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Objectives The immune status of the tumor microenvironment has a marked impact on clinical outcomes. Here we examined the immune environments of tumor-infiltrating leukocytes (TILes) in two murine models of squamous cell carcinoma and compared the effects of immunotherapeutic agents, including a TLR7 agonist and an immune checkpoint inhibitor, and a chemotherapeutic agent, gemcitabine, in these models. Materials and methods TILes from NR-S1- and SCCVII-grafted mice were analyzed by flow cytometry. NR-S1-inoculated mice received resiquimod (a synthetic TLR7 agonist), an anti-PD-L1 antibody, or both, and tumor growth and TILs were examined. Gemcitabine was administered to deplete CD11b+ cells. Results More than 50% of TILes from NR-S1- and SCCVII-inoculated mice were CD11b+Gr-1+ cells. A major fraction of NR-S1 CD11b+ cells was Ly6GhighLy6Clow-negaF4/80− tumor-associated neutrophils (TANs) and the majority of SCCVII CD11b+ cells were Ly6GlowLy6C−F4/80+ tumor-associated macrophages. NR-S1 TANs did not express MHC class II and CD86, but did express reactive oxygen species and PD-L1. Resiquimod, alone and in combination with an anti-PD-L1 antibody, did not regress NR-S1 tumors, but the combination increased the CD8/regulatory T cell-ratio, and IFN-γ and PD-1 expression in CD8+ TILes. Pre-administration of low-dose gemcitabine prior to the combination treatment suppressed the progression of NR-S1 tumors. Conclusions NR-S1 tumors with abundant recruitment of TANs were resistant to treatments with a TLR7 agonist, alone and in combination with PD-1 blockade, and required an additional gemcitabine treatment. The phenotype and status of tumor-infiltrating CD11b+ myeloid cells may influence the efficacy of immunotherapeutic agents.

Research on immune checkpoint blockade therapy has made great progress in cancer immunotherapy, but the number of patients who benefit from this therapy remains limited. In this study, we examined the effects of monotherapy with systemic low-dose resiquimod, a synthesized TLR7 agonist, and examined its combined effects with PD-L1 blockade in two PD-L1 blockade-resistant tumor models (SCCVII and Colon 26). Resiquimod monotherapy in SCCVII tumors, representing impaired CD8+ T cell function and accelerated regulatory T cells (Tregs) within the tumors, efficiently reduced tumor growth with more recruitment of CD8+ T cells and a reduction of Treg. The results of resiquimod monotherapy in Colon 26, representing impaired Treg recruitment, were inferior to that in SCCVII. Combined resiquimod treatment with PD-L1 blockade exerted clear additional effects, as it was associated with reduced tumor size, attenuation of Tregs, and an increased ratio of CD8+ T cells/Tregs in both tumors. Systemic administration of low-dose resiquimod induced a transient and rapid activation of plasmacytoid and conventional dendritic cells, resulting in enhanced priming of T cells in regional lymph nodes. Experiments with more limited doses of resiquimod that did not yield beneficial effects after single treatment, showed additional effects to PD-L1 blockade and comparable antitumor effects when the frequency of anti-PD-L1 therapy was decreased. Our results suggest that systemic administration of low-dose resiquimod is useful as a companion drug to PD-1/PD-L1 blockade therapy.

Geological disasters such as rock burst coal and gas outburst in coal mines have inevitable link with micro-seismic phenomenon intrinsically. Monitoring the underground microseismic signals could determine the scope and extent of the underground rock and provide strong evidence for underground mine safety monitoring. A microseismic real-time monitoring system design based on virtual instrument was presented, using thirty two channels front microseismic signal processing unit, data acquisition card DAQ-6343, realizing multi-channel analog microseismic signals acquisition, achieved a real-time monitoring and analysis of microseismic signals combined with the microseismic method and improved adaptive wavelet transform processing algorithms in the LabVIEW platform. System monitoring results agree well with the actual mine earthquake, the error of obtained positioning results is small, realizing a real-time microseismic monitoring and analysis.

