Context Consistency between Training and Testing in Simultaneous Machine Translation

Simultaneous Machine Translation (SiMT) aims to yield a real-time partial translation with a monotonically growing the source-side context. However, there is a counterintuitive phenomenon about the context usage between training and testing: e.g., the wait-k testing model consistently trained with wait-k is much worse than that model inconsistently trained with wait-k' (k' is not equal to k) in terms of translation quality. To this end, we first investigate the underlying reasons behind this phenomenon and uncover the following two factors: 1) the limited correlation between translation quality and training (cross-entropy) loss; 2) exposure bias between training and testing. Based on both reasons, we then propose an effective training approach called context consistency training accordingly, which makes consistent the context usage between training and testing by optimizing translation quality and latency as bi-objectives and exposing the predictions to the model during the training. The experiments on three language pairs demonstrate our intuition: our system encouraging context consistency outperforms that existing systems with context inconsistency for the first time, with the help of our context consistency training approach

Degradable polyethylenimine derivate coupled to a bifunctional peptide R13 as a new gene-delivery vector

Kehai Liu1,2,*, Xiaoyu Wang1,*, Wei Fan1, Qing Zhu2, Jingya Yang2, Jing Gao3, Shen Gao1 1Department of Pharmaceutics, Shanghai Hospital, Second Military Medical University, 2Department of Biopharmaceutics, School of Food Science and Technology, Shanghai Ocean University, 3Department of Pharmaceutics, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China*The first two authors contributed equally to this workBackground: To solve the efficiency versus cytotoxicity and tumor-targeting problems of polyethylenimine (PEI) used as a nonviral gene delivery vector, a degradable PEI derivate coupled to a bifunctional peptide R13 was developed.Methods: First, we synthesized a degradable PEI derivate by crosslinking low-molecular-weight PEI with pluronic P123, then used tumor-targeting peptide arginine-glycine-aspartate-cysteine (RGDC), in conjunction with the cell-penetrating peptide Tat (49–57), to yield a bifunctional peptide RGDC-Tat (49–57) named R13, which can improve cell selection and increase cellular uptake, and, lastly, adopted R13 to modify the PEI derivates so as to prepare a new polymeric gene vector (P123-PEI-R13). The new gene vector was characterized in terms of its chemical structure and biophysical parameters. We also investigated the specificity, cytotoxicity, and gene transfection efficiency of this vector in avß3-positive human cervical carcinoma Hela cells and murine melanoma B16 cells in vitro.Results: The vector showed controlled degradation, strong targeting specificity to avß3 receptor, and noncytotoxicity in Hela cells and B16 cells at higher doses, in contrast to PEI 25 KDa. The particle size of P123-PEI-R13/DNA complexes was around 100–250 nm, with proper zeta potential. The nanoparticles can protect plasmid DNA from being digested by DNase I at a concentration of 6 U DNase I/µg DNA. The nanoparticles were resistant to dissociation induced by 50% fetal bovine serum and 600 µg/mL sodium heparin. P123-PEI-R13 also revealed higher transfection efficiency in two cell lines as compared with PEI 25 KDa.Conclusion: P123-PEI-R13 is a potential candidate as a safe and efficient gene-delivery carrier for gene therapy.Keywords: nonviral gene vector, polyethylenimine, P123, αvß3, cell-penetrating peptide

A Biodegradable Polyethylenimine-Based Vector Modified by Trifunctional Peptide R18 for Enhancing Gene Transfection Efficiency In Vivo

Lack of capacity to cross the nucleus membrane seems to be one of the main reasons for the lower transfection efficiency of gene vectors observed in vivo study than in vitro. To solve this problem, a new non-viral gene vector was designed. First, a degradable polyethylenimine (PEI) derivate was synthesized by crosslinking low-molecular-weight (LMW) PEI with N-octyl-N-quaternary chitosan (OTMCS), and then adopting a designed trifunctional peptide (RGDC- TAT-NLS) with good tumor targeting, cell uptake and nucleus transport capabilities to modify OTMCS-PEI. The new gene vector was termed as OTMCS- PEI-R18 and characterized in terms of its chemical structure and biophysical parameters. Gene transfection efficiency and nucleus transport mechanism of this vector were also evaluated. The polymer showed controlled degradation and remarkable buffer capabilities with the particle size around 100–300 nm and the zeta potential ranged from 5 mV to 40 mV. Agraose gel electrophoresis showed that OTMCS-PEI-R18 could effectively condensed plasmid DNA at a ratio of 1.0. Besides, the polymer was stable in the presence of sodium heparin and could resist digestion by DNase I at a concentration of 63U DNase I/DNA. OTMCS-PEI-R18 also showed much lower cytotoxicity and better transfection rates compared to polymers OTMCS-PEI-R13, OTMCS-PEI and PEI 25 KDa in vitro and in vivo. Furthermore, OTMCS-PEI-R18/DNA complexes could accumulate in the nucleus well soon and not rely on mitosis absolutely due to the newly incorporated ligand peptide NLS with the specific nuclear delivery pathway indicating that the gene delivery system OTMCS-PEI-R18 could reinforce gene transfection efficiency in vivo

