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We propose a simple and effective method to inject word-level information into character-aware neural language models. Unlike previous approaches which usually inject word-level information at the input of a long short-term memory (LSTM) network, we inject it into the softmax function. The resultant model can be seen as a combination of character-aware language model and simple word-level language model. Our injection method can also be used together with previous methods. Through the experiments on 14 typologically diverse languages, we empirically show that our injection method, when used together with the previous methods, works better than the previous methods, including a gating mechanism, averaging, and concatenation of word vectors. We also provide a comprehensive comparison of these injection methods.

OBJECTIVE Based on cybernetics, a large system can be divided into subsystems, and the stability of each can determine the overall properties of the system. However, this stability analysis perspective has not yet been employed in electrocardiogram (ECG) signals. This is the first study to attempt to evaluate whether the stability of decomposed ECG subsystems can be analyzed in order to effectively investigate the overall performance of ECG signals, and aid in disease diagnosis. METHODS We used seven different cardiac pathologies (myocardial infarction, cardiomyopathy, bundle branch block, dysrhythmia, hypertrophy, myocarditis, and valvular heart disease) to illustrate our method. Dynamic mode decomposition (DMD) was first used to decompose ECG signals into dynamic modes (DMs) which can be regarded as ECG subsystems. Then, the features related to the DMs stabilities were extracted, and nine common classifiers were implemented for classification of these pathologies. RESULTS Most features were significant for differentiating the above-mentioned groups (value

Recent studies have investigated bilateral gaits based on the causality analysis of kinetic (or kinematic) signals recorded using both feet. However, these approaches have not considered the influence of their simultaneous causation, which might lead to inaccurate causality inference. Furthermore, the causal interaction of these signals has not been investigated within their frequency domain. Therefore, in this study we attempted to employ a causal-decomposition approach to analyze bilateral gait. The vertical ground reaction force (VGRF) signals of Parkinson's disease (PD) patients and healthy control (HC) individuals were taken as an example to illustrate this method. To achieve this, we used ensemble empirical mode decomposition to decompose the left and right VGRF signals into intrinsic mode functions (IMFs) from the high to low frequency bands. The causal interaction strength (CIS) between each pair of IMFs was then assessed through the use of their instantaneous phase dependency. The results show that the CISes between pairwise IMFs decomposed in the high frequency band of VGRF signals can not only markedly distinguish PD patients from HC individuals, but also found a significant correlation with disease progression, while other pairwise IMFs were not able to produce this. In sum, we found for the first time that the frequency specific causality of bilateral gait may reflect the health status and disease progression of individuals. This finding may help to understand the underlying mechanisms of walking and walking-related diseases, and offer broad applications in the fields of medicine and engineering.

Methyleugenol (ME) is a ubiquitous component in spices and other culinary herbal products. A prevailing theory in ME toxicity is its ability to be metabolically activated by P450 enzymes and sulfotransferases, which initiates sequential reactions of the resulting metabolites with functional biomolecules. The present study aimed at a potential interaction between the reactive metabolites of ME and RNA. Cultured mouse primary hepatocytes were incubated with ME followed by RNA extraction and NaOH and alkaline phosphatase-based RNA hydrolysis. Three adenosine adducts were detected in the hydrolytic mixture by LC-MS/MS. The same adenosine adducts were also detected in hepatic tissues harvested from ME-treated mice. These three adducts were chemically synthesized and structurally characterized by 1H NMR. Additionally, two guanosine adducts and one cytidine adduct were detected in the in vivo samples. These results provided solid evidence that the reactive metabolites of ME attacked RNA, resulting in RNA adduction.

Background The R1441G mutation in the leucine-rich repeat kinase 2 (LRRK2) gene results in late-onset Parkinson’s disease (PD). Peripheral inflammation and gut microbiota are closely associated with the pathogenesis of PD. Chronic periodontitis is a common type of peripheral inflammation, which is associated with PD. Porphyromonas gingivalis (Pg), the most common bacterium causing chronic periodontitis, can cause alteration of gut microbiota. It is not known whether Pg-induced dysbiosis plays a role in the pathophysiology of PD. Methods In this study, live Pg were orally administrated to animals, three times a week for 1 month. Pg-derived lipopolysaccharide (LPS) was used to stimulate mononuclear cells in vitro. The effects of oral Pg administration on the gut and brain were evaluated through behaviors, morphology, and cytokine expression. Results Dopaminergic neurons in the substantia nigra were reduced, and activated microglial cells were increased in R1441G mice given oral Pg. In addition, an increase in mRNA expression of tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β) as well as protein level of α-synuclein together with a decrease in zonula occludens-1 (Zo-1) was detected in the colon in Pg-treated R1441G mice. Furthermore, serum interleukin-17A (IL-17A) and brain IL-17 receptor A (IL-17RA) were increased in Pg-treated R1441G mice. Conclusions These findings suggest that oral Pg-induced inflammation may play an important role in the pathophysiology of LRRK2-associated PD.

