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Irinotecan (CPT-11) is a camptothecin derivative whose potent anti-tumor activity depends on the rapid formation of an in vivo active metabolite, SN38 (7-ethyl-10-hydroxycamptothecin). CPT-11 combine with other agents are often the treatment of choice for patients with advanced or metastatic colorectal cancer (CRC). This study evaluates the cytotoxic mechanism of a novel CPT-11 derivative, ZBH-1207 in CRC cells in vitro.The anti-proliferation effect of ZBH-1207 on tumor cells was assessed by MTT assay. The inhibition of TOP1, the alteration of cell cycle and apoptosis, and the expression of caspase-3 and PARP in CRC cells induced by ZBH-1207 were detected by DNA relaxation assay, flow cytometry, and Western blot, respectively.ZBH-1207 significantly inhibits the proliferation of seven tumor cell lines and retains the activity of TOP1 as compared with CPT-11. Treatment with ZBH-1207 results in more apparent cell cycle arrests and apoptosis of CRC cells than that of CPT-11 and SN38. Accordingly, up-regulation of active caspase-3 and PARP expression were relatively higher in ZBH-1207 group than that in CPT-11 and SN38 group.ZBH-1207 has higher cytotoxicity than CPT-11/SN38 in CRC cells. Its molecular mechanism involves apoptosis signaling pathway.

Background: Chronic neck pain is frequently encountered in clinical practice, but its etiology is still poorly understood. The degenerative cervical intervertebral disc is the main cause of chronic neck pain reported, accounting for about 16%-41% of all incidents. Inflammation is associated with intervertebral disc degeneration and the occurrence of discogenic low back pain; however, whether inflammation plays a key role in the pathogenesis of discogenic neck pain has not been reported in the literature. The aim of the present study was to explore the relationship between inflammatory cytokines and discogenic neck pain and to elucidate the possible pathogenesis of discogenic neck pain. Methods: A total of 111 intervertebral disc samples were collected during the present study: 38 samples from the discogenic neck pain group, 41 samples from the symptomatic control group, and 32 samples from the normal control group. The concentration in each sample of NO, IL-1, IL-6 and TNF- α was determined using ELISA and then statistically analyzed as to whether there were significant differences among the three groups. Results: The expression of inflammatory cytokines in disc samples from patients with severe neck pain was increased in comparison with the disc samples from patients without or with only mild neck pain and fresh cadavers. The differences are statistically significant（P＜0.001). However, the difference of the degree of disc degeneration was not statistically significant between the discogenic neck pain group and symptomatic control group（P＞0.05). Conclusions: The increased expression of inflammatory cytokines in diseased cervical intervertetral discs may play a key role in the pathogenesis of discogenic neck pain. Although inflammation is involved in intervertebral disc degeneration, there is no linear positive correlation between the concentration of inflammatory cytokines and the degree of disc degeneration.

We propose a computational design tool to enable casual end-users to easily design, fabricate, and assemble flat-pack furniture with guaranteed manufacturability. Using our system, users select parameterized components from a library and constrain their dimensions. Then they abstractly specify connections among components to define the furniture. Once fabrication specifications (e.g. materials) designated, the mechanical implementation of the furniture is automatically handled by leveraging encoded domain expertise. Afterwards, the system outputs 3D models for visualization and mechanical drawings for fabrication. We demonstrate the validity of our approach by designing, fabricating, and assembling a variety of flat-pack (scaled) furniture on demand., 21 pages, 14 figures, submitted to Robotica

By violating semantic constraints that the control process impose, the semantic attack leads the Industry Control Systems (ICS) into an undesirable state or critical state. The spread of semantic attack has caused huge economic losses and casualties to critical infrastructure. Therefore, detecting semantic attack is referred to an urgent and critical task. However, few existing detecting techniques can achieve satisfactory effects in detecting semantic attack of ICS, due to the high requirements of complete critical state-based semantic behavior features description, joint detection on multivariate type state variables, and validity of field states datasets under semantic attacks. In an effort to deal with above challenges, We label device states databases with temporal characteristics and divide impacts on states of field devices under semantic attacks into three categories, including absent in states set, confused sequences, irregular frequency. On this basis, we establish a behavioral model based on secondary labeling of states-duration evolution graph (BMSLS), then implement an adaptive secure state-based semantic attack detection framework furtherly. Compared with the traditional Auto Regression (AR) algorithm, the newer time series correlation graph model, and other five deep learning algorithms, our proposed framework demonstrates the superior effect on the detection of semantic attack.