Binding Affinity, Cellular Uptake, and Subsequent Intracellular Trafficking of the Nano-Gene Vector P123-PEI-R13

A nano-gene vector PEI-P123-R13 was synthesized by cross-linking low molecular weight PEI with P123 and further coupling bifunctional peptide R13 to the polymer for targeting tumor and increasing cellular uptake. The binding assessment of R13 to αvβ3 positive cells was performed by HRP labeling. The internalization pathways of P123-PEI-R13/DNA complexes were investigated based on the effect of specific endocytic inhibitors on transfection efficiency. The mechanism of intracellular trafficking was investigated based on the effect of endosome-lysosome acidification inhibitors, cytoskeleton, and dynein inhibitors on transfection efficiency. The results indicated that the bifunctional peptide R13 had the ability of binding to αvβ3 positive cells in vitro. The modification of P123-PEI-R13 with R13 made it display new property of internalization. P123-PEI-R13/DNA complexes were conducted simultaneously via clathrin-mediated endocytosis, caveolin-mediated endocytosis, macropinocytosis, and possible energy-independent route. After internalization, P123-PEI-R13/DNA complexes could escape from the endosome-lysosome system because of its acidification and further took microtubule as the track and dynein as the dynamic source to be transported toward the microtubule (+) end, to wit nucleus, under the action of microfilament, and with the aid of intermediate filament

Translation Prediction with Source Dependency-Based Context Representation

Learning context representations is very promising to improve translation results, particularly through neural networks. Previous efforts process the context words sequentially and neglect their internal syntactic structure. In this paper, we propose a novel neural network based on bi-convolutional architecture to represent the source dependency-based context for translation prediction. The proposed model is able to not only encode the long-distance dependencies but also capture the functional similarities for better translation prediction (i.e., ambiguous words translation and word forms translation). Examined by a large-scale Chinese-English translation task, the proposed approach achieves a significant improvement (of up to +1.9 BLEU points) over the baseline system, and meanwhile outperforms a number of context-enhanced comparison system

Isolation of polysaccharides from Dendrobium officinale leaves and anti-inflammatory activity in LPS-stimulated THP-1 cells

Abstract Dendrobium officinale stem is rich in polysaccharides, which play a great role in the medicinal effects of this plant. However, little was known about the polysaccharides from Dendrobium officinale leaves. Two kinds of polysaccharides in the leaves, DLP-1 and DLP-2, were obtained by hot water extraction, alcohol sedimentation and chromatographic separation (DEAE-52 cellulose column and Sephadex G-100 column). The average molecular weights were determined as 28,342 Da and 41,143 Da, respectively. Monosaccharide compositions were analyzed using gas chromatography–mass spectrometer. DLP-1 was composed of d-(+)-galactose, dl-arabinose, and l-(+)-rhamnose with a molar ratio of 3.21:1.11:0.23, and traces of d-xylose, d-glucose, and d-(+)-mannose. DLP-2 was consisted of d-glucose and d-(+)-galactose with a molar ratio of 3.23:1.02, and traces of d-xylose, dl-arabinose. Then, we established inflammatory cell model by LPS acting THP-1 cells to investigate the anti-inflammatory effects of DLP-1 and DLP-2. The results indicated that DLP-1 (5 μg/mL) and DLP-2 (50 μg/mL) were effective in protecting THP-1 cells from LPS-stimulated cytotoxicity, as well as inhibiting reactive oxygen species formation. In addition, both DLP-1 (5 μg/mL) and DLP-2 (50 μg/mL) significantly suppressed toll-like receptor-4 (TLR-4), myeloid differentiation factor (MyD88) and tumour necrosis factor receptor-associated factor-6 (TRAF-6) mRNA and protein expression in LPS-stimulated THP-1 cells

Pterostilbene and 4′-Methoxyresveratrol Inhibited Lipopolysaccharide-Induced Inflammatory Response in RAW264.7 Macrophages

