Babesia Bovis Ligand-Receptor Interaction: AMA-1 Contains Small Regions Governing Bovine Erythrocyte Binding

Apical membrane antigen 1 is a microneme protein which plays an indispensable role during Apicomplexa parasite invasion. The detailed mechanism of AMA-1 molecular interaction with its receptor on bovine erythrocytes has not been completely defined in Babesia bovis. This study was focused on identifying the minimum B. bovis AMA-1-derived regions governing specific and high-affinity binding to its target cells. Different approaches were used for detecting ama-1 locus genetic variability and natural selection signatures. The binding properties of twelve highly conserved 20-residue-long peptides were evaluated using a sensitive and specific binding assay based on radio-iodination. B. bovis AMA-1 ectodomain structure was modelled and refined using molecular modelling software. NetMHCIIpan software was used for calculating B- and T-cell epitopes. The B. bovis ama-1 gene had regions under functional constraint, having the highest negative selective pressure intensity in the Domain I encoding region. Interestingly, B. bovis AMA-1-DI (¹⁰⁰YMQKFDIPRNHGSGIYVDLG¹¹⁹ and ¹²⁰GYESVGSKSYRMPVGKCPVV¹³⁹) and DII (³⁰²CPMHPVRDAIFGKWSGGSCV³²¹)-derived peptides had high specificity interaction with erythrocytes and bound to a chymotrypsin and neuraminidase-treatment sensitive receptor. DI-derived peptides appear to be exposed on the protein’s surface and contain predicted B- and T-cell epitopes. These findings provide data (for the first-time) concerning B. bovis AMA-1 functional subunits which are important for establishing receptor-ligand interactions which could be used in synthetic vaccine development.     

Topology optimization of flexure hinges with a prescribed compliance matrix based on the adaptive spring model and stress constraint

This paper focuses on the configuration design of flexure hinges with a prescribed compliance matrix and preset rotational center position. A new method for the topology optimization of flexure hinges is proposed based on the adaptive spring model and stress constraint. The hinge optimization model is formulated by maximizing the bending displacement with a spring while optimizing the compliance matrix to a prescribed value. To avoid numerical instability, an artificial spring is used as an auxiliary calculation, and a new strategy is developed for adaptively adjusting the spring stiffness according to the prescribed compliance matrix. The maximum stress of flexure hinge is limited by using a normalized P-norm of the effective von Mises stress, and a position constraint of rotational center is proposed to predetermine the position of the rotational center. In addition, to reduce the error of the stress measurement, a simple but effective filtering method is presented to obtain a complete black-and-white design. Numerical examples are used to verify the proposed method. Topology results show that the obtained flexure hinges have the prescribed compliance matrix and preset rotational center position while also meeting the stress requirements.     

Blends of Bio-Based Poly(Limonene Carbonate) with Commodity Polymers

In this study, blends of the bio-based poly(limonene carbonate) (PLimC) with different commodity polymers are investigated in order to explore the potential of PLimC toward generating more sustainable polymer materials by reducing the amount of petro- or food-based polymers. PLimC is employed as minority component in the blends. Next to the morphology and thermal properties of the blends the impact of PLimC on the mechanical properties of the matrix polymers is studied. The interplay of incompatibility and zero-shear melt viscosity contrast determines the blend morphology, leading for all blends to a dispersed droplet morphology for PLimC. Blends with polymers of similar structure to PLimC (i.e., aliphatic/aromatic polyester) show the best performance with respect to mechanical properties, whereas blends with polystyrene or poly(methyl methacrylate) are too brittle and polyamide 12 blends show very low elongations at break. In blends with Ecoflex (poly(butylene adipate-co-terephthalate)) and Arnitel EM400 (copoly(ether ester)) with poly(butylene terephthalate) hard and polytetrahydrofuran soft segments) a threefold increase in E-modulus can be achieved, while keeping the elongation at break at reasonable high values of ≈200%, making these blends highly interesting for applications.     

