Flexibility and binding affinity in protein–ligand,protein–protein and multi-component protein interactions: limitations of current computational approaches

The recognition process between a protein and a partner represents a significant theoretical challenge. In silico structure-based drug design carried out with nothing more than the three-dimensional structure of the protein has led to the introduction of many compounds into clinical trials and numerous drug approvals. Central to guiding the discovery process is to recognize active among non-active compounds. While large-scale computer simulations of compounds taken from a library (virtual screening) or designed de novo are highly desirable in the post-genomic area, many technical problems remain to be adequately addressed. This article presents an overview and discusses the limits of current computational methods for predicting the correct binding pose and accurate binding affinity. It also presents the performances of the most popular algorithms for exploring binary and multi-body protein interactions.     

A review of manufacturing flexibility: systematising the concept

The present work is an attempt to contribute to the conceptual systematisation of the manufacturing flexibility types by synthesising the vast literature available after a systematic review. We classified the papers in two perspectives (hierarchical and strategic), and engaged in a systematic process of standardisation of the definitions and names of various flexibility types leading to a better understanding of them. This process allowed us to clearly show: (a) the existence of a broader consensus in the field than expected; (b) that problems are limited to concrete aspects related to the level of analysis or the scope of certain flexibility types; (c) the possibility of a theoretical integration between the two perspectives which would permit a standardisation of the names and definitions for the flexibility types which make up the manufacturing flexibility construct.     

Product mix strategy and manufacturing flexibility

The manufacturing industry is facing a turbulent and constantly changing environment, with growing complexity and high levels of customisation. Any investment solution should address these problems for a dynamic market and within limited budget boundaries, so that companies try to remain competitive. The authors propose a real options model to support firms making important investment decisions, specifically decisions associated with the acquisition of new equipment aimed at allowing firms to increase their manufacturing flexibility for the production of both standard and customized products. This paper is partially based on a real operating experience related to visual finishing technology features in an industrial company that conforms to the definitions of the product mix. The authors’ motivation for this work is driven by firms’ desire to satisfy specific customer needs, and to respond to them quickly under uncertain demand. Our goal, using theories from finance, production management, and product offering management, is to conclude that there is a relevant difference between the evaluation of the technology that is to be chosen, and the potential value due to product mix adaptations that are able to provide the maximum return from investment. We address problems related to standard and customized production systems, and the decision to invest in a set of resources that will enable this choice.     

工程合同柔性的本质及不同范本下的条款比较

工程合同柔性作为一种应对项目不确定性的能力,能够有效地改善项目管理绩效。在工程项目管理研究领域中,针对工程合同柔性的研究,真正结合工程项目、工程合同特征的研究却很少见,因此,通过文献研究并且结合法经济学与契约经济学理论,深刻剖析工程合同柔性的本质是价格柔性;基于13版《施工合同范本》与FIDIC合同条件,阐明工程合同柔性条款运作机理,即工程合同柔性程度的改变主要是通过柔性点的数量以及同一柔性点责任与权利划分的原则来确定。     

Economic Evaluation of Power System Flexibility by Commercial Air Conditioner Control with Large Penetration of Photovoltaic Generation

High penetration of intermittent renewable energy such as photovoltaic (PV) and wind power could cause shortage of power system flexibility. Demand response is expected to help supply ancillary service instead of the conventional power plant. Commercial air conditioners are a promising responsive load for demand response because they account for a large proportion of power consumption in the power system. We calculate a system operation cost and hourly operation pattern of each power plant by using the optimal power generation model considering flexibility supply from controlling commercial air conditioner. We obtained the following results as an effect of commercial air conditioner control. (1) The power generation of oil fired power plants decreases at peak time and annual fuel cost of oil fired plant is reduced by approximately 30% at most in Kanto area. (2) The percentage of rated operation mode of LNG combined cycle plants increases. (3) Curtailed energy rate of PV decreases because a power storage amount by pumped hydropower generation increases. (4) Required battery capacity to reduce PV curtailed amount decreased by combining battery energy storage system in case of high penetration of PV.     