Many-objective optimization refers to the optimization aiming at four or more objectives. More complex than multi-objective optimization, which copes with two or three objectives, many-objective optimization represents a challenging problem due to the complex trade-off relationships among the optimization objectives. In this study, a four-objective optimization system was proposed for reducing the resistance and the non-uniformity of wake flow of a deep-sea aquaculture vessel at design speed in full load and ballast conditions. The numerical optimization system was mainly composed of the uniform design (UD), free-form deformation method (FFD), radial basis neural network (RBFNN) and a series of genetic algorithms (GAs). During the optimization process, nine design variables were selected to reconstruct the hull geometry. UD and FFD were utilized to generate a series of derivative ship forms. According to CFD calculation results of all derivative ship forms, four surrogate models were constructed, using RBFNN optimized by the particle swarm optimization (PSO), to replace direct numerical calculations. To verify the prediction accuracy advantage of improved RBFNN-based surrogate models based on small sample size, the accuracy comparison was made among surrogate models based on RBFNN, kriging and support vector regression (SVR). Moreover, Sobol' method was employed to analyze the influence of design variables on the optimization objectives. GAs were applied to perform from single-objective to four-objective optimization of the resistance and non-uniformity of wake flow. Eventually, the optimal ship form was selected from the Pareto front of four-objective optimization. Numerical results of the optimized shape showed that the resistance and the non-uniformity of wake flow in full load and ballast conditions were reduced, and the results of the verification and validation (V&V) procedure proved the validation of the many-objective optimization system.

The Transformer architecture has led to significant gains in machine translation. However, most studies focus on only sentence-level translation without considering the context dependency within documents, leading to the inadequacy of document-level coherence. Some recent research tried to mitigate this issue by introducing an additional context encoder or translating with multiple sentences or even the entire document. Such methods may lose the information on the target side or have an increasing computational complexity as documents get longer. To address such problems, we introduce a recurrent memory unit to the vanilla Transformer, which supports the information exchange between the sentence and previous context. The memory unit is recurrently updated by acquiring information from sentences, and passing the aggregated knowledge back to subsequent sentence states. We follow a two-stage training strategy, in which the model is first trained at the sentence level and then finetuned for document-level translation. We conduct experiments on three popular datasets for document-level machine translation and our model has an average improvement of 0.91 s-BLEU over the sentence-level baseline. We also achieve state-of-the-art results on TED and News, outperforming the previous work by 0.36 s-BLEU and 1.49 d-BLEU on average., Comment: Accepted by NAACL-2022 Findings

The drag reduction effect of interceptors on planing boats has been widely proven, but the mechanism of the effect has been rarely studied in terms of drag components, especially for spray resistance. The resistance was caused by the high gauge pressure under the boats transformed from the dynamic pressure, and it is the largest drag component in the high-speed planing mode. In this study, numerical simulations of viscous flow fields around a planing boat with and without interceptors were conducted. A two degrees of freedom motion model was employed to simulate the trim and sinkage. The numerical results were validated against the experimental data. The flow details with and without the interceptor were visualized and compared to reveal the underlying physics. A thinner and longer waterline could be achieved by the interceptor, which made the boat push the water away more gradually, and hence, the wave-making resistance could be decreased. The improved waterline also reduced the component of the freestream normal to the hull surface and led to the less transformed dynamic pressure, resulting in the lowAer spray resistance. Furthermore, the suppression of the flow separation could also be benefited from the interceptor; the viscous pressure resistance was therefore decreased.

Benzbromarone (BBR), a uricosuric agent, has been known to induce hepatotoxicity, and its toxicity has a close relation to cytochrome P450-mediated metabolic activation. An oxidative debromination metabolite of BBR has been reported in microsomal incubations. The present study attempted to define the oxidative debromination pathway of BBR in vivo. One urinary mercapturic acid (M1) and one glutathione (GSH) conjugate (M2) derived from the oxidative debromination metabolite were detected in BBR-treated mice after solid phase extraction. M1 and M2 shared the same chromatographic behavior and mass spectral identities as those detected in N-acetylcysteine/GSH- and BBR-fortified microsomal incubations. The structure of M1 was characterized by chemical synthesis, along with mass spectrometry analysis. In addition, hepatic protein modification that occurs at cysteine residues (M'3) was observed in mice given BBR. The observed protein adduction reached its peak 4 hours after administration and occurred in a dose-dependent manner. A GSH conjugate derived from oxidative debromination of BBR was detected in livers of mice treated with BBR, and the formation of the GSH conjugate apparently took place earlier than the protein adduction. In summary, our in vivo work provided strong evidence for the proposed oxidative debromination pathway of BBR, which facilitates the understanding of the mechanisms of BBR-induced hepatotoxicity. SIGNIFICANCE STATEMENT: This study investigated the oxidative debromination pathway of benzbromarone (BBR) in vivo. One urinary mercapturic acid (M1) and one glutathione (GSH) conjugate (M2) derived from the oxidative debromination metabolite were detected in BBR-treated mice. M1 and M2 were also observed in microsomal incubations. The structure of M1 was characterized by chemical synthesis followed by mass spectrometry analyses. More importantly, protein adduction derived from oxidative debromination of BBR (M'3) was observed in mice given BBR, and occurred in dose- and time-dependent manners. The success in detection of GSH conjugate, urinary N-acetylcysteine conjugate, and hepatic protein adduction in mice given BBR provided solid evidence for in vivo oxidative debromination of BBR. The studies allowed a better understanding of the metabolic activation of BBR.

We address the task of generating live soccer-match commentaries from play event data. This task has characteristics that (i) each commentary is only partially aligned with events, (ii) play event data contains many types of categorical and numerical attributes, (iii) live commentaries often mention player names and team names. For these reasons, we propose an encoder for play event data, which is enhanced with a gate mechanism. We also introduce an attention mechanism on events. In addition, we introduced placeholders and their reconstruction mechanism to enable the model to copy appropriate player names and team names from the input data. We conduct experiments on the play data of the English Premier League, provide a discussion on the result including generated commentaries.

