bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevation Angle Characterization for LEO Satellites: First and Second Order Statistics
Authors: Gongora-Torres Juan Misael , Vargas-Rosales Cesar , Aragón-Zavala Alejandro , Villalpando-Hernandez Rafaela
Published: March 2023

The elevation angle θ is relevant for the Low Earth orbit (LEO) satellite communications since it is always changing its relative position with respect to fixed Earth stations (ES’s), and this affects the link length and received power, PR. This article provides a new methodology to compute the probability density function (PDF) and cumulative distribution function (CDF) of the elevation angle, θ, for diverse ES locations. This methodology requires as input parameters an ES latitude, ϕ, an orbit inclination value, i, and an orbit altitude, h. The elevation angle is characterized through a well known random variable, which facilitates the computation of the first and second-order statistics, and helps to determine the expected value and measures of dispersion of the angle θ for a particular ES location. The proposed methodology allows an easy and quick calculation of the elevation angle’s CDF, facilitating comparisons against CDF’s of more ES’s located at different latitudes, and longitudes, λ; as well as the comparisons of CDF’s of the elevation angle produced by different orbits. Extensive simulation results are summarized in a small table, which allows computation of the elevation angle’s CDF and PDF for multiple ES locations without requiring of simulations and statistical fitting. Finally, the proposed methodology is validated through an extensive error analysis that show the suitability of the obtained results to characterize the elevation angle.
Comparing the Pore Networks of Coal, Shale, and Tight Sandstone Reservoirs of Shanxi Formation, Qinshui Basin: Inspirations for Multi-Superimposed Gas Systems in Coal-Bearing Strata
Authors: Zhao Difei , Zhang Jiaming , Guan Xin , Liu Dandan , Wang Qinxia , Jiao Weiwei , Zhou Xueqing , Li Yingjie , Wang Geoff , Guo Yinghai
Published: March 2023

Transitional upper carboniferous Shanxi Formation coal-bearing strata in Qinshui Basin have been proven to be a set of mixed unconventional gas-bearing reservoirs forming a multi-superimposed gas system that consists of multiple independent fluid pressure systems vertically through the strata. An experimental protocol was designed to compare the pore networks in high-rank coal, shale, and tight sandstone reservoirs from Shanxi Formation using quantitative and qualitative experimental methods, including high-pressure mercury injection porosimetry (MIP), low-pressure nitrogen gas adsorption (LN2GA), and argon ion polishing–field emission scanning electron microscope (AIP-FESEM). The results show that genetic and structural differences in pore types, morphology, abundance, and proportion in coal, shale, and tight sandstone reservoirs are significant, reflecting strong heterogeneity characteristics. Pore networks determine the roles of different types of reservoirs in gas-bearing systems through differentiated pore structure, development degree, and spatial distribution. Due to the differences in nanopore development and connectivity, coal and tight sandstone reservoirs provide important reservoir spaces for adsorbed and free gas in the system. Thus, they become influential factors controlling the relationship between the gas-bearing subsystems with different fluid pressures. The lack of mesopores in shale and relatively weaker heterogeneity between layers lead to the phenomenon that continuously developed shales of a specific thickness are more likely to be the interlayers that divide the superimposed gas-bearing system. Systematic comparison of pore development characteristics will provide scientific support to further explain the formation mechanism of multi-superimposed gas systems in coal-bearing strata from the perspective of pore networks and provide guidance for the development of unconventional natural gas in coal-bearing strata.
Design of a Mixed Reality System for Simulating Indoor Disaster Rescue
Authors: Chae Yoon-Jae , Lee Ho-Won , Kim Jong-Hyuk , Hwang Se-Woong , Park Yoon-Young
Published: March 2023

Modern buildings are large and complex, and as more time is spent inside them, the risk of indoor disasters such as fires and gas leaks increases. In the event of such a disaster, the success of the rescue operation depends on the ability of the rescue team to navigate and respond to the complex environment. To address this challenge, we designed a mixed reality (MR)-based system simulating indoor disaster rescue. This system uses augmented indoor maps and MR technology to help rescue teams quickly, and effectively respond to unexpected environmental variables and carry out rescue activities. To test the effectiveness of the system, we created a virtual disaster scenario and evaluated the rescue and escape performance within a shortened “golden time” of 2 min, as opposed to 5 min, given the virtual characteristics of the simulation. The results showed that the system is particularly effective at increasing the speed of rescue activities. Additionally, our results indicated the potential for further improvement through additional research. By applying this system for disaster rescue simulations and training, the safety of firefighters and rescuers can be improved by reducing the risk of injury during rescue operations.
Soil-Surface-Image-Feature-Based Rapid Prediction of Soil Water Content and Bulk Density Using a Deep Neural Network
Authors: Kim Donggeun , Kim Taejin , Jeon Jihun , Son Younghwan
Published: March 2023

