Transglycosylation Activity of Engineered Bifidobacterium Lacto-N-Biosidase Mutants at Donor Subsites for Lacto-N-Tetraose Synthesis

The health benefits of human milk oligosaccharides (HMOs) make them attractive targets as supplements for infant formula milks. However, HMO synthesis is still challenging and only two HMOs have been marketed. Engineering glycoside hydrolases into transglycosylases may provide biocatalytic routes to the synthesis of complex oligosaccharides. Lacto-N-biosidase from Bifidobacterium bifidum (LnbB) is a GH20 enzyme present in the gut microbiota of breast-fed infants that hydrolyzes lacto-N-tetraose (LNT), the core structure of the most abundant type I HMOs. Here we report a mutational study in the donor subsites of the substrate binding cleft with the aim of reducing hydrolytic activity and conferring transglycosylation activity for the synthesis of LNT from p-nitrophenyl β-lacto-N-bioside and lactose. As compared with the wt enzyme with negligible transglycosylation activity, mutants with residual hydrolase activity within 0.05% to 1.6% of the wild-type enzyme result in transglycosylating enzymes with LNT yields in the range of 10–30%. Mutations of Trp394, located in subsite -1 next to the catalytic residues, have a large impact on the transglycosylation/hydrolysis ratio, with W394F being the best mutant as a biocatalyst producing LNT at 32% yield. It is the first reported transglycosylating LnbB enzyme variant, amenable to further engineering for practical enzymatic synthesis of LNT.     

The Function of Sialidase Revealed by Sialidase Activity Imaging Probe

Sialidase cleaves sialic acid residues from glycans such as glycoproteins and glycolipids. In the brain, desorption of the sialic acid by sialidase is essential for synaptic plasticity, learning and memory and synaptic transmission. BTP3-Neu5Ac has been developed for sensitive imaging of sialidase enzyme activity in mammalian tissues. Sialidase activity in the rat hippocampus detected with BTP3-Neu5Ac increases rapidly by neuronal depolarization. It is presumed that an increased sialidase activity in conjunction with neural excitation is involved in the formation of the neural circuit for memory. Since sialidase inhibits the exocytosis of the excitatory neurotransmitter glutamate, the increased sialidase activity by neural excitation might play a role in the negative feedback mechanism against the glutamate release. Mammalian tissues other than the brain have also been stained with BTP3-Neu5Ac. On the basis of information on the sialidase activity imaging in the pancreas, it was found that sialidase inhibitor can be used as an anti-diabetic drug that can avoid hypoglycemia, a serious side effect of insulin secretagogues. In this review, we discuss the role of sialidase in the brain as well as in the pancreas and skin, as revealed by using a sialidase activity imaging probe. We also present the detection of influenza virus with BTP3-Neu5Ac and modification of BTP3-Neu5Ac.     

Shared human–robot path following control of an unmanned ground vehicle

This paper considers the shared path following control of an unmanned ground vehicle by a single person. A passive measure of human intent is used to blend the human and machine inputs in a mixed initiative approach. The blending law is combined with saturated super-twisting sliding mode speed and heading controllers, so that exogenous disturbances can be counteracted via equivalent control. It is proven that when the proposed blending law is used, the combined control signals from both the human and automatic controller respect the actuator magnitude constraints of the machine. To demonstrate the approach, shared control experiments are performed using an unmanned ground vehicle, which follows a lawn mower pattern shaped path.     

Nacre-Inspired,Liquid Metal-Based Ultrasensitive Electronic Skin by Spatially Regulated Cracking Strategy

The realization of liquid metal-based wearable systems will be a milestone toward high-performance, integrated electronic skin. However, despite the revolutionary progress achieved in many other components of electronic skin, liquid metal-based flexible sensors still suffer from poor sensitivity due to the insufficient resistance change of liquid metal to deformation. Herein, a nacre-inspired architecture composed of a biphasic pattern (liquid metal with Cr/Cu underlayer) as “bricks” and strain-sensitive Ag film as “mortar” is developed, which breaks the long-standing sensitivity bottleneck of liquid metal-based electronic skin. With 2 orders of magnitude of sensitivity amplification while maintaining wide (>85%) working range, for the first time, liquid metal-based strain sensors rival the state-of-art counterparts. This liquid metal composite features spatially regulated cracking behavior. On the one hand, hard Cr cells locally modulate the strain distribution, which avoids premature cut-through cracks and prolongs the defect propagation in the adjacent Ag film. On the other hand, the separated liquid metal cells prevent unfavorable continuous liquid-metal paths and create crack-free regions during strain. Demonstrated in diverse scenarios, the proposed design concept may spark more applications of ultrasensitive liquid metal-based electronic skins, and reveals a pathway for sensor development via crack engineering.     

