GO Hessian for Expectation-Based Objectives

An unbiased low-variance gradient estimator, termed GO gradient, was proposed recently for expectation-based objectives $\mathbb{E}_{q_{\boldsymbol{\gamma}}(\boldsymbol{y})} [f(\boldsymbol{y})]$, where the random variable (RV) $\boldsymbol{y}$ may be drawn from a stochastic computation graph with continuous (non-reparameterizable) internal nodes and continuous/discrete leaves. Upgrading the GO gradient, we present for $\mathbb{E}_{q_{\boldsymbol{\boldsymbol{\gamma}}}(\boldsymbol{y})} [f(\boldsymbol{y})]$ an unbiased low-variance Hessian estimator, named GO Hessian. Considering practical implementation, we reveal that GO Hessian is easy-to-use with auto-differentiation and Hessian-vector products, enabling efficient cheap exploitation of curvature information over stochastic computation graphs. As representative examples, we present the GO Hessian for non-reparameterizable gamma and negative binomial RVs/nodes. Based on the GO Hessian, we design a new second-order method for $\mathbb{E}_{q_{\boldsymbol{\boldsymbol{\gamma}}}(\boldsymbol{y})} [f(\boldsymbol{y})]$, with rigorous experiments conducted to verify its effectiveness and efficiency

The Evaluation of Dynamic FDG-PET for Detecting Epileptic Foci and Analyzing Reduced Glucose Phosphorylation in Refractory Epilepsy

Aims: Static fluorodeoxyglucose (FDG)-positron emission tomographic (PET) imaging plays an important role in the localization of epileptic foci. Dynamic FDG PET allows calculation of kinetic parameters. The aim of this study was to investigate whether kinetic parameters have potential for identifying epileptic foci, and to assess the correlation of parameters asymmetry indexes (ASYM) between dynamic and static FDG PET for understanding the pathophysiology of hypometabolism within intractable epilepsy.Methods: Seventeen patients who had refractory epilepsy correctly localized by static FDG PET with good outcome after foci resection were included. Eight controls were also studied. We performed dynamic and static FDG PET scan before operation. Images of both scans were coregistered to the montreal neurological institute space, regional time activity curves and activity concentration (AC) were obtained by applying the automated anatomical labeling template to the two spatially normalized images, respectively. Kinetic parameters were obtained using a two-tissue non-reversible compartmental model with an image-derived input function. AC from the static scan was used. Side-to-side ASYM of both static AC and kinetic parameters were calculated and analyzed in the hypometabolic epileptogenic regions and non-epileptogenic regions.Results: Higher values of ASYM from both kinetic parameters and static AC were found in the patients compared to the controls from epileptogenic regions. In the non-epileptogenic regions, no ASYM differences were seen between patients and controls for all parameters. In patients, static AC showed larger ASYM than influx (K1) and efflux (k2) of capillaries, but there were no statistical differences of ASYM between net metabolic flux (Ki) or the phosphorylation (k3) and static AC. ASYM of static AC positively correlated with ASYM of k3.Conclusion: Dynamic FDG PET can provide equally effective in detecting the epileptic foci compared to static FDG PET in this small cohort. In addition, compared to capillary influx, the hypometabolism of epileptic foci may be related to reduced glucose phosphorylation

Rare Copy Number Variants Identify Novel Genes in Sporadic Total Anomalous Pulmonary Vein Connection

Total anomalous pulmonary venous connection (TAPVC) is a rare congenital heart anomaly. Several genes have been associated TAPVC but the mechanisms remain elusive. To search novel CNVs and candidate genes, we screened a cohort of 78 TAPVC cases and 100 healthy controls for rare copy number variants (CNVs) using whole exome sequencing (WES). Then we identified pathogenic CNVs by statistical comparisons between case and control groups. After that, we identified altogether eight pathogenic CNVs of seven candidate genes (PCSK7, RRP7A, SERHL, TARP, TTN, SERHL2, and NBPF3). All these seven genes have not been described previously to be related to TAPVC. After network analysis of these candidate genes and 27 known pathogenic genes derived from the literature and publicly database, PCSK7 and TTN were the most important genes for TAPVC than other genes. Our study provides novel candidate genes potentially related to this rare congenital birth defect (CHD) which should be further fundamentally researched and discloses the possible molecular pathogenesis of TAPVC

The regulations on cortical activation and functional connectivity of the dorsolateral prefrontal cortex-primary somatosensory cortex elicited by acupuncture with reinforcing-reducing manipulation

IntroductionTraditional acupuncture with reinforcing-reducing manipulation is essential for clinical effectiveness, whereas the underlying central mechanism of it remains unknown. This study with multiple-channels functional near-infrared spectroscopy (fNIRS) aims to explore cerebral-response modes during acupuncture with reinforcing-reducing manipulations.Materials and methodsFunctional near-infrared spectroscopy data were recorded from 35 healthy participants during the lifting-thrusting reinforcing manipulation, the lifting-thrusting reducing manipulation, and the even reinforcing-reducing manipulation with lifting-thrusting. The general linear model based (GLM) cortical activation analysis and the functional connectivity (FC) based on region of interest (ROI) analysis were combined to be conducted.ResultsIn comparison with the baseline, the results showed that three acupuncture with reinforcing-reducing manipulations similarly induced the hemodynamic responses in the bilateral dorsolateral prefrontal cortex (DLPFC) and increased FC between the DLPFC and primary somatosensory cortex (S1). Specifically, the even reinforcing-reducing manipulation deactivated the bilateral DLPFC, the frontopolar area (FP), the right primary motor cortex (M1), the bilateral S1, and the bilateral secondary somatosensory cortex (S2); The reducing manipulation deactivated the bilateral DLPFC; The reinforcing manipulation activated the bilateral DLPFC, the left S1, and the right S2. The between-group comparisons indicated that the reinforcing-reducing manipulation induced opposite hemodynamic responses in the bilateral DLPFC and the left S1 and exhibited different FC patterns in the left DLPFC-S1, within the right DLPFC, and between the left S1 and the left orbitofrontal cortex (OFC).ConclusionThese findings verified the feasibility of fNIRS for investigating cerebral functional activities of acupuncture manipulations, suggesting that the regulations on the DLPFC-S1 cortex may be the potential central mechanism for the realization of acupuncture with reinforcing-reducing manipulation’s effect.Clinical trial registrationClinicalTrials.gov, identifier, ChiCTR2100051893