This study aimed to develop a deep neural network model for predicting the soil water content and bulk density of soil based on features extracted from in situ soil surface images. Soil surface images were acquired using a Canon EOS 100d camera. The camera was installed in the vertical direction above the soil surface layer. To maintain uniform illumination conditions, a dark room and LED lighting were utilized. Following the acquisition of soil surface images, soil samples were collected using a metal cylinder to obtain measurements of soil water content and bulk density. Various features were extracted from the images, including color, texture, and shape features, and used as inputs for both a multiple regression analysis and a deep neural network model. The results show that the deep neural network regression model can predict soil water content and bulk density with root mean squared error of 1.52% and 0.78 kN/m3. The deep neural network model outperformed the multiple regression analysis, achieving a high accuracy for predicting both soil water content and bulk density. These findings suggest that in situ soil surface images, combined with deep learning techniques, can provide a fast and reliable method for predicting important soil properties.
Research on Railway Emergency Resources Scheduling Model under Multiple Uncertainties
Authors: Tang Zhaoping , Li Wenda , Zhou Shengyu , Sun Jianping
Published: March 2023

This paper discusses the optimization of emergency resource scheduling for major railway emergencies under multiple uncertainties while considering the uncertainties in demand, reserve, and transportation costs of resources. We introduce a novel approach that integrates stochastic mathematical programming, interval parameter programming, and fuzzy mathematical programming to study uncertain parameter interactions and coupling. A two-stage interval fuzzy credibility-constrained model is established and solved using an interval interactive algorithm. Finally, through a case study on China Railway Nanchang Group Co., Ltd., the novelty and effectiveness of the proposed method for optimizing emergency resource scheduling strategies under multiple uncertainties are demonstrated.
Trajectory Optimization of High-Speed Robotic Positioning with Suppressed Motion Jerk via Improved Chicken Swarm Algorithm
Authors: Li Yankun , Lu Yuyang , Li Dongya , Zhou Minning , Xu Chonghai , Gao Xiaozhi , Liu Yu
Published: March 2023

For the trajectory optimization of the time–jerk of robotic arms with a chicken swarm optimization algorithm, using five-order B-spline interpolation can ensure smooth and continuous acceleration, but, due to the performance problems of the algorithm, the low solution accuracy and the slow convergence speed, the ideal trajectory curve cannot be obtained. To address these problems, an improved chicken swarm algorithm based on a parallel strategy and dynamic constraints (PDCSO) is proposed, where the rooster update method is employed with a parallel strategy using X-best guidance and a Levy flight step. Dynamic constraints for the rooster are given, followed by the hens, and the optimal rooster position that improved the convergence accuracy while preventing the local optimum was determined. Simulation experiments using 18 classical test functions showed that the PDCSO algorithm outperformed other comparative algorithms in terms of convergence speed, solution accuracy and solution stability. Simulation validation in ADAMS and real machine tests proved that PDCSO can effectively reduce the running time and motion shock for robotic arms and improve the execution efficiency of such arms.
Lithium-Ion Battery Aging Analysis of an Electric Vehicle Fleet Using a Tailored Neural Network Structure
Authors: Lehmann Thomas , Weiß Frances
Published: March 2023

Within the presented research study we want to estimate the State of Health (SOH) of a fleet of electric vehicles solely using field data. This information may not only help operators during mission planning, but it can reveal causes of accelerated aging. For this purpose, we use a customized neural network that is able to process the data of all fleet vehicles simultaneously. Thus, information between batteries of the different vehicles is transferred and the extrapolation properties are enhanced. We firstly show results with data gathered from a fleet of 25 electric buses. A prediction accuracy of below 5 mV could be obtained for most validation sections. Furthermore, a proof-of-concept experiment illustrates the advantages of the fleet learning approach.
Investigation into the Construction Response of Tunnels through Fault: Model Test
Authors: Li Pan , Xie Shaohua , Yang Xiaohua , Wang Zhichao , Wang Shaofei
Published: March 2023

The fractured zone poses a significant risk to construction safety and structure durability in tunnel engineering. However, the effect of excavation methods has not been thoroughly investigated in previous studies. This paper presents a series of 1:30 scale 3D model tests on fault tunnels under the coupling effect of different fault dip angles and construction steps. We measured and analyzed the rock mass deformation and lining structure stress to explore the influence of tunnel excavation by the CD method. The model test results were verified by numerical simulation using the prototype tunnel parameters. Our results show that steeper fault dips correspond to greater radial pressure of the surrounding rock, and pressure in both haunt positions changes more significantly than that in the vault position, while pressure in the side-wall position changes only slightly. Additionally, considerable deformation can be observed in the vault and both haunt positions, with a rock mass relaxation range of less than 1.0 D. For the lining structure stress of each point in the second excavation cycle, larger lining stress is measured in the case of a fault dip of 75° than that in cases when the fault dip equals 45° and 60°, respectively. The biggest stress is observed in the side-wall position after the mid-partition is mantled to form a closed-loop lining structure. Overall, our findings provide valuable insights into the construction response of tunnels through faults and highlight the importance of considering excavation methods in tunnel engineering.
Wear Effect on the Contact between a Metallic Pin and a Rotating Polymeric Specimen
Authors: Visco Annamaria , Epasto Gabriella , Giudice Fabio , Scolaro Cristina , Sili Andrea
Published: March 2023