Unreliable numbers: error and harm induced by bad design can be reduced by better design

Number entry is a ubiquitous activity and is often performed in safety- and mission-critical procedures, such as healthcare, science, finance, aviation and in many other areas. We show that Monte Carlo methods can quickly and easily compare the reliability of different number entry systems. A surprising finding is that many common, widely used systems are defective, and induce unnecessary human error. We show that Monte Carlo methods enable designers to explore the implications of normal and unexpected operator behaviour, and to design systems to be more resilient to use error. We demonstrate novel designs with improved resilience, implying that the common problems identified and the errors they induce are avoidable.     

Role of Zinc (Zn) in Human Reproduction: A Journey from Initial Spermatogenesis to Childbirth

Zinc (Zn), the second-most necessary trace element, is abundant in the human body. The human body lacks the capacity to store Zn; hence, the dietary intake of Zn is essential for various functions and metabolism. The uptake of Zn during its transport through the body is important for proper development of the three major accessory sex glands: the testis, epididymis, and prostate. It plays key roles in the initial stages of germ cell development and spermatogenesis, sperm cell development and maturation, ejaculation, liquefaction, the binding of spermatozoa and prostasomes, capacitation, and fertilization. The prostate releases more Zn into the seminal plasma during ejaculation, and it plays a significant role in sperm release and motility. During the maternal, labor, perinatal, and neonatal periods, the part of Zn is vital. The average dietary intake of Zn is in the range of 8–12 mg/day in developing countries during the maternal period. Globally, the dietary intake of Zn varies for pregnant and lactating mothers, but the average Zn intake is in the range of 9.6–11.2 mg/day. The absence of Zn and the consequences of this have been discussed using critical evidence. The events and functions of Zn related to successful fertilization have been summarized in detail. Briefly, our current review emphasizes the role of Zn at each stage of human reproduction, from the spermatogenesis process to childbirth. The role of Zn and its supplementation in in vitro fertilization (IVF) opens opportunities for future studies on reproductive biology.     

Ageing workforce management in manufacturing systems: state of the art and future research agenda

The workforce ageing phenomenon is recently affecting most of the Organisation for Economic Co-operation and Development (OECD) member countries, due to a general ageing of their populations and a higher average retirement age of the workforce. In this paper, the topic of ageing workforce management is addressed from a production research standpoint, with the aim of understanding how older workers can be supported and involved in a manufacturing system. First, the current state of the art related to the ageing workforce in production systems is presented. This is structured according to four main topics: (1) analysis and evaluation of ageing workers’ functional capacities, (2) consideration of ageing workers’ capacities in industrial system modelling and management, (3) analysis and exploitation of ageing workers’ expertise, (4) acknowledgement, analysis, design and integration of supporting technologies. Next, the discussion on the impact of the ageing workforce on manufacturing systems’ performances leads to the comparison of some technological advances that are related to the Industry 4.0 paradigms. Finally, a future research agenda on this topic is proposed, based on the same topics classification proposed for the literature analysis. Five different research areas are derived, suggesting future directions for appropriate research concerning the employ of older workers in production environments.     

基于深度学习的人体姿态估计方法综述

基于深度学习的人体姿态估计方法旨在通过构建合适的神经网络，直接从二维的图像特征中回归出人体姿态信息。主要按照2D人体姿态估计到3D人体姿态估计的顺序，并从单人检测与多人检测、稀疏的关节点检测与密集的模型构建等方面，对近年来基于深度学习的人体姿态估计方法进行系统介绍，从而初步了解如何通过深度学习的方法得到人体姿态的各个要素，包括肢体部件的相对朝向和比例尺度、骨骼关节点的位置坐标和连接关系，甚至更为复杂的人体蒙皮模型信息。最后,对当前研究面临的挑战以及未来的热点动向进行概述，清晰地呈现出该领域的发展脉络。