bluuebunny/crossref_metadata_2025 huggingface dataset:
Explainable Hopfield Neural Networks Using an Automatic Video-Generation System
Authors: Rubio-Manzano Clemente , Segura-Navarrete Alejandra , Martinez-Araneda Claudia , Vidal-Castro Christian
Published: June 2021

Hopfield Neural Networks (HNNs) are recurrent neural networks used to implement associative memory. They can be applied to pattern recognition, optimization, or image segmentation. However, sometimes it is not easy to provide the users with good explanations about the results obtained with them due to mainly the large number of changes in the state of neurons (and their weights) produced during a problem of machine learning. There are currently limited techniques to visualize, verbalize, or abstract HNNs. This paper outlines how we can construct automatic video-generation systems to explain its execution. This work constitutes a novel approach to obtain explainable artificial intelligence systems in general and HNNs in particular building on the theory of data-to-text systems and software visualization approaches. We present a complete methodology to build these kinds of systems. Software architecture is also designed, implemented, and tested. Technical details about the implementation are also detailed and explained. We apply our approach to creating a complete explainer video about the execution of HNNs on a small recognition problem. Finally, several aspects of the videos generated are evaluated (quality, content, motivation and design/presentation).
Assessment of Heat-Affected Zone Softening of Hot-Press-Formed Steel over 2.0 GPa Tensile Strength with Bead-On-Plate Laser Welding
Authors: Kim Kwangsoo , Kang Namhyun , Kang Minjung , Kim Cheolhee
Published: June 2021

High-strength hot-press-formed (HPF) steels with a fully martensitic microstructure are being widely used in the fabrication of automotive body structure, and 2.0 GPa-strength HPF steel has recently been commercially launched. However, heat-affected zone (HAZ) softening is unavoidable in welding martensitic steel. In this study, the HAZ softening characteristic of 2.0 GPa HPF steel was investigated by applying a high-brightness laser welding process, wherein the heat input was controlled by varying the welding speed. Microstructural evaluation and hardness test results showed that the base metal with a fully martensitic microstructure was changed to the same type of fully martensitic microstructure in the weld metal, while relatively soft microstructures of tempered martensite and ferrite phase were partially formed in the intercritical HAZ (ICHAZ) and subcritical HAZ (SCHAZ) areas. In the tensile test, the joint strength was 10–20% lower than that of the base metal, and the fracture initiation was estimated at the ICHAZ/SCHAZ boundary, where the lowest hardness was confirmed by the nanoindentation technique.
In Situ Neutron Radiography Investigations of Hydrogen Related Processes in Zirconium Alloys
Authors: Grosse Mirco , Schillinger Burkhardt , Kaestner Anders
Published: June 2021

In situ neutron radiography experiments can provide information about diffusive processes and the kinetics of chemical reactions. The paper discusses requirements for such investigations. As examples of the zirconium alloy Zircaloy-4, the hydrogen diffusion, the hydrogen uptake during high-temperature oxidation in steam, and the reaction in nitrogen/steam and air/steam atmospheres, results of in situ neutron radiography investigations are reviewed, and their benefit is discussed.
Effects of Garden Amendments on Soil Available Lead and Plant Uptake in a Contaminated Calcareous Soil
Authors: Geiger Tara , Norton Urszula
Published: June 2021

Gardeners use organic and inorganic substances to enhance plant growth, which can inadvertently impact soil solubility and plant uptake of unknown contaminants. Consequently, human exposure can increase through gardening and consumption of produce grown in potentially contaminated soils. A greenhouse experiment was established to examine the effects of biochar, compost, and common inorganic fertilizer on soil lead (Pb) availability for radish (Raphanus sativus, L.) and lettuce (Lactuca sativa, L.) grown in a calcareous soil containing excessively high lead (Pb), along with Pb accumulation in radish tissue. Results indicate that soil amended with biochar and planted to radish saw an 18% reduction in available Pb and an 11% decrease in plant tissue content when compared to the control. Compost showed an 8% reduction in available Pb, but a 19% increase in tissue content. In contrast, soil with inorganic fertilizer planted to radish increased in both soil Pb availability by 11% and Pb tissue content by 40%. Adding water-soluble inorganic fertilizers to contaminated calcareous soils without added organic matter enhances soil Pb availability and often asymptomatic plant Pb bioaccumulation. In conclusion, gardeners are encouraged to test their soils for contamination and apply biochar in combination with compost, as this combination is recommended to improve soil health and aid in overcoming initial N deficiencies induced by biochar.
Anti-Aging Effects of Nanovesicles Derived from Human Tonsil-Derived Mesenchymal Stem Cells
Authors: Kim Dohyun , Lee Youngdae , Park Kwangsook , Park Danbi , Lee Won Jai , Roh Tai Suk , Cho Hyungju , Baek Wooyeol
Published: June 2021