Debris formation is a crucial aspect that determines the lifespan of prosthetic joints. The wearing contact between ultra-high molecular weight polyethylene (UHMWPE) and a Ti alloy surface has been studied in the literature. However, when measuring mass loss, potential errors can arise due to the very small values involved (on the order of some units of 0.1 mg in experiments lasting several hours) and be caused by the absorption of humidity in the specimen, in addition to the lack of accuracy typical of weight scales. These errors can hardly be avoided, but accurate cleaning and drying processes can minimize them. With these premises, the present work aims to determine, by pin-on-disc test, the wear effect in the UHMWPE rotating sheet and Ti6Al4V pin produced by Electron Beam Melting (EBM) under dry and lubricated conditions. The morphology of the worn surface was documented by optical microscopy, and the volume loss of both the rotating specimens and the pin was accurately calculated through the detection of the wear track observed by optical microscopy. In particular, the present work proposes a method for directly determining the volume loss of the polymer to compare it with that obtained with the weight measurement. For both procedures, the uncertainty in evaluating the specific wear rate was analyzed, demonstrating that volume measurement allows for avoiding any possible error associated with weighing the polymeric specimens.
A Full-Color Holographic System Based on Taylor Rayleigh–Sommerfeld Diffraction Point Cloud Grid Algorithm
Authors: Yang Qinhui , Zhao Yu , Liu Wei , Bu Jingwen , Ji Jiahui
Published: March 2023

Real objects-based full-color holographic display systems usually collect data with a depth camera and then modulate the input light source to reconstruct the color three-dimensional scene of the real object. However, at present, the main problems of the real-time high quality full-color 3D display are slow speed, low reconstruction quality, and high consumption of hardware resources caused by excessive computing. Based on the hybrid Taylor Rayleigh–Sommerfeld diffraction algorithm and previous studies on full-color holographic systems, our paper proposes Taylor Rayleigh–Sommerfeld diffraction point cloud grid algorithm (TR-PCG), which is to perform Taylor expansion on the radial value of Rayleigh–Sommerfeld diffraction in the hologram generation stage and modify the data type to effectively accelerate the calculation speed and ensure the reconstruction quality. Compared with the wave-front recording plane, traditional point cloud gridding (PCG), C-PCG, and Rayleigh–Sommerfeld PCG without Taylor expansion, the computational complexity is significantly reduced. We demonstrate the feasibility of the proposed method through experiments.
Unsupervised Detection of Multiple Sleep Stages Using a Single FMCW Radar
Authors: Yoo Young-Keun , Jung Chae-Won , Shin Hyun-Chool
Published: March 2023

The paper proposes a unsupervised method for detecting the three stages of sleep—wake, rapid eye movement (REM) sleep, and non-REM sleep—using biosignals obtained from a 61 GHz single frequency modulated continuous wave (FMCW) radar. To detect the subject’s sleep stages based on non-learning techniques, the breathing and movement information characteristic of each sleep stage was extracted from the radar signals of the subject acquired in the sleep state and used as the feature factor tailored to the research objective. The experimental results derived from the clinical data obtained in the actual polysomnography (PSG) environment using FMCW radar show an average of 68% similarity to the actual three sleep stages observed in PSG. These results indicate the feasibility of using the FMCW radar sensor as an alternative to the conventional PSG-based method that poses multiple limitations to sleep-stage detection.
Therapeutic Targets in the Virological Mechanism and in the Hyperinflammatory Response of Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2)
Authors: Astasio-Picado Álvaro , Zabala-Baños María del Carmen , Jurado-Palomo Jesús
Published: March 2023

This work is a bibliographic review. The search for the necessary information was carried out in the months of November 2022 and January 2023. The databases used were as follows: Pubmed, Academic Google, Scielo, Scopus, and Cochrane library. Results: In total, 101 articles were selected after a review of 486 articles from databases and after applying the inclusion and exclusion criteria. The update on the molecular mechanism of human coronavirus (HCoV) infection was reviewed, describing possible therapeutic targets in the viral response phase. There are different strategies to prevent or hinder the introduction of the viral particle, as well as the replicative mechanism ((protease inhibitors and RNA-dependent RNA polymerase (RdRp)). The second phase of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) involves the activation of hyperinflammatory cascades of the host’s immune system. It is concluded that there are potential therapeutic targets and drugs under study in different proinflammatory pathways such as hydroxychloroquine, JAK inhibitors, interleukin 1 and 6 inhibitors, and interferons.
Rotate Vector Reducer Fault Diagnosis Model Based on EEMD-MPA-KELM
Authors: Tu Zhijian , Gao Lifu , Wu Xiaoyan , Liu Yongming , Zhao Zhuanzhe
Published: March 2023

With the increase of service time, the rotation period of rotating machinery may become irregular, and the Ensemble Empirical Mode Decomposition (EEMD)can effectively reflect its periodic state. In order to accurately evaluate the working state of the Rotate Vector (RV) reducer, the torque transfer formula of the RV reducer is first derived to theoretically prove periodicity of torque transfer in normal operation. Then, EEMD is able to effectively reflect the characteristics of data periodicity. A fault diagnosis model based on EEMD-MPA-KELM was proposed, and a bearing experimental dataset from Xi‘an Jiaotong University was used to verify the performance of the model. In view of the characteristics of the industrial robot RV reducer fault was not obvious and the sample data is few, spectrum diagram was used to diagnose the fault from the RV reducer measured data. The EEMD decomposition was performed on the data measured by the RV reducer test platform to obtain several Intrinsic Mode Functions (IMF). After the overall average checking and optimization of each IMF, several groups of eigenvalues were obtained. The eigenvalues were input into the Kernel Extreme Learning Machine (KELM) optimized by the Marine Predators Algorithm (MPA), and the fault diagnosis model was established. Finally, compared with other models, the prediction results showed that the proposed model can judge the working state of RV reducer more effectively.
Study on Head Stabilization Control Strategy of Non-Wheeled Snake Robot Based on Inertial Sensor
Authors: Bao Liming , Sun Yongjun , Wang Qiang , Xie Zongwu
Published: March 2023

