It has been postulated that one of the biggest impediments to a successful chemotherapy is the phenomena of multidrug resistance (MDR) in cancer cells. One of the main mechanisms of MDR is overexpression of the ATP-binding cassette (ABC) transporters in cancer cells which alters absorption, distribution, metabolism, and excretion of various chemotherapeutic drugs. Efforts have been made to find effective inhibitors of ABC transporters. However, none has been approved clinically. This study shows that a novel compound 3-chloro-N-(2-hydroxyphenyl)-4-(3,3,3-trifluoro-2-hydroxy-2-methylpropanamido) benzamide (compound 7d), one of the 2-trifluoromethyl-2-hydroxypropionamide derivatives could reverse ABCG2 (BCRP)-mediated MDR. Cytotoxicity studies show that compound 7d sensitizes the ABCG2-overexpressing cells to chemotherapeutic drugs mitoxantrone and SN-38, which are well-established substrates of the ABCG2 transporter. Western blotting results indicate that compound 7d does not significantly alter the protein level of the ABCG2 transporter. Accumulation and efflux studies demonstrate that compound 7d increases intracellular accumulation of mitoxantrone by inhibiting the function of ABCG2. Overall, these findings indicate a potential use for compound 7d as an adjuvant agent for chemotherapy to inhibit the function of the clinically relevant ABC transporter and sensitize tumor cells to chemotherapeutic drugs. J. Cell. Biochem. 118: 2420-2429, 2017. © 2017 Wiley Periodicals, Inc.

Cancer is a disease whose treatment is often limited due to the development of a phenomenon known as multidrug resistance (MDR). There is an immense demand for development of novel agents that can overcome the MDR in cancer. A group of transmembrane proteins called ATP-binding cassette transporters, present ubiquitously in the human body possesses a modular architecture, contributing immensely towards the development of MDR. An analysis of structural congeners among a group of compounds led to the discovery of CCTA-1523 that could selectively reverse ABCG2-mediated MDR in cancer cells in vitro and in vivo. CCTA-1523 (5 μM) sensitized the ABCG2 overexpressing cancer cells and ABCG2 transfected cells to the substrate chemotherapeutic drugs. The reversal ability of CCTA-1523 was primarily due to the inhibition of the efflux function of ABCG2; also there was no change in the protein expression or the localization of the ABCG2 in the presence of CCTA-1523. The reversal effect of CCTA-1523 was reversible. Importantly, co-administration of CCTA-1523 restored the in vivo antitumor activity of doxorubicin in ABCG2 overexpressing tumor xenografts. Taken together, our findings indicate that CCTA-1523 is a potent, selective and reversible modulator of ABCG2 that may offer therapeutic promise for multidrug- resistant malignancies.

In the actual complex scenes, multi-feature fusion has become a valid method of object representation for tracking video motion targets. Two keys about multi-feature fusion are how to select some valid features and how to fuse the features. In this paper, we propose an object representation fusing global and local features for object tracking. In our method, we select a common hue histogram as the global feature and use a valid SIFT feature as the local feature. In the tracking frame of particle filter, the tracking results show that our proposed object representation can better restrain the disturbing of complex environments with abrupt illumination and partial occlusion, than color-based global representation.

In the field about multi-agent system, the payoff rationality is an important factor for the forming of a multi-agent coalition structure. In this paper, we regard a payoff vector belonging to the bargaining set in classical cooperative game as a stable payoff vector of multi-agents. Then, we propose an approach to find the stable payoff vector based on genetic algorithm. Finally, the experimental results and analysis are showed about success rates and running times of our proposed approach.

Multi-choice games provide a mathematic model for the complex interactions among the rational agents which have several activity levels, based on the fuzzy set theory. For obtaining the stable payoff vectors, this paper extends the core, the dominance core and the bargaining set to the multi-choice games with coalition structure. And then we prove that the core is a subset of the dominance core, that both the core and the dominance core are two subsets of the bargaining set, and that the bargaining set is existent.

A convenient one-pot synthesis of enantiopure (R)-2-amino-3,3,3-trifluoro-2-methyl-N-phenylpropanamide derivatives has been developed. The key step in this synthetic methodology turned out to be the amide formation in which (R)-2-amino-3,3,3-trifluoro-2-methylpropanoic acid hydrochloride was simultaneously protected and activated by Vilsmeier reagent.

In the field about the intersection of game theory and decision making, it is a hot concern how to obtain stable payoff vectors. In this paper, we first extend the solution of bargaining set in classical cooperative game to multi-choice games with coalition structure. The extended bargaining set is a generalization of the classical bargaining set. Then we give an approach to find a stable payoff vector belonging to the extended bargaining set, based on genetic algorithm. Finally, we give some experiments to find a stable payoff vector by our proposed algorithm and evaluate the finding algorithm.