药物相互作用研究在新药研发和审评决策中的应用

药物相互作用改变了剂量效应关系，可能会降低疗效或增加毒性，是临床应用中合并用药治疗时重要的考虑因素。预测具有临床意义的药物相互作用是药物研发过程中获益风险评估的重要环节。本文概述了药物研发过程中药物相互作用研究的目的和意义，体内和体外研究的主要内容；梳理分析了2020年国家药品监督管理局（National Medical Products Administration, NMPA）和美国食品药品监督管理局（Food and Drug Administration, FDA）批准上市的新药药物相互作用研究情况，旨在为我国药物研发过程中药物相互作用研究及其监管审评提供参考。     

Understanding the asymmetric perceptions of smartphone security from security feature perspective: A comparative study

Smartphones are being used and relied on by people more than ever before. The open connectivity brings with it great convenience and leads to a variety of risks that cannot be overlooked. Smartphone vendors, security policy designers, and security application providers have put a variety of practical efforts to secure smartphones, and researchers have conducted extensive research on threat sources, security techniques, and user security behaviors. Regrettably, smartphone users do not pay enough attention to mobile security, making many efforts futile. This study identifies this gap between technology affordance and user requirements, and attempts to investigate the asymmetric perceptions toward security features between developers and users, between users and users, as well as between different security features. These asymmetric perceptions include perceptions of quality, perceptions of importance, and perceptions of satisfaction. After scoping the range of smartphone security features, this study conducts an improved Kano-based method and exhaustively analyzes the 245 collected samples using correspondence analysis and importance satisfaction analysis. The 14 security features of the smartphone are divided into four Kano quality types and the perceived quality differences between developers and users are compared. Correspondence analysis is utilized to capture the relationship between the perceived importance of security features across different groups of respondents, and results of importance-satisfaction analysis provide the basis for the developmental path and resource reallocation strategy of security features. This article offers new insights for researchers as well as practitioners of smartphone security.     

Modeling Sialidosis with Neural Precursor Cells Derived from Patient-Derived Induced Pluripotent Stem Cells

Sialidosis, caused by a genetic deficiency of the lysosomal sialidase gene (NEU1), is a systemic disease involving various tissues and organs, including the nervous system. Understanding the neurological dysfunction and pathology associated with sialidosis remains a challenge, partially due to the lack of a human model system. In this study, we have generated two types of induced pluripotent stem cells (iPSCs) with sialidosis-specific NEU1^G227R and NEU1^V275A/R347Q mutations (sialidosis-iPSCs), and further differentiated them into neural precursor cells (iNPCs). Characterization of NEU1^G227R- and NEU1^V275A/R347Q- mutated iNPCs derived from sialidosis-iPSCs (sialidosis-iNPCs) validated that sialidosis-iNPCs faithfully recapitulate key disease-specific phenotypes, including reduced NEU1 activity and impaired lysosomal and autophagic function. In particular, these cells showed defective differentiation into oligodendrocytes and astrocytes, while their neuronal differentiation was not notably affected. Importantly, we found that the phenotypic defects of sialidosis-iNPCs, such as impaired differentiation capacity, could be effectively rescued by the induction of autophagy with rapamycin. Our results demonstrate the first use of a sialidosis-iNPC model with NEU1^G227R- and NEU1^V275A/R347Q- mutation(s) to study the neurological defects of sialidosis, particularly those related to a defective autophagy–lysosome pathway, and may help accelerate the development of new drugs and therapeutics to combat sialidosis and other LSDs.     

Public perceptions on artificial intelligence driven disaster management: Evidence from Sydney,Melbourne and Brisbane

In recent years, artificial intelligence (AI) is being increasingly utilised in disaster management activities. The public is engaged with AI in various ways in these activities. For instance, crowdsourcing applications developed for disaster management to handle the tasks of collecting data through social media platforms, and increasing disaster awareness through serious gaming applications. Nonetheless, there are limited empirical investigations and understanding on public perceptions concerning AI for disaster management. Bridging this knowledge gap is the justification for this paper. The methodological approach adopted involved: Initially, collecting data through an online survey from residents (n = 605) of three major Australian cities; Then, analysis of the data using statistical modelling. The analysis results revealed that: (a) Younger generations have a greater appreciation of opportunities created by AI-driven applications for disaster management; (b) People with tertiary education have a greater understanding of the benefits of AI in managing the pre- and post-disaster phases, and; (c) Public sector administrative and safety workers, who play a vital role in managing disasters, place a greater value on the contributions by AI in disaster management. The study advocates relevant authorities to consider public perceptions in their efforts in integrating AI in disaster management.     