When the current concurrency control algorithm is used to control of the multi-user information management system, the system’s channel transmission capability is low, and the time it takes is long. In this paper, a concurrency control algorithm for large-scale remote multi-user information management system is proposed. According to the average use rate of the large-scale remote multi-user information management system, the concurrency control structure and state of the system are analyzed and judged; Through the analysis of the results, the delay of data link layer in multi-user information management system is carried out modeling; Combined with the queuing delay and accessing delay, the large-scale remote multi-user information management system control can be realized. Experimental results show that the channel utilization rate of the proposed algorithm is over 98.3%, which can transmit large amounts of information in a relatively short time and concurrency control of information management system. Therefore, the proposed algorithm has high channel utilization and efficiency of information transmission

Designing a secure authentication scheme for session initial protocol (SIP) over internet protocol (VoIP) networks remains challenging. In this paper, we revisit the protocol of Zhang, Tang and Zhu (2015) and reveal that the protocol is vulnerable to key-compromise impersonation attacks. We then propose a SIP authenticated key agreement protocol (AKAP) using elliptic curve cryptography (ECC). We demonstrate the correctness of the protocol using Burrows-Abadi-Needham (BAN), and its security using the AVISPA simulation tool. We also evaluate its performance against those of Zhang, Tang and Zhu, and others.

Deep reinforcement learning (DRL) integrates the feature representation ability of deep learning with the decision-making ability of reinforcement learning so that it can achieve powerful end-to-end learning control capabilities. In the past decade, DRL has made substantial advances in many tasks that require perceiving high-dimensional input and making optimal or near-optimal decisions. However, there are still many challenging problems in the theory and applications of DRL, especially in learning control tasks with limited samples, sparse rewards, and multiple agents. Researchers have proposed various solutions and new theories to solve these problems and promote the development of DRL. In addition, deep learning has stimulated the further development of many subfields of reinforcement learning, such as hierarchical reinforcement learning (HRL), multiagent reinforcement learning, and imitation learning. This article gives a comprehensive overview of the fundamental theories, key algorithms, and primary research domains of DRL. In addition to value-based and policy-based DRL algorithms, the advances in maximum entropy-based DRL are summarized. The future research topics of DRL are also analyzed and discussed.

Mobile cloud computing (MCC) is an emerging computing model with the growing demands of mobile devices by services diversity using mobile cloud technology. Authentication plays a fundamental role between the smart portable devices located in different places and the mobile cloud computing service providers in MCC. Several authors presented many authentication schemes using different cryptographic approaches for MCC in the past years. However, those schemes have not solved the impersonation attack well. To conquer this suffering and support more security functionalities, we propose an impersonation resistance for a biometric-based authentication scheme using hashing and symmetric parameter function in an MCC environment. The proposed scheme can provide mutual authentication and anonymity using the software AVISPA. The security of the proposed scheme is formally proved in the random oracle model. Regarding functionality and performance analysis, the comparative studies demonstrate that the design has a trade-off between resource consumption and security strengthens for MCC services. Therefore, the proposed scheme is more practical in MCC application.

This investigation aims to make clear the relationships among geometric features, macrostructures, microstructures, and mechanical performances of the weld bead in the gas metal arc welding (GMAW) process for ASTM A606 type IV weathering steel. The results indicate that with the increase of welding heat input, the geometry of the top reinforcement and penetration increases proportionally until reaching the peak value, and then declines with the further increase of welding heat input; while the values of bottom reinforcement increase continuously with the increase of welding heat input. The average ultimate tensile strength (F), maximum displacement (L), and failure energy (E) of the welded joint produced by the moderate welding heat input are 10.27 kN, 1.88 mm, and 13.55 J, respectively, which are obviously larger than those obtained by the insufficient welding heat input (F: 8.33 kN, L: 1.20 mm, and E: 7.10 J). Although the mechanical properties of the welds achieved by the overlarge welding heat inputs present comparable levels (F: 9.73 kN, L: 1.86 mm, and E: 13.51 J), their standard deviation is much higher. Acicular ferrite, grain boundary ferrite, side plate ferrite, Widmanstatten ferrite, and pearlite are noticed in the fusion zone (FZ), while the coarse grain heat-affected zone (CGHAZ) is composed of upper and lower bainite, grain boundary ferrite, Widmanstӓtten ferrite, polygonal ferrite, and pearlite. As the welding heat input increases, the pre-austenite grain width in the FZ and CGHAZ decreases. The descending order of the microhardness distributed in the welded joints is fusion line, CGHAZ, FZ, fine grain heat-affected zone (FGHAZ), and base metal. In addition, the microhardness values of FZ and CGHAZ decline with the rise of the welding heat input. Nonetheless, no apparent links are found between the microhardness levels of the FGHAZ and welding heat input.