Pansharpening technology has been an important tool in remote sensing applications. It aims at increasing the spatial resolution of multispectral (MS) image with the aid of panchromatic (PAN) image. A key point of pansharpening is spatial detail extraction and injection. Since MS and PAN images contain objects in different sizes and structures of various scales, scale-sensitive detail extraction is desired. In this paper, we present a scale-aware pansharpening method which uses rolling guidance filter to separate structure from details and injects the details through Gram-Schmidt transformation. The experimental results show that our proposed method can obtain high-quality sharpened results and outperforms some existing methods.

Axial force monitoring of steel support is one of the important factors for foundation pit safety monitoring. In the monitoring of steel support, there are many problems, such as unreasonable installation of axonometer, irregular monitoring behavior of axonometer, incomplete analysis of axial force and imperfect early warning system. Collecting many engineering cases, and in-depth analysis and research on the problems and irregular behavior of steel support axial force monitoring in every link. The influencing factors and control measures of steel support axial force are discussed in detail, and some useful conclusions are obtained. It has been applied in the actual monitoring work and achieved good results. It is of great significance to guide subway safety construction and promote the development of axle force monitoring industry.

In recent years, low dose cyclophosphamide has been used clinically either as a single agent or as combination therapy to treat lymphomas, and breast and ovarian cancers. The efficacy of low dose cyclophosphamide is primarily due to its ability to immune-modulate in addition to its direct anti-tumor effects. This ability highlights the potential for synergism between conventional chemotherapy and novel immunotherapy. Toll-like receptors (TLRs) are a crucial part of the innate immunity and present the first line of defense against pathogens. Resiquimod is the ligand for TLR7 and 8 and directly activate innate immune cells, including myeloid dendritic cells, plasmacytoid dendritic cells, and monocytes/macrophages. This activation may result in activation of co-stimulatory molecules, production of antiviral cytokines, and stimulation of cell-mediated NK and T cell immune responses. The aim of this study was to analyze whether immunopotentiating TLR7/8 agonist might synergize with low doses of cyclophosphamide in the treatment of colorectal carcinoma. The effect of combining a weekly dosing of cyclophosphamide intraperitoneally with systemic administration of Resiquimod was evaluated in an in vivo murine C26 synergistic model. Systemic administration of Resiquimod in mice induced significant systemic immune responses as evidenced by upregulating IFNα inducible gene clusters. The combined therapy with Resiquimod and cyclophosphamide was superior to each single treatment and increased efficacy of tumor inhibition and prolonged their survival significantly. Importantly, the combined treatment generated a significant numbers of tumor-specific T cell infiltration in tumor microenvironment. Our data suggest that systemic administration of TLR7/8 agonist enhances anti-tumor effect of low dose of cyclophosphamide. The data supports the use of a combination of TLR7/8 agonist and cyclophosphamide as a novel therapeutic strategy against colorectal carcinoma. Citation Format: Jing Yang, Patrick Z. Li, Xiangyun Yin, Xiaohua Nie, Jingshu Wang, Walter Lau, Liguo Zhang, Lixin Li. Synergistic immunotherapeutic effects of TLR7/8 agonist on low-dose cyclophosphamide-treated C26 model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2746.

PurposeThis paper aims to explore the extent of adequacy and confidence that can be enjoyed by minority shareholders in the supervisory controls on Boards in listed companies in China.Design/methodology/approachThis study draws upon the legislative controls and case‐studies in China.FindingsBeing the cornerstone of the development of capital markets, listed companies are in complementary relationship with the latter, which in turn serves as the financing tool for the former. Recently, the financial markets all over the world have been thrown into deep crisis and the financing functions of the domestic capital markets have almost been paralyzed. In this context, it is high time for us to exert more efforts to improve the institutional arrangements of the supervisory functions in the governance of listed companies in China, to strengthen corporate governance, to restrain the actions and behaviors of major shareholders, directors and the executives, to strengthen their concerned responsibilities, to put greater attention and more protection on the promotion of minor shareholders' confidence on capital markets, and to maintain the steady and sustainable development of capital markets in the long run.Originality/valueThis study and findings should be of interest to those seeking to assess the adequacy of minority protection in China.