Using a photothrombotic mouse model of single stroke, we show that a single stroke onset increases the nuclear factor-κB (NF-κB), NLR family CARD domain containing protein 4 (NLRC4), and absent in melanoma 2 (AIM2) inflammasomes, as well as the mRNA levels of NLRP3. Next, using a photothrombotic mouse model of recurrent stroke, we found that recurrent strokes increased the activation of NLRP3, exacerbated the brain damage and the pro-inflammatory response in wild type (WT) mice, but not in NLRP3 knockout ( NLRP3 KO) mice. Additionally, we found that apoptosis-associated speck-like protein containing a CARD (ASC) protein level surrounding the infarct area was comparatively increased, but that ASC specks outside of microglia in both the ipsilateral and contralateral of stroke site were decreased in NLRP3 KO mice relative to wild-type (WT) controls, and the number of ASC specks surrounding the second infarct area was positively correlated to the damage scores. Mechanistically, we found that recombinant ASC (RecASC) activated NLRP3 and induced pro-inflammatory responses, exacerbating the outcome of ischemic stroke, in WT mice, but not in NLRP3 KO mice. We therefore conclude that the NLRP3 inflammasome is activated by two attacks of stroke, which act together with ASC to exacerbate recurrent strokes.

In order to improve the accuracy of vehicle detection, this paper proposes a vehicle detection method based on improved YOLOv3. First, the loss function of the YOLOv3 algorithm is improved by introducing the GIoU and focal loss strategies, meanwhile, the detection accuracy of the network is improved. Secondly, by adopting the method of data augmentation for preprocessing, adding label smoothing strategy improves the generalization ability of the model and further improves the average accuracy of detection. During training, multi-scale training is used, and the cosine decay learning rate decay strategy is used to replace the step learning rate decay strategy, which reduces the negative impact of improper learning rate and decay steps, speeds up model training, and reduces the network training cycle. Experimental results show that the improved method can significantly improve the detection accuracy of the original model in fewer training cycles, has good robustness, and can effectively detect road vehicles.

Character-aware neural language models can capture the relationship between words by exploiting character-level information and are particularly effective for languages with rich morphology. However, these models are usually biased towards information from surface forms. To alleviate this problem, we propose a simple and effective method to improve a character-aware neural language model by forcing a character encoder to produce word-based embeddings under Skip-gram architecture in a warm-up step without extra training data. We empirically show that the resulting character-aware neural language model achieves obvious improvements of perplexity scores on typologically diverse languages, that contain many low-frequency or unseen words.

Objective: Previous studies have already shown that electroencephalography (EEG) brain network (BN) can reflect the health status of individuals. However, novel methods are still needed for BN analysis. Therefore, in this study, BNs were constructed based on stable and unstable EEG components, and these may be implemented for disease diagnosis. Methods: Parkinson's disease (PD) was used as an example to illustrate this method. First, EEG signals were decomposed into dynamic modes (DMs). Each DM contains one eigenvalue that can determine not only the stability of that mode, but also its corresponding oscillatory frequency. Second, the stable and unstable components of EEG signals in each frequency band (delta, theta, alpha and beta) were calculated, which are based on the stable and unstable DMs within each respective frequency band. Third, newly developed BNs were constructed, including stable brain network (SBN), unstable brain network (UBN) and inter-connected brain network (IBN). Finally, their topological attributes were extracted in order to differentiate between PD patients and healthy controls (HC). Furthermore, topological attributes were also derived from traditional brain network (TBN) for comparison. Results: Most topological attributes of SBN, UBN and IBN can significantly differentiate between PD patients and HC ( $p$ value $ 0.05). Furthermore, the area under the curve (AUC), precision and recall values of SBN analysis are all significantly higher than TBN. Conclusion: We proposed a new perspective on EEG BN analysis. Significance: These newly developed BNs not only have biological significance, but also could be widely applied in most medical and engineering fields.

Microinfarcts are common among the elderly, and patients with microinfarcts are more vulnerable to another stroke. However, the potential effect of microinfarct on recurrent stroke remains elusive. In this study, we investigated the detrimental effect of microinfarct on recurrent stroke in mice. Microinfarct was induced using two-photon laser and photothrombotic stroke was induced in the cortex contralateral to microinfarct four weeks later. We found that CMI could trigger the formation of innate immune memory, which exacerbated the pro-inflammatory response and ischemic injury in second photothrombotic stroke. Furthermore, we clarified the role of NLRP3 inflammasome in the nuclei of microglia, which interacts with the MLL1 complex and thereby increases H3K4 methylation, suggesting that NLRP3 is critical in microinfarct-induced innate immune memory. Additionally, NLRP3 knockout in microglia attenuated microinfarct-induced detrimental effects on recurrent stroke. Our study highlights the detrimental effect of trained immunity on the recurrent stroke and reveals the important role of NLRP3 in mediating the formation of this memory, which may be a therapeutic target to mitigate recurrent strokes.

