Cross-Utterance Conditioned VAE for Non-Autoregressive Text-to-Speech

Modelling prosody variation is critical for synthesizing natural and expressive speech in end-to-end text-to-speech (TTS) systems. In this paper, a cross-utterance conditional VAE (CUC-VAE) is proposed to estimate a posterior probability distribution of the latent prosody features for each phoneme by conditioning on acoustic features, speaker information, and text features obtained from both past and future sentences. At inference time, instead of the standard Gaussian distribution used by VAE, CUC-VAE allows sampling from an utterance-specific prior distribution conditioned on cross-utterance information, which allows the prosody features generated by the TTS system to be related to the context and is more similar to how humans naturally produce prosody. The performance of CUC-VAE is evaluated via a qualitative listening test for naturalness, intelligibility and quantitative measurements, including word error rates and the standard deviation of prosody attributes. Experimental results on LJ-Speech and LibriTTS data show that the proposed CUC-VAE TTS system improves naturalness and prosody diversity with clear margins

Cross-Utterance Conditioned VAE for Speech Generation

Speech synthesis systems powered by neural networks hold promise for multimedia production, but frequently face issues with producing expressive speech and seamless editing. In response, we present the Cross-Utterance Conditioned Variational Autoencoder speech synthesis (CUC-VAE S2) framework to enhance prosody and ensure natural speech generation. This framework leverages the powerful representational capabilities of pre-trained language models and the re-expression abilities of variational autoencoders (VAEs). The core component of the CUC-VAE S2 framework is the cross-utterance CVAE, which extracts acoustic, speaker, and textual features from surrounding sentences to generate context-sensitive prosodic features, more accurately emulating human prosody generation. We further propose two practical algorithms tailored for distinct speech synthesis applications: CUC-VAE TTS for text-to-speech and CUC-VAE SE for speech editing. The CUC-VAE TTS is a direct application of the framework, designed to generate audio with contextual prosody derived from surrounding texts. On the other hand, the CUC-VAE SE algorithm leverages real mel spectrogram sampling conditioned on contextual information, producing audio that closely mirrors real sound and thereby facilitating flexible speech editing based on text such as deletion, insertion, and replacement. Experimental results on the LibriTTS datasets demonstrate that our proposed models significantly enhance speech synthesis and editing, producing more natural and expressive speech.Comment: 13 pages

The ubiquitin-conjugating enzyme HR6B is required for maintenance of X chromosome silencing in mouse spermatocytes and spermatids

<p>Abstract</p> <p>Background</p> <p>The ubiquitin-conjugating enzyme HR6B is required for spermatogenesis in mouse. Loss of HR6B results in aberrant histone modification patterns on the trancriptionally silenced X and Y chromosomes (XY body) and on centromeric chromatin in meiotic prophase. We studied the relationship between these chromatin modifications and their effects on global gene expression patterns, in spermatocytes and spermatids.</p> <p>Results</p> <p>HR6B is enriched on the XY body and on centromeric regions in pachytene spermatocytes. Global gene expression analyses revealed that spermatid-specific single- and multicopy X-linked genes are prematurely expressed in <it>Hr6b </it>knockout spermatocytes. Very few other differences in gene expression were observed in these cells, except for upregulation of major satellite repeat transcription. In contrast, in <it>Hr6b </it>knockout spermatids, 7298 genes were differentially expressed; 65% of these genes was downregulated, but we observed a global upregulation of gene transcription from the X chromosome. In wild type spermatids, approximately 20% of the single-copy X-linked genes reach an average expression level that is similar to the average expression from autosomes.</p> <p>Conclusions</p> <p>Spermatids maintain an enrichment of repressive chromatin marks on the X chromosome, originating from meiotic prophase, but this does not interfere with transcription of the single-copy X-linked genes that are reactivated or specifically activated in spermatids. HR6B represses major satellite repeat transcription in spermatocytes, and functions in the maintenance of X chromosome silencing in spermatocytes and spermatids. It is discussed that these functions involve modification of chromatin structure, possibly including H2B ubiquitylation.</p

Histone H2BK123 monoubiquitination is the critical determinant for H3K4 and H3K79 trimethylation by COMPASS and Dot1