Growing evidence has demonstrated that biomimetic nanovesicles produced from specific cells show bioactive properties such as anti-tumor or anti-inflammatory activities. However, the properties of these nanovesicles are very diverse, depending on their cell sources. In this study, human tonsil-derived mesenchymal stem cells (TMSCs) were used in the production of functional biomimetic nanovesicles with anti-senescence. TMSCs were isolated from human tonsil tissue obtained by tonsillectomy. TMSC-derived nanovesicles (TMSC-NVs) were produced by serial extrusion using a mini-extruder. Western blotting and particle analysis were performed for characterization of TMSC-NVs. They were applied to both replicative and ultraviolet B-induced senescent human dermal fibroblasts in vitro. Following six days of treatment, analysis of the proliferation and senescence level of fibroblasts was performed using cell counting and senescence-associated β-galactosidase assay, respectively. Treatment with TMSC-NVs enhanced the cell proliferation and reduced the activity of senescence-associated β-galactosidase in both replicative and ultraviolet B-induced senescent cells. Treatment with TMSC-NVs resulted in increased expression of extracellular matrix and anti-oxidant genes. Treatment with TMSC-NVs resulted in reduced expression of vinculin in focal adhesion. These results show that TMSC-NVs have an effect on recovering from cellular senescence by oxidative stress and can be applied as useful materials for the development of skin rejuvenation.
A Predictive Analytics Infrastructure to Support a Trustworthy Early Warning System
Authors: Baneres David , Guerrero-Roldán Ana Elena , Rodríguez-González M. Elena , Karadeniz Abdulkadir
Published: June 2021

Learning analytics is quickly evolving. Old fashioned dashboards with descriptive information and trends about what happened in the past are slightly substituted by new dashboards with forecasting information and predicting relevant outcomes about learning. Artificial intelligence is aiding this revolution. The accessibility to computational resources has increased, and specific tools and packages for integrating artificial intelligence techniques leverage such new analytical tools. However, it is crucial to develop trustworthy systems, especially in education where skepticism about their application is due to the risk of teachers’ replacement. However, artificial intelligence systems should be seen as companions to empower teachers during the teaching and learning process. During the past years, the Universitat Oberta de Catalunya has advanced developing a data mart where all data about learners and campus utilization are stored for research purposes. The extensive collection of these educational data has been used to build a trustworthy early warning system whose infrastructure is introduced in this paper. The infrastructure supports such a trustworthy system built with artificial intelligence procedures to detect at-risk learners early on in order to help them to pass the course. To assess the system’s trustworthiness, we carried out an evaluation on the basis of the seven requirements of the European Assessment List for trustworthy artificial intelligence (ALTAI) guidelines that recognize an artificial intelligence system as a trustworthy one. Results show that it is feasible to build a trustworthy system wherein all seven ALTAI requirements are considered at once from the very beginning during the design phase.
Numerical Modeling of Single Pile Behaviors Due to Groundwater Level Rising
Authors: Phoban Harutus , Seeboonruang Uma , Lueprasert Prateep
Published: June 2021

Behaviors of the pile foundation due to groundwater level rising were analyzed by a series two-dimensional finite element analyses with fully coupled flow-deformation analysis. The different numerical models of single bore pile depth and diameter in Bangkok subsoil were represented with the parametric study. The pile–soil movement due to groundwater levels rising between numerical simulation and a previous experiment of the centrifuge test as the same condition are in good agreement. With rising groundwater level, the reduction of pile capacity can be evidently performed by the increase of pile settlement relative to soil surface. Moreover, the development of the plastic point captured by the finite element analysis revealed the mechanism behind the reduction of pile capacity. In this study, the evaluation of pile stability due to groundwater level rising for preliminary guidelines to protect existing structures are proposed.
Buffer Compliance Control of Space Robots Capturing a Non-Cooperative Spacecraft Based on Reinforcement Learning
Authors: Ai Haiping , Zhu An , Wang Jiajia , Yu Xiaoyan , Chen Li
Published: June 2021

Aiming at addressing the problem that the joints are easily destroyed by the impact torque during the process of space robot on-orbit capturing a non-cooperative spacecraft, a reinforcement learning control algorithm combined with a compliant mechanism is proposed to achieve buffer compliance control. The compliant mechanism can not only absorb the impact energy through the deformation of its internal spring, but also limit the impact torque to a safe range by combining with the compliance control strategy. First of all, the dynamic models of the space robot and the target spacecraft before capture are obtained by using the Lagrange approach and Newton-Euler method. After that, based on the law of conservation of momentum, the constraints of kinematics and velocity, the integrated dynamic model of the post-capture hybrid system is derived. Considering the unstable hybrid system, a buffer compliance control based on reinforcement learning is proposed for the stable control. The associative search network is employed to approximate unknown nonlinear functions, an adaptive critic network is utilized to construct reinforcement signal to tune the associative search network. The numerical simulation shows that the proposed control scheme can reduce the impact torque acting on joints by 76.6% at the maximum and 58.7% at the minimum in the capturing operation phase. And in the stable control phase, the impact torque acting on the joints were limited within the safety threshold, which can avoid overload and damage of the joint actuators.
Method for Establishing a Traveling Wave Sound Field with Adaptive Control in a Water-Filled Sound Tube
Authors: Xiao Yan , Zhang Xuesong
Published: June 2021

