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.     

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.     

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.     

Optimal resilient power grid operation during the course of a progressing wildfire

We study a two-stage stochastic and nonlinear optimization model for operating a power grid exposed to a natural disaster. Although this approach can be generalized to any natural hazard of continuous (and not instantaneous) nature, our focus is on wildfires. We assume that an approaching wildfire impacts the power grid by reducing the transmission capacity of its overhead lines. At the time when proactive decisions have to be taken, the severity of the wildfire is not known. This introduces uncertainty. In this paper, we extend previous work by more realistically capturing this uncertainty and by strengthening the mathematical programming formulation through standard reformulation techniques. With these reformulation techniques, the resulting two-stage, convex mixed-integer quadratically constrained programming formulation can be efficiently solved using commercial quadratic programming solvers as demonstrated on a case study on a modified version of the IEEE 123-bus test system with 100 scenarios. We also quantify the uncertainties through a second case study using the following three standard metrics of two-stage stochastic optimization: the expected value of perfect information, the expected result of using the expected value solution and the value of the stochastic solution.     

Data sharing mechanism of various mineral resources based on blockchain

Basins with various mineral resources coexisting and enriching often occupy an important strategic position. The exploration of various mineral resources is repetitive at present due to unshared data and imperfect management mechanism. This situation greatly increases the cost of energy exploitation in the country. Traditional data-sharing mode has several disadvantages, such as high cost, difficulty in confirming the right of data, and lack of incentive mechanism, which make achieving real data sharing difficult. In this paper, we propose a data-sharing mechanism based on blockchain and provide implementation suggestions and technical key points. Compared with traditional data-sharing methods, the proposed data-sharing mechanism can realize data sharing, ensure data quality, and protect intellectual property. Moreover, key points in the construction are stated in the case study section to verify the feasibility of the data-sharing system based on blockchain proposed in this paper.     

Learning keyword phrases from query logs of USPTO patent examiners for automatic query scope limitation in patent searching

Professional search in patent repositories poses several unique challenges. One key requirement is to search the entire affected space of concepts, following well-defined procedures to ensure traceability of results obtained. Several techniques have been introduced to enhance query generation, preferably via automated query term expansion, to improve retrieval effectiveness. Currently, these approaches are mostly limited to computing additional query terms from patent documents based on statistical measures. For conceptual search to solve the limitation of traditional keyword search standard dictionaries are used to provide synonyms and keyword phrases for query refinement. Studies show that these are insufficient in such highly specialized domains. In this paper, we present an approach to extract keyword phrases from query logs created during the validation procedure of the patent applications. This creates valuable domain-specific lexical databases for several specific patent classes that can be used to both expand as well as limit the scope of a patent search. This provides a more powerful means to guide a professional searcher through the search process. We evaluate the lexical databases based on real query sessions of patent examiners.