Alteration of the Route to Menaquinone towards Isochorismate-Derived Metabolites

Chorismate and isochorismate constitute branch-point intermediates in the biosynthesis of many aromatic metabolites in microorganisms and plants. To obtain unnatural compounds, we modified the route to menaquinone in Escherichia coli. We propose a model for the binding of isochorismate to the active site of MenD ((1R,2S, 5S,6S)-2-succinyl-5-enolpyruvyl-6-hydroxycyclohex-3-ene-1-carboxylate (SEPHCHC) synthase) that explains the outcome of the native reaction with α-ketoglutarate. We have rationally designed variants of MenD for the conversion of several isochorismate analogues. The double-variant Asn117Arg–Leu478Thr preferentially converts (5S,6S)-5,6-dihydroxycyclohexa-1,3-diene-1-carboxylate (2,3-trans-CHD), the hydrolysis product of isochorismate, with a >70-fold higher ratio than that for the wild type. The single-variant Arg107Ile uses (5S,6S)-6-amino-5-hydroxycyclohexa-1,3-diene-1-carboxylate (2,3-trans-CHA) as substrate with >6-fold conversion compared to wild-type MenD. The novel compounds have been made accessible in vivo (up to 5.3 g L⁻¹). Unexpectedly, as the identified residues such as Arg107 are highly conserved (>94 %), some of the designed variations can be found in wild-type SEPHCHC synthases from other bacteria (Arg107Lys, 0.3 %). This raises the question for the possible natural occurrence of as yet unexplored branches of the shikimate pathway.     

Event-triggered distributed receding horizon control for tracking and formation of homogeneous multi-agent systems

This paper proposes an event-triggered distributed receding horizon control (DRHC) approach for the formation and tracking problems of homogeneous multi-agent systems. For each agent, an event-triggering condition, based on assumed predictive information of the neighbours, is derived from stability analysis. Considering the uncertain deviation between the assumed and true predictive information, we design a time-varying compatibility constraint for the individual optimization problem. In the event-triggered DRHC algorithm, each agent solves the optimization problem and communicates with its neighbours only when the event-triggering condition is satisfied, so the communication and computation burden are reduced. Moreover, guarantees for the recursive feasibility and asymptotic stability of the overall system are proved. A simulation example is provided to illustrate effectiveness of the proposed approach.     

Hydroxyapatite cages with aligned pores for bone grafting – Seeding of human osteoblast-like cells in vitro and their response in dynamic culture mode

Hydroxyapatite (HA) is a highly regarded synthetic bone graft material. Porous HA ceramics blocks are used to substitute harvested natural bone grafts. Being similar to bone mineral, HA material integrates with the host bone through surface osteointegration and slowly resorb along with the natural bone remodeling process. The blocks in use currently have random and tortuous pore structures. The present work explores the usefulness of cage-like HA ceramic design with end-to-end open pores, with the help of in vitro cell culture methods. Such a structure, on implantation, will take up the blood factors and cells and host the bone remodeling process inside the bulk of the cage, leading to early healing. In the study, HA samples with aligned through-pores were prepared and explored in vitro, with a focus on how the pores host the cells inside and to what level the cells maintain their activity. Human osteoblast-like cells (HOS) were used, at different seeding and culturing approaches. Cell seeding was done through (i) conventional large volume cell suspension, (ii) a confined mini chamber with a limited volume of cell suspension, and (iii) placing a concentrated drop of cell suspension directly on top of the scaffold. The third approach gave the best cell adhesion and proliferation, and hence used for further explorations. A dynamic culture system was designed in-house by bifurcating the cell culture wells using vertical inserts, holding the samples horizontally with their ends open to both sides, and making the media flow across using a rocker platform. The HOS cell adhesion, viability and proliferation were tested in the HA cages, in static and dynamic culture conditions, with conventional porous ceramics as the control. The cell infiltration was deeper and the cell viability over a period of 7 days was significantly higher in dynamic culture conditions in the test samples.     

Pressure control of an electro-hydraulic actuated clutch via novel hysteresis model

This paper mainly focuses on the development of pressure tracking control logic of electro-hydraulic actuators for vehicle application. This is done to improve and ensure the performance of a precise lower-level controller for evolving modern shift control logic. The required performance is obtained by hysteresis model-based feed-forward control and additional feedback control. The hysteresis and the time delay, which adversely affect pressure control, are well known nonlinear behaviors in electro-hydraulic actuators. In order to cope with the hysteresis, a novel hysteresis model is proposed based on a physical phenomenon. A mathematical model based on a characteristic curve obtained in preliminary experiments is presented using only one tuning parameter, and this model can be inverted easily to construct a feed-forward controller. In addition, a feedback controller is designed considering the stability margin of a time delay system. The feedback control inputs ensure compensation of the feed-forward errors caused by model error and uncertainty. The proposed controller is designed to lower computational cost considering applicability for production vehicles. As a result, the developed pressure controller is applied to a transmission control unit of a production vehicle and verified experimentally for various driving scenarios.     