The transfer function method is a common method for establishing a traveling wave field in a sound tube to measure the reflection and transmission coefficient of underwater material. The voltage applied to the secondary sound source can be calculated in accordance with the transfer matrix between the sound sources and hydrophones, then a traveling wave field can be established in the sound tube. However, the transfer function must be remeasured when the measurement frequency needs to be changed. A checking procedure of the traveling wave field in the sound tube is essential before measuring underwater acoustic material. If it is not an accurate traveling wave field, the secondary sound source signal should be corrected until the traveling wave field meets the requirements. To address these problems, an adaptive control method for generating plane traveling waves is proposed. The phase difference of sound pressures measured using the two hydrophones between the secondary sound source and the sample is used as the objective function in the adaptive algorithm, and the amplitude and phase of the secondary sound source can be obtained using the adaptive control system in the frequency domain. When a traveling wave field is formed, the reflection and transmission coefficient of the sample can be measured at the same time. With this method, the procedure of testing the traveling wave field is omitted. If the state of the primary sound source changes, the signal form of the secondary sound source can be changed immediately. Therefore, the efficiency of material measurement is improved. Theoretically, this method can obtain the most matching signal form of the secondary sound source, such that the accuracy of this method is remarkably high. Simulation and experimental results in this paper show that the measurement accuracy is reliable within the frequency range of 100–2500 Hz.
Digital Workflow to Fabricate Complete Dentures for Edentulous Patients Using a Reversing and Superimposing Technique
Authors: Lee Hwa-Jung , Jeon Jeongho , Moon Hong Seok , Oh Kyung Chul
Published: June 2021

This technical procedure demonstrates a 4-step completely digital workflow for the fabrication of complete dentures in edentulous patients. The digital scan data of the edentulous arches were obtained using an intraoral scanner, followed by the fabrication of modeless trial denture bases using additive manufacturing. Using the trial denture base and a wax rim assembly, the interarch relationship was recorded. This record was digitized using an intraoral scanner and reversed for each maxillary and mandibular section individually. The digital scan data directly obtained using the intraoral scanner were superimposed over the reversed data, establishing a proper interarch relationship. The artificial teeth were arranged virtually and try-in dentures were additively manufactured. Subsequently, the gingival and tooth sections were additively manufactured individually and characterized. Thus, fabrication of digital complete dentures can be accomplished using digital data characteristics. The workflow includes data acquisition using an intraoral scanner, data processing using reverse engineering and computer-aided design software programs, and additive manufacturing.
Divergent Accumulation of Microbial Residues and Amino Sugars in Loess Soil after Six Years of Different Inorganic Nitrogen Enrichment Scenarios
Authors: Anning Dominic Kwadwo , Li Zhilong , Qiu Huizhen , Deng Delei , Zhang Chunhong , Ghanney Philip , Shen Qirong
Published: June 2021

Amino sugars are key microbial biomarkers for determining the contribution of microbial residues in soil organic matter (SOM). However, it remains largely unclear as to what extent inorganic nitrogen (N) fertilization can lead to the significant degradation of SOM in alkaline agricultural soils. A six-year field experiment was conducted from 2013 to 2018 to evaluate the effects of chronic N enrichment on microbial residues, amino sugars, and soil biochemical properties under four nitrogen (urea, 46% N) fertilization scenarios: 0 (no-N, control), 75 (low-N), 225 (medium-N), and 375 (high-N) kg N ha−1. The results showed that chronic N enrichment stimulated microbial residues and amino sugar accumulation over time. The medium-N treatment increased the concentration of muramic acid (15.77%), glucosamine (13.55%), galactosamine (18.84%), bacterial residues (16.88%), fungal residues (11.31%), and total microbial residues (12.57%) compared to the control in 2018; however, these concentrations were comparable to the high-N treatment concentrations. The ratio of glucosamine to galactosamine and of glucosamine to muramic acid decreased over time due to a larger increase in bacterial residues as compared to fungal residues. Microbial biomass, soil organic carbon, and aboveground plant biomass positively correlated with microbial residues and amino sugar components. Chronic N enrichment improved the soil biochemical properties and aboveground plant biomass, which stimulated microbial residues and amino sugar accumulation over time.
Discrete-Time Position Control for Autonomous Underwater Vehicle under Noisy Conditions
Authors: Liu Qiang , Li Muguo
Published: June 2021

This paper deals with the discrete-time position control problem for an autonomous underwater vehicle (AUV) under noisy conditions. Due to underwater noise, the velocity measurements returned by the AUV’s on-board sensors afford low accuracy, downgrading its control quality. Additionally, most of the hydrodynamic parameters of the AUV model are uncertain, further degrading the AUV control accuracy. Based on these findings, a discrete-time control law that improves the position control for the AUV trajectory tracking is presented to reduce the impact of these two factors. The proposed control law extends the Ensemble Kalman Filter and solves the problem of the traditional Ensemble Kalman Filter that underperforms when the hydrodynamic parameters of the AUV model are uncertain. The effectiveness of the proposed discrete-time controller is tested on various simulated scenarios and the results demonstrate that the proposed controller has appealing precision for AUV position tracking under noisy conditions and hydrodynamic parameter uncertainty. The proposed controller outperforms the conventional time-delay controller in root-mean-square error by a percentage range of approximately 72.1–97.4% and requires at least 89.5% less average calculation time than the conventional model predictive control.
Fabrication of Conductive and Gas-Sensing Microstructures Using Focused Deposition of Copper Nanoparticles Synthesized by Spark Discharge
Authors: Efimov Alexey A. , Kornyushin Denis V. , Buchnev Arseny I. , Kameneva Ekaterina I. , Lizunova Anna A. , Arsenov Pavel V. , Varfolomeev Andrey E. , Pavzderin Nikita B. , Nikonov Alexey V. , Ivanov Victor V.
Published: June 2021