By analyzing the condition of the electricity market, this paper described the current development of the renewable energy and its future trend with a Population Competition Model. In this open Distributed Generation and Demand-Supply-Interacted Smart Grid platform, the development of the traditional energy and renewable energy is similar to the population competition. Also, this paper has predicted the developing trend of renewable energy and traditional energy by the same model, with which the Smart Grid platform could lead optimized utilization of renewable energy.

As the command center of Strong Smart Grid, the safe and stable operation of the power grid dispatching automation system is the firm guarantee of electric power supply. And dispatching platform is the foundation platform of the power grid dispatching automation system. To make full use of the computing resources and enhance the availability and flexibility of system, this paper puts forward the construction of uniform resource management platform for power grid dispatching automation system based on virtualization technology, thus to provide required computation, storage, network and other resources. With the introduction of virtualization technology including server virtualization, storage virtualization, network virtualization and other technologies, and the construction of corresponding resource pool, the paper designs uniform resources management platform based on virtualization technology and provides new architecture for power grid dispatching automation system. The new system can allocate and dispatch the resources as a whole, thus to enhance the availability and flexibility of system and realize on-demand allocation and high efficient utilization of resources. DOI : http://dx.doi.org/10.11591/telkomnika.v12i3.4569 Full Text: PDF

[Aim] Toll like receptor (TLRs) are expressed in many types of immune cells and function as a key sensor of microbial products. Ligand binding to TLRs leads to activation of signaling pathways in innate immune cells, particularly dendritic cells and subsequent induction of adaptive immune responses. TLR7/8 agonists have been shown to enhance antiviral and antitumor immune responses via multiple cytokine production such as IFN-α, IL-1β, IL-6 and TNFα. Resiquimod (R-848) is a synthetic imidazoquinoline-like molecule that binds to TLR7 and TLR8. Presently, resiquimod has been used as a topical drug for skin cancer and viral infection, because of severe side effects of systemic administration. Thus far, the clinical results of anti-PD-1 or anti-PD-L1 therapy have showed great benefits by inducing tumor regression and improving survival. However, the patients obtained the benefits of this treatment are around one third. An additional approach is required to enhance the efficacy of PD-1 blockade therapy. In this study, we examined the effects of combined treatment with anti-PD-L1 antibody and a low dose of resiquimod administration in two murine tumor models (a squamous cell carcinoma cell line, SCCVII and a colon carcinoma cell line, Colon26). [Methods] Anti-PD-L1 mAb (MIH5, 200 μg/mouse) and/or resiquimod (1.73 μg/mouse) were intraperitonealy administrated at three times a week and tumor growth was evaluated. [Results and Discussion] In a Colon26 model, either anti-PD-L1 (MIH5) mAb or resiquimod treatment alone slightly decreased tumor growth, but the combined treatment dramatically reduced the tumor growth and completely eradicated the tumor in some of mice. In a SCCVII model, monotherapy with resiquimod markedly reduced the tumor growth and completely eradicated the tumor in some of mice. The combined treatment further enhanced the efficacy. The delayed combined treatment at day 7 also showed the reduction of tumor size. Functional analyses at 3-4 wks after the tumor inoculation revealed that monotherapy with resiquimod in the SCCVII model and the combined treatment in both models significantly enhanced the percentages of IFN-γ+-expressing CD8+ T cells, but did not clearly affect the percentages of Foxp3+ regulatory T cells. Our results suggest that TLR7/8 agonist administration alone markedly enhanced antitumor responses in a selected tumor model and the combined treatment with PD-L1 blockade and a TLR7/8 agonist further amplify their effects. Citation Format: Naoto Nishii, Yuta Kondo, Lixin Li, Walter Lau, Hiroyuki Harada, Miyuki Azuma. Combined treatment with PD-L1 blockade and a TLR7/8 agonist dramatically enhances antitumor immunity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 563.

Disasters cause the damage of energy management systems, causing power grid monitoring and dispatching interrupt and abnormal operation, imposing a great impact on society. Establishing disaster backup system is in urgent need to improve the reliability and tolerance. The paper presents an analysis and evaluation model of backup system constructing, indicates the advantages of integrated inter-reserve scheme after analyzing of various alternative schemes and proposes the reverse order design principles of dispersion of reserve risk and the disaster probability and loss in allusion to the multi-function module, the distribution nonuniformity of regional disaster probability and so on. Analyse the need of the backup system show the real-time synchronism and seamless switchover principles between primary control center and disaster recovery center,mainly containing three levels of backup such as data level backup,business level backup and system level backup.The cloud computing technology fit the need of integrated inter-backup system.