In this paper, the head stabilization problem of the snake robot in planar motion is studied. When the snake robot performs a planar movement with an inchworm locomotion gait, the head controller of the snake robot swings up and down due to a fluctuation in the joint angle of the neck joint. However, the snake robot usually has a laser radar and other visual instruments on the head, and the swing of the head causes the visual instrument to fail to obtain external visual information normally, which affects the navigation and detection of the snake robot. In this paper, a head stabilization method for a snake robot in planar motion is proposed. The inertial sensor is used to obtain the direction parameters to control the swing of the head when the snake robot moves, and the effectiveness of the method is verified by a simulation and an experiment of the real robot.
Existence and Uniqueness Theorems for a Variable-Order Fractional Differential Equation with Delay
Authors: Telli Benoumran , Souid Mohammed Said , Alzabut Jehad , Khan Hasib
Published: March 2023

This study establishes the existence and stability of solutions for a general class of Riemann–Liouville (RL) fractional differential equations (FDEs) with a variable order and finite delay. Our findings are confirmed by the fixed-point theorems (FPTs) from the available literature. We transform the RL FDE of variable order to alternate RL fractional integral structure, then with the use of classical FPTs, the existence results are studied and the Hyers–Ulam stability is established by the help of standard notions. The approach is more broad-based and the same methodology can be used for a number of additional issues.
Local Existence and Blow-Up of Solutions for Wave Equation Involving the Fractional Laplacian with Nonlinear Source Term
Authors: Bidi Younes , Beniani Abderrahmane , Bouhali Keltoum , Zennir Khaled , ElKhair Hatim M. , Hassan Eltegani I. , Alarfaj Almonther
Published: March 2023

The aim of this paper is to investigate the local weak existence and vacuum isolating of solutions, asymptotic behavior, and blow-up of the solutions for a wave equation involving the fractional Laplacian with nonlinear source. By means of the Galerkin approximations, we prove the local weak existence and finite time blow-up of the solutions and we give the upper and lower bounds for blow-up time.
Rough-Fuzzy Based Synthetic Data Generation Exploring Boundary Region of Rough Sets to Handle Class Imbalance Problem
Authors: Naushin Mehwish , Das Asit Kumar , Nayak Janmenjoy , Pelusi Danilo
Published: March 2023

Class imbalance is a prevalent problem that not only reduces the performance of the machine learning techniques but also causes the lacking of the inherent complex characteristics of data. Though the researchers have proposed various ways to deal with the problem, they have yet to consider how to select a proper treatment, especially when uncertainty levels are high. Applying rough-fuzzy theory to the imbalanced data learning problem could be a promising research direction that generates the synthetic data and removes the outliers. The proposed work identifies the positive, boundary, and negative regions of the target set using the rough set theory and removes the objects in the negative region as outliers. It also explores the positive and boundary regions of the rough set by applying the fuzzy theory to generate the samples of the minority class and remove the samples of the majority class. Thus the proposed rough-fuzzy approach performs both oversampling and undersampling to handle the imbalanced class problem. The experimental results demonstrate that the novel technique allows qualitative and quantitative data handling.
A High-Performance Vortex Adjustment Design for an Air-Cooling Battery Thermal Management System in Electric Vehicles
Authors: Zhao Gang , Wang Xiaolin , Negnevitsky Michael , Li Chengjiang , Zhang Hengyun , Cheng Yingyao
Published: March 2023

To boost the performance of the air-cooling battery thermal management system, this study designed a novel vortex adjustment structure for the conventional air-cooling battery pack used in electric vehicles. T-shape vortex generating columns were proposed to be added between the battery cells in the battery pack. This structure could effectively change the aerodynamic patterns and thermodynamic properties of the battery pack, including turbulent eddy frequency, turbulent kinetic energy, and average Reynolds number, etc. The modified aerodynamic patterns and thermodynamic properties increased the heat transfer coefficient with little increase in energy consumption and almost no additional cost. Different designs were also evaluated and optimized under different working conditions. The results showed that the cooling performance of the Design 1 improved at both low and high air flow rates. At a small flow rate of 11.88 L/s, the Tmax and ΔT of Design 1 are 0.85 K and 0.49 K lower than the conventional design with an increase in pressure drop of 0.78 Pa. At a relative high flow rate of 47.52 L/s, the Tmax and ΔT of the Design 1 are also 0.46 K and 0.13 K lower than the conventional design with a slight increase in pressure drop of 17.88 Pa. These results demonstrated that the proposed vortex generating design can improve the cooling performance of the battery pack, which provides a guideline for the design and optimization of the high-performance air-cooling battery thermal management systems in electric vehicles.
Evaluation of Glyoxal-Based Electrolytes for Lithium-Sulfur Batteries
Authors: Kirchhoff Sebastian , Leibing Christian , Härtel Paul , Abendroth Thomas , Dörfler Susanne , Althues Holger , Kaskel Stefan , Balducci Andrea
Published: March 2023

