Towards understanding the mechanism of action of the multidrug resistance-linked half-ABC transporter ABCG2: a molecular modeling study

The ATP-binding cassette protein ABCG2 is a member of a broad family of ABC transporters with potential clinical importance as a mediator of multidrug resistance. We carried out a homology and knowledge-based, and mutationally improved molecular modeling study to establish a much needed structural framework for the protein, which could serve as guidance for further genetic, biochemical, and structural analyses. Based on homology with known structures of both full-length and nucleotide-binding domains (NBD) of ABC transporters and structural knowledge of integral membrane proteins, an initial model of ABCG2 was established. Subsequent refinement to conform to the lipophilic index distributions in the transmembrane domain (TMD) and to the results of site-directed mutagenesis experiments led to an improved model. The complete ABCG2 model consists of two identical subunits facing each other in a closed conformation. The dimeric interface in the nucleotide-binding domain (NBD) involves a characteristic nucleotide sandwich and the interface in the TMD consists of the TM helices 1–3 of one subunit and the helices 5 and 6 of the other. The interface between the NBD and the TMD is bridged by the conserved structural motif between TM2 and TM3, the intracellular domain 1 (ICD1), and the terminal β-strand (S6) of the central β-sheet in the NBD. The apparent flexibility of the ICD1 may play a role in transmitting conformational changes from the NBD to the TMD or from the TMD to the NBD.     

Generating Instances for MAX2SAT with Optimal Solutions

A test instance generator (an instance generator for short) for MAX2SAT is a procedure that produces, given a number n of variables, a 2-CNF formula F of n variables (randomly chosen from some reasonably large domain), and simultaneously provides one of the optimal solutions for F. We propose an outline to design an instance generator using an expanding graph of a certain type, called here an "exact 1/2-enlarger". We first show a simple algorithm for constructing an exact 1/2-enlarger, thereby deriving one concrete polynomial-time instance generator GEN. We also show that an exact 1/2-enlarger can be obtained with high probability from graphs randomly constructed. From this fact, we propose another type of instance generator RGEN; it produces a 2-CNF formula with a solution which is optimal for the formula with high probability. However, RGEN produces less structured formulas and a much larger class of formulas than GEN. In fact, we prove the NP-hardness of MAX2SAT over the set of 2-CNF formulas produced by RGEN.     

A Dynamic Motion Control Technique for Human-like Articulated Figures

This paper presents a dynamic motion control technique for human-like articulated figures in a physically based character animation system. This method controls a figure such that the figure tracks input motion specified by a user. When environmental physical input such as an external force or a collision impulse are applied to the figure, this method generates dynamically changing motion in response to the physical input. We have introduced comfort and balance control to compute the angular acceleration of the figure's joints. Our algorithm controls the several parts of a human-like articulated figure separetely through the minimum number of degrees-of-freedom. Using this approach, our algorithm simulates realistic human motions at efficient computational cost. Unlike existing dynamic simulation systems, our method assumes that input motion is already realistic, and is aimed at dynamically changing the input motion in real-time only when unexpected physical input is applied to the figure. As such, our method works efficiently in the framework of current computer games.     

Strength Analysis of Yttria-Stabilized Tetragonal Zirconia Polycrystals

Tensile strength of Y₂O₃-stabilized ZrO₂ polycrystals (Y-TZP) was measured by a newly developed tensile testing method with a rectangular bar. The tensile strength of Y-TZP was lower than that of the three-point bend strength, and the shape of the tensile strength distribution was quite different from that of the three-point bend strength distribution. It was difficult to predict the distribution curve of the tensile strength using the data of the three-point bend strength by one-modal Weibull distribution. The distribution of the tensile strength was analyzed by two- or three-model Weibull distribution coupled with an analysis of fracture origins. The distribution curve of the three-point bend strength which was estimated by multimodal Weibull distribution agreed favorably with that of the measured three-point bend strength values. A two-modal Weibull distribution function was formulated approximately from the distributions of the tensile and three-point bend strengths, and the estimated two-modal Weibull distribution function for the four-point bend strength agreed well with the measured four-point bend strength.     

Agglomeration control of hydroxyapatite nano-crystals grown in phase-separated microenvironments

Materials synthesis processes that require high temperatures consume large quantities of energy that generate an environmental burden. We attempted to synthesize hydroxyapatite (HAp) nano-crystals without firing or melting. “Water in oil” (W/O) emulsions were employed as microreactors for HAp formation. The surfactant-bounded water mediated HAp crystal nucleation, and HAp nano-crystallites were obtained. The obtained particles were aggregates composed of plate-like nano-crystals and monodisperse tiny crystals. Utilization of the W/O emulsions resulted in tunable nucleation frequency and the reactant provision, and yielded HAp nano-crystals with characteristic agglomeration properties.     

Preparation of Laminin-apatite-polymer Composites Using Metastable Calcium Phosphate Solutions

1Introduction Themostimportantrequirementofapercutaneous deviceisthepreventionofbacterialinfectionthroughtheinterfacebetweenthematerialandtheskin.Therefore,a percutaneousdevicehastoadherefirmlytoskintissueandpreventepidermaldowngrowth.Previously,Aokietalp…     

A novel chromatographic separation technique using tertiary pyridine resin for the partitioning of trivalent actinides and lanthanides

A novel chromatographic separation technique using a tertiary pyridine type resin has been applied to the partitioning of the trivalent actinides (An) and lanthanides (Ln) and several successful results have been shown. In an alcoholic hydrochloric acid system, the trivalent An were clearly separated from the Ln, while no such group separation was achieved in an alcoholic nitric acid system. On the other hand, the nitric acid system was more effective for the intragroup (i.e. individual) separation of the trivalent An and the Ln than the hydrochloric acid system. On the basis of these results, a novel concept for the partitioning of the trivalent An and Ln using the present separation technique and its flowchart have been proposed with its advantages and disadvantages.     

Study on Pb-Bi natural circulation phenomena

For the development of 45w%Pb-55w%Bi cooled direct contact boiling water small fast reactor (PBWFR), experimental study on Pb-Bi-water direct contact boiling two-phase flow has been performed using Pb-Bi-water direct contact boiling two-phase flow loop. For stable start-up of the boiling flow operation, Pb-Bi single-phase natural circulation must be realized in a Pb-Bi flow system of the loop before water injection into Pb-Bi. The Pb-Bi flow system consists of a four-heater-pin bundle, a chimney, an upper plenum, a level meter tank, a cooler, and an electromagnetic flow meter. A stable Pb-Bi single-phase natural circulation was realized in the range of flow rate from 1.5 l/min to 4.8 l/min by heating Pb-Bi in the heater-pin bundle with a power up to 7.7 kW. The inlet and outlet temperatures of the heater bundle were in the ranges from 243°C to 278°C, and from 251°C to 278°C, respectively. The natural circulation flow was simulated analytically using one-dimensional flow model including frictional, form and drag forces. Total hydraulic head through the loop were calculated from Pb-Bi densities at measured Pb-Bi temperatures in the loop. It was found that the calculated flow rate agreed well with the measured ones, which indicated the validity of the analytical models.