In many actual application fields, solution concepts and their relationships in multi-choice games play important roles. For obtaining stable payoff vectors in multi-choice game, we extend several key solutions about bargaining set, kernel and nucleolus in classical cooperative game to multi-choice games with coalition structure, considering that multi-choice game is commonly with coalition structure. The extended bargaining set, kernel and nucleolus are generalizations to them in classical cooperative game. Furthermore, we deduce many relationships, that the kernel is a subset of the bargaining set, that the nucleolus is a subset of the kernel, that the nucleolus is existent and unique, and that the kernel and the bargaining set are existent.

For the data-intensive scientific workflows, large mount of data need to be stored and often been distributed into several data centers. So the data movements between different data centers become inevitable when the application executed. The more time the data movements, the less efficiency of the data-intensive application. This paper proposed a data placement method based on Bayesian network for data-intensive scientific workflows, which could effectively reduce the data movement time between different data centers. The validity of this method is discussed and illustrated by experiment.

In a specific domain, the attributes or mutual relationships connected with realistic objects are often variable dynamically and especially partially. For multi-objective categorization [2], it has been a research hotspot how to rapidly update the categorized result with the partial variations. Aiming at this problem, we propose an approach for dynamic multi-objective categorization based on the game theory, partially updating the influenced part, measuring the object's satisfaction degree by Shapley value, and improving the efficiency of calculating Shapley value by the concept of priority groups. The experimental results and the performance analyses show its better efficiency and effectiveness.

Our earlier research has shown that mono-substituted N-phenyl-2, 2-dichloroacetamide exhibited much higher anti-cancer activity than the lead compound sodium dichloroacetate (DCA). In this paper, a variety of multi-substituted N-phenyl-2, 2-dichloroacetamides were synthesized and biologically evaluated. The results showed that 3, 5-disubstituted N-phenyl-2, 2-dichloroacetamide analogues had satisfactory potency. Among them, N-(3, 5-diiodophenyl)-2, 2-dichloroacetamide had an IC50 of 2.84 micromol x L(-1) against non-small cell lung cancer cell line A549 and could induce cancer cell apoptosis.

A current study shows that sodium dichloroacetate (DCA) can induce cancer cell apoptosis and inhibit tumor growth, but its cytotoxic activity is low (IC50 > 1000 μM for A549). In this paper, a variety of DCA derivatives were synthesized, and their cytotoxic activities were evaluated. The result showed that the N-phenyl-2,2-dichloroacetamide analogues had satisfactory potencies. Among them, N-(3-iodophenyl)-2,2-dichloroacetamide (3e), an optimized lead compound, has an IC50 against A549 as low as 4.76 μM. Furthermore, it can induce cancer cell apoptosis and has a low toxicity in mice (LD50 = 1117 mg/kg).

Numerical simulation of transient mass transfer to a single drop controlled by the internal resistance or by the resistance in both phases was mathematically formulated and simulated in a boundary-fitted orthogonal coordinate system. The simulated results on the transient mass transfer dominated by the internal resistance are in good agreement with the Newman and Kronig-Brink models for drops with low Reynolds number. When the drop Reynolds number is up to 200, the mass transfer coefficient from numerical simulation is very low as compared with the Handlos-Baron model. The cases with mass transfer resistance residing in both the continuous and drop phases were simulated successfully and compared with the experimental data in three extraction systems recommended by European Confederation of Chemical Engineering (EFCE). For single drops with Re < 200, the numerically predicted values of the extraction fraction and overall mass transfer coefficient are in reasonable coincidence with the experimental data. It is concluded that the numerical simulation can be resorted in some cases of solvent extraction for conducting numerical experiments and parametric study. Nevertheless, for better resolution as higher Reynolds number drops are simulated, more sophisticated techniques should be developed and incorporated to deal with the large deformation and transient shape oscillation as well as possible Marangoni effect.

For the mass transfer to single drops during the stage of steady buoyancy-driven motion, experimental measurement is complicated with the terminal effect of additional mass transfer during drop formation and coa lescence at the drop collector. Analysis reveals that consistent operating conditions and experimental procedure are of critical significance for minimizing the terminal effect of drop coalescence on the accuracy of mass transfer measurements. The novel design of a totally-closed extraction column is proposed for this purpose, which guaran tees that the volumetric rate of drop phase injection is exactly equal to that of withdrawal of drops. Tests in two extraction systems demonstrate that the experimental repeatability is improved greatly and the terminal effect of mass transfer during drop coalescence is brought well under control.