Solvent-free aerosol jet printing has been investigated for fabricating metallic and semiconductor (gas-sensitive) microstructures based on copper nanoparticles on alumina, borosilicate glass, and silicon substrates. The synthesis of nanoparticles was carried out using a spark discharge directly in the printing process without the stage of preparing nano-ink. Printed lines with a width of 100–150 µm and a height of 5–7 µm were formed from submicron agglomerates consisting of primary nanoparticles 10.8 ± 4.9 nm in size with an amorphous oxide shell. The electrical resistivity, surface morphology, and shrinkage of printed lines were investigated depending on the reduction sintering temperature. Sintering of copper oxides of nanoparticles began at a temperature of 450 °C in a hydrogen atmosphere with shrinkage at the level of 45–60%. Moreover, aerosol heat treatment was used to obtain highly conductive lines by increasing the packing density of deposited nanoparticles, providing in-situ transformation of submicron agglomerates into spherical nanoparticles with a size of 20–50 nm. Copper lines of spherical nanoparticles demonstrated excellent resistivity at 5 μΩ·cm, about three times higher than that of bulk copper. In turn, semiconductor microstructures based on unsintered agglomerates of oxidized copper have a fairly high sensitivity to NH3 and CO. Values of response of the sensor based on non-sintered oxidized copper nanoparticles to ammonia and carbon monoxide concentration of 40 ppm were about 20% and 80%, respectively.
Nonparametric Bayesian Learning of Infinite Multivariate Generalized Normal Mixture Models and Its Applications
Authors: Bourouis Sami , Alroobaea Roobaea , Rubaiee Saeed , Andejany Murad , Bouguila Nizar
Published: June 2021

This paper addresses the problem of data vectors modeling, classification and recognition using infinite mixture models, which have been shown to be an effective alternative to finite mixtures in terms of selecting the optimal number of clusters. In this work, we propose a novel approach for localized features modelling using an infinite mixture model based on multivariate generalized Normal distributions (inMGNM). The statistical mixture is learned via a nonparametric MCMC-based Bayesian approach in order to avoid the crucial problem of model over-fitting and to allow uncertainty in the number of mixture components. Robust descriptors are derived from encoding features with the Fisher vector method, which considers higher order statistics. These descriptors are combined with a linear support vector machine classifier in order to achieve higher accuracy. The efficiency and merits of the proposed nonparametric Bayesian learning approach, while comparing it to other different methods, are demonstrated via two challenging applications, namely texture classification and human activity categorization.
Exploring the Role of Distraction in Weak Flow–Performance Link Based on VR Searching Tasks
Authors: Liu Weiying , Hu Haoxiang , Zhou Chao , Bian Yulong , Liu Juan
Published: June 2021

The weak association between flow experience and task performance (also known as weak flow-performance link) can reduce the positive effect of virtual reality (VR) applications. Distraction caused by incongruence between the primary task and interactive artifacts may be a direct factor leading to the weak link, but it has still not been tested. To empirically test this assumption and explore approaches to alleviate it, we developed the ‘VR searching paradigm’ and a prototype VR system, based on which three comparative experiments were conducted. Study 1 tested the effect of distraction and proved that high levels of distraction caused by incongruence can lead to the weak link (β = 0.198, p = 0.391). Next, two common design guidelines were proposed to deal with distraction. Study 2 tested the effect of reducing conspicuous but task-irrelevant distractors (guideline 1) on flow-performance link. Study 3 tested the effect of providing visual cues (utilizing distractors to achieve task-oriented selective attention), which is guideline 2, on flow-performance link. The results of studies 2 and 3 revealed that both guidelines helped enhance the task performance without damaging flow experience, alleviating the weak link problem (β = 0.351, p = 0.031; β = 0.255, p = 0.041). Our results provide the first piece of evidence that directly proves the effect of distraction on weak flow-performance link, which helps improve the explanation of the mechanism. Moreover, this paper is the first that proves the effectiveness of two easy approaches to alleviating the weak link by way of guiding the user’s task-relevant attention.
Animals in Human Situations in Ancient Egyptian Ostraca and Papyri
Authors: Ezzat Azza
Published: June 2021

It has been said that the ancient Egyptians were raised to tolerate all kinds of toil and hardship; they nevertheless also liked to amuse themselves with comic relief in their everyday life. For example, ancient Egyptian drawing can be quite accurate and at times even spirited. What scholars have described as caricatures are as informative and artistic as supposed serious works of art. Ancient Egyptians have left countless images representing religious, political, economic, and/or social aspects of their life. Scenes in Egyptian tombs could be imitated on ostraca (potsherds) that portray animals as characters performing what would normally be human roles, behaviors, or occupations. These scenes reveal the artists’ sense of comedy and humor and demonstrate their freedom of thought and expression to reproduce such lighthearted imitations of religious or funeral scenes. This paper will focus on a selection of drawings on ostraca as well as three papyri that show animals—often dressed in human garb and posing with human gestures—performing parodies of human pursuits (such as scribes, servants, musicians, dancers, leaders, and herdsmen).
The Optimization of Aircraft Acceleration Response and EDR Estimation Based on Linear Turbulence Field Approximation
Authors: Wang Debao , Gao Zhenxing , Gu Hongbin , Guan Xinyu
Published: June 2021