Optimization of room-temperature TCR of polycrystalline La0.9-xSrxK0.1MnO3 ceramics by Sr adjustment

High-density La_0.9-xSr_xK_0.1MnO₃ ceramics (LSKMO, A-site = La, Sr and K, 0 ≤ x ≤ 0.25) are successfully fabricated by using facile sol-gel method. Electrical properties are performed by using combination of phenomenological percolation (PP) model, double exchange (DE) mechanism, and Jahn-Teller (JT) effect. Moreover, X-ray diffraction and scanning electron microscopy are employed to analyze the structure and morphology of LSKMO ceramics. Valence states and ionic stoichiometry are assessed by using X-ray photoemission spectrometry. Results reveal that Sr²⁺ ions, substituting La³⁺ ions, significantly influenced DE mechanism and JT effect. In addition, Sr-doping plays essential role in improving electrical properties of LSKMO ceramics. At optimal doping content of x = 0.09, peak temperature coefficient of resistance (TCR) of the resistivity is found to be 11.56% K^?1 at 297.15 K, which is optimal TCR for A-site K-occupied perovskite manganese oxides. These results confirm that polycrystalline LSKMO ceramics render high room-temperature TCR values due to Sr-doping.     

Nanolayer CrAlN/TiSiN coating designed for tribological applications

With the goal to produce a hard and tough coating intended for tribological applications, CrAlN/TiSiN nanolayer coating was prepared by alternative deposition of CrAlN and TiSiN layers. In the first part of the article, a detailed study of phase composition, microstructure, and layer structure of CrAlN/TiSiN coating is presented. In the second part, its mechanical properties, fracture and tribological behavior are compared to the nanocomposite TiSiN coating. An industrial magnetron sputtering unit was used for coating deposition. X-ray photoelectron spectroscopy, energy dispersive X-ray spectroscopy, X-ray diffraction, scanning electron microscopy, and transmission electron microscopy were used for compositional and microstructural analysis. Mechanical properties and fracture behavior were studied by instrumented indentation and focused ion beam techniques. Tribological properties were evaluated by ball-on-disk test in a linear reciprocal mode. A complex layer structure was found in the nanolayer coating. The TiSiN layers were epitaxially stabilized inside the coating which led to formation of dislocations at interfaces, to introduction of disturbances in the coating growth, and as a result, to development of fine-grained columnar microstructure. Indentation load required for the onset of fracture was twice lower for the nanolayer CrAlN/TiSiN, compared to the nanocomposite TiSiN coating. This agrees very well with their mechanical properties, with H³/E² being twice higher for the TiSiN coating. However, the nanolayer coating experienced less severe damage, which had a strong impact on tribological behavior. A magnitude of order lower wear rate and four times lower steady state friction coefficient were found for the nanolayer coating.     

Revealing the high sensitivity in the metal toinsulator transition properties of the pulsed laser deposited VO2 thin films

Vanadium dioxide (VO₂) is known as a typical 3d-orbital transition metal oxide exhibiting the metal-to-insulator-transition (MIT) property near room temperature. However, their electronic applications have been challenged by the quality and uniformity of VO₂ thin films. In this work, we demonstrate the high sensitivity in the valence charge of vanadium and the MIT properties of the VO₂ thin films to the deposition temperature. This observation indicates the necessity to eliminate the inhomogeneity in the temperature distribution of substrate during the vacuum-deposition process of VO₂. In addition, a high thermoelectric power factor (PF, e.g., exceeding 1 μWcm⁻¹K⁻²) was achieved in the metallic phase of the VO₂ thin films and this value is comparable to typical organic or oxide thermoelectric materials. We believe this high PF enriches the potential functionality in thermoelectric energy conversions beyond the existing electronic applications of the current vacuum-grown VO₂ thin films.