Lithium-sulfur batteries (LSBs) are among the most promising next generation battery technologies. First prototype cells show higher specific energies than conventional Li-ion batteries (LIBs) and the active material is cost-effective and ubiquitously abundant. However, Li-S batteries still suffer from several limitations, mainly the cycle life, inflation of cells, and also the lack of a component production value chain. As this battery system is based on a complex conversion mechanism, the electrolyte plays a key role, not only for specific energy, but also for rate capability, cycle stability and costs. Herein, we report on electrolytes based on glyoxylic-acetal based solvents, Tetraethoxyglyoxal (TEG) and Tetramethoxyglyoxal (TMG). These solvents have been examined before for supercapacitors and LIBs, but never for LSBs, although they exhibit some beneficial properties, and the production value chain has already been well established as they are precursors for several chemicals. A specially adapted electrolyte composition is established by adjusting solvent ratio and LiTFSI concentration in a TXG:DOL solvent blend. The obtained electrolytes show long cycle life as well as high coulombic efficiencies without the use of LiNO3, a component leading normally to cell inflation and safety issues. In addition, a successful evaluation in a multilayer Li-S-pouch cell was performed. The electrolytes were thoroughly characterized, and their sulfur conversion mechanism is discussed.
Byssus of Green-Lipped Mussel Perna viridis as a Biomonitoring Biopolymer for Zinc Pollution in Coastal Waters
Authors: Yap Chee Kong , Al-Mutairi Khalid Awadh
Published: March 2023

The present study aimed to confirm the use of the byssus (BYS) of the green-lipped mussel Perna viridis as a biomonitoring biopolymer for zinc (Zn) by comparing it to copper (Cu) and cadmium (Cd) pollution in coastal waters under experimental field conditions, based on the transplantation of caged mussels between polluted and unpolluted sites in the Straits of Johore (SOJ). Four important evidential points were found in the present study. First, the 34 field-collected populations with BYS/total soft tissue (TST) ratios > 1 indicated that the BYS was a more sensitive, concentrative, and accumulative biopolymer for the three metals than TST. Significant (p < 0.05) and positive correlations between BYS and TST in terms of the levels of the three metals were observed. Second, the data obtained in the present study were well-supported by the interspecific comparison, which indicated that the BYS of P. viridis was a significantly better biomonitoring biopolymer for the identification of coastal areas exposed to Zn, Cd, and Cu pollution and played the role of an excretion route of metal wastes. Third, the higher positive correlation coefficients for the metals between the BYS sedimentary geochemical fractions than the TST sedimentary geochemical fractions indicated that the BYS was more reflective of metal bioavailability and contamination in coastal waters. Fourth, and most importantly, the field-based cage transplantation study clearly indicated the accumulation and elimination of the three metals by the BYS in both polluted and unpolluted sites in the Straits of Johore. In sum, the BYS of P. viridis was confirmed as a better biopolymer than TST for Zn, as well as Cd and Cu, bioavailability and contamination in tropical coastal waters.
Heteroresistance of Mycobacterium tuberculosis in the Sputum Detected by Droplet Digital PCR
Authors: Aung Ye Win , Faksri Kiatichai , Sangka Arunnee , Tomanakan Kanchana , Namwat Wises
Published: March 2023

Heteroresistance in MTB refers to the presence of distinct subpopulations of bacteria with varying levels of antibiotic susceptibility within a population. Multidrug-resistant and rifampicin-resistant TB are serious global health concerns. In this study, we aimed to determine the prevalence of heteroresistance in MTB from sputum samples of new TB cases using Droplet Digital PCR mutation detection assays for katG and rpoB genes, which are commonly associated with resistance to isoniazid and rifampicin, respectively. We found that out of 79 samples, 9 (11.4%) exhibited mutations in katG and rpoB genes. INH mono-resistant TB, RIF mono-resistant TB, and MDR-TB samples constituted 1.3%, 6.3%, and 3.8% of new TB cases, respectively. Heteroresistance in katG, rpoB, and both genes were found in 2.5%, 5%, and 2.5% of total cases, respectively. Our results suggest that these mutations may have arisen spontaneously, as the patients had not yet received anti-TB drugs. ddPCR is a valuable tool for the early detection and management of DR-TB, as it can detect both mutant and wild-type strains in a population, enabling the detection of heteroresistance and MDR-TB. Overall, our findings highlight the importance of early detection and management of DR-TB for effective TB control (in katG, rpoB, and katG/rpoB).
Tumor-Suppressive Functions of the Aryl Hydrocarbon Receptor (AhR) and AhR as a Therapeutic Target in Cancer
Authors: Elson Daniel J. , Kolluri Siva K.
Published: March 2023