The estimation of aircraft vertical acceleration response to atmospheric turbulence is fundamental to acceleration-based eddy dissipation rate (EDR) estimation. The linear turbulence field approximation with the wind gradients effects is utilized to describe the turbulence effects on civil aviation aircraft. To consider the wind gradients effects, the aircraft was modeled by a cruciform assembly in this study. A vertical acceleration estimation based on the unsteady vortex lattice method (UVLM) was proposed, in which the air-compression effects in high-subsonic flight were compensated by the Karman–Tsien rule. Results indicate that compared with the wing-tail assembly, the cruciform assembly with the wind gradients effects has better accuracy in computing acceleration response. The vertical acceleration response only induced by turbulence can be obtained for acceleration-based EDR estimation. Furthermore, with the optimized acceleration response, the estimated EDR value has got better accuracy and stability.
A Preliminary Validation of a New Surgical Procedure for the Treatment of Primary Bladder Neck Obstruction Using a Computational Modeling Approach
Authors: Serpilli Michele , Zitti Gianluca , Dellabella Marco , Castellani Daniele , Maranesi Elvira , Morettini Micaela , Lenci Stefano , Burattini Laura
Published: June 2021

A new surgical procedure for the treatment of primary bladder neck obstruction with maintenance of anterograde ejaculation is proposed. In place of monolateral or bilateral bladder neck incision, associated with a loss of ejaculation rate of up to 30%, the new surgical procedure consists of laser drilling the bladder neck with a number of holes and without muscle fiber disruption. The effect of this novel procedure has been studied numerically, with a simplified two-dimensional numerical model of the internal urethral sphincter, varying the position and the number of holes in the fibrotic region of the urethral tissue. Results show an improvement of the urethral sphincter opening by increasing the number of holes, ranging from about 6% to 16% of recovery. Moreover, a non-aligned position of holes positively influences the opening recovery. The concentrations of maximum principal strain and stress have been registered in the proximity of the interface between the physiologic and diseased sphincter, and in those regions where the radial thickness is significantly thinner. The effects on the first five patients have been included in the study, showing improvement in micturition, lower urinary tract symptoms, sustained ejaculatory function, and quality of life.
Electrospun Microfibers Modulate Intracellular Amino Acids in Liver Cells via Integrin β1
Authors: Huang Tianjiao , Terrell John A. , Chung Jay H. , Chen Chengpeng
Published: June 2021

Although numerous recent studies have shown the importance of polymeric microfibrous extracellular matrices (ECMs) in maintaining cell behaviors and functions, the mechanistic nexus between ECMs and intracellular activities is largely unknown. Nevertheless, this knowledge will be critical in understanding and treating diseases with ECM remodeling. Therefore, we present our findings that ECM microstructures could regulate intracellular amino acid levels in liver cells mechanistically through integrin β1. Amino acids were studied because they are the fundamental blocks for protein synthesis and metabolism, two vital functions of liver cells. Two ECM conditions, flat and microfibrous, were prepared and studied. In addition to characterizing cell growth, albumin production, urea synthesis, and cytochrome p450 activity, we found that the microfibrous ECM generally upregulated the intracellular amino acid levels. Further explorations showed that cells on the flat substrate expressed more integrin β1 than cells on the microfibers. Moreover, after partially blocking integrin β1 in cells on the flat substrate, the intracellular amino acid levels were restored, strongly supporting integrin β1 as the linking mechanism. This is the first study to report that a non-biological polymer matrix could regulate intracellular amino acid patterns through integrin. The results will help with future therapy development for liver diseases with ECM changes (e.g., fibrosis).
Molecular Mechanisms of Borrelia burgdorferi Phagocytosis and Intracellular Processing by Human Macrophages
Authors: Woitzik Philipp , Linder Stefan
Published: June 2021

Lyme disease is the most common vector-borne illness in North America and Europe. Its causative agents are spirochetes of the Borrelia burgdorferi sensu latu complex. Infection with borreliae can manifest in different tissues, most commonly in the skin and joints, but in severe cases also in the nervous systems and the heart. The immune response of the host is a crucial factor for preventing the development or progression of Lyme disease. Macrophages are part of the innate immune system and thus one of the first cells to encounter infecting borreliae. As professional phagocytes, they are capable of recognition, uptake, intracellular processing and final elimination of borreliae. This sequence of events involves the initial capture and internalization by actin-rich cellular protrusions, filopodia and coiling pseudopods. Uptake into phagosomes is followed by compaction of the elongated spirochetes and degradation in mature phagolysosomes. In this review, we discuss the current knowledge about the processes and molecular mechanisms involved in recognition, capturing, uptake and intracellular processing of Borrelia by human macrophages. Moreover, we highlight interactions between macrophages and other cells of the immune system during these processes and point out open questions in the intracellular processing of borreliae, which include potential escape strategies of Borrelia.
Remdesivir MD Simulations Suggest a More Favourable Binding to SARS-CoV-2 RNA Dependent RNA Polymerase Mutant P323L Than Wild-Type
Authors: Mohammad Anwar , Al-Mulla Fahd , Wei Dong-Qing , Abubaker Jehad
Published: June 2021

SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) protein is the target for the antiviral drug Remdesivir (RDV). With RDV clinical trials on COVID-19 patients showing a reduced hospitalisation time. During the spread of the virus, the RdRp has developed several mutations, with the most frequent being A97V and P323L. The current study sought to investigate whether A97V and P323L mutations influence the binding of RDV to the RdRp of SARS-CoV-2 compared to wild-type (WT). The interaction of RDV with WT-, A97V-, and P323L-RdRp were measured using molecular dynamic (MD) simulations, and the free binding energies were extracted. Results showed that RDV that bound to WT- and A97V-RdRp had a similar dynamic motion and internal residue fluctuations, whereas RDV interaction with P323L-RdRp exhibited a tighter molecular conformation, with a high internal motion near the active site. This was further corroborated with RDV showing a higher binding affinity to P323L-RdRp (−24.1 kcal/mol) in comparison to WT-RdRp (−17.3 kcal/mol). This study provides insight into the potential significance of administering RDV to patients carrying the SARS-CoV-2 P323L-RdRp mutation, which may have a more favourable chance of alleviating the SARS-CoV-2 illness in comparison to WT-RdRp carriers, thereby suggesting further scientific consensus for the usage of Remdesivir as clinical candidate against COVID-19.
Rifamycin W Analogues from Amycolatopsis mediterranei S699 Δrif-orf5 Strain
Authors: Shi Yanrong , Ye Feng , Song Yuliang , Zhang Xiaochun , Lu Chunhua , Shen Yuemao
Published: June 2021

Rifamycin W, the most predominant intermediate in the biosynthesis of rifamycin, needs to undergo polyketide backbone rearrangement to produce rifamycin B via an oxidative cleavage of the C-12/C-29 double bond. However, the mechanism of this putative oxidative cleavage has not been characterized yet. Rif-Orf5 (a putative cytochrome P450 monooxygenase) was proposed to be involved in the cleavage of this olefinic moiety of rifamycin W. In this study, the mutant strain Amycolatopsis mediterranei S699 Δrif-orf5 was constructed by in-frame deleting the rif-orf5 gene to afford thirteen rifamycin W congeners (1–13) including seven new ones (1–7). Their structures were elucidated by extensive analysis of 1D and 2D NMR spectroscopic data and high-resolution ESI mass spectra. Presumably, compounds 1–4 were derivatized from rifamycin W via C-5/C-11 retro-Claisen cleavage, and compounds 1–3, 9 and 10 featured a hemiacetal. Compounds 5–7 and 11 showed oxygenations at various sites of the ansa chain. In addition, compounds 1–3 exhibited antibacterial activity against Staphylococcus aureus with minimal inhibitory concentration (MIC) values of 5, 40 and 0.5 µg/mL, respectively. Compounds 1 and 3 showed modest antiproliferative activity against HeLa and Caco-2 cells with half maximal inhibitory concentration (IC50) values of about 50 µM.
A Metalloproteinase Induces an Inflammatory Response in Preadipocytes with the Activation of COX Signalling Pathways and Participation of Endogenous Phospholipases A2
Authors: Janovits Priscila Motta , Leiguez Elbio , Portas Viviane , Teixeira Catarina
Published: June 2021

Matrix metalloproteinases (MMPs) are proteolytic enzymes that have been associated with the pathogenesis of inflammatory diseases and obesity. Adipose tissue in turn is an active endocrine organ capable of secreting a range of proinflammatory mediators with autocrine and paracrine properties, which contribute to the inflammation of adipose tissue and adjacent tissues. However, the potential inflammatory effects of MMPs in adipose tissue cells are still unknown. This study investigates the effects of BmooMPα-I, a single-domain snake venom metalloproteinase (SVMP), in activating an inflammatory response by 3T3-L1 preadipocytes in culture, focusing on prostaglandins (PGs), cytokines, and adipocytokines biosynthesis and mechanisms involved in prostaglandin E2 (PGE2) release. The results show that BmooMPα-I induced the release of PGE2, prostaglandin I2 (PGI2), monocyte chemoattractant protein-1 (MCP-1), and adiponectin by preadipocytes. BmooMPα-I-induced PGE2 biosynthesis was dependent on group-IIA-secreted phospholipase A2 (sPLA2-IIA), cytosolic phospholipase A2-α (cPLA2-α), and cyclooxygenase (COX)-1 and -2 pathways. Moreover, BmooMPα-I upregulated COX-2 protein expression but not microsomal prostaglandin E synthase-1 (mPGES-1) expression. In addition, we demonstrate that the enzymatic activity of BmooMPα-I is essential for the activation of prostanoid synthesis pathways in preadipocytes. These data highlight preadipocytes as important targets for metalloproteinases and provide new insights into the contribution of these enzymes to the inflammation of adipose tissue and tissues adjacent to it.
Gelatin-Graphene Oxide Nanocomposite Hydrogels for Kluyveromyces lactis Encapsulation: Potential Applications in Probiotics and Bioreactor Packings
Authors: Patarroyo Jorge Luis , Fonseca Eduardo , Cifuentes Javier , Salcedo Felipe , Cruz Juan C. , Reyes Luis H.
Published: June 2021