Dioscorea bulbifera L. (DBL), a traditional Chinese medicine, is a well-known herb with hepatotoxicity, and the biochemical mechanisms of the toxic action remain unknown. Diosbulbin B (DSB), a major component of DBL, can induce severer liver injury which requires cytochrome P450-catalyzed oxidation of the furan ring. It is reported that a cis-enedial reactive intermediate resulting from metabolic activation of DSB can react with thiols and amines to form pyrrole or pyrroline derivatives. In this study, we investigated the interaction of the reactive intermediate with polyamines, biogenic amines, and amino acids involved in the polyamine metabolic pathway, including putrescine, spermidine, spermine, histamine, arginine, ornithine, lysine, glutamine, and asparagine. Seven DSB-derived amine adducts were detected in microsomal incubations supplemented with DSB and individual amines. Six adducts were observed in cultured rat primary hepatocytes after exposure to DSB. DSB was found to induce apoptosis and cell death in time- and concentration-dependent manners. Apparently, the observed apoptosis was associated with the detected amine adduction. The findings facilitate the understanding of the mechanisms of toxic action of DSB.

Background Machado-Joseph disease is the most common autosomal dominant hereditary ataxia worldwide without effective treatment. Mesenchymal stem cells (MSCs) could slow the disease progression, but side effects limited their clinical application. Besides, MSC-derived exosomes exerted similar efficacy and have many advantages over MSCs. The aim of this study was to examine the efficacy of MSC-derived exosomes in YACMJD84.2 mice. Methods Rotarod performance was evaluated every 2 weeks after a presymptomatic administration of intravenous MSC-derived exosomes twice in YACMJD84.2 mice. Loss of Purkinje cells, relative expression level of Bcl-2/Bax, cerebellar myelin loss, and neuroinflammation were assessed 8 weeks following treatment. Results MSC-derived exosomes were isolated and purified through anion exchange chromatography. Better coordination in rotarod performance was maintained for 6 weeks in YACMJD84.2 mice with exosomal treatment, compared with those without exosomal treatment. Neuropathological changes including loss of Purkinje cells, cerebellar myelin loss, and neuroinflammation were also attenuated 8 weeks after exosomal treatment. The higher relative ratio of Bcl-2/Bax was consistent with the attenuation of loss of Purkinje cells. Conclusions MSC-derived exosomes could promote rotarod performance and attenuate neuropathology, including loss of Purkinje cells, cerebellar myelin loss, and neuroinflammation. Therefore, MSC-derived exosomes have a great potential in the treatment of Machado-Joseph disease.

Latcripin-16 (Lp16-PSP) is a gene that was extracted as a result ofde novocharacterization of theLentinula edodes strainC91-3transcriptome. The aim of the present study was to clone, express and investigate the selectivein vitroanticancer potential of Lp16-PSP in human cell lines. Lp16-PSP was analyzed using bioinformatics tools, cloned in a prokaryotic expression vector pET32a (+) and transformed intoE. coliRosetta gami. It was expressed and solubilized under optimized conditions. The differential scanning fluorometry (DSF)-guided refolding method was used with modifications to identify the proper refolding conditions for the Lp16-PSP protein. In order to determine the selective anticancer potential of Lp16-PSP, a panel of human cancerous and non-cancerous cell lines was used. Lp16-PSP protein was identified as endoribonuclease L-PSP protein and a member of the highly conserved YjgF/YER057c/UK114 protein superfamily. Lp16-PSP was expressed under optimized conditions (37°C for 4 h following induction with 0.5 mM isopropyl β-D-1-thiogalactopyranoside). Solubilization was achieved with mild solubilization buffer containing 2M urea using the freeze-thaw method. The DSF guided refolding method identified the proper refolding conditions (50 mM Tris-HCl, 100 mM NaCl, 1 mM EDTA, 400 mM Arginine, 0.2 mM GSH and 2 mM GSSG; pH 8.0) for Lp16-PSP, with a melting transition of ~58°C. A final yield of ~16 mg of purified Lp16-PSP from 1 L of culture was obtained following dialysis and concentration by PEG 20,000. A Cell Counting Kit-8 assay revealed the selective cytotoxic effect of Lp16-PSP. The HL-60 cell line was demonstrated to be most sensitive to Lp16-PSP, with an IC50value of 74.4±1.07 μg/ml. The results of the present study suggest that Lp16-PSP may serve as a potential anticancer agent; however, further investigation is required to characterize this anticancer effect and to elucidate the molecular mechanism underlying the action of Lp16-PSP.

Mission drift is a common phenomenon in non-profits. However, related studies on employees remain scant. In this study, we combine mission drift and employees' turnover intention literature, and investigate mission drift at employee level based on interviews in the context of six nonprofits in China. The results show that: (1) employees who choose to work in nonprofits have a strong sense of prosocial mission; (2) employees believe that organizations have some defects, which are inconsistent with their own image of prosocial mission; (3) employees’mission drift exists in nonprofits, which may lead to their high turnover intention. Taken together, we believe mission drift deserves our future research attention.

The shape of a ship's hull has a significant impact on the resistance and propulsive performance of the ship, especially for wide ships. In this study, experimental and numerical analyses of an offshore aquaculture vessel were carried out, while multidisciplinary design optimization aimed to improve the resistance performance and the wake field quality of the vessel. Numerical analysis was performed using a Reynolds-averaged-Navier_Stokes (RANS) solver, and the numerical method was validated by comparing the numerical results from the original shape to the experimental results. Three support vector regression (SVR)-based surrogate models with different numbers of sample points were built, and the influence of the sample set size on the prediction precision was determined. An SVR surrogate model with 60 sample points was applied and optimized to replace direct numerical simulations. An optimization framework using Latin hypercube sampling (LHS), the free-form deformation (FFD) method, the SVR surrogate model, and the non-dominated sorting genetic algorithm II (NSGAII) was developed. Nine design variables were employed to modify the shape of the vessel. Because of the trade-off between the minimum resistance and the minimum circumferential nonuniformity of the wake flow, the optimal solution of the hull shape was selected from the Pareto-optimal solutions to balance the two objectives. Model tests for the optimized shape were then performed to validate the design results. The results showed that the resistance and the circumferential nonuniformity of the wake flow of the optimized shape were reduced by 1.59% and 17.80%, respectively, when compared to the results of the original shape.

