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Plants comprise an expanded endomembrane system, and transport within the network requires well-organized and accurate vesicle transport. Tethering complexes facilitate the early, exact contact among donor and acceptor membranes, operate to bring vesicles into a closer proximity for trans-SNARE complex assembly docking; these are classified as either long coiled-coil proteins or multi-subunit tethering complexes (MTCs). Numerous MTCs that function at different membrane trafficking steps have been recognized, where they function as significant interfaces between SNARE proteins, Rabs, and phosphoinositides. SNARE proteins assemble into complexes that catalyze the fusion between a donor and a target membrane. Studies of the diverse SNARE proteins provided further valuable information about vacuole biogenesis and vacuolar trafficking pathways related to cell-type specificity, plant development, growth, and the plant developed a specific traffic route to overcome environmental stress. In conclusion, tethers' selective recruitment during membrane fusion is controlled via diverse small GTPases, such as those in the RAB family. The MTCs promote SNARE complex assembly by direct interactions of MTC subunits with Q-SNAREs. A subset of MTC subunits exploits structurally similar CATCHR domains to mediate inter-subunit interactions as well as SNARE protein interactions. MTCs are subdivided into CATCHR (complexes associated with tethering containing helical rods: Dsl1, COG, GARP, EARP, and exocyst) and non‐CATCHR (TRAPP I, II and III, HOPS and CORVET) complexes based on the structure of their subunits. This review summarized new information about SNARE proteins and tethering complexes, highlight new insights about their function, and discuss current debates and future perspectives.

The stress–strain curves of a bainite steel have been measured with hot compression experiments at temperatures of 1173, 1273, 1373, 1473 K and strain rates of 0.01, 0.1, 1, 10 s−1 on a thermo-mechanical simulator (Gleeble-1500). The processing maps, activation energy maps, and the overlap regions of dynamic recrystallization zones and flow stability domains have been obtained by utilizing the stress–strain data experimented. The feasible process windows have been determined according to a new criterion that these windows are in the overlap regions where the activation energy isoline is the sparsest with its variation no more than 1%. Moreover, the optimum temperature and strain rate for a given strain have been ascertained by the largest power dissipation efficiency within the feasible process windows.

Increasing evidence indicates that the oncoprotein murine double minute (MDM2) binding protein (MTBP) can be considered a pro-oncogene of human malignancies; however, its function and mechanisms in hepatocellular carcinoma (HCC) are still not clear. In the present work, our results demonstrate that MTBP could function as a co-activator of transcription factor E26 transformation-specific sequence (ETS-1), which plays an important role in HCC cell proliferation and/or metastasis and promotes proliferation of HCC cells. Using luciferase and real-time polymerase chain reaction (qPCR) assays, MTBP was found to enhance the transcription factor activation of ETS-1. The results from chromatin co-immunoprecipitation showed that MTBP enhanced the recruitment of ETS-1 to its downstream gene’s (mmp1’s) promoter region with ETS-1 binding sites. In cellular and nude mice models, overexpression of MTBP was shown to promote the proliferation of MHCC97-L cells with low endogenous MTBP levels, whereas the knockdown of MTBP led to inhibition of the proliferation of MHCC97-H cells that possessed high endogenous levels of MTBP. The effect of MTBP on ETS-1 was confirmed in the clinical specimens; the expression of MTBP was positively correlated with the downstream genes of ETS-1, mmp3, mmp9, and uPA. Therefore, by establishing the role of MTBP as a novel co-activator of ETS-1, this work expands our knowledge of MTBP or ETS-1 and helps to provide new ideas concerning HCC-related research.

A model predictive feedback control strategy based on time-varying efficiency is investigated and applied to a hydraulic hub-motor auxiliary system (HHMAS) in this paper. Adding HHMAS to a traditional heavy commercial vehicle can improve fuel economy and traction performance on roads with low adhesion coefficients. However, the hydraulic drive system experiences serious disturbance imposed by time-varying parameters and external conditions. Model predictive feedback control based on time-varying efficiency offers a solution for HHMAS to cope with the disadvantage of the hydraulic drive system and improve the environmental adaptability of the vehicle controller. In this study, the control law of hydraulic variable pump (HVP) target displacement is established based on temperature compensation in consideration of the influence of multiple factors on pump target displacement. For coordinated power distribution of HHMAS, the minimum wheel speed difference and the reduction in system impact are regarded as optimal control targets in adjusting the engine torque and HVP displacement and designing the model predictive controller. Simulation results show that the proposed model predictive control method can reduce the speed difference between front and rear wheels by up to 64% and can achieve the wheel speed following effect faster than the traditional proportional-integral-derivative algorithm. Given that the control parameters do not need to be calibrated in the proposed method, the calibration time is saved, and the actual development process of the hydraulic hub-motor driving vehicle is remarkably improved.

