The effect of small dose of topiroxostat on serum uric acid in patients receiving hemodialysis

Introduction : Topiroxostat, a recently developed xanthine oxidase inhibitor, is expected to have fewer adverse effects than allopurinol because it has different mechanism of action from alloprinol. However, its dosage, usage and safety have not been established in patients with impaired renal function or those undergoing dialysis at the development since no studies was conducted in these patients. Methods : Cross over clinical trial using 3 months of allopurinol and topiroxostat on 27 maintain Japanese HD patients were carried out. The effects on oxidative stress status of both drugs were also evaluated by measuring oxidation reduction potential. Findings : Twenty‐five of twenty‐seven patients completed study. The mean serum uric acid levels in the topiroxostat‐treated arm was significantly lower than it in the allopurinol‐treated arm time‐dependently (P < 0.0001). Corrected oxidative stress ratio defined as biological antioxidant potential/diacron reactive oxygen metabolites was significantly increased in topiroxostat‐arm (*P = 0.0035), but not in allopurinol‐arm (P = 0.1429). No significant difference was seen in diacron reactive oxygen metabolites, biological antioxidant potential, static oxidation‐reduction potential, and capacity oxidation‐reduction potential between pre and post treatment of both drugs. Discussion : It is suggested that a low dose of topiroxostat decreased serum uric acid sufficiently to maintain it below 7.0 mg/dL in patients receiving hemodialysis.     

Fractal analysis of the surface cracks on continuously cast steel slabs

Data concerning the length of longitudinal cracks on the surface of continuously cast steel slabs were collected from two plants. The data were analyzed to find the relation between crack length and crack frequency. The analysis revealed the following.

Studies of 2D Cryocrystals by STM Techniques

Scanning tunneling microscopy (STM) studies of two-dimensional (2D) cryocrystals ⁴ He, Kr, Xe) physisorbed on graphite surfaces are presented. Individual helium atoms, usually thought to be invisible with STM, were recently observed on graphite surfaces at a density corresponding to the commensurate solid. Here we show that a local elastic deformation seems to be the principal mechanism responsible to render the atoms visible. Recent tight-binding calculations of the local density of states (LDOS) of graphite which predict the appearance of an energy gap support this picture. I-z curve measurements for the case of ⁴ He show a sharp drop (increase) of the tunneling current I at a certain tip-surface distance z during retraction (approach) of the tip. This drop (increase) may be associated with the tunneling of a single He adatom, opening new possibilities to study the quantum tunneling of atoms via STM.     

3He Melting Pressure Measurements in High Magnetic Fields

Experimental methods and preliminary results of high-precision measurements of the ³ He melting curve in high magnetic fields have been described. The purpose of this work is twofold. One is to establish a reliable millikelvin temperature scale in high fields (T 10 mK, B 15 T), The other is to investigate a high field region of the magnetic phase diagram of solid ³ He by measuring the melting pressure down to temperatures below 1 mK. Besides the two superfluid transitions, the phase transition temperatures between the spin ordered solid and the paramagnetic solid, T _HFP , were determined at B = 12 and 10 T with good accuracy, which is an extension of previous measurements up to 8 T. The present T _HFP (B) line can not be scaled to that at a higher density with a single Grüneisen parameter, indicating a variation of density dependencies of the multiple-spin exchange interactions.     

A Hilbert warping method for handwriting gesture recognition

We propose a novel sequence alignment algorithm for recognizing handwriting gestures by a camera. In the proposed method, an input image sequence is aligned to the reference sequences by phase-synchronization of analytic signals which are transformed from original feature values. A cumulative distance is calculated simultaneously with the alignment process, and then used for the classification. A major benefit of this method is that over-fitting to sequences of incorrect categories is restricted. The proposed method exhibited higher recognition accuracy in handwriting gesture recognition, compared with the conventional dynamic time warping method which explores optimal alignment results for all categories.     

The effects of amino-acid mutations on specific interactions between urokinase-type plasminogen activator and its receptor: Ab initio molecular orbital calculations

During cancer invasion, the binding of urokinase-type plasminogen activator (uPA) to its receptor (uPAR) on the surface of a cancer cell is considered a trigger for invasion. Here, we present a stable structure of the solvated complex formed between uPA and uPAR (uPA-uPAR) and investigate the specific interactions between uPA and uPAR by ab initio fragment molecular orbital (FMO) calculations. The result indicates that the electrostatic interactions between the charged amino acid residues existing in both uPA and uPAR make a large contribution to the binding between uPA and uPAR. In particular, Lys23, Lys46, Lys98 and Lys61 of uPA are found to have strong attractive interactions with uPAR. To elucidate the effect of these residues on the interactions between uPA and uPAR, we substituted each of them with the uncharged amino acid Leu and investigated the interactions between the mutated uPA and wild-type uPAR. The interaction energies indicate that Lys46 and Lys98, which bind uPA to the rim of the central ligand-binding cavity of uPAR, make greater contributions to the binding between uPA and uPAR than Lys23, which is positioned at the bottom of the ligand-binding cavity of uPAR. The effect of hydrating water molecules located between uPA and uPAR is also investigated to be significant for the specific interactions between uPA and uPAR. These results are expected to be informative for developing new peptide antagonists that block the binding of uPA to uPAR.     

Automatic detection of the topographical distribution of EEG rhythms based on an iterative adjustment of the averaged reference potential

Electroencephalogram (EEG) interpretation is important for the investigation of brain diseases. In this study, an automatic technique was developed to detect the topographical distribution of EEG rhythms. In order to obtain the topographical distribution, the amplitude of the EEG rhythm was analyzed based on the referential derivation where the reference potential was adjusted iteratively. The result of the automatic detection of the topographical distribution was helpful in highlighting the EEG rhythms of interest for automatic EEG interpretation. The technique developed has application significance for real clinics.     

Hybrid Petri net based modeling for biological pathway simulation

Hybrid Petri net (HPN) is an extension of the Petri net formalism, which enables us to handle continuous information in addition to discrete information. Firstly, this paper demonstrates how biological pathways can be modeled by the integration of discrete and continuous elements, with an example of the λ phage genetic switch system including induction and retroregulation mechanisms. Although HPN allows intuitive modeling of biological pathways, some fundamental biological processes such as complex formation cannot be represented with HPN. Thus, this paper next provides the formal definition of hybrid functional Petri net with extension (HFPNe), which has high potential for modeling various kinds of biological processes. Cell Illustrator is a software tool developed on the basis of the definition of HFPNe. Hypothesis creation by Cell Illustrator is demonstrated with the example of the cyanobacterial circadian gene clock system. Finally, our ongoing tasks, which include the development of a computational platform for systems biology, are presented.     

A Linear-Time Algorithm for Symmetric Convex Drawings of Internally Triconnected Plane Graphs

We study a crossing minimization problem of drawing a bipartite graph with a radial drawing of two orbits. Radial drawings are one of well-known drawing conventions in social network analysis and visualization, in particular, displaying centrality indices of actors (Wasserman and Faust, Social Network Analysis: Methods and Applications. Cambridge University Press, Cambridge, 1994). The main problem in this paper is called the one-sided radial crossing minimization, if the positions of vertices in the outer orbit are fixed. The problem is known to be NP-hard (Bachmaier, IEEE Trans. Vis. Comput. Graph. 13, 583–594, 2007), and a number of heuristics are available (Bachmaier, IEEE Trans. Vis. Comput. Graph. 13, 583–594, 2007). However, there is no approximation algorithm for the crossing minimization problem in radial drawings. We present the first polynomial time constant-factor approximation algorithm for the one-sided radial crossing minimization problem.