Frontiers in combustion techniques and burner designs for emissions control and CO2 capture: A review

The use of fossil fuel is expected to increase significantly by midcentury because of the large rise in the world energy demand despite the effective integration of renewable energies in the energy production sector. This increase, alongside with the development of stricter emission regulations, forced the manufacturers of combustion systems, especially gas turbines, to develop novel combustion techniques for the control of NO_x and CO₂ emissions, the latter being a greenhouse gas responsible for more than 60% to the global warming problem. The present review addresses different burner designs and combustion techniques for clean power production in gas turbines. Combustion and emission characteristics, flame instabilities, and solution techniques are presented, such as lean premixed air‐fuel (LPM) and premixed oxy‐fuel combustion techniques, and the combustor performance is compared for both cases. The fuel flexibility approach is also reviewed, as one of the combustion techniques for controlling emissions and reducing flame instabilities, focusing on the hydrogen‐enrichment and the integrated fuel‐flexible premixed oxy‐combustion approaches. State‐of‐the‐art burner designs for gas turbine combustion applications are reviewed in this study, including stagnation point reverse flow (SPRF) burner, dry low NO_x (DLN) and dry low‐emission (DLE) burners, EnVironmental burners (including EV, AEV, and SEV burners), perforated plate (PP) burner, and micromixer (MM) burner. Special emphasis is made on the MM combustor technology, as one of the most recent advances in gas turbines for stable premixed flame operation with wide turndown and effective control of NO_x emissions. Since the generation of pure oxygen is prerequisite to oxy‐combustion, oxygen‐separation membranes became of immense importance either for air separation for clean oxy‐combustion applications or for conversion/splitting of the effluent CO₂ into useful chemical and energy products. The different carbon‐capture technologies, along with the most recent carbon‐utilization approaches towards CO₂ emissions control, are also reviewed.     

An intermittent control model of flexible human gait using a stable manifold of saddle-type unstable limit cycle dynamics

Stability of human gait is the ability to maintain upright posture during walking against external perturbations. It is a complex process determined by a number of cross-related factors, including gait trajectory, joint impedance and neural control strategies. Here, we consider a control strategy that can achieve stable steady-state periodic gait while maintaining joint flexibility with the lowest possible joint impedance. To this end, we carried out a simulation study of a heel-toe footed biped model with hip, knee and ankle joints and a heavy head-arms-trunk element, working in the sagittal plane. For simplicity, the model assumes a periodic desired joint angle trajectory and joint torques generated by a set of feed-forward and proportional-derivative feedback controllers, whereby the joint impedance is parametrized by the feedback gains. We could show that a desired steady-state gait accompanied by the desired joint angle trajectory can be established as a stable limit cycle (LC) for the feedback controller with an appropriate set of large feedback gains. Moreover, as the feedback gains are decreased for lowering the joint stiffness, stability of the LC is lost only in a few dimensions, while leaving the remaining large number of dimensions quite stable: this means that the LC becomes saddle-type, with a low-dimensional unstable manifold and a high-dimensional stable manifold. Remarkably, the unstable manifold remains of low dimensionality even when the feedback gains are decreased far below the instability point. We then developed an intermittent neural feedback controller that is activated only for short periods of time at an optimal phase of each gait stride. We characterized the robustness of this design by showing that it can better stabilize the unstable LC with small feedback gains, leading to a flexible gait, and in particular we demonstrated that such an intermittent controller performs better if it drives the state point to the stable manifold, rather than directly to the LC. The proposed intermittent control strategy might have a high affinity for the inverted pendulum analogy of biped gait, providing a dynamic view of how the step-to-step transition from one pendular stance to the next can be achieved stably in a robust manner by a well-timed neural intervention that exploits the stable modes embedded in the unstable dynamics.     

A new mathematical model for integrating all incidence matrices in multi-dimensional cellular manufacturing system

In the past several years, many studies have been carried out on cellular manufacturing based on a two-dimensional machine–part incidence matrix. Since workers have important role in doing jobs on machines, assignment of workers to cells becomes a crucial factor for fully utilization of cellular manufacturing systems. In this paper, an attempt is made to solve cell formation problem and minimize the number of voids and exceptional elements in a three dimensional (cubic) machine–part–worker incidence matrix. The proposed mathematical model captures the capability of workers in doing different jobs. To demonstrate the effectiveness of the proposed model, the solution of some test problems is compared with the literature method.     

玻璃纤维增强塑料夹砂管物理性能检测的研究

研究了玻璃纤维增强塑料夹砂管环刚度、挠曲水平、环向拉伸强力和轴向拉伸强力检测方法,比较分析了各种方法的优缺点与适用范围,同时比较全面地总结了夹砂管物理性能的检测方法。在实际检测过程中应当结合管道的设计参数,充分考虑夹砂管各结构层之间的相对关系以及每个结构层内各部分的关系,选择最合适的检测方法。     

多样化空间

随着中国经济进入高速发展阶段,几乎所有的城市都在进行前所未有的大规模建设活动。在过分追求速度的建设过程中,一部分城市规划和建筑项目只考虑当前功能需求而忽略了今后的功能需求,使建筑和城市空间过早地失去使用价值,造成对空间的资源和自然资源的浪费。所以,我们要注重多样化空间的设计,摒弃单一而固定的空间形式,增强空间的适应能力,创造有生命力的空间。