A graph-theory algorithm for rapid protein side-chain prediction

Fast and accurate side-chain conformation prediction is important for homology modeling, ab initio protein structure prediction, and protein design applications. Many methods have been presented, although only a few computer programs are publicly available. The SCWRL program is one such method and is widely used because of its speed, accuracy, and ease of use. A new algorithm for SCWRL is presented that uses results from graph theory to solve the combinatorial problem encountered in the side-chain prediction problem. In this method, side chains are represented as vertices in an undirected graph. Any two residues that have rotamers with nonzero interaction energies are considered to have an edge in the graph. The resulting graph can be partitioned into connected subgraphs with no edges between them. These subgraphs can in turn be broken into biconnected components, which are graphs that cannot be disconnected by removal of a single vertex. The combinatorial problem is reduced to finding the minimum energy of these small biconnected components and combining the results to identify the global minimum energy conformation. This algorithm is able to complete predictions on a set of 180 proteins with 34342 side chains in <7 min of computer time. The total chi(1) and chi(1 + 2) dihedral angle accuracies are 82.6% and 73.7% using a simple energy function based on the backbone-dependent rotamer library and a linear repulsive steric energy. The new algorithm will allow for use of SCWRL in more demanding applications such as sequence design and ab initio structure prediction, as well addition of a more complex energy function and conformational flexibility, leading to increased accuracy.     

Protein motif extraction with neuro-fuzzy optimization

MOTIVATION: It is attempted to improve the speed and flexibility of protein motif identification. The proposed algorithm is able to extract both rigid and flexible protein motifs. RESULTS: In this work, we present a new algorithm for extracting the consensus pattern, or motif, from a group of related protein sequences. This algorithm involves a statistical method to find short patterns with high frequency and then neural network training to optimize the final classification accuracies. Fuzzy logic is used to increase the flexibility of protein motifs. C2H2 Zinc Finger Protein and epidermal growth factor protein sequences are used to demonstrate the capability of the proposed algorithm in finding motifs. AVAILABILITY: This program is freely available for academic use by request.     

A C++ Template Library for Efficient Forward-Time Population Genetic Simulation of Large Populations

fwdpp is a C++ library of routines intended to facilitate the development of forward-time simulations under arbitrary mutation and fitness models. The library design provides a combination of speed, low memory overhead, and modeling flexibility not currently available from other forward simulation tools. The library is particularly useful when the simulation of large populations is required, as programs implemented using the library are much more efficient than other available forward simulation programs.     

Development of biosensors for cancer clinical testing

Biosensors are devices that combine a biochemical recognition/binding element (ligand) with a signal conversion unit (transducer). Biosensors are already used for several clinical applications, for example for electrochemical measurement of blood glucose concentrations. Application of biosensors in cancer clinical testing has several potential advantages over other clinical analysis methods including increased assay speed and flexibility, capability for multi-target analyses, automation, reduced costs of diagnostic testing and a potential to bring molecular diagnostic assays to community health care systems and to underserved populations. They have the potential for facilitating Point of Care Testing (POCT), where state-of-the-art molecular analysis is carried out without requiring a state-of-the-art laboratory. However, not many biosensors have been developed for cancer-related testing. One major challenge in harnessing the potential of biosensors is that cancer is a very complex set of diseases. Tumors vary widely in etiology and pathogenesis. Oncologists rely heavily on histological characterization of tumors and a few biomarkers that have demonstrated clinical utility to aid in patient management decisions. New genomic and proteomic molecular tools are being used to profile tumors and produce "molecular signatures." These signatures include genetic and epigenetic signatures, changes in gene expression, protein profiles and post-translational modifications of proteins. These molecular signatures provide new opportunities for utilizing biosensors. Biosensors have enormous potential to deliver the promise of new molecular diagnostic strategies to patients. This article describes some of the basic elements of cancer biology and cancer biomarkers relevant for the development of biosensors for cancer clinical testing, along with the challenges in using this approach.     

