Free energy perturbation approach for the rational engineering of the antibody for human hepatitis B virus

HzKR127 is the humanized monoclonal antibody effective for the neutralization of human hepatitis B virus. By means of the free energy perturbation (FEP) calculations based on molecular dynamic (MD) simulations, we examine the mutation-induced variations in the energetic and structural features associated with the interactions between HzKR127 and its antigen. N58A, Y96A, D97A, and D97A/Y102A mutants of HzKR127 are taken in account in this study for which the experimental data for relative efficacies with respect to the wild-type antibody are available. The results of the present MD-FEP simulation studies show that in order to enhance the affinity for the antigen, the engineering of HzKR127 should be made in such a way as to promote the dynamic stability of the overall protein conformation and that of the translational motion of the antigen in the antibody-antigen complex. The relative binding free energies of the four mutant antibodies obtained from MD-FEP calculations compare pretty well with the experimental mutagenesis data with the associated squared correlation coefficient of 0.96. This indicates that MD-FEP calculations may serve as a useful computational tool for rational antibody engineering. Discussed in detail are the differences in the structural features of antibody-antigen interactions between the wild-type and the mutant antibodies that are responsible for the change in binding affinities for the antigen.     

Credible sets for risk ratios in over-reported two-sample binomial data using the double-sampling scheme

We consider point and interval estimation for risk ratios based on two independent samples of binomial data subject to false positive misclassification. For such data it is well known that the model is unidentifiable. We consider incorporating training data obtained by using a double-sampling scheme to make the model identifiable. In this identifiable model, we propose a Bayesian method to make statistical inferences. In particular, we derive an easy-to-implement closed-form algorithm for drawing from the posterior distributions. The algorithm is illustrated using a real data example and further examined via Monte Carlo simulation studies.     

Improving traversability of quadruped walking robots using body movement in 3D rough terrains

This paper presents a study on improving the traversability of a quadruped walking robot in 3D rough terrains. The key idea is to exploit body movement of the robot. The position and orientation of the robot are systematically adjusted and the possibility of finding a valid foothold for the next swing is maximized, which makes the robot have more chances to overcome the rough terrains. In addition, a foothold search algorithm that provides the valid foothold while maintaining a high traversability of the robot, is investigated and a gait selection algorithm is developed to help the robot avoid deadlock situations. To explain the algorithms, new concepts such as reachable area, stable area, potential search direction, and complementary kinematic margin are introduced, and the effectiveness of the algorithms is validated via simulations and experiments.     

Distraction 'on the buses': a novel framework of ergonomics methods for identifying sources and effects of bus driver distraction

Driver distraction represents a significant problem in the public transport sector. Various methods exist for investigating distraction; however, the majority are difficult to apply within the context of naturalistic bus driving. This article investigates the nature of bus driver distraction at a major Australian public transport company, including the sources of distraction present, and their effects on driver performance, through the application of a novel framework of ergonomics methods. The framework represents a novel approach for assessing distraction in a real world context. The findings suggest that there are a number of sources of distraction that could potentially distract bus drivers while driving, including those that derive from the driving task itself, and those that derive from the additional requirements associated with bus operation, such as passenger and ticketing-related distractions. A taxonomy of the sources of bus driver distraction identified is presented, along with a discussion of proposed countermeasures designed to remove the sources identified or mitigate their effects on driver performance.     

Investigation of point-to-point performance test of touch trigger probes on coordinate-measuring machines

A major factor contributing to the total measuring error of coordinate measuring machines (CMMs) is the performance of the probing sub-system. Probing test methods are typically used to detect errors due to the probing sub-system. The probe performance evaluation method specified in the ANSI B89 standard is investigated in this paper. The sampling plan associated in the probe performance evaluation was tested by using experimental probing data from a CMM. Research findings indicate that the performance of touch trigger probes is overestimated due to a systematic bias in the vertical direction of the best-fit reference ball center in the probe performance test. A two-latitude sampling plan synthesis method based on a pretravel model for touch trigger probes is proposed in this paper. The proposed method can be used to accurately identify the reference ball center in the performance test of touch trigger probes.     

CQI and technology: partnership drives improvement

CQI plus technology equals increased financial success, according to Parkview Episcopal Medical Center. For this Pueblo, Colo., community hospital, the results of this equation are impressive--time saved, a motivated workforce and last but not least, more revenue.