When geothermal fluid flows to the wellhead along the wellbore, there is a thermal transfer from the high-temperature geothermal fluid to the low-temperature formation. This process can directly lead to the decrease of wellhead temperature and loss of geothermal energy. Even though previous studies have confirmed that reducing the thermal conductivity of cement could validly cut down the heat loss of geothermal fluid, the influence factors of thermal conductivity are limited. In this research, we conducted detailed studies of the influence factors of thermal conductivity and compressive strength for cement. The results show that with the increase of water-cement ratio and thermal insulation materials, thermal conductivity and compressive strength decline. Furthermore, curing temperature is another important factor to improve the thermal preservation effect, but the testing temperature has the opposite influence. Based on these results, the present study concluded that porosity, Skeleton ingredients, curing temperature, and test temperature are vital factors for thermal conductivity. This research provides theoretical guidance for increasing the wellhead temperature of geothermal fluid and enhancing the efficiency of geothermal energy.

A three high planetary mill is used to produce bismuth-containing stainless-steel bars with high production efficiency. However, due to the influence of bismuth metal properties, the selection of processing parameters must be optimized to avoid the generation of cracking in the bar core. To solve this contradiction and find a suitable processing zone, the thermal simulation experiment of bismuth-containing stainless-steel material was carried out first to determine the constitutive relationship of the material. Three-roll planetary rolling experiments were carried out to determine the crack-producing region. Based on the Brozzo ductile fracture criterion, the fracture threshold of bismuth-containing austenitic stainless-steel bars in three-roll planetary rolling was determined by the finite element (FE) simulation. Five key process parameters were selected, with five factors and four levels of the orthogonal test designed. Through FE simulations, the possibility of cracking of stainless-steel bars with bismuth austenites in different technologic conditions was judged, and a set of optimal technologic parameters was obtained. Based on range analysis, the influence of various process parameters on bar cracking was discussed. Then, based on the dynamic material model and Murty criterion, the processing map of free-cutting austenitic stainless containing bismuth was established. It was found that the optimum process parameters were consistent with the processable range of the hot-working chart. Finally, the field rolling was carried out with the optimum process parameters, showing that there was no crack in the bar.

The scientific and reasonable layout of jack-up drilling platform can improve the efficiency and safety of drilling platform operation. Through the application of analytic hierarchy process (AHP) and the establishment of comprehensive evaluation and analysis model, this paper analyzes the commonly used drilling platform layout scheme and optimizes the scheme to meet operational requirements and to improve the ability of the drilling platform operation.

In order to improve the tribological properties of zinc-based alloy, SiC nanoparticles (an average grain size of 100 nm) were reinforced into Zn–38Al–3.5Cu–1.2 Mg alloy through a high-pressure jetting powder and semisolid stirring-assisted ultrasonic vibration process. In the present study, the effects of different SiC contents (0 wt%, 0.07 wt%, 0.13 wt%, and 0.22 wt%) on microstructural properties and wear behavior of the as-cast alloy were investigated in detail. The results indicated that a uniform and dispersive distribution of SiC nanoparticles was observed in the Zn–Al matrix, thus leading to a significant enhancement in wear behavior of Zn–38Al–3.5Cu–1.2 Mg alloy. Further, with the increasing mass fraction of SiC nanoparticles, wear resistance of Zn–38Al–3.5Cu–1.2 Mg alloy was noticeably improved in spite of the increasing friction temperature. The increased wear resistance of Zn–38Al–3.5Cu–1.2 Mg alloy at high friction temperature could be attributed to the presence of uniformly dispersed thermostable SiC nanoparticles, which inhibited the transformation of the abrasion-resistant phase of α + η mixture to the soft phase of α and η on the friction heating interface.