In recent years, haze has become a critical environmental issue. As a crucial precursor of haze, volatile organic compounds (VOCs) have become a major research focus. In this study, microwave-induced metal discharge was developed for VOC decomposition. Toluene was used as the VOC model compound. Four types of metal strips were investigated for their decomposition efficiency of toluene using a microwave-induced metal discharge process. All discharges, regardless of the metal type, achieved a high decomposition efficiency of toluene [> 60% (mol/mol)]. In addition, the effects of reaction conditions such as metal strip weight, gas flow rate, microwave power, and gas initial concentration were studied to investigate the decomposition efficiency. The reaction conditions were optimized following a multi-factor orthogonal experiment. The weight of the metal strips and gas flow rate had greater impacts on the decomposition efficiency, whereas the microwave power had a moderate impact. The major reaction products were CO2, CO, O3 and H2O. Both hydroxyl radicals and active oxygen atoms were very important for toluene oxidation. This study offers an important reference for the development of new technology to support the decomposition of VOCs.

The numerical prediction of the hydrodynamic characteristics for planing hulls has always been challenging due to numerical ventilation (NV), which is the unphysical entrainment of air under a hull. The capture of the wetted surface, the pressure distribution, the spray, and wave-making phenomena may suffer from this. In this paper series, the characteristics of the NV were analyzed, and anti-ventilation techniques based on the volume of fluid (VOF) method were developed and applied. The NV was formed by the unphysically transported air phase in the wetted surface. To counteract the unphysical transport, pseudo diffusive fluxes in specific directions were introduced by adding an artificial diffusion term to the VOF equation for the pressure area (PA). The unphysical results caused by other numerical issues could also be dissipated by this term. The boundness of the underlying discretization scheme for the modified VOF equation was proved by stability analysis. Based on the anti-ventilation techniques, a novel systematic procedure for the hydrodynamic assessment of planing hulls was developed to improve the accuracy, stability, and convergence rate. Part 1 of this paper series contains the details of the NV and the theory of the anti-ventilation techniques. Part 2 provides the application and validation cases.

The glymphatic system contributes to a large proportion of brain waste clearance, including removal of amyloid β (Aβ). We have demonstrated that glutamate and γ-aminobutyric acid (GABA) influence glymphatic clearance through distinct mechanisms whereby GABA exerts modulatory effects in an aquaporin-4 (AQP4)-dependent manner while the actions of glutamate are pulsation-dependent. The efficacy of GABA and glutamate in alleviating Aβ in APP-PS1 and Angiotensin-II (Ang-II) induced hypertension mouse models was further evaluated. Notably, increasing GABA or inhibiting glutamate levels led to reduced binding of Aβ to pre-labeled plaques to similar extents in APP-PS1 mice while GABA appeared more efficient in Aβ clearance in hypertensive animals than the glutamate inhibitor. Our findings support the modulation of neurotransmitters that influence the glymphatic pathway via distinct mechanisms as a potentially effective therapeutic strategy for clearance of Aβ deposits from the brain.

Recent studies have shown that balance performance assessment based on artificial intelligence (AI) is feasible. However, balance control is very complex and requires different subsystems to participate, which have not been evaluated individually yet. Furthermore, these studies only classified individual’s balance performance across limited grades. Therefore, in this study we attempted to implement AI to precisely evaluate different types of balance control subsystems (BCSes). First, a total of 224 commonly used and newly developed features were extracted from the center of pressure (CoP) data for each participant, respectively. Then, regressors were employed in order to map these features to the evaluation scores given by physical therapists, which include the total score in Mini-Balance-Evaluation-Systems-Tests (Mini-BESTest) and its sub-scores on BCSes, namely anticipatory postural adjustments (APA), reactive postural control (RPC), sensory orientation (SO), and dynamic gait (DG). Their scoring ranges should be 0-28, 0-6, 0-6, 0-6, and 0-10, respectively. The results show that their minimum mean absolute errors from AI estimation reach up to 2.658, 0.827, 0.970, 0.642, and 0.98, respectively. In sum, our study is a preliminary study for assessing BCSes based on AI, which shows its possibility to be used in the clinics in the future.

To investigate the hydrodynamics of undulatory swimming, a key issue in numerical analysis is to determine the correlation between undulatory locomotion and the flow characteristics. In this study, a novel dynamic-grid generation method, the adaptive control method, is implemented to deal with the moving and morphing boundaries in an unsteady flow field at all Reynolds numbers. This method, based on structured grids, can ensure the orthogonality and absolute controllability of the grids and is performed to precisely simulate the wake and the boundary layer. The NACA0010 wing is employed as a two-dimensional (2D) body model of a fish in the simulations. To maintain the calculation stability, the increase stage of the amplitude is defined as a smooth transitional stage. Analysis of hydrodynamic coefficients reveals that undulation results in a significant increase of frictional force in laminar flow [Formula: see text]. However, the undulation also results in a reduction of the frictional force when the fish swims in turbulent flow [Formula: see text]. The vorticity distribution and the [Formula: see text]-criterion are both used to accurately capture the shedding vortexes in the wake. Furthermore, these vortex pairs have a substantial impact on the turbulence and the wake, in which the turbulent kinetic energy and the turbulent viscosity ratio both decrease at [Formula: see text]. The wake of an undulatory fish presents different vortex patterns with various kinematic parameters. When the phase velocity is greater than the incoming velocity and the wave number is sufficiently large, thrust is yielded, accompanying the distinct reverse Karman Street in the wake.

