, has fascinated people since its discovery, yet has remained surprisingly poorly known. Until the mid-19th century, almost all that was known about the dodo was based on illustrations and written accounts by 17th century mariners, often of questionable accuracy. Furthermore, only a few fragmentary remains of dodos collected prior to the bird's extinction exist. Our understanding of the dodo's anatomy was substantially enhanced by the discovery in 1865 of subfossil bones in a marsh called the Mare aux Songes, situated in southeastern Mauritius. However, no contextual information was recorded during early excavation efforts, and the majority of excavated material comprised larger dodo bones, almost all of which were unassociated. Here we present a modern interdisciplinary analysis of the Mare aux Songes, a 4200-year-old multitaxic vertebrate concentration Lagerstätte. Our analysis of the deposits at this site provides the first detailed overview of the ecosystem inhabited by the dodo. The interplay of climatic and geological conditions led to the exceptional preservation of the animal and associated plant remains at the Mare aux Songes and provides a window into the past ecosystem of Mauritius. This interdisciplinary research approach provides an ecological framework for the dodo, complementing insights on its anatomy derived from the only associated dodo skeletons known, both of which were collected by Etienne Thirioux and are the primary subject of this memoir.publishedVersio

SARS-CoV Pathogenesis Is Regulated by a STAT1 Dependent but a Type I, II and III Interferon Receptor Independent Mechanism

Severe acute respiratory syndrome coronavirus (SARS-CoV) infection often caused severe end stage lung disease and organizing phase diffuse alveolar damage, especially in the elderly. The virus-host interactions that governed development of these acute end stage lung diseases and death are unknown. To address this question, we evaluated the role of innate immune signaling in protection from human (Urbani) and a recombinant mouse adapted SARS-CoV, designated rMA15. In contrast to most models of viral pathogenesis, infection of type I, type II or type III interferon knockout mice (129 background) with either Urbani or MA15 viruses resulted in clinical disease outcomes, including transient weight loss, denuding bronchiolitis and alveolar inflammation and recovery, identical to that seen in infection of wildtype mice. This suggests that type I, II and III interferon signaling play minor roles in regulating SARS pathogenesis in mouse models. In contrast, infection of STAT1−/− mice resulted in severe disease, high virus titer, extensive pulmonary lesions and 100% mortality by day 9 and 30 post-infection with rMA15 or Urbani viruses, respectively. Non-lethal in BALB/c mice, Urbani SARS-CoV infection in STAT1−/− mice caused disseminated infection involving the liver, spleen and other tissues after day 9. These findings demonstrated that SARS-CoV pathogenesis is regulated by a STAT1 dependent but type I, II and III interferon receptor independent, mechanism. In contrast to a well documented role in innate immunity, we propose that STAT1 also protects mice via its role as an antagonist of unrestrained cell proliferation