Predicting P-Glycoprotein-Mediated Drug Transport Based On Support Vector Machine and Three-Dimensional Crystal Structure of P-glycoprotein

Human P-glycoprotein (P-gp) is an ATP-binding cassette multidrug transporter that confers resistance to a wide range of chemotherapeutic agents in cancer cells by active efflux of the drugs from cells. P-gp also plays a key role in limiting oral absorption and brain penetration and in facilitating biliary and renal elimination of structurally diverse drugs. Thus, identification of drugs or new molecular entities to be P-gp substrates is of vital importance for predicting the pharmacokinetics, efficacy, safety, or tissue levels of drugs or drug candidates. At present, publicly available, reliable in silico models predicting P-gp substrates are scarce. In this study, a support vector machine (SVM) method was developed to predict P-gp substrates and P-gp-substrate interactions, based on a training data set of 197 known P-gp substrates and non-substrates collected from the literature. We showed that the SVM method had a prediction accuracy of approximately 80% on an independent external validation data set of 32 compounds. A homology model of human P-gp based on the X-ray structure of mouse P-gp as a template has been constructed. We showed that molecular docking to the P-gp structures successfully predicted the geometry of P-gp-ligand complexes. Our SVM prediction and the molecular docking methods have been integrated into a free web server (http://pgp.althotas.com), which allows the users to predict whether a given compound is a P-gp substrate and how it binds to and interacts with P-gp. Utilization of such a web server may prove valuable for both rational drug design and screening

A Method for Active Global Localization in Multi-robot System

In multi-robot system the ability to exchange information can reduce the uncertainty in the estimated location when robots can see each other. In this paper, a kind of dynamically evolving coordination architecture is proposed for cooperative localization according to the relative positions between robots. And to further improve the efficiency of cooperative localization, a decision theory based mechanism is proposed to make the robots cooperate actively during the localization process. Since stably tracking the multi-hypothesis of the robots' own position and their partners' position is of great importance for making a good decision of where to go in active localization, the co-evolution based adaptive Monte Carlo localization method in which samples are clustered into species to represents a hypothesis of robot's pose in a higher level than a single sample is adopted. Experiments are designed and carried out to prove the efficiency and stability of the proposed method

A Method for Active Global Localization in Multi-robot System

In multi-robot system the ability to exchange information can reduce the uncertainty in the estimated location when robots can see each other. In this paper, a kind of dynamically evolving coordination architecture is proposed for cooperative localization according to the relative positions between robots. And to further improve the efficiency of cooperative localization, a decision theory based mechanism is proposed to make the robots cooperate actively during the localization process. Since stably tracking the multi-hypothesis of the robots' own position and their partners' position is of great importance for making a good decision of where to go in active localization, the co-evolution based adaptive Monte Carlo localization method in which samples are clustered into species to represents a hypothesis of robot's pose in a higher level than a single sample is adopted. Experiments are designed and carried out to prove the efficiency and stability of the proposed method

Orthogonal Analysis and Numerical Simulation of Rock Mechanics Parameters in Stress Field of Shaft Heading Face

This paper focuses on improving the blasting effect of the drilling and blasting method in the deep rock mass and solves the problems of blasthole collapse and misfire accident in the process of drilling and blasting construction of heading face. FEM software, ABAQUS, is used to simulate the stress distribution around the blasthole by extending a certain depth in the vertical direction of the shaft heading face. The sensitivity of different depths, different heading face sizes, and different lithologies on the horizontal stress distribution is analyzed by using a six-factor four-level orthogonal analysis method. The results show that the change of the radius of the heading face has the most considerable influence on the distance of the distressed zone and the stress concentration zone, followed by the lithology and the excavation depth. Also, the excavation depth has the most significant influence on the peak stress value. Through the industrial field experiment, the in situ stress of the shaft heading face is tested, and the numerical simulation results are consistent with the field monitoring results. The results reveal the law of stress distribution near the heading face, which can provide some reference for the design of blasthole depth in the drilling and blasting construction scheme

The Research of Motion Planning of Humanoid Robot

Abstract: This paper proposed a strategy for humanoid robot motion planning using GA-based fuzzy neural network controller, which is stable self-learning fuzzy neural networks control system. The system is composed of two parts: (1) A FNNC which use GA to search optimal fuzzy rules and membership function; (2) A supervisor which use gradient learning algorithm to train the network weights. And we apply this controller to robot motion planning. The simulation result shows its effectiveness

Insights on genetic characterization and pathogenesis of a GI-19 (QX-like) infectious bronchitis virus isolated in China