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.

The plant cytoskeleton forms a stereoscopic network that regulates cell morphogenesis. The cytoskeleton also provides tracks for trafficking of vesicles to the target membrane. Fusion of vesicles with the target membrane is promoted by SNARE proteins, etc. The vesicle-SNARE, Sec22, regulates membrane trafficking between the ER and Golgi in yeast and mammals. Arabidopsis AtSEC22 might also regulate early secretion and is essential for gametophyte development. However, the role of AtSEC22 in plant development is unclear. To clarify the role of AtSEC22 in the regulation of plant development, we isolated an AtSEC22 knock-down mutant, atsec22-4, and found that cell morphogenesis and development were seriously disturbed. atsec22-4 exhibited shorter primary roots (PRs), dwarf plants, and partial abortion. More interestingly, the atsec22-4 mutant had less trichomes with altered morphology, irregular stomata, and pavement cells, suggesting that cell morphogenesis was perturbed. Further analyses revealed that in atsec22-4, vesicle trafficking was blocked, resulting in the trapping of proteins in the ER and collapse of structures of the ER and Golgi apparatus. Furthermore, AtSEC22 defects resulted in impaired organization and stability of the cytoskeleton in atsec22-4. Our findings revealed essential roles of AtSEC22 in membrane trafficking and cytoskeleton dynamics during plant development.

Honeybees are prone to poisoning after collecting jujube nectar during the jujube flowering period (‘honeybee's jujube flower disease’). To explore the mechanism of honeybee poisoning, the gut microbiota of honeybees undergoing the disease were characterised based on amplicon sequencing of the 16 S rRNA gene. Our results showed that the composition and diversity of the gut microbiota were significantly altered in diseased honeybees. We observed a decrease in the relative abundance of Proteobacteria and increased abundances of Firmicutes and Actinobacteria in the midgut and hindgut of diseased honeybees. Moreover, linear discriminant analysis (LDA) effect size revealed significantly selected enrichment of Fructobacillus and Snodgrassella in the midguts from diseased honeybees and Lactobacillus, Bifidobacterium, and Snodgrassella in the hindguts from diseased honeybees. Tax4Fun anylasis indicated that the functional potential of the diseased honeybee gut bacterial community was significantly changed relative to the healthy honeybee. Carbohydrate metabolism, nucleotides metabolism, amino acid synthesis metabolism, coenzyme and vitamins metabolism were increased, while energy metabolism and xenobiotic biodegradation and metabolism were decreased in the diseased honeybees. These results provide a new perspective for evaluating the response of honeybees to jujube flower disease based on changes in the intestinal microflora.

A novel topology leaf spring as a substitute for the traditional spring was designed to expand the effective bandwidth of a seismometer. The finite element analysis showed that the seismometer with the new topology spring has better performance than that with the traditional spring. Compared with the traditional pendulum, the proposed topology structure was featured with lower natural frequency and higher spurious frequency. The bandwidth of the proposed seismometer was enhanced to [2 s, 72 Hz] with an increase of 43% over the traditional seismometer bandwidth of [1 s, 51 Hz] as well as the signal distortion of the seismometer was also reduced with the proposed topology spring.

In this article, we describe an in-house polymerase chain reaction-sequence specific priming (PCR-SSP) assay designed for undergraduate medical students as part of the experimental pathogen biology and immunology (EPBI) course. It screens human leukocyte antigen (HLA)-DR2 allotype from genomic DNA samples using a rapid and single-tube PCR technique, yielding definitive typing result without conventional post-amplification step like probing or Sanger sequencing. This laboratory exercise offers the undergraduate medical students an opportunity to learn about current molecular biology techniques in HLA genotyping with limited effort and cost, in addition to a better understanding of concepts presented in the classroom lectures. Upon completing this experiment module, the students show statistically significant improvement in several key indexes, such as the knowledge about the mainstream HLA DNA typing techniques, awareness of the relevance of this knowledge for their future scientific research, immunogenetics-related basic laboratory skills they acquire, and interest and desire for mastering this assay (all p < .05). This easy to implement set of experiments is composed of a two-session lab module occupying eight teaching hours, and has been run successfully in our laboratory.