Methyleugenol (ME), an alkenylbenzene compound, is a natural ingredient of several herbs and is used as flavoring agent in foodstuffs and fragrance in cosmetics. The hepatotoxicity, cytotoxicity, and carcinogenesis of ME have been well documented, and metabolic activation has been suggested to involve in ME-induced toxicities. The objective of this study was to identify chemical identity of interactions of protein with reactive metabolites of ME. Modification of cysteine residues of protein was observed in microsomal incubations and mice after exposure to ME. Three types of protein modification derived from the corresponding epoxide, α,β-unsaturated aldehyde, and carbonium ion of ME were detected in vitro and in vivo. The protein adduction took place in time- and dose-dependent manners. Dexamethasone, ketoconazole, and l-buthionine sulfoximine increased the protein modification induced by ME, which was proportional to the hepatotoxicity of ME. The findings facilitate the understanding of mechanism action of ME toxicities.

Benzbromarone (BBR) is a therapeutically useful uricosuric agent but can also cause acute liver injury. The hepatotoxicity of BBR is suggested to be associated with its metabolic activation. Our recent metabolic study demonstrated that BBR was metabolized to epoxide intermediate(s) by cytochrome P450 3A, and the intermediate(s) was reactive to N-acetylcysteine. The objectives of the present study were to determine the chemical identity of the interaction of protein with the epoxide intermediate(s) of BBR and to define the association of the protein modification with hepatotoxicity induced by BBR. Microsomal incubation study showed that the reactive intermediate(s) covalently modified microsomal protein at cysteine residues. Such adduction was also observed in hepatic protein obtained from liver of mice given BBR. The protein covalent binding occurred in time- and dose-dependent manners. Pretreatment with ketoconazole attenuated BBR-induced protein modification and hepatotoxicity, while pretreatment with dexamethasone or buthionine sulfoximine potentiated the protein adduction and hepatotoxicity induced by BBR. A good correlation was observed between BBR-induced hepatotoxicity and the epoxide-derived hepatic protein modification in mice. The present study provided in-depth mechanistic insight into BBR-induced hepatotoxicity.

Circadian clock relies on a transcription and translation feedback loop (TTFL). Two transcription factors, i.e. Bmal1 and Clock, activate the transcription of Period (Per) and Cryptochrome (Cry), which inhibit their own transcription when accumulated to a critical concentration. NAD+-dependent deacylase Sirt1 deacetylates Bmal1 and Per2 to regulate circadian rhythms. Sirt6 interacts with Bmal1 to regulate clock-controlled gene (CCG) expression by local chromatin remodeling. Whether Sirt6 directly modify clock components is elusive. Here, we found that loss of Sirt6 jeopardizes circadian phase. At molecular level, Sirt6 interacts with and deacetylates Per2, thus preventing its proteasomal degradation. These data highlight an important function of Sirt6 in the direct regulation of TTFL and circadian rhythms.

Scholars in inter-disciplinary fields like the Digital Humanities are increasingly interested in semantic annotation of specialized corpora. Yet, under-resourced languages, imperfect or noisily structured data, and user-specific classification tasks make it difficult to meet their needs using off-the-shelf models. Manual annotation of large corpora from scratch, meanwhile, can be prohibitively expensive. Thus, we propose an active learning solution for named entity recognition, attempting to maximize a custom model’s improvement per additional unit of manual annotation. Our system robustly handles any domain or user-defined label set and requires no external resources, enabling quality named entity recognition for Humanities corpora where such resources are not available. Evaluating on typologically disparate languages and datasets, we reduce required annotation by 20-60% and greatly outperform a competitive active learning baseline.

Cerebral cortical microinfarct (CMI) is common in patients with dementia and cognitive decline. Emerging studies reported that intestinal dysfunction influenced the outcome of ischemic stroke and that vagus nerve stimulation (VNS) protected against ischemic stroke. However, the effects of intestinal dysfunction and VNS on CMI are not clear. Therefore, we examined the influence of colitis and VNS on CMI and the mechanisms of VNS attenuating CMI in mice with colitis. CMI was induced using a two-photon laser. Colitis was induced using oral dextran sodium sulfate (DSS). The cervical vagus nerve was stimulated using a constant current. In vivo blood-brain barrier (BBB) permeability was evaluated using two-photon imaging. Infarct volume, microglial and astrocyte activation, oxidative stress and proinflammatory cytokine levels were assessed using immunofluorescent and immunohistochemical staining. The BBB permeability, infarct volume, activation of microglia and astrocytes and oxidative stress increased significantly in mice with colitis and CMI compared to those in mice with CMI. However, these processes were reduced in CMI mice when VNS was performed. Brain lesions in mice with colitis and CMI were significantly ameliorated when VNS was performed during the acute phase of colitis. Our study demonstrated that VNS alleviated CMI and this neuroprotection was associated with the suppression of BBB permeability, neuroinflammation and oxidative stress. Also, our results indicated that VNS reduced colitis-induced microstroke aggravation.

