Singing Voice Synthesis with Vibrato Modeling and Latent Energy Representation

This paper proposes an expressive singing voice synthesis system by introducing explicit vibrato modeling and latent energy representation. Vibrato is essential to the naturalness of synthesized sound, due to the inherent characteristics of human singing. Hence, a deep learning-based vibrato model is introduced in this paper to control the vibrato's likeliness, rate, depth and phase in singing, where the vibrato likeliness represents the existence probability of vibrato and it would help improve the singing voice's naturalness. Actually, there is no annotated label about vibrato likeliness in existing singing corpus. We adopt a novel vibrato likeliness labeling method to label the vibrato likeliness automatically. Meanwhile, the power spectrogram of audio contains rich information that can improve the expressiveness of singing. An autoencoder-based latent energy bottleneck feature is proposed for expressive singing voice synthesis. Experimental results on the open dataset NUS48E show that both the vibrato modeling and the latent energy representation could significantly improve the expressiveness of singing voice. The audio samples are shown in the demo website

N-Acetyl-Serotonin Protects HepG2 Cells from Oxidative Stress Injury Induced by Hydrogen Peroxide

Oxidative stress plays an important role in the pathogenesis of liver diseases. N-Acetyl-serotonin (NAS) has been reported to protect against oxidative damage, though the mechanisms by which NAS protects hepatocytes from oxidative stress remain unknown. To determine whether pretreatment with NAS could reduce hydrogen peroxide- (H2O2-) induced oxidative stress in HepG2 cells by inhibiting the mitochondrial apoptosis pathway, we investigated the H2O2-induced oxidative damage to HepG2 cells with or without NAS using MTT, Hoechst 33342, rhodamine 123, Terminal dUTP Nick End Labeling Assay (TUNEL), dihydrodichlorofluorescein (H2DCF), Annexin V and propidium iodide (PI) double staining, immunocytochemistry, and western blot. H2O2 produced dramatic injuries in HepG2 cells, represented by classical morphological changes of apoptosis, increased levels of malondialdehyde (MDA) and intracellular reactive oxygen species (ROS), decreased activity of superoxide dismutase (SOD), and increased activities of caspase-9 and caspase-3, release of cytochrome c (Cyt-C) and apoptosis-inducing factor (AIF) from mitochondria, and loss of membrane potential (ΔΨm). NAS significantly inhibited H2O2-induced changes, indicating that it protected against H2O2-induced oxidative damage by reducing MDA levels and increasing SOD activity and that it protected the HepG2 cells from apoptosis through regulating the mitochondrial apoptosis pathway, involving inhibition of mitochondrial hyperpolarization, release of mitochondrial apoptogenic factors, and caspase activity

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Spectroscopic study of gap-surface plasmons in a metallic convex groove array and their applications in nanofocusing and plasmonic sensing

Plasmonic tapered grooves have been proven to be good candidates for the excitation of gap surface plasmons (GSPs), surface plasmons trapped vertically inside a metallic tapered groove or slit. GSPs have attracted tremendous interest due to their unique properties of concentrating light in nanosized gaps with significant field enhancement, thus offering potential applications such as ultracompact nanocircuits, broadband light absorbers, and plasmonic sensors. In this paper, we focus on GSPs supported by periodic arrays of narrow convex grooves and study in detail their properties by using visible-near-infrared (VIS-NIR) spectroscopy. We identify strong second- and third-order GSP modes excited in ultrasharp convex grooves. The dependence of GSP resonances on the groove profile is analyzed with the help of detailed full-wave simulations, revealing the fact that an ultrasharp, but finite, gap exists at the groove bottom and plays a crucial role in determining both the GSP resonance positions and the nanofocusing capability with much improved field enhancement inside the grooves. Spectral shifts of the observed GSP resonances relative to the simulation results are found in a shorter wavelength range and are qualitatively explained as nonlocal effects originating from the nonclassical microscopic behavior of local currents and charges at imperfect interfaces. Utilizing such strong and distinguishable GSP resonance line shapes in an otherwise flat reflectivity spectral baseline, we experimentally demonstrate the capability of convex groove arrays to perform dual-band refractive index sensing in the VIS-NIR range. </p

Modeling Hydroclimatic Change in Southwest Louisiana Rivers

We applied the newly developed WRF-Hydro model to investigate the hydroclimatic trend encompassing the three basins in Southwest Louisiana as well as their connection with large-scale atmospheric drivers. Using the North American Land Data Assimilation System Phase 2 (NLDAS-2), we performed a multi-decadal model hindcast covering the period of 1979&ndash;2014. After validating the model&rsquo;s performance against available observations, trend and wavelet analysis were applied on the time series of hydroclimatic variables from NLDAS-2 (temperature and precipitation) and model results (evapotranspiration, soil moisture, water surplus, and streamflow). Trend analysis of model-simulated monthly and annual time series indicates that the regional climate is warming and drying over the past decades, specifically during spring and summer (growing season). Wavelet analysis reveals that, since the late 1990s, the anomaly of evapotranspiration, soil moisture, and streamflow exhibits high coherency with that of precipitation. Pettitt&rsquo;s test detects a possible change-point around the year 2004, after which the monthly precipitation decreased from 140 to 120 mm, evapotranspiration slightly increased from 80 to 83 mm, and water surplus decreased from 60 to 38 mm. Changes in regional climate conditions are closely correlated with large-scale climate dynamics such as the Atlantic Multidecadal Oscillation (AMO) and El Ni&ntilde;o Southern Oscillation (ENSO)

Protective Effect of N-Acetylserotonin against Acute Hepatic Ischemia-Reperfusion Injury in Mice

The purpose of this study was to investigate the possible protective effect of N-acetylserotonin (NAS) against acute hepatic ischemia-reperfusion (I/R) injury in mice. Adult male mice were randomly divided into three groups: sham, I/R, and I/R + NAS. The hepatic I/R injury model was generated by clamping the hepatic artery, portal vein, and common bile duct with a microvascular bulldog clamp for 30 min, and then removing the clamp and allowing reperfusion for 6 h. Morphologic changes and hepatocyte apoptosis were evaluated by hematoxylin-eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, respectively. Activated caspase-3 expression was evaluated by immunohistochemistry and Western blot. The activation of aspartate aminotransferase (AST), malondialdehyde (MDA), and superoxide dismutase (SOD) was evaluated by enzyme-linked immunosorbent assay (ELISA). The data show that NAS rescued hepatocyte morphological damage and dysfunction, decreased the number of apoptotic hepatocytes, and reduced caspase-3 activation. Our work demonstrates that NAS ameliorates hepatic IR injury