This study investigated the effects of a CoCl2-simulated hypoxic environment on the muscle fiber switching signaling pathways calcineurin A/nuclear factor of activated T cells cytoplasmic 1 (CnA/NFATc1) and myostatin. In this study, C2C12 muscle cells were cultured in vitro under CoCl2-simulated chemical hypoxic conditions, the expression levels of CnA and myostatin were detected through qRT-PCR and Western blot analyses, and a positioning study of NFATc1 was carried out by immunofluorescence labeling. Results showed that CoCl2 treatment significantly increased the expression levels of CnA and myostatin. Moreover, the position of NFATc1 expression changed; actually, its expression in the nucleus considerably increased. Furthermore, CoCl2-induced hypoxia inhibited the differentiation of C2C12 cells and reduced the expression levels of many slow- and fast-twitch muscles marker genes, but immunofluorescence staining results showed that the proportion of MyHC I type muscle fiber increased after CoCl2 treatment. The hypoxic environment simulated by CoCl2 can activate the signaling pathways CnA/NFATc1 and myostatin and increases the proportion of MyHC I type muscle fibers.

For the distortion problem of traditional denoising threshold function exists, a seismic signal denoising method based on wavelet packet multi-threshold function was present. Seismic wave signals were done wavelet packet decomposition and wavelet packet decomposition coefficients were arranged in the order of magnitude of the frequency, the appropriate threshold criteria was selected on different frequency bands and threshold processing was done on different frequency bands. Synthetic seismic signals and real seismic data were done multi-threshold wavelet packet decomposition, which better remove high frequency random noise and retain useful signals. Experimental results showed that multi-threshold wavelet packet decomposition method can effectively remove noises and improve the resolution of seismic data, with better denoising effect.

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.

The horizontal displacement monitoring of the supporting piles plays a vital role in the safety judgment of deep foundation pit excavation and construction of main structure. In urban rail transit engineering, the monitoring of horizontal displacement of retaining pile top of deep foundation pit should be carried out according to the characteristics of the project, formulated a scientific monitoring plan, and selected a reasonable monitoring method. If necessary, the monitoring methods should be optimized and integrated, so as to get the real and effective monitoring data, which can reflect the change of the horizontal displacement of the foundation pit support structure to the greatest extent. By analyzing several common methods of deep foundation pit monitoring in current urban rail transit projects, the advantages and disadvantages of each method are summarized, and reasonable suggestions are proposed for accurate monitoring.

In the urban rail transit engineering, there is a great risk in the underground excavation construction of the existing railway station, and the monitoring accuracy of the underground excavation construction is very high. Taking station A of a project as the research object, combined with the construction situation and the structural characteristics of the station, this paper discusses the influencing factors of the vault settlement monitoring in the undercut section of the existing metro station, and formulates the vault settlement monitoring scheme in the undercut section. The feasibility of the method is verified by setting up two sets of independent elevation system and adopting the method of setting up a single station to measure the inverted ruler, and then the error control measures are given. The results show that the method can meet the accuracy requirements of the vault settlement monitoring in the underground excavation section of metro station. This method can provide some technical reference for the similar monitoring project of underground subway station.

Large capacity synchronous condenser can provide strong dynamic reactive power demand for HVDC transmission system, and its operation characteristics are related to excitation parameters. The force excitation voltage ratio and low excitation voltage ratio of synchronous condenser can affect dynamic reactive response and HVDC system voltage. This paper studied the influence of force excitation voltage ratio on voltage stability of HVDC after voltage sag of sending and receiving end, and the influence of low excitation voltage ratio on voltage stability after overvoltage of sending-end caused by DC Bi-polar block fault. The voltage of AC-DC systems, the reactive power of synchronous condenser and transmission power of HVDC are compared under the different excitation limit, respectively. The results show that the output reactive power of synchronous condenser increases by 400MVar and the system voltage increases by 10% of rated value as the force excitation voltage ratio changing from 2 to 3.5 during the process of voltage sag. The recovered time of system voltage of AC system decreases by 3.35s and reactive power of synchronous condenser decreases by 5.14s as the force excitation voltage ratio changing from 2.5 to 3.5. The absorbed reactive power of synchronous condenser increases by 40MVar as the low excitation voltage ratio change from 10% to 0 during the process of DC Bi-polar Block Fault. The results can provide theory basis for the operation of synchronous condenser connected to HVDC.