Kinematics and kinetics of the shoe during human slips

This paper quantified the heel kinematics and kinetics during human slips with the goal of guiding available coefficient of friction (ACOF) testing methods for footwear and flooring. These values were then compared to the testing parameters recommended for measuring shoe-floor ACOF. Kinematic and kinetic data of thirty-nine subjects who experienced a slip incident were pooled from four similar human slipping studies for this secondary analysis. Vertical ground reaction force (VGRF), center of pressure (COP), shoe-floor angle, side-slip angle, sliding speed and contact time were quantified at slip start (SS) and at the time of peak sliding speed (PSS). Statistical comparisons were used to test if any discrepancies exist between the state of slipping foot and current ACOF testing parameters. The main findings were that the VGRF (26.7 %BW, 179.4 N), shoe-floor angle (22.1°) and contact time (0.02 s) at SS were significantly different from the recommended ACOF testing parameters. Instead, the testing parameters are mostly consistent with the state of the shoe at PSS. We argue that changing the footwear testing parameters to conditions at SS is more appropriate for relating ACOF to conditions of actual slips, including lower vertical forces, larger shoe-floor angles and shorter contact duration.     

有氧锻炼对心脏自主神经调节的影响：心率变异性分析结果

为阐明有氧锻炼对心脏自主神经调节功能的影响,以及这种变化与卧位／坐位下体负压（ＬＢＮＰ）作用下的心率调节及立位耐力之间是否有一定联系,用频域、动态谱及非线性指标较全面分析了大学生有氧锻炼６个月前、后心率变异性（ＨＲＶ）的变化。结果表明：常规ＡＲ谱分析的批处理结果只能代表一段时间内ＨＲＶ信号的平均统计特性,方差大,得不出有显著意义的结果。而时变ＡＲ谱则可反映ＬＢＮＰ作用下心迷走撤除及交感激活的动态过程。非线性的β估计得不出有显著意义的结果;但ＡｐＥｎ分析则可敏感地检测出有氧锻炼关联的心率动力学细微变化,且初步揭示ΔＡｐＥｎ与立位耐力变化（ΔＤＮＰ）间显著相关。以上对阐明有氧锻炼对心率动力学调节的影响以及改进ＨＲＶ信号分析工作均有一定意义。     

A methodology for evaluating biocide release rate, surface roughness and leach layer formation in a TBT-free, self-polishing antifouling coating

Due to the forthcoming IMO ban on the use of tributyltin (TBT) antifouling paints, a new generation of TBT-free coatings has been developed that typically contain cuprous oxide and an organic co-biocide. Accurate and reproducible test methods are needed to evaluate the performance and environmental impact of these new coatings. This study investigated a methodology for evaluating TBT-free, AF coatings containing cuprous oxide. A commercially available AF coating underwent rotary immersion testing at 0, 0.51 and 2.05 m s-1. Scanning electron microscopy (SEM) and energy dispersive x-ray (EDX) analysis were used to assess leach layer formation, percentage cuprous oxide by weight and particle size distribution (PSD). Biocide release rates and surface roughness were also measured. An increase in rotary speed caused a spike in Cu2+ release rate after which the release rate stabilised to previous levels. An increase in leach layer thickness was also observed after the rotary speed increase. A model is suggested to account for the observations.     

The impact of football training on motor development in male children

The aim of the study was to determine the effect of football school program and physical education curriculum on changes in the motor abilities of 7- and 8-year-old boys. The study included a sample of 180 boys divided into group 1 (7-year-old boys), subdivided to experimental (n = 40) and control (n = 50) groups, and group 2 (8-year-old boys), subdivided to experimental (n = 40) and control (n = 50) groups. Experimental groups included children attending three training units of football training over a 9-month period, in addition to the conventional physical education curriculum. Control groups included children attending only conventional physical education curriculum. All study subjects underwent testing with a battery of 12 motor tests at the beginning and at the end of the study. Results obtained by discriminative canonic analysis showed no statistically significant between-group difference in motor abilities at the beginning of the study. However, significant differences in favor of experimental groups were recorded at the end of the study. Favorable changes in all motor variables were observed in both experimental and control groups of children from the initial through the final state. These changes were more pronounced in experimental groups. Analysis of variance for difference variables (final to initial measurement) indicated programmed education in the form of football training in addition to regular physical education curriculum to predominantly influence the development of aerobic endurance, agility, speed and flexibility in 7-year-old boys, and of explosive strength, aerobic endurance, flexibility and speed in 8-year-old boys. In the latter, football training led to the formation of a motor complex integrating explosiveness, speed, coordination, endurance and flexibility as a general motor factor determining future quality development in football.     