Histone H2B monoubiquitination by Rad6/Bre1 is required for the trimethylation of both histone H3K4 and H3K79 by COMPASS and Dot1 methyltransferases, respectively. The dependency of methylation at H3K4 and H3K79 on the monoubiquitination of H2BK123 was recently challenged, and extragenic mutations in the strain background used for previous studies or epitope-tagged proteins were suggested to be the sources of this discrepancy. In this study, we show that H3K4 and H3K79 methylation is solely dependent on H2B monoubiquitination regardless of any additional alteration to the H2B sequence or genome. Furthermore, we report that Y131, one of the yeast histone H2A/H2B shuffle strains widely used for the last decade in the field of chromatin and transcription biology, carries a wild-type copy of each of the HTA2 and HTB2 genes under the GAL1/10 promoter on chromosome II. Therefore, we generated the entire histone H2A and H2B alanine-scanning mutant strains in another background, which does not express wild-type histones

HLA-matched sibling transplantation with G-CSF mobilized PBSCs and BM decreases GVHD in adult patients with severe aplastic anemia

<p>Abstract</p> <p>Background</p> <p>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for severe aplastic anemia (SAA). However, graft failure and graft-versus-host disease (GVHD) are major causes of the early morbidity in Allo-HSCT.</p> <p>Methods</p> <p>To reduce graft failure and GVHD, we treated fifteen patients with SAA using high- dose of HSCT with both G-CSF mobilized PB and BMSCs from HLA-identical siblings to treat patients with SAA.</p> <p>Results</p> <p>All patients had successful bone marrow engraftment. Only one patient had late rejection. Median time to ANC greater than 0.5 × 10⁹/L and platelet counts greater than 20 × 10⁹/L was 12 and 16.5 days, respectively. No acute GVHD was observed. The incidence of chronic GVHD was 6.67%. The total three-year probability of disease-free survival was 79.8%.</p> <p>Conclusion</p> <p>HSCT with both G-CSF mobilized PB and BMSCs is a promising approach for heavily transfused and/or allo-immunized patients with SAA.</p

CRISPR-Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity.

Hexanucleotide-repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). The nucleotide-repeat expansions are translated into dipeptide-repeat (DPR) proteins, which are aggregation prone and may contribute to neurodegeneration. We used the CRISPR-Cas9 system to perform genome-wide gene-knockout screens for suppressors and enhancers of C9ORF72 DPR toxicity in human cells. We validated hits by performing secondary CRISPR-Cas9 screens in primary mouse neurons. We uncovered potent modifiers of DPR toxicity whose gene products function in nucleocytoplasmic transport, the endoplasmic reticulum (ER), proteasome, RNA-processing pathways, and chromatin modification. One modifier, TMX2, modulated the ER-stress signature elicited by C9ORF72 DPRs in neurons and improved survival of human induced motor neurons from patients with C9ORF72 ALS. Together, our results demonstrate the promise of CRISPR-Cas9 screens in defining mechanisms of neurodegenerative diseases

Heteroatom Doped High Porosity Carbon Nanomaterials as Electrodes for Energy Storage in Electrochemical Capacitors: A Review

At present it is indispensable to develop and implement new/state-of-the-art carbon nanomaterials as electrodes in electrochemical capacitors, since conventional activated carbon based supercapacitor cells cannot fulfil the growing demand of high energy and power densities of electronic devices of the present era, as a result of the rapid developments in this field. Functionalized carbon nanomaterials symbolize the type of materials with huge potential for their use in energy related applications in general and as an electrode active material for electrochemical capacitors in particular. Nitrogen doping of carbons has shown promising results in the field of energy storage in electrochemical capacitors, gaining attention of researchers to evaluate the performance of new heteroatoms functionalised materials such as sulphur, phosphorus and boron lately. Literature is widely available on nitrogen doped materials research for energy storage applications; however, there has been a limited number of review works on other functional materials beyond nitrogen. This review article thus aims to provide important insights and an up-to-date analysis of the most recent developments, the directions of future research, and the techniques used for the synthesis of these functional materials. A critical review of the electrochemical performance including specific capacitance and energy/power densities is made, when these single doped or co-doped active materials are used as electrodes in electrochemical capacitors