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in regulating a wide range of biological responses. A diverse array of xenobiotics and endogenous small molecules bind to the receptor and drive unique phenotypic responses. Due in part to its role in mediating toxic responses to environmental pollutants, AhR activation has not been traditionally viewed as a viable therapeutic approach. Nonetheless, the expression and activation of AhR can inhibit the proliferation, migration, and survival of cancer cells, and many clinically approved drugs transcriptionally activate AhR. Identification of novel select modulators of AhR-regulated transcription that promote tumor suppression is an active area of investigation. The development of AhR-targeted anticancer agents requires a thorough understanding of the molecular mechanisms driving tumor suppression. Here, we summarized the tumor-suppressive mechanisms regulated by AhR with an emphasis on the endogenous functions of the receptor in opposing carcinogenesis. In multiple different cancer models, the deletion of AhR promotes increased tumorigenesis, but a precise understanding of the molecular cues and the genetic targets of AhR involved in this process is lacking. The intent of this review was to synthesize the evidence supporting AhR-dependent tumor suppression and distill insights for development of AhR-targeted cancer therapeutics.
Single-Particle Tracking of Thermomyces lanuginosus Lipase Reveals How Mutations in the Lid Region Remodel Its Diffusion
Authors: Iversen Josephine F. , Bohr Søren S.-R. , Pinholt Henrik D. , Moses Matias E. , Iversen Lars , Christensen Sune M. , Hatzakis Nikos S. , Zhang Min
Published: March 2023

The function of most lipases is controlled by the lid, which undergoes conformational changes at a water–lipid interface to expose the active site, thus activating catalysis. Understanding how lid mutations affect lipases’ function is important for designing improved variants. Lipases’ function has been found to correlate with their diffusion on the substrate surface. Here, we used single-particle tracking (SPT), a powerful tool for deciphering enzymes’ diffusional behavior, to study Thermomyces lanuginosus lipase (TLL) variants with different lid structures in a laundry-like application condition. Thousands of parallelized recorded trajectories and hidden Markov modeling (HMM) analysis allowed us to extract three interconverting diffusional states and quantify their abundance, microscopic transition rates, and the energy barriers for sampling them. Combining those findings with ensemble measurements, we determined that the overall activity variation in the application condition is dependent on surface binding and lipase mobility when bound. Specifically, the L4 variant with a TLL-like lid and wild-type (WT) TLL displayed similar ensemble activity, but WT bound stronger to the surface than L4, while L4 had a higher diffusion coefficient and thus activity when bound to the surface. These mechanistic elements can only be de-convoluted by our combined assays. Our findings offer fresh perspectives on the development of the next iteration of enzyme-based detergent.
Dupilumab in Inflammatory Skin Diseases: A Systematic Review
Authors: Olbrich Henning , Sadik Christian D. , Ludwig Ralf J. , Thaçi Diamant , Boch Katharina
Published: March 2023

Dupilumab was first approved for the treatment of atopic dermatitis (AD) and blocks the signaling of interleukin (IL)-4 and -13. Several other chronic skin conditions share mechanistic overlaps with AD in their pathophysiology, i.e., are linked to type 2 inflammation. Most recently, dupilumab was approved by the U.S. Food and Drug Administration for prurigo nodularis (PN). Given its relatively good safety profile, effective off-label use of dupilumab has been reported for a multitude of dermatologic diseases and several clinical trials for dermatologic skin conditions are currently ongoing. We conducted a systematic review of applications of dupilumab in dermatology other than AD and PN by searching the databases PubMed/Medline, Scopus, Web of Science and Cochrane Library as well as the clinical trial registry ClinicalTrials.gov. We found several reports for effective treatment of bullous autoimmune diseases, eczema, prurigo, alopecia areata, chronic spontaneous urticaria, Netherton syndrome and a variety of other chronic inflammatory skin diseases.
Engineering of a Bispecific Nanofitin with Immune Checkpoint Inhibitory Activity Conditioned by the Cross-Arm Binding to EGFR and PDL1
Authors: Jacquot Perrine , Muñoz-Garcia Javier , Fleury Maurine , Cochonneau Denis , Gaussin Rémi , Enouf Elise , Roze Caroline , Ollivier Emilie , Cinier Mathieu , Heymann Dominique
Published: March 2023

Re-education of the tumor microenvironment with immune checkpoint inhibitors (ICI) has provided the most significant advancement in cancer management, with impressive efficacy and durable response reported. However, low response rates and a high frequency of immune-related adverse events (irAEs) remain associated with ICI therapies. The latter can be linked to their high affinity and avidity for their target that fosters on-target/off-tumor binding and subsequent breaking of immune self-tolerance in normal tissues. Many multispecific protein formats have been proposed to increase the tumor cell’s selectivity of ICI therapies. In this study, we explored the engineering of a bispecific Nanofitin by the fusion of an anti-epidermal growth factor receptor (EGFR) and anti-programmed cell death ligand 1 (PDL1) Nanofitin modules. While lowering the affinity of the Nanofitin modules for their respective target, the fusion enables the simultaneous engagement of EGFR and PDL1, which translates into a selective binding to tumor cells co-expressing EGFR and PDL1 only. We demonstrated that affinity-attenuated bispecific Nanofitin could elicit PDL1 blockade exclusively in an EGFR-directed manner. Overall, the data collected highlight the potential of this approach to enhance the selectivity and safety of PDL1 checkpoint inhibition.
A Direct Catalytic Ethanol Fuel Cell (DCEFC) Modified by LDHs, or by Catalase-LDHs, and Improvement in Its Kinetic Performance: Applications for Human Saliva and Disinfectant Products for COVID-19
Authors: Tomassetti Mauro , Pezzilli Riccardo , Leonardi Claudio , Prestopino Giuseppe , Di Natale Corrado , Campanella Luigi , Medaglia Pier Gianni
Published: March 2023