Flexible Na/K‐Ion Full Batteries from the Renewable Cotton Cloth–Derived Stable,Low‐Cost,and Binder‐Free Anode and Cathode

Flexible Na/K‐ion batteries (NIBs/KIBs) exhibit great potential applications and have drawn much attention due to the continuous development of flexible electronics. However, there are still many huge challenges, mainly the design and construction of flexible electrodes (cathode and anode) with outstanding electrochemical properties. In this work, a unique approach to prepare flexible electrode is proposed by utilizing the commercially available cotton cloth–derived carbon cloth (CC) as a flexible anode and the substrate of a cathode. The binder‐free, self‐supporting, and flexible cathodes (FCC@N/KPB) are prepared by growing Prussian blue microcubes on the flexible CC (FCC). Na/K‐ion full batteries (FCC//FCC@N/KPB) are assembled by using FCC and FCC@N/KPB as anode and cathode, respectively. Electrochemical performance, mechanical flexibility, and practicability of FCC//FCC@N/KPB Na/K‐ion full batteries are evaluated in both coin cells and flexible pouch cells, demonstrating their superior energy‐storage properties (excellent rate performance and cycling stability) and remarkable flexibility (they can work under different bending states). This work provides a new and profound strategy to design flexible electrodes, promoting the development of flexible NIBs/KIBs to be practical and sustainable.     

Real-Time Strategy Game Training: Emergence of a Cognitive Flexibility Trait

Training in action video games can increase the speed of perceptual processing. However, it is unknown whether video-game training can lead to broad-based changes in higher-level competencies such as cognitive flexibility, a core and neurally distributed component of cognition. To determine whether video gaming can enhance cognitive flexibility and, if so, why these changes occur, the current study compares two versions of a real-time strategy (RTS) game. Using a meta-analytic Bayes factor approach, we found that the gaming condition that emphasized maintenance and rapid switching between multiple information and action sources led to a large increase in cognitive flexibility as measured by a wide array of non-video gaming tasks. Theoretically, the results suggest that the distributed brain networks supporting cognitive flexibility can be tuned by engrossing video game experience that stresses maintenance and rapid manipulation of multiple information sources. Practically, these results suggest avenues for increasing cognitive function.     

Developing a Model Driven Approach for engineering applications based on mOSAIC

In many scientific and engineering areas there are emerging software services available over the Web. The reason for deploying such services in the Cloud is either to reduce the operational costs or to support the peaks in their usage profiles. The algorithms employed in such services are usually result of a long term research and technology development work, so it is beneficial to reuse those critical application parts when developing new Cloud applications. This paper investigates the possibilities to introduce a Model Driven Architecture (MDA) for the Cloud computing domain, which would support composition, customization, flexibility, maintenance and reusability of Cloud application components in the particular case of scientific and engineering applications. The underlying middleware technology of choice is the mOSAIC Platform as a Service (PaaS) solution. This choice is motivated by the fact that in mOSAIC a Cloud application consists of loosely coupled components, which are either generic and provide for key resource types needed by an application (computation, storage, communication) or custom made, e.g. based on existing legacy software. The MDA approach is illustrated through the design and operation of an application for analysis of structures under static loading. It is shown that a relatively simple design can be used to address two application bottlenecks: the varying number of users and the computational complexity of the given problem. The design reduces the necessary application development efforts and the key components can be reused for similar applications.     