Adaptive compensation of persistent actuator failures of nonlinear systems

In this article, adaptive compensation designs are developed for nonlinear systems with uncertainties from the system functions and persistent actuator failures of characterizations that (i) some unknown system inputs are stuck at some unknown fixed or varying values at unknown time instants and (ii) the failure pattern always switches from one to another and the switching does not stop. Such a controlled plant is described by an uncertain time-varying nonlinear system, and some robust adaptive feedback linearization based failure compensation results are studied for closed-loop system stabilization and bounded output tracking for some specific conditions. To improve the tracking performance in the presence of persistent actuator failures, a new adaptive control scheme is developed, using the failure indicator function which contains the failure pattern and failure time in the formulation. Detailed stability and tracking performance are shown. Simulation results are shown to verify the effectiveness of the proposed adaptive actuator failure compensation method.     

Semirigid inclusions in elastic bodies: Mechanical interplay and optimal control

The paper concerns an analysis of an equilibrium problem for 2D elastic body with two semirigid inclusions. It is assumed that inclusions have a joint point, and we investigate a junction problem for these inclusions. The existence of solutions is proved, and different equivalent formulations of the problem are proposed. We investigate a convergence to infinity of a rigidity parameter of the semirigid inclusion. It is proved that in the limit, we obtain an equilibrium problem for the elastic body with a rigid inclusion and a semirigid one. A parameter identification problem is investigated. In particular, the existence of a solution to a suitable optimal control problem is proved.     

On one boundary problem for nonlinear stationary controlled system

The object of study is nonlinear stationary controlled system of ordinary differential equations with constant disturbance in the right part. The problem of constructing the synthesising control function providing the transfer of this system from the initial state to the origin is considered. The sufficiently simple for numerical implementation algorithm of solution of the above-mentioned problem is obtained. It is shown that for local null controllability of the considered system, it is sufficient that the conditions of the Kalman's type were satisfied. In addition, the estimates restricting the choice of initial conditions and external disturbances under which the transfer is guaranteed are obtained. The main idea of the method of construction of the desired control function consists in reducing the original problem to stabilisation of a special kind linear non-stationary system and solving the Cauchy problem for an auxiliary system of ordinary differential equations closed by stabilising control. The simplicity of the realisation of this algorithm is determined by the construction of the auxiliary system and its stabilisation that could be obtained by analytical methods. The effectiveness of the method is illustrated by solving the problem of crane control and its numerical simulation.     

Integration of imitation learning using GAIL and reinforcement learning using task-achievement rewards via probabilistic graphical model

The integration of reinforcement learning (RL) and imitation learning (IL) is an important problem that has long been studied in the field of intelligent robotics. RL optimizes policies to maximize the cumulative reward, whereas IL attempts to extract general knowledge about the trajectories demonstrated by experts, i.e, demonstrators. Because each has its own drawbacks, many methods combining them and compensating for each set of drawbacks have been explored thus far. However, many of these methods are heuristic and do not have a solid theoretical basis. This paper presents a new theory for integrating RL and IL by extending the probabilistic graphical model (PGM) framework for RL, control as inference. We develop a new PGM for RL with multiple types of rewards, called probabilistic graphical model for Markov decision processes with multiple optimality emissions (pMDP-MO). Furthermore, we demonstrate that the integrated learning method of RL and IL can be formulated as a probabilistic inference of policies on pMDP-MO by considering the discriminator in generative adversarial imitation learning (GAIL) as an additional optimality emission. We adapt the GAIL and task-achievement reward to our proposed framework, achieving significantly better performance than policies trained with baseline methods.     

A knowledge construction methodology to automate case-based learning using clinical documents

The case-based learning (CBL) approach has gained attention in medical education as an alternative to traditional learning methodology. However, current CBL systems do not facilitate and provide computer-based domain knowledge to medical students for solving real-world clinical cases during CBL practice. To automate CBL, clinical documents are beneficial for constructing domain knowledge. In the literature, most systems and methodologies require a knowledge engineer to construct machine-readable knowledge. Keeping in view these facts, we present a knowledge construction methodology (KCM-CD) to construct domain knowledge ontology (i.e., structured declarative knowledge) from unstructured text in a systematic way using artificial intelligence techniques, with minimum intervention from a knowledge engineer. To utilize the strength of humans and computers, and to realize the KCM-CD methodology, an interactive case-based learning system(iCBLS) was developed. Finally, the developed ontological model was evaluated to evaluate the quality of domain knowledge in terms of coherence measure. The results showed that the overall domain model has positive coherence values, indicating that all words in each branch of the domain ontology are correlated with each other and the quality of the developed model is acceptable.     

结合优化支持向量机与K-means++的工控系统入侵检测方法

针对工业控制系统传统单一检测算法模型对不同攻击类型检测率和检测速度不佳的问题，提出一种优化支持向量机和K-means++算法结合的入侵检测模型。首先利用主成分分析法（PCA）对原始数据集进行预处理，消除其相关性；其次在粒子群优化（PSO）算法的基础上加入自适应变异过程避免在训练的过程中陷入局部最优解；然后利用自适应变异粒子群优化（AMPSO）算法优化支持向量机的核函数和惩罚参数；最后利用密度中心法改进K-means算法与优化后的支持向量机组合成入侵检测模型，从而实现工业控制系统的异常检测。实验结果表明，所提方法在检测速度和对各类攻击的检测率上得到明显提升。