ABSTRACT: Infectious bronchitis virus (IBV) causes respiratory diseases in chickens, incurring great losses to the poultry industry worldwide. In this study, we isolated an IBV strain, designated as AH-2020, from the chickens vaccinated with H120 and 4/91 in Anhui, China. The sequence homology analysis based on the S1 gene revealed that AH-2020 shares low similarities with the 3 vaccine strains, namely, H120, LDT3-A, and 4/91 (78.19, 80.84, and 81.6%, respectively). Phylogenetic analysis based on the S1 gene revealed that AH-2020 clustered with the GI-19 type. Furthermore, protein modeling revealed that the mutations in the amino acids in AH-2020 were mainly located in the N-terminal domain of S1 (S1-NTD), and the pattern of deletion and insertion mutations in the S1 protein may have influenced the structural changes on the surface of S1. Further, approximately 7-day-old SPF chickens were inoculated with AH-2020 at 106.0 EID50. These chickens exhibited clinical signs of the infection such as listlessness, huddling, and head-shaking, accompanied by depression and 40% mortality. Serum antibody test demonstrated that in response to the AH-2020 infection, the antibody level increased the fastest at 7 dpi, with virus shedding rate of cloaca being 100% at 14 dpi. The viral titer in various tissues was detected using hematoxylin and eosin staining and immunohistochemistry, which revealed that AH-2020 infection can damage the kidney, trachea, lung, cecal tonsil, and bursa of Fabricius. Our study provided evidence that the GI-19-type IBV is undergoing more complex mutations, and effective measures are urgently needed to prevent the spread of these variant strains

Ginsenoside Rk3 Inhibits the Extramedullary Infiltration of Acute Monocytic Leukemia Cell via miR-3677-5p/CXCL12 Axis

Background. Acute monocytic leukemia belongs to type M5 of acute myeloid leukemia (AML) classified by FAB, which appears a high incidence of extramedullary infiltration (EMI) and poor prognosis. In this study, we observed the inhibitory effect of ginsenoside Rk3 on the EMI of monocytic leukemia cells and initially explored its related mechanism of targeting the miR-3677-5p/CXCL12 axis. Methods. The MTT assay and colony formation assay were used to detect the inhibitory effect of Rk3 on proliferation. Both cellular migration and invasion were observed by the Transwell assay. The expression levels of miR-3677-5p, CXCL12, and CXCR4 were detected by RT-qPCR and Western blot, as well as overexpression of miR-3677-5p by transfected with lentivirus and detection of a dual luciferase reporter gene. The expression of MMP2 and TIMP2 was detected by immunofluorescence. Results. Rk3 effectively inhibits the proliferation, migration, and invasion associated with EMI of leukemia. The leukemia cells of M5 patients with EMI showed low expression of miR-3677-5p but high expression of the mRNA of CXCL12 and CXCR4. Overexpression of miR-3677-5p or intervention of CXCL12 effectively inhibited the proliferation, migration, and invasion of SHI-1 cells. The luciferase assay showed that CXCL12 was the downstream target gene of miR-3677-5p. After overexpression of miR-3677-5p or intervention of CXCL12 in combination with Rk3, the inhibitory effect on the proliferation, migration, and invasion of SHI-1 cells was more obvious. Importantly, Rk3 significantly regulated the expression levels of miR-3677-5p, CXCL12, CXCR4, and EMI-related functional proteins including MMP2 and TIMP2. Overexpression of miR-3677-5p or intervention of CXCL12 also regulated the expression of MMP2 and TIMP2. Conclusions. The leukemia cells of M5 patients with EMI appeared to have low expression of miR-3677-5p and high expression of the mRNA of CXCL12 and CXCR4, which may be used as indicators of EMI and poor prognosis. Rk3 is effective in inhibiting the EMI of SHI-1 cells by targeting the miR-3677-5p/CXCL12 axis

A Facile Hydrothermal Synthesis and Resistive Switching Behavior of α-Fe₂O₃ Nanowire Arrays

A facile hydrothermal process has been developed to synthesize the α-Fe2O3 nanowire arrays with a preferential growth orientation along the [110] direction. The W/α-Fe2O3/FTO memory device with the nonvolatile resistive switching behavior has been achieved. The resistance ratio (RHRS/RLRS) of the W/α-Fe2O3/FTO memory device exceeds two orders of magnitude, which can be preserved for more than 103s without obvious decline. Furthermore, the carrier transport properties of the W/α-Fe2O3/FTO memory device are dominated by the Ohmic conduction mechanism in the low resistance state and trap-controlled space-charge-limited current conduction mechanism in the high resistance state, respectively. The partial formation and rupture of conducting nanofilaments modified by the intrinsic oxygen vacancies have been suggested to be responsible for the nonvolatile resistive switching behavior of the W/α-Fe2O3/FTO memory device. This work suggests that the as-prepared α-Fe2O3 nanowire-based W/α-Fe2O3/FTO memory device may be a potential candidate for applications in the next-generation nonvolatile memory devices