A series of novel saccharin derivatives containing 1,2,3-triazole moiety was synthesized in satisfactory yields. The structures of all the compounds were elucidated and confirmed by Fourier transform infrared(FTIR) spectroscopy, 1H and 13C nuclear magnetic resonance(1H NMR, 13C NMR) spectroscopy, and high resolution mass spectrometry(HRMS). The bioassays indicated that most of the title compounds displayed some extent herbicidal activities at 100 μg/mL.

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.

Captopril is a New Delhi metallo-β-lactamase-1 (NDM-1) inhibitor with an IC50 value of 7.9μM. It is composed of two units: a 3-mercapto-2-methylpropanoyl fragment and a proline residue. In this study, we synthesized simple amide derivatives of 3-mercapto-2-methylpropanoic acid, and then tested them as NDM-1 inhibitors in order to identify the pharmacophore for NDM-1 inhibition. We found that the lead compound 22 had an IC50 value of 1.0μM. Further structure simplification provided compounds 31 and 32, which had IC50 values of 15 and 10μM, respectively. As compound 32 is a clinically used antidote for metal poisoning, it has great potential to be repurposed to treat bacterial infections.

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.

An economic microalgae Haematococcus pluvialis CH-1 was used as experimental material. An experiment of adding six grades of concentrations of Vitamin-B12 and Vitamin-H respectively was conducted. Cell density, biomass and astaxanthin content were measured. The results showed that the growth of H. pluvialis was accelerated significantly by adding of Vitamin-B12 and Vitamin-H, respectively. The optimal adding concentration of Vitamin-B12 and Vitamin-H respectively for H. pluvialis was 50 and 500 µg/L. Under the optimal concentration for H. pluvialis, cells density, biomass and astaxanthin content were enhanced with Vitamin-B12: 29.5, 30.0 and 28.3%; Vitamin-H: 17.1, 29.2 and 22.6% higher than the blank, respectively. On the mass culture of motile cells of H. pluvialis, properly adding Vitamin-B12 and Vitamin-H, respectively was effective for increase cells density, biomass and astaxanthin content.

The energy efficiency (EE) of a multi-user multi-relay system with the maximum diversity network coding (MDNC) is studied. We explicitly find the connection among the outage probability, energy consumption and EE and formulate the maximizing EE problem under the outage probability constraints. Relay scheduling (RS) and power allocation (PA) are applied to schedule the relay states (transmitting, sleeping, \emph{etc}) and optimize the transmitting power under the practical channel and power consumption models. Since the optimization problem is NP-hard, to reduce computational complexity, the outage probability is first tightly approximated to a log-convex form. Further, the EE is converted into a subtractive form based on the fractional programming. Then a convex mixed-integer nonlinear problem (MINLP) is eventually obtained. With a generalized outer approximation (GOA) algorithm, RS and PA are solved in an iterative manner. The Pareto-optimal curves between the EE and the target outage probability show the EE gains from PA and RS. Moreover, by comparing with the no network coding (NoNC) scenario, we conclude that with the same number of relays, MDNC can lead to EE gains. However, if RS is implemented, NoNC can outperform MDNC in terms of the EE when more relays are needed in the MDNC scheme., Comment: 13 pages, 7 figures, Part of this work was presented at the International Conference on Telecommunications (ICT), 2016

In order to investigate section capacities of thick‐wall cold formed steel with square and rectangular hollow cross‐sections, experiments were carried out on mechanical properties of the flat coupons, corner coupons, parent steel coupons and full section stub columns. Strain hardening of cold forming thick‐wall cold formed sections was investigated. The stub column test strengths were compared with the design compressive strengths specified by the Australian/New Zealand and Chinese standards for the design of the cold formed steel structural members respectively. It has been shown that the strength predicted by the Australian/New Zealand standard using material properties and that forecasted by the Chinese standard based on the average design yield stress of the full section are a little conservative. The two mean strengths predicted by Australian/New Zealand standard based on the mean design yield stress and forecasted by the Chinese standard using material properties tests are identical, which a...

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.

