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.     

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.     

Optimal configuration for the self-identification of a two-dimensional variable geometry truss

This study addresses the optimal changes in geometry of a two-dimensional variable geometry truss (VGT) to identify the stiffness matrix of the truss using the concept of self-identification. The optimization of the geometry changing of the VGT is a problem of selecting the optimal combination of multiple design variables from a large number of candidate sets. This study proposes a simple optimization method for determining a set of optimal geometric parameters; in this method, the approximated mode shape matrix obtained using spline interpolation techniques is used to calculate the objective function for self-identification. The objective function used in this paper is a function of the condition number of the coefficient matrix of a linear matrix equation and a criterion for self-identification. The proposed algorithm can be used to reduce the number of actual vibration tests required for measuring the mode shapes and modal frequency while it maximizes the objective function. Numerical experiments are conducted to investigate the relationship between the convergence characteristics of the optimization and the target vibration modes. The effectiveness of the optimized geometry changing is verified by comparing the identification error for the uniform geometry changing, the optimized one for the three lower modes of the VGT, and the one found by a classical QR decomposition. Furthermore, the numerical results show that the identification sensitivity with respect to noisy data is reduced by the optimization.     

Shape Reconstruction and Camera Self-Calibration Using Cast Shadows and Scene Geometries

Recently, various techniques of shape reconstruction using cast shadows have been proposed. These techniques have the advantage that they can be applied to various scenes, including outdoor scenes, without using special devices. Previously proposed techniques usually require calibration of camera parameters and light source positions, and such calibration processes limit the range of application of these techniques. In this paper, we propose a method to reconstruct 3D scenes even when the camera parameters or light source positions are unknown. The technique first recovers the shape with 4-DOF indeterminacy using coplanarities obtained by cast shadows of straight edges or visible planes in a scene, and then upgrades the shape using metric constraints obtained from the geometrical constraints in the scene. In order to circumvent the need for calibrations and special devices, we propose both linear and nonlinear methods in this paper. Experiments using simulated and real images verified the effectiveness of this technique.     

Ergonomic design and evaluation of the handle for an endoscopic dissector

The purpose of this study was to design an endoscopic dissector handle and objectively assess its usability. The handles were designed with increased contact area between the fingers and thumb and the eye rings, and the eye rings were modified to have a more perpendicular insertion angle to the finger midline. Four different handle models were compared, including a conventional product. Subjects performed dissection, exclusion, grasping, precision manipulation and precision handling tasks. Electromyography and subjective evaluations were measured. Compared to conventional handles, the designated handle reduced the muscle load in the extensor and flexor muscles of the forearm and increased subjective stability. The activity of the first dorsal interosseous muscle was sometimes influenced by the shape of the other parts. The ergonomically designed endoscopic dissector handle used in this study achieved high usability. Medical instrument designs based on ergonomic concepts should be assessed with objective indices.

Practitioner Summary: The endoscopic dissector handles were designed with increased contact area and more suitable insertion angle between the fingers and thumb and the eye rings. Compared to conventional handles, the designated handle reduced the muscle load in the extensor and flexor muscles of the forearm and increased subjective stability.     

Descent three-term conjugate gradient methods based on secant conditions for unconstrained optimization

The conjugate gradient method is an effective method for large-scale unconstrained optimization problems. Recent research has proposed conjugate gradient methods based on secant conditions to establish fast convergence of the methods. However, these methods do not always generate a descent search direction. In contrast, Y. Narushima, H. Yabe, and J.A. Ford [A three-term conjugate gradient method with sufficient descent property for unconstrained optimization, SIAM J. Optim. 21 (2011), pp. 212–230] proposed a three-term conjugate gradient method which always satisfies the sufficient descent condition. This paper makes use of both ideas to propose descent three-term conjugate gradient methods based on particular secant conditions, and then shows their global convergence properties. Finally, numerical results are given.     

Gender differences in hand stability of normal young people assessed at low force levels

To examine gender differences in hand stability, finger position and force holding tasks at low force levels were conducted with 30 male and 30 female young adults. Total fluctuation was defined as the standard deviation of measured data and fluctuation and the 10-Hz component of the physiological tremor were compared between maleand female subjects. In all tasks, the total fluctuation and the 10-Hz tremor were significantly larger in male subjects than females. On average, the fluctuation was 1.3 times larger and the 10-Hz tremor was 1.6 times larger. The results of this study suggest that women have superior hand stability compared with men at low force levels. Finger length, maximal voluntary contraction and surface electromyography were also measured and factors related to gender differences in hand stability are discussed. STATEMENT OF RELEVANCE: Hand stability is crucial for precise manual operations. This study demonstrated gender differences in hand steadiness at low force levels. Though hand dexterity cannot be explained only by hand stability, the results of this study are useful not only for occupational aptitude tests but also for neuropsychological tests.