The primary epithelial tumors of the liver (PETL) are composed of a series of heterogeneous tumors. Although the classification of PETLs has been updated several times by the World Health Organization, the cellular origins of some tumors in this family remain to be precisely depicted. In addition, certain tumors in different categories have similar histology, molecular phenotypes and biological characteristics, suggesting that they may have the same cellular origin. In this work, a narrative review method was adopted to review the relevant papers. By comparing the expression profiles of biomarkers of liver epithelium at different lineages and stages of differentiation, the cells-of-origin of some major members of the PETL family were reassessed. We propose that 1) hepatic adenomas, hepatocellular carcinomas (HCCs) and pure fetal hepatoblastomas (HBs) share the same spectrum in their cellular origin including the hepatocytic-committed progenitors (HCP) and their differentiated descendants. 2) Bile duct adenomas, peribiliary cysts and intrahepatic cholangiocellular carcinomas (ICCs) can share the same spectrum in their cellular origin including the cholangiocytic-committed progenitors (CCP) and their differentiated descendants. 3) The cells-of-origin of embryonal HBs include liver stem cells (LSCs), hepatoblasts, and transitional cells between them. Embryonal HB with small cell element, small cell undifferentiated HB and small cell neuroendocrine carcinoma of the liver can have the same or similar cells-of-origin from LSC. Embryonal HB lacking the small cell component of the LSC phenotype and presenting both hepatocytic and bile duct/ductule components may originate from actual hepatoblasts/hepatic progenitor cells (HPCs) as the combined HCC-ICC does. 4) Teratoid hepatoblastoma and mixed epithelial/mesenchymal HBs can be derived from the LSCs or even less committed extrahepatic pluripotent stem cell. 5) Many members of the PETLs family, including those derived from LSCs, hepatoblasts/HPCs, early HCPs and CCPs, have neuroendocrine potentiality. Except for those primary hepatic neuroendocrine tumor (PHNET) exhibit hepatocytic and/or cholangiocytic phenotypes, other PHNETs subtype may be derived from the descendants of LSC that differentiate towards the upper digestive tract, pancreas or other lineages.

The minimum dominating set (MDS) of the network is a node subset of smallest size that every node in the network is either in this subset or is adjacent to one or more nodes of this subset. MDS has found wide applications, ranging from network monitoring, routing, to epidemic control, and text processing. However, the majority of existing studies on MDS problem are confined to single networks. In real world, more and more complex systems consist of a set of elements linked up by different types of connections, which are best modeled as multiplex networks with interacting network layers. Though vastly important, the MDS of the multiplex networks has not yet been formally defined and its application and identification remain open issues. In this article, we present the definition of the MDS of the multiplex network and show some of its possible applications. For solving the MDS problem of the multiplex network, we built a spin-glass model and solve it through the belief-propagation (BP) equations under the replica symmetry mean-field theory. As a consequence, we can predict the relative size of the MDS of the multiplex network theoretically and we can propose a BP-guided decimation algorithm to construct an approximate optimal dominating set in practice. Then the algorithm is improved in both accuracy and efficiency by embedding a novel multiplex network-oriented leaf-removal strategy. The effectiveness of the proposed algorithms is finally verified by comparing with other methods on a number of the multiplex network examples.