In this work, it has been experimentally proven that the kinetic performance of a common Direct Catalytic Ethanol Fuel Cell (DCEFC) can be increased by introducing nanostructured (ZnII,AlIII(OH)2)+NO3−·H2O Layered Double Hydroxides (LDHs) into the anode compartment. Carrying out the measurements with the open-circuit voltage method and using a kinetic format, it has been shown that the introduction of LDHs in the anodic compartment implies a 1.3-fold increase in the calibration sensitivity of the method. This improvement becomes even greater in the presence of hydrogen peroxide in a solution. Furthermore, we show that the calibration sensitivity increased by 8-times, when the fuel cell is modified by the enzyme catalase, crosslinked on LDHs and in the presence of hydrogen peroxide. The fuel cell, thus modified (with or without enzyme), has been used for analytical applications on real samples, such as biological (human saliva) and hand disinfectant samples, commonly used for the prevention of COVID-19, obtaining very positive results from both analytical and kinetic points of view on ethanol detection. Moreover, if the increase in the calibration sensitivity is of great importance from the point of view of analytical applications, it must be remarked that the increase in the speed of the ethanol oxidation process in the fuel cell can also be extremely useful for the purposes of improving the energy performance of a DCEFC.
Effects of Methylone Pre-Exposure on Fluoxetine-Induced Conditioned Taste Avoidance in Male and Female Sprague-Dawley Rats
Authors: Manke Hayley N. , Rice Kenner C. , Riley Anthony L.
Published: March 2023

Background: Prior work has reported that a drug’s aversive effects (as indexed by taste avoidance conditioning) are attenuated when the pre-exposure and conditioning drugs are the same or different. The latter, otherwise known as cross-drug pre-exposure, is especially interesting as it has been used as a tool to assess mechanisms underlying the aversive effects of drugs. We previously reported that methylone pre-exposure differentially impacted the aversive effects of MDPV and MDMA (MDPV > MDMA), a difference consistent with the dopaminergic mediation of methylone’s aversive effects. To examine the possible role of serotonin (5-HT) in methylone’s aversive effects, the present study assessed the effects of methylone pre-exposure on taste avoidance induced by the 5-HT reuptake inhibitor fluoxetine. Methods: Male and female Sprague-Dawley rats were exposed to 10 mg/kg of methylone every 4th day (for a total of 5 injections) prior to taste avoidance training with 10 mg/kg of fluoxetine. Results: Fluoxetine induced significant taste avoidance (each p < 0.05) that was independent of sex. Methylone pre-exposure had no impact on avoidance produced by fluoxetine in either males or females (each p > 0.05). Conclusions: Methylone pre-exposure had no impact on fluoxetine-induced avoidance. These findings suggest that it is unlikely that 5-HT mediates the aversive effects of methylone. The implications of the present results for the mechanisms mediating methylone’s aversive effects were discussed. Understanding such mechanisms is important in predictions relevant to drug history and abuse liability as a variety of subject and experiential factors known to affect (reduce) a drug’s aversive effects may increase its use and potential for abuse.
Intravenous Injection of GluR2-3Y Inhibits Repeated Morphine-Primed Reinstatement of Drug Seeking in Rats
Authors: Zhang Jianjun , Liu Zhuo , Liu Xiaodong , Wang Xiaoqian , Yu Longchuan
Published: March 2023

Studies have demonstrated that the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor is essential to drug addiction. In this study, we explored the influence of GluR2-3Y, an interfering peptide to prevent the endocytosis of AMPA receptors containing the GluR2 subunit, on morphine-seeking behavior in the rat self-administration model. After self-administration was established, the rats received intravenous injections of GluR2-3Y during the extinction sessions. There were no significant differences in both active and inactive pokes compared to the control group of rats that received GluR2-3S, indicating that GluR2-3Y has no significant influences on the extinction of morphine self-administration. The other two groups of rats were trained, extinguished, and reinstated by repeated morphine priming (respectively, called Prime 1, Prime 2, and Prime 3). Only one intravenous injection of GluR2-3Y was performed before Prime 1. Compared to the control group, GluR2-3Y did not affect Prime 1, but significantly attenuated the morphine-seeking behavior during repeated morphine-primed reinstatement, indicating an inhibitory after effect of GluR2-3Y on morphine-seeking behavior in rats. The long-term depression (LTD) in the nucleus accumbens (NAc) shell was also assessed. Pretreatment with GluR2-3Y altered the ability of LTD induction to the level of that in the naive group, while pretreatment with GluR2-3S had no effects on LTD. Our results demonstrated that the intravenous injection of GluR2-3Y, to block the endocytosis of AMPA receptors, inhibited the reinstatement of morphine-seeking behavior, which may be induced by modulating the neuronal plasticity in the NAc shell of rats.
Swept-Source Optical Coherence Tomography Thresholds in Differentiating Clinical Outcomes in a Real-World Cohort of Treatment-Naïve Multiple Sclerosis Patients
Authors: Rzepiński Łukasz , Kucharczuk Jan , Tkaczyńska Magda , Parisi Vincenzo , Grzybowski Andrzej
Published: March 2023