Microwave-metal discharge was proposed as a facile methodology to prepare unique Fe-cored carbon nanocapsules (Fe@CNCs) with high purity, novel stability and extraordinary electromagnetic wave (EMW) absorption performance. The effect of microwave power, irradiation time and cyclohexane/ferrocene ratio on the production of Fe@CNCs was examined and the properties of the nanocapsules, such as their Fe content, phase, yield, degree of graphitization and associated microstructures were investigated in detail. It was found that the prepared Fe@CNCs, which can easily be separated from the reaction system, displayed exceedingly high electromagnetic wave (EMW) absorption performance over the 2–18 GHz range. At the minimal reflection loss (RL) values over −10 dB, the EMW absorption bandwidth can reach up to 13.8 GHz with an absorber thickness of 1.5–5 mm. In addition, novel thermo-oxidative stability and super anti-corrosion property were also obtained for the Fe@CNCs as no signs of any corrosion or oxidative degradation loss were observed from the accelerated degradation tests in air and acid at temperatures up to 420 °C. The exceedingly high EMW absorption performance coupled with the superior anti-degradation and anti-corrosion properties of the prepared nanocomposite microcapsules highlights the novel capability of microwave-metal discharge in synthesizing advanced metal-cored nanocarbon microcapsules with promising application potentials in diverse fields, such as but not limited to microwave absorption, EM shielding and advanced separations etc.

Ischemic stroke is one of the most common diseases leading to death and is the primary cause of physical handicap. Recent studies have reported that chronic colitis increases the risk of ischemic stroke, but it is unknown whether chronic colitis participates in ischemic brain injury directly. A combined mouse model of chronic colitis induced by dextran sodium sulfate (DSS) and ischemic stroke induced by photochemical infarction was used in this study. We demonstrated that chronic colitis significantly increased the infarction volume, activated microglia/macrophage numbers, proliferation of M1 microglia/macrophage, non-gut-derived CD4+ T lymphocyte penetration and decreased neuron numbers in the peri-infarction at 7 d after stroke. Furthermore, gut-derived CD4+ T cell accumulation on the meninges was observed at 7 d after stroke. In addition, selective depletion of meningeal macrophages resulted in a reduction of infarction volume and the non-gut-derived CD4+ T lymphocyte penetration. We concluded that chronic colitis exacerbated ischemic stroke by promoting CD4+ T cell migration from the gut to the meninges and disequilibrium of M1 and M2 microglia/macrophages. We speculated that the gut-derived CD4+ T cells may interact with meningeal macrophages and result in non-gut-derived CD4+ T lymphocyte infiltration that aggravated brain injury in ischemic stroke.

Methyleugenol (ME), a natural ingredient of several herbs and spices used in the human diet, is hepatocarcinogenic in rodents. Following metabolic activation to reactive carbocation intermediate, ME can bind covalently to DNA, which is directly associated with its carcinogenicity. In this work, a non-invasive approach to determine ME exposure was established by monitoring urinary ME-dA adduct. The developed method entails liquid-liquid extraction enrichment of the urinary ME-dA, incorporation of deuterated ME-dA as internal standard, and analysis by liquid chromatography coupled tandem mass spectrometry. Male rats (10-12 weeks, 180-200 g) were treated (p.o.) with ME, and ME-dA was excreted in urine in a dose- and time-dependent manner. The noninvasive approach enabled us to successfully determine exposure to ME-containing herbs and spices. These results suggest that ME-dA can potentially serve as an effective biomarker of ME exposure in rats. It is expected that the developed approach of detecting urinary...

Using a photothrombotic mouse model of single stroke, we show here that a single stroke onset increases the nuclear factor -κB (NF-κB), NLR family CARD domain containing protein 4 (NLRC4), and absent in melanoma 2 (AIM2) inflammasomes, as well as the mRNA levels of NLRP3. Next, using a photothrombotic mouse model of recurrent stroke, we found that recurrent strokes increased the level of NLRP3 activation and exacerbated the brain damage score and the pro-inflammatory response in wild type (WT) mice, but not in NLRP3 KO mice. Additionally, we found that apoptosis-associated speck-like protein containing a CARD (ASC) protein levels surrounding the infarct area were comparatively increased, but that ASC specks outside of microglia in both the ipsilateral and contralateral of stroke site were decreased in NLRP3 knock out (KO) mice relative to wild-type (WT) controls. Mechanistically, we found that recombinant ASC (recASC) activated NLRP3 and induced pro-inflammatory responses, exacerbating the outcome of ischemic stroke, in WT mice, but not in NLRP3 KO mice. We therefore conclude that the NLRP3 inflammasome is activated by two attacks of stroke, which act together with ASC to exacerbate recurrent strokes. Funding: This work was supported by grants from the National Natural Science Foundation of China (grant numbers: 81671102, 81572224, 81572230, 81371255 and 81772438), The National Key Research and Development Program of China, Stem Cell and Translational Research (2017YFA0105104), the National Key Clinical Department, National Key Discipline, Guangdong Provincial Key Laboratory For Diagnosis and Treatment of Major Neurological Disease (2014B030301035), the Science and Technology Planning Project of Guangdong Province, China (grant numbers: 2016A020213003, 2016B040404053, 2014B020212001, 2014A030304018, 2014B040404053, 2016B030230002 and 2017A040406007), the National Science and Technology Support Program (grant numbers: 2015BAI07B01), and the Science and Technology Planning Project of Guangzhou, China (grant numbers: 2016201604030036). Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases（2017B030314103）; The Southern China International Cooperation Base for Early Intervention and Functional Rehabilitation of Neurological Diseases (2015B050501003); Guangzhou Clinical Research and Translational Center for Major Neurological Diseases (201604020010; Guangdong Provincial Engineering Center for Major Neurological Disease Treatment. The funding bodies had no involvement in the experimental design or the interpretation of the results. Declaration of Interest: No conflicts of interest, financial or otherwise, are declared by the authors. Ethical Approval: This study was approved by the Animal Research Committee of the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China; committee’s reference number: [2013]97).