Electrode degradation in continuous resistance spot welding of BH 220 steel was evaluated by electrode life test, and weldability tests were conducted by measuring the geometric features, mechanical property analysis, and measuring electrode diameter with 88 or 176 weld intervals. The analysis of weld geometries shows that the HAZ width, nugget diameter, and nugget area tend to decrease rapidly, while the nugget height tends to firstly increase with the weld repetitions till the welding heat input becomes too small to form the valid nugget. The peak load showed a rapid downward trend, while failure energy and maximum displacement slightly increases till the 176th weld and then decreases. The cavities and pores in the nugget mainly appeared after the 176th spot weld. The electrode diameter increases during welding. The reason for the increase in electrode diameter may be that the contact area between the electrode and BH 220 steel sheets becomes smaller in the welding process, which causes the continuous sticking phenomenon between the electrode and the BH 220 steel sheets. In the absence of alloying, the edge of the electrode is geometrically deformed due to the deformation of the electrode, while Cu-Zn-Fe alloying occurs in the area in contact with the BH 220 steel sheet.

With the widespread popularity of online social networks (OSNs), the number of users has also increased exponentially in recent years. At the same time, Social bots, i.e. accounts that controlled by program, are also on the rise. Service providers of OSNs often use them to keep social networks active. Meanwhile, some social bots are also registered for malicious purposes. It is necessary to detect these malicious social bots to present a real public opinion environment. We propose BotFinder, a framework to detect malicious social bots in OSNs. Specifically, it combines machine learning and graph methods so that the potential features of social bots can be effectively extracted. Regarding the feature engineering, we generate second order features and use coding methods to encode variables that have high cardinality. These features make full use of both labelled and unlabeled samples. With respect to the graphs, we firstly generate node vectors through embedding method, following which the similarity between vectors of humans and bots can be further calculated; Then, we use an unsupervised method to diffuse labels and thus the performance can be improved again. To valid the performance of the proposed method, we conduct extensive experiments on the dataset provided by an artificial intelligence contest which is composed of over eight million records of users. Results show that our approach reaches a F1-score of 0.8850, which is much better compared to the state of the art.

Photocatalytic CO2 reduction is a sustainable and inexpensive method to solve the energy crisis and the greenhouse effect. However, the major stumbling blocks such as poor product selectivity, low yield of the multi-carbon products, and serious recombination of electron-hole pairs hinder practical application of photocatalysts. Herein, a high-performance Bi@Bi2 MoO6 photocatalyst, Bi nanoparticles grown on the surface of Bi2 MoO6 nanosheets with oxygen vacancies, was fabricated via a simple solvothermal approach. Benefiting from the abundant active sites and effective separation of photogenerated carriers of Bi2 MoO6 nanosheets, and the localized surface plasmon resonance effect of Bi nanoparticles, the Bi@Bi2 MoO6 sample exhibited great photocatalytic CO2 reduction activity. Furthermore, adding NaHCO3 into the system not only significantly increased the C2 H5 OH generation rate but also enhanced the product selectivity. In the photocatalytic measurement (0.17 mol L-1 CO2 -saturated NaHCO3 solution), the highest formation rates of CO, CH3 OH, and C2 H5 OH were reached at 0.85, 0.59, and 17.93 μmol g-1 h-1 (≈92 % selectivity), respectively.

Hydraulic flushing drilling technology can not only improve the efficiency of high-pressure and low-permeability geological reservoir coalbed methane drainage but also effectively reduce the probability of coal and gas outburst disasters through pressure relief. The main mechanism of this technology is to expand the borehole diameter through hydraulic flushing measures, increase the strain of the coal around the borehole, and increase the development of cracked pores, to improve the permeability of the coal seam and realize the dual reduction of ground and gas pressure. However, in the actual application process, the interaction mechanism among the stress field, the structure field, and the seepage field is still not clear, and there is no clear method to accurately determine the pressure relief range based on the pressure relief mechanism in order to carry out reasonable drilling arrangements. Therefore, this article comprehensively uses laboratory experiments, numerical simulations, and field practices to fully explain the hydraulic flushing pressure relief mechanism and proposes a method to accurately determine the pressure relief range based on the radial line strain law. The results based on radial line strain showed that the effective relief radius expands to 0.86 m once adopting the Φ579 mm hydraulic flushing borehole compared to Φ160 mm; the borehole’s equivalent diameter of drilling field #11 is 2 to 3 times than that of #10 and 1.2 times the average CBM extraction amount. Therefore, as the borehole diameter increases, the permeability and radial line strain of the coal around the borehole increase significantly, but the tendency of the increase in permeability decreases with increasing vertical stress. The findings of this study can help for a better understanding of the pressure relief and permeability enhancement mechanism of hydraulic flushing, and the method of determining the pressure relief range based on radial strain can also provide a new way for other mines to practice ideas.