An Impact Study of the Design of Exergaming Parameters on Body Intensity from Objective and Gameplay-Based Player Experience Perspectives,Based on Balance Training Exergame

Kinect-based exergames allow players to undertake physical exercise in an interactive manner with visual stimulation. Previous studies focused on investigating physical fitness based on calories or heart rate to ascertain the effectiveness of exergames. However, designing an exergame for specific training purposes, with intensity levels suited to the needs and skills of the players, requires the investigation of motion performance to study player experience.This study investigates how parameters of a Kinect-based exergame, combined with balance training exercises, influence the balance control ability and intensity level the player can tolerate, by analyzing both objective and gameplay-based player experience, and taking enjoyment and difficulty levels into account.The exergame tested required participants to maintain their balance standing on one leg within a posture frame (PF) while a force plate evaluated the player''s balance control ability in both static and dynamic gaming modes. The number of collisions with the PF depended on the frame''s travel time for static PFs, and the leg-raising rate and angle for dynamic PFs. In terms of center of pressure (COP) metrics, significant impacts were caused by the frame''s travel time on MDIST-AP for static PFs, and the leg-raising rate on MDIST-ML and TOTEX for dynamic PFs. The best static PF balance control performance was observed with a larger frame offset by a travel time of 2 seconds, and the worst performance with a smaller frame and a travel time of 1 second. The best dynamic PF performance was with a leg-raising rate of 1 second at a 45-degree angle, while the worst performance was with a rate of 2 seconds at a 90-degree angle.The results demonstrated that different evaluation methods for player experience could result in different findings, making it harder to study the design of those exergames with training purposes based on player experience.     

Estimation of the radial force on the tokamak vessel wall during fast transient events

The radial force balance in a tokamak during fast transient events with a duration much shorter than the resistive time of the vacuum vessel wall is analyzed. The aim of the work is to analytically estimate the resulting integral radial force on the wall. In contrast to the preceding study [Plasma Phys. Rep. 41, 952 (2015)], where a similar problem was considered for thermal quench, simultaneous changes in the profiles and values of the pressure and plasma current are allowed here. Thereby, the current quench and various methods of disruption mitigation used in the existing tokamaks and considered for future applications are also covered. General formulas for the force at an arbitrary sequence or combination of events are derived, and estimates for the standard tokamak model are made. The earlier results and conclusions are confirmed, and it is shown that, in the disruption mitigation scenarios accepted for ITER, the radial forces can be as high as in uncontrolled disruptions.     

Reshaping the optical dimension in optogenetics

Optogenetics has been revolutionizing circuit neuroscience in the last few years. Optical methods combined with genetics and molecular techniques have provided new tools for stimulation of neurons, which hold great promise to provide a solution to the circuit mapping problem and more generally provide us with the ability to artificially control the natural stimulus space. Nevertheless, until very recently almost all applications of optogenetics have been based on relatively simple optical schemes mainly used for inducing population activity in neuronal assembles. In this context, alternative optical schemes that enhance the spatial or temporal resolution of excitation and allow for flexible and arbitrary generation of light patterns have all synergetic impact on the development of new optogenetic actuators. In the following we discuss and compare the main new optical techniques that have become available in the recent years. Their respective strengths and limitations as well as their application to different biological contexts are illustrated.     

A methodology for evaluating biocide release rate,surface roughness and leach layer formation in a TBT-free,self-polishing antifouling coating

Abstract

Due to the forthcoming IMO ban on the use of tributyltin (TBT) antifouling paints, a new generation of TBT-free coatings has been developed that typically contain cuprous oxide and an organic co-biocide. Accurate and reproducible test methods are needed to evaluate the performance and environmental impact of these new coatings. This study investigated a methodology for evaluating TBT-free, AF coatings containing cuprous oxide. A commercially available AF coating underwent rotary immersion testing at 0, 0.51 and 2.05 m s^?1. Scanning electron microscopy (SEM) and energy dispersive x-ray (EDX) analysis were used to assess leach layer formation, percentage cuprous oxide by weight and particle size distribution (PSD). Biocide release rates and surface roughness were also measured. An increase in rotary speed caused a spike in Cu²⁺ release rate after which the release rate stabilised to previous levels. An increase in leach layer thickness was also observed after the rotary speed increase. A model is suggested to account for the observations.     