Searching for X-ray binaries and establishing a large sample are the foundation of answering many scientific problems, such as, how many BH X-ray binaries are there within our Milky Way galaxy? Does there exist a real gap between the mass distribution of neutron stars and black holes? Is there any black hole system within globular clusters? The planned mission Einstein Probe (EP) has a much better sensitivity compared to the past missions, so it is expected to discover many new X-ray binary systems over its operating period, which will play a key role in helping solve the problems above then.

Plug-in hybrid electric vehicle is one of the potential candidates to tackle the stringent fuel economy standards. Many previous studies focus on optimal fuel economy by coordinating primary power source and assistant power source in plug-in hybrid electric vehicles, which usually neglects vehicle dynamic performance. All-wheel-drive plug-in hybrid electric vehicle has advantages both in fuel economy and dynamic performance. However, when all-wheel-drive plug-in hybrid electric vehicle is traveling on low cohesive roads, how to balance the conflict between traction performance and fuel economy undoubtedly will be the crucial problem. To address the issue, an integrated control strategy is proposed for all-wheel-drive plug-in hybrid electric vehicle in this article, namely, traction control system–integrated energy management strategy. A charge depletion/charge sustaining strategy is employed to realize the torque distribution mainly according to the engine optimal working region to achieve better fuel economy. Traction control system is integrated to prevent slipping of the wheels during starting and acceleration by applying engine throttle control, motor torque control, and active braking control, which improves the vehicle dynamic performance. The traction enhancement is beneficial to the improvement of fuel efficiency. By the co-simulation of MATLAB/Simulink and AMESim, the results demonstrate the effectiveness of the proposed integrated control strategy, which increases the vehicle velocity greatly and optimizes fuel economy as well.

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

Mass spectrometry-based platforms have gained increasing success in discovery of ligands bound to therapeutic targets as drug candidates. We established both a nanoelectrospray ionization mass spectrometry (nanoESI-MS) assay and an ultrafiltration liquid chromatography/mass spectrometry (LC/MS) assay to identify new ligands for New Delhi metallo-β-lactamase 1 (NDM-1), responsible for worldwide antibiotic resistance. To alleviate nonspecific binding of hydrophobic compounds and eliminate false positives typically encountered in the indirect LC/MS-based assay, we introduced a blocking protein in the control, which remarkably enhances the selectivity and accuracy of the indirect approach. Side-by-side comparison of the two MS-based approaches for the first time further reveals unique advantages of the indirect approach, including better reproducibility and tolerance of interference. Moreover, the success of fishing out a potent ligand from a mixture of small-molecule fragments demonstrates great potential of the indirect LC/MS-based approach for constructing a robust screening platform against combinatorial libraries or natural product extracts. More importantly, by combining the results of MS-based analyses, enzymatic activity assay, competition experiments, and structural simulation, we discovered a new compound as a promising drug candidate targeting NDM-1.

[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.

In this paper a suggestion of summation over steepest-descent contours in path integral approach to quantum cosmology is given, with which the wave function describing the evolution of the universe can be uniquely specified.

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.

We present an observational study towards the young high-mass star forming region G23.44-0.18 using the Submillimeter Array. Two massive, radio-quiet dusty cores MM1 and MM2 are observed in 1.3 mm continuum emission and dense molecular gas tracers including thermal CH$_3$OH, CH$_3$CN, HNCO, SO, and OCS lines. The $^{12}$CO (2--1) line reveals a strong bipolar outflow originated from MM2. The outflow consists of a low-velocity component with wide-angle quasi-parabolic shape and a more compact and collimated high-velocity component. The overall geometry resembles the outflow system observed in the low-mass protostar which has a jet-driven fast flow and entrained gas shell. The outflow has a dynamical age of $6\times10^3$ years and a mass ejection rate $\sim10^{-3} M_{\odot}$ year$^{-1}$. A prominent shock emission in the outflow is observed in SO and OCS, and also detected in CH$_3$OH and HNCO. We investigated the chemistry of MM1, MM2 and the shocked region. The dense core MM2 have molecular abundances of 3 to 4 times higher than those in MM1. The abundance excess, we suggest, can be a net effect of the stellar evolution and embedded shocks in MM2 that calls for further inspection., Comment: 8 figures, 3 tables, accepted to MNRAS

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.