This study aimed to determine whether peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell–inner plexiform layer (GCIPL) thickness thresholds for single-time-point swept-source optical coherence tomography (SS-OCT) measures can differentiate the clinical outcomes of treatment-naïve people with multiple sclerosis (pwMS). A total of 275 patients with the clinically isolated syndrome (n = 23), benign MS (n = 8), relapsing–remitting MS (n = 185), secondary progressive MS (n = 28), primary progressive MS (n = 31), and with no history of optic neuritis were included. The mean Expanded Disability Status Scale (EDSS) score was 3.0 ± 1.6. The cut-off values of pRNFL (87 µm and 88 µm) and GCIPL (70 µm) thicknesses have been adopted from previous studies using spectral-domain OCT. PwMS with pRNFL ≤87 µm and ≤88 µm had a longer disease duration, more advanced disability, and more frequently progressive MS variants compared to those with greater pRNFL thicknesses. In distinguishing pwMS with disability greater than or equal to the mean EDSS score (EDSS ≥ 3) from those with less severe disability, GCIPL thickness <70 µm had the highest sensitivity, while pRNFL thickness ≤87 µm had the greatest specificity. The optimal cut-off values differentiating patients with EDSS ≥ 3 from those with less severe disability was 63 µm for GCIPL thickness and 93.5 µm for pRNFL thickness. In conclusion, pRNFL and GCIPL thickness thresholds for single-time-point SS-OCT measurements may be helpful in differentiating the disability status of treatment-naïve pwMS.
Hypomagnesemia Is Associated with the Acute Kidney Injury in Traumatic Brain Injury Patients: A Pilot Study
Authors: Liu Zhenjun , Wang Ruoran , He Min , Kang Yan
Published: March 2023

Background: Acute kidney injury (AKI) commonly develops among traumatic brain injury (TBI) patients and causes poorer outcomes. We perform this study to explore the relationship between serum magnesium and the risk of AKI among TBI. Methods: TBI patients recorded in the Medical Information Mart for Intensive Care-III database were eligible for this research. The restricted cubic spline (RCS) was utilized to fit the correlation between serum magnesium level and the AKI. Univariate and subsequent multivariate logistic regression analysis were utilized to explore risk factors of AKI and confirmed the correlation between serum magnesium and AKI. Results: The incidence of AKI in included TBI was 21.0%. The RCS showed that the correlation between magnesium level and risk of AKI was U-shaped. Compared with patients whose magnesium level was between 1.5 and 2.0 mg/dL, those with a magnesium level of <1.5 mg/dL or >2.0 mg/dL had a higher incidence of AKI. Multivariate logistic regression confirmed age, chronic renal disease, ISS, serum creatinine, vasopressor, mechanical ventilation, and serum magnesium <1.5 mg/dL were independently related with the AKI in TBI. Conclusion: Abnormal low serum magnesium level is correlated with AKI development in TBI patients. Physicians should pay attention on renal function of TBI patients especially those with hypomagnesemia.
Psychotherapy with Psilocybin for Depression: Systematic Review
Authors: Dawood Hristova Jonathan Joseph , Pérez-Jover Virtudes
Published: March 2023

Depression is a common mental health issue that affects 280 million people in the world with a high mortality rate, as well as being a leading cause of disability. Psychopharmacological therapies with psychedelics, particularly those with psilocybin, are showing promising potential for the treatment of depression, among other conditions. Some of their benefits include a rapid and exponential improvement in depressive symptoms and an increased sense of well-being that can last for months after the treatment, as well as a greater development of introspective capacity. The aim of this project was to provide experimental evidence about therapeutic procedures along with psilocybin for the treatment of major depressive disorder. The project highlights eight studies that examined this condition. Some of them dealt with treatment-resistant depression while others dealt with depression due to a life-threatening disease such as cancer. These publications affirm the efficiency of the psilocybin therapy for depression, with only one or two doses in conjunction with psychological support during the process.
Optimization of the Temperature and Thermo-Stressed State of a Concrete Dam Constructed from Particularly Lean Roller-Compacted Concrete
Authors: Aniskin Nikolai Alekseevich , Shaytanov Alexey Mikhailovich
Published: March 2023

In this paper, we consider the optimization of temperature conditions and the thermo-stressed state of a concrete gravity dam made of extra lean roller-compacted concrete constructed in climate conditions corresponding to the Pskem HPP in the Republic of Uzbekistan. We show the need to take into account the effect of solar radiation on the heating of the concrete mass during the layer-by-layer construction of a gravity dam. A methodology was used to estimate solar radiation, considering cloud cover and the use of field and satellite observations. The seasonality of the concrete work and the terrain surrounding the construction site were also examined. We assessed the degree of influence of the factors acting on the formation of the temperature regime and the thermo-stressed state using the factor experiment technique. Regression equations, which allowed us to estimate the values of temperature and thermal stress arising in the structure during the construction period, were obtained. The created numerical model has been used for the estimation and optimization of the thermo-stressed state of the Pskem HPP dam option made of low-cement roller-compacted concrete. On the basis of calculations of the stress–strain state in elastic and elastic-plastic formulations, the possible cracking of concrete was evaluated. The competitiveness of the considered concrete option of the dam with the ground one is shown.