Microstructure and Strengthening-Toughening Mechanism of Nitrogen-Alloyed 4Cr5Mo2V Hot-Working Die Steel

The microstructure and strengthening-toughening mechanism of a modified 4Cr5Mo2V hot-working die steel with nitrogen (0.08% N) were investigated using hardness and toughness measurements, optical microscopy, scanning electron microscopy, X-ray diffraction experiments, transmission electron microscopy, and dilatometry. The results showed that the nitrogen addition could increase the hardness and temperability of 4Cr5Mo2V steel without toughness loss with a suitable heat treatment procedure. The fair match of high strength and toughness of the nitrogen-alloyed 4Cr5Mo2V steel is associated with the refinement of the prior austenite grain, the solution hardening of nitrogen atoms, and the increase of retained austenite. Before quenching, nitrogen tends to precipitate in the form of a large amount of undissolved finer V(C, N), imposing a stronger effect on restricting the growth of prior austenitic grains and increasing the grain refining efficiency of VC by 6.8 times according to an estimate. During the quenching process, the nitrogen decreases the MS of the martensitic transformation, increasing retained austenite, which is a benefit for toughness. During the tempering process, some of the N atoms in M(C, N) were dissolved in the matrix, causing crystal lattice distortions, thus boosting the solution reinforcing effect. Meanwhile, the solid-dissolved nitrogen inhibits the diffusion of carbon, decreasing the growth rate of the carbides and increasing tempering resistance

Tunnel Manganese Oxides Prepared Using Recovered LiMn2O4 from Spent Lithium-ion Batteries : Co adsorption behavior and mechanism

The purpose of this study was to investigate Cobalt (Co) removal from wastewater using synthesized manganese oxides from the recovered LiMn2O4. An efficient ultrasonication leaching method was utilized to recycle LiMn2O4 from spent lithium-ion batteries (LIBs). The recovered LiMn2O4 was used to synthesize tunnel lambda-MnO2, gamma-MnO2 and beta-MnO2 by acid leaching and hydrothermal methods. Meanwhile, Li + in the supernatant was recycled by the precipitation of Li3PO4. Subsequently, for the synthesized tunnel MnO2 , various characterizations and sodium hydroxide titration in NaNO3 solution were performed. The effect of sorption studies presented the uptake of Co increased with the pH increasing from pH similar to 1 to pH similar to 8 and the isothermal sorption at pH similar to 6 showed that gamma-MnO2 possessed the highest uptake amount 0.44 meq/g, and the highest distribution coefficient 2.5 x 10(5) mL/g. Moreover, gamma-MnO2 was found without Mn3+/Mn2+ leached during the sorption process. The ion exchange-surface complexation model was adopted to study the titration, effect of pH and isotherm sorption on the ion exchange reaction mechanism of Co adsorption. Overall, this work provides an economically feasible and environmentally friendly method to recycle the spent LIBs and the gamma-MnO2 synthesized from the recovered LiMn2O4 was proved to be promising adsorbents for Co removal.Peer reviewe

Leveraging Oxidative Stress to Regulate Redox Balance-Based, In Vivo Growth Selections for Oxygenase Engineering.

Directed evolution methods based on high-throughput growth selection enable efficient discovery of enzymes with improved function in vivo. High-throughput selection is particularly useful when engineering oxygenases, which are sensitive to structural perturbations and prone to uncoupled activity. In this work, we combine the principle that reactive oxygen species (ROS) produced by uncoupled oxygenase activity are detrimental to cell fitness with a redox balance-based growth selection method for oxygenase engineering that enables concurrent advancement in catalytic activity and coupling efficiency. As a proof-of-concept, we engineered P450-BM3 for degradation of acenaphthene (ACN), a recalcitrant environmental pollutant. Selection of site-saturation mutagenesis libraries in E. coli strain MX203 identified P450-BM3 variants GVQ-AL and GVQ-D222N, which have both improved coupling efficiency and catalytic activity compared to the starting variant. Computational modeling indicates that the discovered mutations cooperatively optimize binding pocket shape complementarity to ACN, and shift the proteins conformational dynamics to favor the lid-closed, catalytically competent state. We further demonstrated that the selective pressure on coupling efficiency can be tuned by modulating cellular ROS defense mechanisms

Structure observation of single solidified droplet by in situ controllable quenching based on nanocalorimetry

Fast scanning calorimetry (FSC) based on nanocalorimetry and thin film technique is a newly developed attractive tool to investigate the solidification behavior of single droplet by in situ controllable ultrafast cooling. In this paper, we introduced this novel technique to in situ control the quenching of single Sn3.5Ag metallic droplet at cooling rate up to 15,000 K/s with corresponding undercooling of 110.9 K. In particular, the solidification structure of this real time quenched single droplet was observed and analyzed with focused ion beam (FIB), scanning electron microscopy (SEM) and high resolution transmission electron microscopy (HRTEM). This research proposed a new approach to research the solidification structure of single droplet with precisely controlled size and extreme cooling rate