Practices of strength and conditioning coaches in Brazilian elite soccer

Brazil is the leading global exporter of soccer players, with approximately 2,000 international transfers to different clubs per year. Although Brazilian players compete in the most prestigious soccer leagues worldwide, the habitual training methods, strategies, and routines of Brazilian soccer strength and conditioning coaches (SCCs) are undocumented. This study used a standard online survey to collect and characterize the strength and conditioning practices of Brazilian soccer SCCs. Forty-nine SCCs (age: 40.4 ± 7.5 years; professional experience: 15.3 ± 7.5 years) working in Brazilian professional soccer teams participated in this study. The survey consisted of eight sections: 1) background information; 2) muscular strength-power development; 3) speed training; 4) plyometrics; 5) flexibility training; 6) physical testing; 7) technology use; and 8) programing. Results indicated that training and testing practices of Brazilian SCCs are strongly affected by the congested fixture schedules, extensive traveling distances, and socio-economic disparities between different regions of the country. We describe all these different strategies and methods in detail, providing a comprehensive view and a critical examination of Brazilian soccer strength and conditioning practices. Brazilian SCCs and professional soccer organizations can use the findings from this study to develop training strategies and customize education programs. Practitioners from other countries can use this information to design training programs closely tailored to the background of Brazilian athletes, which may support their adaptation to different competitive scenarios and game demands, such as those found in the most important soccer leagues worldwide.     

The inference of stepwise changes in substitution rates using serial sequence samples.

It is frequently true that molecular sequences do not evolve in a strictly clocklike manner. Instead, substitution rate may vary for a number of reasons, including changes in selection pressure and effective population size, as well as changes in mean generation time. Here we present two new methods for estimating stepwise changes in substitution rates when serially sampled molecular sequences are available. These methods are based on multiple rates with dated tips (MRDT) models and allow different rates to be estimated for different intervals of time. These intervals may correspond to the sampling intervals or to a priori--defined intervals that are not coincident with the times the serial samples are obtained. Two methods for obtaining estimates of multiple rates are described. The first is an extension of the phylogeny-based maximum-likelihood estimation procedure introduced by Rambaut. The second is a new parameterization of the pairwise distance least-squares procedure used by Drummond and Rodrigo. The utility of these methods is demonstrated on a genealogy of HIV sequences obtained at five different sampling times from a single patient over a period of 34 months.     

Comparison of Rosetta flexible-backbone computational protein design methods on binding interactions

Computational design of binding sites in proteins remains difficult, in part due to limitations in our current ability to sample backbone conformations that enable precise and accurate geometric positioning of side chains during sequence design. Here we present a benchmark framework for comparison between flexible-backbone design methods applied to binding interactions. We quantify the ability of different flexible backbone design methods in the widely used protein design software Rosetta to recapitulate observed protein sequence profiles assumed to represent functional protein/protein and protein/small molecule binding interactions. The CoupledMoves method, which combines backbone flexibility and sequence exploration into a single acceptance step during the sampling trajectory, better recapitulates observed sequence profiles than the BackrubEnsemble and FastDesign methods, which separate backbone flexibility and sequence design into separate acceptance steps during the sampling trajectory. Flexible-backbone design with the CoupledMoves method is a powerful strategy for reducing sequence space to generate targeted libraries for experimental screening and selection.     

A framework for three-dimensional simulation of morphogenesis

We present COMPUCELL3D, a software framework for three-dimensional simulation of morphogenesis in different organisms. COMPUCELL3D employs biologically relevant models for cell clustering, growth, and interaction with chemical fields. COMPUCELL3D uses design patterns for speed, efficient memory management, extensibility, and flexibility to allow an almost unlimited variety of simulations. We have verified COMPUCELL3D by building a model of growth and skeletal pattern formation in the avian (chicken) limb bud. Binaries and source code are available, along with documentation and input files for sample simulations, at http:// compucell.sourceforge.net.