Nutraceutical formulations based on probiotic microorganisms have gained significant attention over the past decade due to their beneficial properties on human health. Yeasts offer some advantages over other probiotic organisms, such as immunomodulatory properties, anticancer effects and effective suppression of pathogens. However, one of the main challenges for their oral administration is ensuring that cell viability remains high enough for a sustained therapeutic effect while avoiding possible substrate inhibition issues as they transit through the gastrointestinal (GI) tract. Here, we propose addressing these issues using a probiotic yeast encapsulation strategy, Kluyveromyces lactis, based on gelatin hydrogels doubly cross-linked with graphene oxide (GO) and glutaraldehyde to form highly resistant nanocomposite encapsulates. GO was selected here as a reinforcement agent due to its unique properties, including superior solubility and dispersibility in water and other solvents, high biocompatibility, antimicrobial activity, and response to electrical fields in its reduced form. Finally, GO has been reported to enhance the mechanical properties of several materials, including natural and synthetic polymers and ceramics. The synthesized GO-gelatin nanocomposite hydrogels were characterized in morphological, swelling, mechanical, thermal, and rheological properties and their ability to maintain probiotic cell viability. The obtained nanocomposites exhibited larger pore sizes for successful cell entrapment and proliferation, tunable degradation rates, pH-dependent swelling ratio, and higher mechanical stability and integrity in simulated GI media and during bioreactor operation. These results encourage us to consider the application of the obtained nanocomposites to not only formulate high-performance nutraceuticals but to extend it to tissue engineering, bioadhesives, smart coatings, controlled release systems, and bioproduction of highly added value metabolites.
Composition of Transcription Machinery and Its Crosstalk with Nucleoid-Associated Proteins and Global Transcription Factors
Authors: Muskhelishvili Georgi , Sobetzko Patrick , Mehandziska Sanja , Travers Andrew
Published: June 2021

The coordination of bacterial genomic transcription involves an intricate network of interdependent genes encoding nucleoid-associated proteins (NAPs), DNA topoisomerases, RNA polymerase subunits and modulators of transcription machinery. The central element of this homeostatic regulatory system, integrating the information on cellular physiological state and producing a corresponding transcriptional response, is the multi-subunit RNA polymerase (RNAP) holoenzyme. In this review article, we argue that recent observations revealing DNA topoisomerases and metabolic enzymes associated with RNAP supramolecular complex support the notion of structural coupling between transcription machinery, DNA topology and cellular metabolism as a fundamental device coordinating the spatiotemporal genomic transcription. We analyse the impacts of various combinations of RNAP holoenzymes and global transcriptional regulators such as abundant NAPs, on genomic transcription from this viewpoint, monitoring the spatiotemporal patterns of couplons—overlapping subsets of the regulons of NAPs and RNAP sigma factors. We show that the temporal expression of regulons is by and large, correlated with that of cognate regulatory genes, whereas both the spatial organization and temporal expression of couplons is distinctly impacted by the regulons of NAPs and sigma factors. We propose that the coordination of the growth phase-dependent concentration gradients of global regulators with chromosome configurational dynamics determines the spatiotemporal patterns of genomic expression.
Molecular Biomarkers of Oxygen Therapy in Patients with Diabetic Foot Ulcers
Authors: Oropallo Alisha R. , Serena Thomas E. , Armstrong David G. , Niederauer Mark Q.
Published: June 2021

Hyperbaric oxygen therapy (HBOT) and topical oxygen therapy (TOT) including continuous diffuse oxygen therapy (CDOT) are often utilized to enhance wound healing in patients with diabetic foot ulcerations. High pressure pure oxygen assists in the oxygenation of hypoxic wounds to increase perfusion. Although oxygen therapy provides wound healing benefits to some patients with diabetic foot ulcers, it is currently performed from clinical examination and imaging. Data suggest that oxygen therapy promotes wound healing via angiogenesis, the creation of new blood vessels. Molecular biomarkers relating to tissue inflammation, repair, and healing have been identified. Predictive biomarkers can be used to identify patients who will most likely benefit from this specialized treatment. In diabetic foot ulcerations, specifically, certain biomarkers have been linked to factors involving angiogenesis and inflammation, two crucial aspects of wound healing. In this review, the mechanism of how oxygen works in wound healing on a physiological basis, such as cell metabolism and growth factor signaling transduction is detailed. Additionally, observable clinical outcomes such as collagen formation, angiogenesis, respiratory burst and cell proliferation are described. The scientific evidence for the impact of oxygen on biomolecular pathways and its relationship to the outcomes in clinical research is discussed in this narrative review.
Effect of Gender and Anthropometrics on the Kinematics of the Lunge in Young Foil Fencers (Lunge Kinematics in Young Fencers)
Authors: Mocco Alessio , Wang Jun , Cicchella Antonio
Published: June 2021

