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In order to extract the correct sentiment polarity from word of mouth (WOM), a wide-scale and well-organized sentiment lexicon is generally beneficial. SenticNet is one such lexicon. However, it consists of a high proportion of objective words, which are generally considered to be of little use for sentiment classification due to their ambiguity and lack of sentiments. In the literature, there is a dearth of models that focus on this issue. An objective word appearing more frequently in positive sentences than in negative sentences implies a strong relationship in a positive sentiment orientation, and conversely, an objective word appearing more frequently in negative sentences implies a strong relationship in a negative sentiment orientation. Thus, the ratio of an objective word appearing in positive and negative sentences provides the sentiment orientation. Based on this concept, this paper re-assigns the sentiment values to the objective words in SenticNet and builds a revised SenticNet. Three classification techniques, the J48 decision tree, support vector machine, and multilayer perceptron neural network are used for classification. According to the experiments, the proposed models which extract sentiment values from the revised SenticNet, significantly outperform those models which extract sentiment values from the original non-revised SenticNet.

A group of clinically approved cancer therapeutic tyrosine kinase inhibitors was screened to test their effects on the expression of angiotensin-converting enzyme 2 (ACE2), the cell surface receptor for SARS-CoV-2. Here, we show that the receptor tyrosine kinase inhibitor imatinib (also known as STI571, Gleevec) can inhibit the expression of the endogenous ACE2 gene at both the transcript and protein levels. Treatment with imatinib resulted in inhibition of cell entry of the viral pseudoparticles (Vpps) in cell culture. In FVB mice orally fed imatinib, tissue expression of ACE2 was reduced, specifically in the lungs and renal tubules, but not in the parenchyma of other organs such as the heart and intestine. Our finding suggests that receptor tyrosine kinases play a role in COVID-19 infection and can be therapeutic targets with combined treatments of the best conventional care of COVID-19.

Epidermal growth factor receptor (EGFR) plays a significant role in promoting breast cancer progression. However, targeting EGFR as a single treatment only resulted in moderate efficacy to the disease. The underlying mechanism of low responsiveness to EGFR inhibition remains largely unclear. Tumor-secreted extracellular vesicles (EVs) play a crucial role in mediating intercellular communication between tumor and stromal cells in local microenvironment and distant metastatic niche. Extracellular vesicles mediate cell-to-cell transfer of lipids, nucleic acids, and proteins. Although numerous recent studies have demonstrated exchanges of extracellular vesicles between cancer cells and the recipient cells contribute to tumor proliferation, invasion, and metastasis, yet little is known how the exosomal compartment responds to targeted therapies and their role in promoting drug resistance. In the current study we used a triple-negative breast cancer model to show that EV-encapsulated EGFR is protected from targeted inhibitors of EGFR and can trigger signaling pathway in recipient cancer cells, promoting proliferation and migration ability in vitro. Taken together, our study suggested a novel mechanism of drug resistance entailing the EV compartment, such as exosomes, as a target shelter which when released can signal for tumor promotion in the recipient cancer cells.

Summary: Increased DNA replication and metastasis are hallmarks of cancer progression, while deregulated proliferation often triggers sustained replication stresses in cancer cells. How cancer cells overcome the growth stress and proceed to metastasis remains largely elusive. Proliferating cell nuclear antigen (PCNA) is an indispensable component of the DNA replication machinery. Here, we show that phosphorylation of PCNA on tyrosine 211 (pY211-PCNA) regulates DNA metabolism and tumor microenvironment. Abrogation of pY211-PCNA blocks fork processivity, resulting in biogenesis of single-stranded DNA (ssDNA) through a MRE11-dependent mechanism. The cytosolic ssDNA subsequently induces inflammatory cytokines through a cyclic GMP-AMP synthetase (cGAS)-dependent cascade, triggering an anti-tumor immunity by natural killer (NK) cells to suppress distant metastasis. Expression of pY211-PCNA is inversely correlated with cytosolic ssDNA and associated with poor survival in patients with cancer. Our results pave the way to biomarkers and therapies exploiting immune responsiveness to target metastatic cancer.