Sequence labeling of biomedical entities, e.g., side effects or phenotypes, was a long-term task in BioNLP and MedNLP communities. Thanks to effects made among these communities, adverse reaction NER has developed dramatically in recent years. As an illuminative application, to achieve knowledge discovery via the combination of the text mining result and bioinformatics idea shed lights on the pharmacological mechanism research.

Volatile organic compounds (VOCs) are air pollutants that pose a major concern, and novel treatment technologies must be continuously explored and developed. In this study, microwave-induced metal discharge was applied to investigate the destruction of acetone as a representative model VOC compound. Results revealed that metal discharge intensity largely depended on microwave output power and the number of metal strips. Microwave metal discharge exerted the distinct combined effects of intense heat, strong light, and plasma. In the case of MW without metal discharge, the decrease in acetone at 200 ppm was remarkably limited (approximately 5.5% (mol/mol)). By contrast, in the case of microwave-induced metal discharge, a considerably high destruction efficiency of up to 65% (mol/mol) was obtained at low concentrations. This finding highlights the potential of microwave-induced discharge for VOC removal. Initial assessment indicated that energy consumption can be acceptable.

In the present paper, the multi-objective optimization of a waterjet-propelled trimaran was carried out based on computational fluid dynamics (CFD) considering the interactions between the waterjet and the hull. Numerical results were validated with experimental data for one waterjet propulsor and the original hull. The simulation-based design (SBD) optimization was performed for the waterjet and the hull. Furthermore, the parametric reconstruction of the duct was executed based on its shape characteristics. The Lackenby method and the free-form deformation method were applied to transform the hull shape. The optimal Latin hypercube design (Opt LHD) method was used to generate samples, and the surrogate model was developed based on the support vector regression (SVR) method. The non-dominated sorting genetic algorithm II (NSGA-II) was employed to optimize design objectives at the design speed of Fr = 0.628. In comparison to the original shape, the total resistance, the thrust, the torque, and the power consumption of the optimized trimaran at self-propulsion, respectively, decreased by 3.85%, increased by 6.38%, increased by 1.73%, and decreased by 10.39%. Therefore, it can be inferred that the SBD technique is effective to solve multi-objective optimization problems of ship hydrodynamics.

A simple and efficient liquid chromatography-mass spectrometry (LC-MS) method was developed and validated for simultaneous quantitation of catalpol and harpagide in normal and diabetic rat plasma. Protein precipitation extraction with acetonitrile was carried out using salidroside as the internal standard (IS). The LC separation was performed on an Elite C18 column (150 × 4.6 mm, 5 µm) with the mobile phase consisting of acetonitrile and water within a runtime of 12.0 min. The analytes were detected without endogenous interference in the selected ion monitoring mode with positive electrospray ionization. Calibration curves offered satisfactory linearity (r > 0.99) at linear range of 0.05–50.0 µg/mL for catalpol and 0.025–5.0 µg/mL for harpagide with the lower limits of quantitation of 0.05 and 0.025 µg/mL, respectively. Intra- and inter-day precisions (RSD) were 76.5% and the matrix effects of the analytes ranged from 86.5 to 106.0%. The method was successfully applied to the pharmacokinetic study of catalpol and harpagide after oral administration of Zeng-Ye-Decoction to normal and diabetic rats, respectively. Copyright © 2013 John Wiley & Sons, Ltd.

This paper explores the automatic learning of distributed representations of the target’s context for semantic frame labeling with target-based neural model. We constrain the whole sentence as the model’s input without feature extraction from the sentence. This is different from many previous works in which local feature extraction of the targets is widely used. This constraint makes the task harder, especially with long sentences, but also makes our model easily applicable to a range of resources and other similar tasks. We evaluate our model on several resources and get the state-of-the-art result on subtask 2 of SemEval 2015 task 15. Finally, we extend the task to word-sense disambiguation task and we also achieve a strong result in comparison to state-of-the-art work.

An acidic α-amylase was purified from thermoacidophilic Alicyclobacillus sp. A4 by ion exchange chromatography with 22% recovery, and showed a molecular mass of 64 kDa by SDS–PAGE. Its amino acid sequence was determined by sequencing three internal peptides and the complete genome of strain A4, and shared highest identity (64%) with Alicyclobacillus acidocaldarius α-amylase. Compared with other reported α-amylases, the purified enzyme had some distinct characteristics. The optimal activity was found to occur at 75 °C and pH 4.2, similar to the glucamylase widely used in the starch industry. The enzyme was Ca2+ independent, and had strong ability to digest raw starch (96.71%) with commercial glucamylase in one step. These properties of the purified enzyme make up the deficiency of the commercial α-amylases currently used and avoid repeated adjustment of pH and temperature in double-enzymatic sugar-making process. The purified enzyme will be commercially valuable in the starch industry.