Knowledge of the kinematics of young fencers is important when teaching fencing, but it has been minimally investigated in the literature, especially in young subjects, and further research is needed. Our aims were to assess whether anthropometric factors or kinematic factors are more closely related to lunge performance (speed and range of motion) in young fencers and to investigate gender differences in relation to kinematics. Fifteen fencers participated in this study (8 females and 7 males; age 12.9 ± 2.7 years, height 157.4 ± 15.1 cm, weight 49.7 ± 11.7 kg). Lunge kinematics and anthropometrics were collected with a 10-camera optoelectronic system. Descriptive statistics, bivariate correlation, t-test, and simple regression were performed. Peak lunge velocity was mainly correlated with posterior knee extension (r = 0.56, p = 0.031). The lunge distance and mean hip velocity were mostly correlated with the fencers’ height (r = 0.85, p = 0.000 and r = 0.76, p = 0.001) and fat-free mass (r = 0.79, p = 0.000 and r = 0.73, p = 0.002). Young fencers use a lower limb-driven strategy to perform the lunge, while adults are reported to use an upper limb-driven strategy for the lunge attack. Linear and angular velocities and ranges of motion were lower in young fencers in comparison to those of adults. Based on these results, we suggest a different approach to teaching the lunge action in young foil fencers. The implications of our study are that when teaching the lunge technique to this age group, a different approach for males and females is not required, and that strength is not a discriminant physical quality for the correctness of performance.
Neuroinflammation in Ischemic Stroke: Inhibition of cAMP-Specific Phosphodiesterases (PDEs) to the Rescue
Authors: Ponsaerts Laura , Alders Lotte , Schepers Melissa , de Oliveira Rúbia Maria Weffort , Prickaerts Jos , Vanmierlo Tim , Bronckaers Annelies
Published: June 2021

Ischemic stroke is caused by a thromboembolic occlusion of a major cerebral artery, with the impaired blood flow triggering neuroinflammation and subsequent neuronal damage. Both the innate immune system (e.g., neutrophils, monocytes/macrophages) in the acute ischemic stroke phase and the adaptive immune system (e.g., T cells, B cells) in the chronic phase contribute to this neuroinflammatory process. Considering that the available therapeutic strategies are insufficiently successful, there is an urgent need for novel treatment options. It has been shown that increasing cAMP levels lowers neuroinflammation. By inhibiting cAMP-specific phosphodiesterases (PDEs), i.e., PDE4, 7, and 8, neuroinflammation can be tempered through elevating cAMP levels and, thereby, this can induce an improved functional recovery. This review discusses recent preclinical findings, clinical implications, and future perspectives of cAMP-specific PDE inhibition as a novel research interest for the treatment of ischemic stroke. In particular, PDE4 inhibition has been extensively studied, and is promising for the treatment of acute neuroinflammation following a stroke, whereas PDE7 and 8 inhibition more target the T cell component. In addition, more targeted PDE4 gene inhibition, or combined PDE4 and PDE7 or 8 inhibition, requires more extensive research.
The Pathways Underlying the Multiple Roles of p62 in Inflammation and Cancer
Authors: Hennig Paulina , Fenini Gabriele , Di Filippo Michela , Karakaya Tugay , Beer Hans-Dietmar
Published: June 2021

p62 is a highly conserved, multi-domain, and multi-functional adaptor protein critically involved in several important cellular processes. Via its pronounced domain architecture, p62 binds to numerous interaction partners, thereby influencing key pathways that regulate tissue homeostasis, inflammation, and several common diseases including cancer. Via binding of ubiquitin chains, p62 acts in an anti-inflammatory manner as an adaptor for the auto-, xeno-, and mitophagy-dependent degradation of proteins, pathogens, and mitochondria. Furthermore, p62 is a negative regulator of inflammasome complexes. The transcription factor Nrf2 regulates expression of a bundle of ROS detoxifying genes. p62 activates Nrf2 by interaction with and autophagosomal degradation of the Nrf2 inhibitor Keap1. Moreover, p62 activates mTOR, the central kinase of the mTORC1 sensor complex that controls cell proliferation and differentiation. Through different mechanisms, p62 acts as a positive regulator of the transcription factor NF-κB, a central player in inflammation and cancer development. Therefore, p62 represents not only a cargo receptor for autophagy, but also a central signaling hub, linking several important pro- and anti-inflammatory pathways. This review aims to summarize knowledge about the molecular mechanisms underlying the roles of p62 in health and disease. In particular, different types of tumors are characterized by deregulated levels of p62. The elucidation of how p62 contributes to inflammation and cancer progression at the molecular level might promote the development of novel therapeutic strategies.
Sex Difference in Peripheral Inflammatory Biomarkers in Drug-Naïve Patients with Major Depression in Young Adulthood
Authors: Kim Jinho , Kim Jong-Hoon , Chang Keun-A
Published: June 2021

The number of patients with major depressive disorder (MDD) is increasing worldwide. In particular, the early onset of MDD from adolescence to young adulthood is more problematic than the later onset. The specific and expeditious identification of MDD before the occurrence of severe symptoms is significant for future interventions or therapies; however, there is no accurate diagnostic marker that has sufficient sensitivity and specificity for clinical use. In the present study, to identify the possibility of blood markers for depression, we first measured the baseline inflammatory biomarkers in the peripheral blood of 50 treatment-naïve young adults with MDD and 50 matched healthy controls. We then analyzed the correlation between prospective biomarkers and depressive symptoms using scores from various clinical depression indices. We also identified differential responses between males and females in prospective biomarkers. In young adulthood, men with MDD had increased peripheral interleukin (IL)-17 levels, whereas women with MDD had significantly increased IL-1β, IL-6, and C-reactive protein (CRP) levels compared with healthy controls. However, tumor necrosis factor-α (TNF-α), CCL1, CCL2, adiponectin, and cortisol were not significantly different in young adult individuals with MDD. Higher levels of IL-17 in the male group and of IL-1β, IL-6, and CRP in the female group may have been associated with the clinical symptoms of MDD, including depressive moods, hopelessness, suicidal ideation, low self-esteem, and reduced psychological resilience. Our findings will be useful in developing diagnostic tools or treatments for MDD in young adulthood.