Chronic psychostimulant treatment in rodents readily produces behavioral sensitization, which reflects altered brain function in response to repeated drug exposure. Numerous morphological and biochemical investigations implicate altered neural plasticity in striatal medium spiny neurons (MSNs) as an essential component in behavioral sensitization. The mammalian target of the rapamycin (mTOR) signaling pathway, a key regulator of synaptic neuroplasticity, in the ventral striatum of methamphetamine (METH) -sensitized mice was investigated to determine if a link exists with the development of METH sensitization. Behaviorally, METH-sensitized mice possessed increased levels of phosphorylated mTOR/S2448 and its down-stream regulator p70S6K and pS6 in the ventral striatum. Systemic treatment with rapamycin, a specific mTOR inhibitor, coincident with a daily METH injection suppressed the induction of METH sensitization and reduced the number of dendritic spines in the shell and core of the nucleus accumbens. The infusion of lentivirus-expressing mTOR-shRNA into the shell region of the nucleus accumbens inhibited the induction of behavioral sensitization to METH, which was comparable to the effect of rapamycin. These results suggest that mTORC1-mediated signaling in the nucleus accumbens mediates the development of behavioral sensitization to METH.

Cancer cells are known to produce and secret extracellular vesicles for intercellular communication through the carried cargos. HOTAIR (HOX transcript antisense intergenic RNA), a well-studied long non-coding RNA (lncRNA), plays a critical role in cancer progression. In several cancer types it has been shown that HOTAIR-containing exosomes are produced by cancer cells. Here we show that circulatory exosomal HOTAIR is present in breast cancer patients and explores the pathological correlation with the disease. Exosomes were isolated by matrix-based precipitation from conditioned media of cultured breast cancer cell lines as well as blood samples of recently recruited breast cancer patients. HOTAIR RNA in exosomes was detected by quantitative reverse transcriptase-mediated polymerase chain reaction (qRT-PCR). Expression of exosomal HOTAIR was positively correlated with status of the receptor tyrosine kinase (RTK) ErbB2 (also known as HER2/neu) in tumor tissues. The causal correlation of ErbB2 and HOTAIR was validated in isogenic breast cancer cell lines with and without ectopic ErbB2 expression. Our finding provides a molecular basis to develop novel liquid biopsy biomarkers and targeted therapies with improved precision for malignant breast cancer.

Cancer metastasis is the fundamental cause of cancer-related death. While 5-year survival rate of breast cancer with local involvement is very optimistic, the number precipitately dropped for patients whose disease has spread to distant organs. Some cancer cells can remain dormant for a long time and evolve to full blown malignancy at a later time. Despite intensive study, the mechanisms underpinning metastasis and tumor dormancy continue to drive cancer morbidity. PCNA forms a homotrimer ring encircling the DNA double helix and acts as a sliding platform indispensable for DNA replication, DNA damage repair, and chromatin remodeling. While a positive role of PCNA in is conceivable, how PCNA functions in tumor progression remains elusive due to the embryonic lethal phenotype in PCNA-deficient mice. We have shown that PCNA is regulated by phosphorylation at tyrosine 211 (Y211) meditated through multiple growth factor-stimulated signaling pathways. Y211 phosphorylation enhances chromatin-bound PCNA to promote cell proliferation and is frequently detected in multiple human cancers including breast cancer. To further dissect its biological functions, we have generated genetic mouse strain in which Y211 is replaced with phenylalanine which is structurally similar to tyrosine but cannot be phosphorylated. Comparing to wild-type mice, 211F mice have significantly reduced mammary tumor formation upon induction by the carcinogen DMBA. To understand its biological role in oncogene-induced mammary tumorigenesis, mice were crossed with the MMTV-PyMT mice in which mammary gland expression of the oncogene polyoma virus middle T antigen (PyMT) is driven by the mouse mammary tumor virus (MMTV) enhancer/promoter. Female 211F/PyMT mice have statistically significant but only moderate decrease in mammary tumor development. However, their lung metastasis is dramatically ablated compared to WT/PyMT mice harboring primary tumors of similar size. These results suggest that pY211-PCNA has an essential function not only in tumorigenesis but more importantly in progression to distant metastasis. Consistently, mammary tumors derived from WT/PyMT mice exhibits more pronounced stromal activity than tumors of 211F/PyMT mice. The suppression of metastasis and stromal activity in 211F/PyMT mice is associated with reduced number of tumor-initiating cells (TICs) as determined by in vitro and in vivo analyses. Further study using syngeneic orthotopic model of transplanting murine cancer cells into the mammary glands of WT and 211F mice unveils an unexpected function of pY211-PCNA in the stromal compartment on tumor development. Thus, our study reveals a novel tumor-promoting function of PCNA in both parenchymal and stromal compartments besides its traditional role in cell proliferation. Numerous FDA-approved drugs are targeting the signaling pathways leading to Y211 phosphorylation, suggesting that pY211-PCNA is a new druggable mechanism to target tumor metastasis. Citation Format: Yuan-Liang Wang, Chuan-Chun Lee, Pei-Le Lin, Yi-Chun Shen, Wan-Rong Wu, Wei-Ya Xia, Mien-Chie Hung, Shao-Chun Wang. Tyrosine 211 phosphorylation of PCNA: A new paradigm of linking cell proliferation to cancer stemness and metastasis [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr B090. doi:10.1158/1535-7163.TARG-19-B090

