Play as You Like: Timbre-enhanced Multi-modal Music Style Transfer

Style transfer of polyphonic music recordings is a challenging task when considering the modeling of diverse, imaginative, and reasonable music pieces in the style different from their original one. To achieve this, learning stable multi-modal representations for both domain-variant (i.e., style) and domain-invariant (i.e., content) information of music in an unsupervised manner is critical. In this paper, we propose an unsupervised music style transfer method without the need for parallel data. Besides, to characterize the multi-modal distribution of music pieces, we employ the Multi-modal Unsupervised Image-to-Image Translation (MUNIT) framework in the proposed system. This allows one to generate diverse outputs from the learned latent distributions representing contents and styles. Moreover, to better capture the granularity of sound, such as the perceptual dimensions of timbre and the nuance in instrument-specific performance, cognitively plausible features including mel-frequency cepstral coefficients (MFCC), spectral difference, and spectral envelope, are combined with the widely-used mel-spectrogram into a timber-enhanced multi-channel input representation. The Relativistic average Generative Adversarial Networks (RaGAN) is also utilized to achieve fast convergence and high stability. We conduct experiments on bilateral style transfer tasks among three different genres, namely piano solo, guitar solo, and string quartet. Results demonstrate the advantages of the proposed method in music style transfer with improved sound quality and in allowing users to manipulate the output

Potential causal association between gut microbiome and posttraumatic stress disorder

Funding Information: We thank the participants and working staff including the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group, the FinnGen consortium, and the MiBioGen consortium. Publisher Copyright: © 2024, The Author(s).Background: The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). Methods: The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD’s causal effects on the relative abundances of specific features of the gut microbiome. Results: In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability. Conclusion: Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms.publishersversionpublishe

Potential causal association between gut microbiome and posttraumatic stress disorder

Background: The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). Methods: The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD’s causal effects on the relative abundances of specific features of the gut microbiome. Results: In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability. Conclusion: Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms

Discovery of 95 PTSD loci provides insight into genetic architecture and neurobiology of trauma and stress-related disorders

Posttraumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 novel). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (e.g., GRIA1, GRM8, CACNA1E ), developmental, axon guidance, and transcription factors (e.g., FOXP2, EFNA5, DCC ), synaptic structure and function genes (e.g., PCLO, NCAM1, PDE4B ), and endocrine or immune regulators (e.g., ESR1, TRAF3, TANK ). Additional top genes influence stress, immune, fear, and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation

Visual Perception Based Intra Coding Algorithm for H.266/VVC

The latest international video coding standard, H.266/Versatile Video Coding (VVC), supports high-definition videos, with resolutions from 4 K to 8 K or even larger. It offers a higher compression ratio than its predecessor, H.265/High Efficiency Video Coding (HEVC). In addition to the quadtree partition structure of H.265/HEVC, the nested multi-type tree (MTT) structure of H.266/VVC provides more diverse splits through binary and ternary trees. It also includes many new coding tools, which tremendously increases the encoding complexity. This paper proposes a fast intra coding algorithm for H.266/VVC based on visual perception analysis. The algorithm applies the factor of average background luminance for just-noticeable-distortion to identify the visually distinguishable (VD) pixels within a coding unit (CU). We propose calculating the variances of the numbers of VD pixels in various MTT splits of a CU. Intra sub-partitions and matrix weighted intra prediction are turned off conditionally based on the variance of the four variances for MTT splits and a thresholding criterion. The fast horizontal/vertical splitting decisions for binary and ternary trees are proposed by utilizing random forest classifiers of machine learning techniques, which use the information of VD pixels and the quantization parameter. Experimental results show that the proposed algorithm achieves around 47.26% encoding time reduction with a Bjøntegaard Delta Bitrate (BDBR) of 1.535% on average under the All Intra configuration. Overall, this algorithm can significantly speed up H.266/VVC intra coding and outperform previous studies

Group A Streptococcus Induces LAPosomes via SLO/β1 Integrin/NOX2/ROS Pathway in Endothelial Cells That Are Ineffective in Bacterial Killing and Suppress Xenophagy

Our previous reports showed that the LC3-associated GAS-containing single membrane vacuoles are inefficient for bacterial clearance in endothelial cells, which may result in bacteremia. However, the characteristics and the induction mechanisms of these LC3-positive vacuoles are still largely unknown. Here we provide the first evidence that these LC3-positive GAS-containing single membrane compartments appear to be LAPosomes, which are induced by NOX2 and ROS. Through NOX2- and ROS-mediated signaling, GAS preferentially induces LAP and inhibits bacteriostatic xenophagy in endothelial cells. We also provide the first demonstration that β1 integrin acts as the receptor for LAP induction through GAS-produced SLO stimulation in endothelial cells. Our findings reveal the underlying mechanisms of LAP induction and autophagy evasion for GAS multiplication in endothelial cells.Group A streptococcus (GAS) is an important human pathogen which can cause fatal diseases after invasion into the bloodstream. Although antibiotics and immune surveillance are the main defenses against GAS infection, GAS utilizes internalization into cells as a major immune evasion strategy. Our previous findings revealed that light chain 3 (LC3)-associated single membrane GAS-containing vacuoles in endothelial cells are compromised for bacterial clearance due to insufficient acidification after fusion with lysosomes. However, the characteristics and the activation mechanisms of these LC3-positive compartments are still largely unknown. In the present study, we demonstrated that the LC3-positive GAS is surrounded by single membrane and colocalizes with NADPH oxidase 2 (NOX2) complex but without ULK1, which are characteristics of LC3-associated phagocytosis (LAP). Inhibition of NOX2 or reactive oxygen species (ROS) significantly reduces GAS multiplication and enhances autolysosome acidification in endothelial cells through converting LAP to conventional xenophagy, which is revealed by enhancement of ULK1 recruitment, attenuation of p70s6k phosphorylation, and formation of the isolation membrane. We also clarify that the inactivation of mTORC1, which is the initiation signal of autophagy, is inhibited by NOX2- and ROS-activated phosphatidylinositol 3-kinase (PI3K)/AKT and MEK/extracellular signal-regulated kinase (ERK) pathways. In addition, streptolysin O (SLO) of GAS is identified as a crucial inducer of ROS for β1 integrin-mediated LAP induction. After downregulation of β1 integrin, GAS multiplication is reduced, accompanied with LAP inhibition and xenophagy induction. These results demonstrate that GAS infection preferentially induces ineffective LAP to evade xenophagic killing in endothelial cells through the SLO/β1 integrin/NOX2/ROS pathway

Design and evaluation of oral formulation for apixaban

Non-valvular atrial fibrillation (NVAF) is a common form of cardiac arrhythmia that affects 1–1.5% of adults and roughly 10% of elderly adults with dysphagia. Apixaban is an anticoagulant referred to as a factor Xa inhibitor, which has been shown to reduce the risk of stroke and systemic embolism in cases of NVAF. Our objective in the current study was to formulate an orally disintegrating film to facilitate the administration of apixaban to elderly patients who have difficulty swallowing. Researchers have used a wide variety of cellulose-based or non-cellulose-based polymers in a variety of combinations to achieve specific characteristics related to film formation, disintegration performance, drug content, in vitro drug release, and stability. One of the two formulations in this study was specify that bioequivalence criteria met with respect to Cmax of the reference drug (ELIQUIS®) in terms of pharmacokinetic profile. Further research will be required to assess the applicability of orodispersible films created using colloidal polymers of high and low molecular weights to other drugs with poor solubility in water