Pterostilbene (Pte) and 4′-Methoxyresveratrol (4MR) are methylated derivatives of resveratrol. We investigated the anti-inflammatory effect of Pte and 4MR in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages. Both Pte and 4MR significantly reduced LPS-induced nitric oxide release by inhibiting the inducible nitric oxide synthase mRNA expression. Moreover, both of them inhibited LPS-induced mRNA expression of inflammatory cytokines including monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6 and IL-1β, and tumor necrosis factor α (TNF-α), and attenuated LPS-induced nuclear factor-κB (NF-κB) activation by decreasing p65 phosphorylation. In addition, 4MR but not Pte inhibited LPS-induced the activator protein (AP)-1 pathway in RAW 264.7 macrophages. Further study suggested that Pte had an inhibitory effect on extracellular regulated protein kinases (ERK) and p38 activation, but not on c-Jun N-terminal kinase (JNK), while 4MR had an inhibitory effect on JNK and p38 activation, but not on ERK. Taken together, our data suggested that Pte induced anti-inflammatory activity by blocking mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways, while 4MR showed anti-inflammatory activity through suppression of MAPK, AP-1, and NF-κB signaling pathways in LPS-treated RAW 264.7 macrophages

Self‐microemulsifying oral fast dissolving films of vitamin D3 for infants: Preparation and characterization

Combining the advantages of self‐microemulsifying technology and oral fast dissolving technology, a self‐microemulsifying oral fast dissolving films (SMEOFDF) of vitamin D3 was developed in this study. The pseudoternary phase diagram of microemulsion was constructed using water titration method, and the formulation of films was optimized by orthogonal experimental design. The prepared SMEOFDF of vitamin D3 was a thin film, in which the liquid drops of self‐microemulsion were embedded. It had good mechanical properties (thickness 166.7 ± 3.30 µm, tensile strength 38.45 ± 3.72 MPa, elongation 23.38 ± 4.23%, and folding endurance >200 times), and its disintegration time was about 18 ± 1.23 s. After being redissolved in water, microemulsion could form spontaneously, with particle size of 181.2 nm and zeta potential of 16.1 mV. The release profile of vitamin D from SMEOFDF could be well described by first‐order equation

Multi-Mode Ultrasonic Guided Waves Based Damage Detection in L-Bars with Asymmetric Cross-Section with Sum of Multiple Signals Method

Bars are significant load-carrying components in engineering structures. In particular, L-bars are typical structural components commonly used in truss structures and have typical irregular asymmetric cross-sections. To ensure the safety of load-carrying bars, much research has been done for non-destructive testing (NDT). Ultrasonic guided waves have been widely applied in various NDT techniques for bars as a result of the long-range propagation, low attenuation, and high sensitivity to damages. Though good for inspection of ultrasonic guided waves in symmetric cross-section bar-like structures, the application in asymmetric ones lacks further research. Moreover, traditional damage detection in bars using ultrasonic guided waves usually depends on a single-mode at a lower frequency with lower sensitivity and accuracy. To make full use of all frequencies and modes, a multi-mode characteristic-based damage detection method is presented with the sum of multiple signals (SoM) strategy for L-bars with asymmetric cross-section. To control the desired mode in multi-mode ultrasonic guided waves, excitation optimization and weighted gathering are carried out by the analysis of the semi-analytical finite element (SAFE) method and the normal mode expansion (NME) method. An L-bar example with the asymmetric cross-section of 35 mm × 20 mm × 3 mm is used to specialize the proposed method, and some finite element (FE) models have been simulated to validate the mode control. In addition, one PZT is applied as a contrast in order to validate the multielement mode control. Then, more FE simulations experiments for damage detection have been performed to validate the damage detection method and verify the improvement in detection accuracy and damage sensitivity

A chemoimmunotherapy-based strategy to enhance tumor therapy by cross-linking a novel size-variable nanocluster via a bifunctional peptide

The combination of chemotherapy and immunotherapy plays a synergistic role in improving the effectiveness of cancer treatment. However, it is a great challenge to deliver drugs accurately and efficiently to the target and exert synergistic effects due to multiple biological obstacles in vivo. Here, we constructed a novel size-variable three-dimensional mesh nanocluster (HA/P-A cluster) cross-linked by bifunctional peptide R14 for tumor targeted co-delivery of doxorubicin (DOX) and pPD-L1 trap. The ERP effect and the targeting effect of the outer layer of HA synergistically mediated the accumulation of nanoclusters in tumor tissues. Subsequently, R14 was broken by matrix metalloproteinase-2 (MMP-2) and the nanoclusters (180 nm) were cleaved into ultra-small size nanoparticles (∼10 nm), achieving deep penetration while targeting tumor cells through RGD at both ends of R14. Based on this strategy, DOX acts as an initiator to induce immunogenic cell death (ICD) while immunodrugs block the PD-L1 pathway. Both in vitro and in vivo studies have shown that HA/P-A cluster effectively retarded tumor growth. Moreover, HA/P-A cluster treatment resulted in a significant increased CD8+ T cell infiltration in tumor tissue. In conclusion, this strategy provides a new direction for targeted co-delivery of nanoplatforms to improve chemoimmunotherapy in solid tumors