To increase the efficiency and reliability of the thermodynamics analysis of the spool valve, the precise function expression of the flow area for the sloping U-shape notch orifice versus the spool stroke and thermal-hydraulic bond graph based on the conservation of mass and energy were introduced. Subsequently, the connection rule for the bond graph elements and the method to construct the complete thermal-hydraulic system model were proposed. On the basis of heat transfer analysis of a typical hydraulic circuit containing the spool valve, the lumped parameter for mathematical model of the system was given. At last, the reliability of the mathematical model of the flow area and the thermal-hydraulic system for the sloping U-shape notch orifice on the spool were demonstrated by the test. The good agreement between the simulation results and experimental data demonstrates the validity of the modeling method.

There are some defects in the traditional over-running load hydraulic system, such as velocity control is poor and prone to velocity jitter, etc. In order to improve these weaknesses, the components and work principle of the separate meter in and separate meter out (SMISMO) were introduced and the actuator’s feature were analyzed , the simulation model of hydraulic studied system was built, the factors affecting the stability of the system are discussed in this paper. Simulation and experiment showed that the novel control system possessed higher velocity control precise and good stable characteristics.

Based on the shortcomings of traditional multi actuator composite action on its coordination and load adaptability, this paper has put forward a hydraulic system model where separate meter-in separate meter-out controls the multi actuator, according to different action working conditions of actuator, it has provided a composite control strategy based on pressure flow, and through AMEsim and MATLAB, it has established the composite action hydraulic transmission model of double-actuator system and simulation model of control system, and then conducted co-simulation to verify the designed controller’s good coordination and load adaptability to the separate meter-in and separate meter-out control system under different composite action working conditions.

According to the working principle of open hydraulic system in concrete pump, and though the theoretical analysis on the phenomenon of hydraulic impact in direction changing process, it concluded that the impact pressure has a linear relation with the displacement of the main oil pump .To solve the hydraulic impact problem ,a variable displacement method was proposed .Under the requirement of piston not striking the bottom of cylinder and piston stroke control accuracy ,the authors optimized the pumping direction changing process time parameters and the displacement control time parameters . Though the AMESim modeling simulation and experimental study , the variable displacement control method is proved feasible on reducing the hydraulic impact in direction changing process.

Drilling frame on TD165CH Down-The-Hole Drill that has large slenderness ratio and be longer than 10m is one component of Down-The-Hole drill which is mainly subjected to load.In the process of drilling, drilling frame is not only subjected to loads which are like tensile, compression and torsion and so on, and be under the influence of impacting and vibration of impactor,the situation of force is complicated.By analysing of working condition of Down-The-Hole drill,there get all kinds of limit states of typical working conditions, and then using Ansys doing finite element analysis, there get distribution of the stress and strain of drilling frame and the result of modal analysis to check whether drilling frame meets the requirements of strength and stiffness or not,and whether it is possible to resonate with the impactor or not.By analysis,Structure strength and stiffness of drilling Frame on TD165CH Down-The-Hole drill meet the requirements of practical engineering, and drilling Frame does not resonate with the impactor.

A new down-the-hole drill (DTH) position method based on binocular stereo vision was presented. In this method, a pair of stereo images containing holes marker were obtained by stereo cameras, which were then segmented by the fuzzy threshold method based on trapezoidal membership functions. The hole mark centre was extracted by image invariant moment principle. Then hole mark 3D locations can be calculated by triangulation principle. Finally, the autonomous position experiments based on binocular stereo vision system were implemented on DTH test-bed. The experiments results show that the binocular stereo vision system applied to DTH drill position is reliable, and the position error is within 25mm.

To investigate the impact of low pressure accumulator to the performance of hydraulic impactor, mathematic model of hydraulic impactor was established. By application of AMESim, The simulation models of hydraulic impactor with low pressure accumulator and hydraulic impactor without low pressure accumulator were obtained. After model calculation, the displacement, velocity of the piston and the return pressure were shown in figures. Rationality of the simulation system was verified by the compare between simulation results and experimental results. The simulation results show that low pressure accumulator can increase the impact energy and frequency of hydraulic impactor in a small degree and reduce the impact of return pressure significantly. Article provides theory basis for the designation of hydraulic impactor.