Based on the analysis of the development condition of the Smart Grid and Distributed Energy, described the current development situation of the Renewable Energy in United States and predicted the future trend of development by establishing mathematical model. Driven by the Smart Grid Technology, the development of renewable energy is promoted greatly. Wind Power is found developing rapidly in United States which is in the exponential growth stage by establishing and solving the Logistic Model and Grey Prediction Model. (4 pages)

Grid-connected photovoltaic power system consists of simulation of solar modules, inverter main circuit, driver circuit, maximum power point tracking circuit, the MCU control display system and the FPGA, protecting circuit. Inverter main circuit is the analog output of solar modules through the inverter main circuit DC into AC power reverse, and then through the filter, the output stable AC; one FPGA processor is SPWM signal generated by the drive circuit driving inverter main circuit switch, SCM complete solar photovoltaic maximum power tracking device calculates and displays; protection circuit is mainly done when the input voltage and output over-current system work to stop in time when the system protection.

Because the PrivacyCA defined in TCG specification may leak user’s privacy and trace his transactions, two PrivacyCA schemes with higher untraceability are proposed. The agents-based one provides higher untraceability by introducing agents and VK certificates to eliminate the linkage between EK and AIK. By adopting Partially Blind Signature algorithm in the generation of AIK triples, PBS-based one provides absolute untraceability to user’s transactions because the public AIK is blinded while being signed by the PrivacyCA. New schemes keep good compatibility to TCG specification and provide different levels of untraceability to satisfy particular applications.

The PrivacyCA defined in Trusted Computing Group (TCG) specifications may be the performance bottleneck of trusted applications, because it needs to be involved in every transaction of attestation to maximize privacy and in a future trust-enabled Internet a PrivacyCA potentially has to serve millions of customers. In this paper we show how the scalability of PrivacyCA can be improved. In this context, we propose two models of PrivacyCA individually based on agents and virtualization technologies. In the agents-based model, the PrivacyCA authorizes a series of agents to issue AIK certificates and only issues a few VK certificates itself. The virtualization-based model provides large number of PrivacyCA instances running on virtual machines to deal with AIK requests. Both models not only improve the scalability of PrivacyCA, but also enhance its security and privacy preserving ability.

Trusted Computing Group developed two solutions to realize remote attestation between platforms, but both of them have drawbacks. Privacy CA defined by Trusted Computing Group needs to be highly available and may collude with verifier to trace user's transactions. Direct Anonymous Attestation proposed in Trusted Platform Module Specification v1.2 is not efficient because it adopts many exponential operations and the Issuer may collude with verifier, too. In this paper, we propose a remote anonymous attestation scheme with an improved Privacy CA. The Privacy CA issues an Anonymous Attribute Credential for a Trusted Computing Platform and doesn't need to be involved in all attestations. It is also not able to leak the privacy of users. The proposed scheme is high efficient and fulfills the requirements of anonymous credential system very well.

Qilu Petrochemical Co. Ltd developed a soft measurement technique based on a neural network and implemented the computer online inferential control to control the propane and propylene consistency in the propylene rectification column.

In recent years, open system concepts and object oriented technologies have been broadly accepted by the electric power industry, and there is no doubt that traditional software programming techniques will be replaced by new techniques one day. This paper intends to focus on the presentation for a new, practical, open and object oriented power network control system which has been jointly developed by the Electric Power Research Institute of China and the Northeast China Electric Power Control Center with significant support from the Ministry of Electric Power of China.

The power system supervisory and control system plays a more and more important role in the security and economic operation of power systems. The power system supervisory and control system includes both energy management systems (EMS) and distribution management systems (DMS), they are employed in transmission system and distributions systems respectively. In this paper the design philosophy of CC-2000 EMS/DMD support system such as the open system architecture, object oriented technology and the event driven mechanism of system management are introduced, so that this tool has strong capability to support application software development. The CC-2000 system has been implemented in many projects in China.