Flexible electronics are a possible alternative for portable consumer applications and have many advantages. However, the circuit design for flexible electronics is still challenging, especially for sensitive analog circuits. Due to the different properties of flexible thin-film transistors (TFTs), conventional CMOS design techniques cannot be used directly on flexible electronics. Significant parameter variations and degradation effects of flexible TFTs further increase difficulties for circuit designers. In this paper, a reliability-aware circuit sizing approach is proposed for the analog circuits with flexible TFTs. The process variation, bending, and degradation effects of flexible TFTs in the optimization flow are considered simultaneously. Instead of optimizing the fresh yield and lifetime yield separately, a unified optimization approach is proposed to consider the two yield issues simultaneously. As shown in the experimental results, the proposed approach can further improve the lifetime yield and significantly reduce the design overhead with a fast computation time.

Based on the geological characteristics of the submarine natural gas hydrates storage and the requirement of the mining environment, combined with the deep sea mining technology and the main characteristics of the double-channel lift pump, a new mining method called the mining method of submarine natural gas hydrates based on a double-channel lift pump is proposed in this paper , whose operating principle is that the hydrates are firstly cut into particles and extracted by a spiral reamer of a mining vehicle, next hoisted by a double-channel lift pump to the decomposing pool on the surface, and then decomposed and collected. After the mining method has been introduced, the hydraulic hoisting system parameters such as the pump head of the double-channel lift pump and the hoisting system parameters are analyzed. From calculation and analysis, it is obtained that the gas hydrate particles at the depth of 4000m pumped up to the sea surface require the pump head only 145 m and the working power only 236kw,which can be easily implemented by the existing technology, and the hydrates at the depth of 1000 pumped up to the sea surface just require the pump head about 50 and the working power about 80 kw, which the existing double-channel slurry pump can meet the requirements. Because the density of the mixture flow of the gas hydrates, the seafloor surface sediments and the seawater is similar to the seawater, the transportation mode that the hydrates are transported as ore slurries directly can ensure that the hoisting system keep working steadily and reliably for a long time. It is proved theoretically that the mining method is suited to exploit the submarine natural gas hydrates.

The paper obtains motor pressure, flow and speed and the engine speed curves with time by theoretically analyzing closed hydraulic system of wheel walk engineering machinery and establishes a mathematical model of the system and AMESim simulation model. The simulation curves show that in some cases the external loads react against motor and drive motor speeding and then motor outlet flow increase that leads to the pressure of low-pressure side increasing and the pressure of high-pressure side reducing. The mutation of system pressure drives bump and engine speeding that equates to the engine speed is lower than the speed corresponding to the motor flow, which is engine stall problem. The simulation results show that the basic reason of engine stall is walking condition mutation leads to motor speeding and system pressure mutation and then motor reacts against bump and engine.

As a solution to the breaking of pipeline under high axial force, carbon fiber composite pipe with low density and high intensity is applied to deep-sea mining transporting system. Based on the fact that the transporting pipe is under the forces of gravity, inner liquid, buoyancy as well as hydrodynamic force, geometric nonlinear finite element theory has been applied to analyzing the transporting system. Conclusions can be drawn as follows. Under the interaction of waves and currents, node forces FX and FZ acted by the transporting pipe on the mining vehicle are less than 2 kN, which indicates that waves and currents have little influence on the spatial shape of the transporting pipe and the mining vehicle movement. On the other hand, the horizontal force acting on the mining ship could be as large as 106 830 N, which has great influence on the mining system.

Identification of noise and vibration is essential in dual-rotor systems with slightly different rotating speeds. This paper investigates the noise and vibration of a decanter centrifuge. Experimental investigations on a horizontal decanter centrifuge indicate that noise is correlated with the vibration in the Z axis. Noise can be classified as mechanical, fluid, air, or coupling noise. Increasing the spiral vane angle reduces mechanical and coupling noise. The optimal angle for a spiral blade is 8°to 10°. Increasing the screw-blade thickness reduces coupling noise. These findings are important in correlation studies on noise and vibration and in optimizations on the structure of a decanter centrifuge.

In power gating designs, it is important to estimate the peak wake-up current at the design stages to avoid possible power issues.In this paper, an analytical approach is proposed toestimate the peak wake-up current of a given wake-up input pattern at gate level. The required information of the proposed approach can be directly obtained from existing library information without extra characterization, which can be easily inserted into existing EDA flow with little overhead.The extra effects of power switches on the current waveformsare also considered in the proposed approach, which significantly improve the estimation accuracy as demonstrated in the experiments.