bluuebunny/crossref_metadata_2025 huggingface dataset:
Water Quality Modelling, Monitoring, and Mitigation
Authors: Kumar Amit , Palmate Santosh Subhash , Shukla Rituraj
Published: November 2022

In the modern era, water quality indices and models have received attention from environmentalists, policymakers, governments, stakeholders, water resource planners, and managers for their ability to evaluate the water quality of freshwater bodies. Due to their wide applicability, models are generally developed based on site-specific guidelines and are not generic; therefore, predicted/calculated values are reported to be highly uncertain. Thus, model and/or index formulation are still challenging and represent a current research hotspot in the scientific community. The inspiration for this Special Issue came from our desire to provide a platform for sharing results and informing young minds around the world to develop suitable models to understand water quality so that mitigation measures can be taken in advance to make water fit for drinking and for life-supporting activities.
Statistical Characterization of Boundary Kinematics Observed on a Series of Triaxial Sand Specimens
Authors: Zhu Yichuan , Medina-Cetina Zenon
Published: November 2022

This paper follows up on a reference paper that inspired MDPI’s topic “Stochastic Geomechanics: From Experimentation to Forward Modeling”, in which the authors populated a spatio–temporal database of boundary displacement fields from a series of triaxial sand specimens using three-dimensional (3D) digital image correlation analysis. The database was curated and is currently available to the scientific community for further study. This paper uses a subset of this database, in which the experimental conditions were similar, to statistically investigate the dominant kinematic phenomena observed on the boundary of triaxial sand specimens under compression. The first-order 3D kinematic operators under the cylindrical coordinates, comprised of the divergence, curl, and gradient, were applied to the boundary displacement fields to illustrate the localization deformation patterns including the translational, rotational, shearing, and volumetric behaviors throughout the triaxial compression processes. Subsequently, the first-order statistics of the kinematic results are estimated, with the aim of revealing the evolution of associated localization effects as well as their corresponding uncertainties in space and time. The results of this research provide an innovative statistical interpretation of the localization effects on soil specimens under three-dimensional stress conditions. The proposed approach advances the interpretation of granular material’s responses under triaxial compression experimental conditions, while opening an opportunity to reproduce the material’s kinematic responses under the triaxial experimental conditions through constitutive modeling or machine learning techniques.
Anaerobic Fermentation of Silage from the Above-Ground Biomass of Jerusalem Artichoke (Helianthus tuberosus L.) and Maize (Zea mayse L.) as a New and Promising Input Raw Material for Biogas Production
Authors: Kintl Antonín , Vítěz Tomáš , Huňady Igor , Brtnický Martin , Novák David , Lochman Jan , Vítězová Monika , Hammerschmiedt Tereza , Holátko Jiří , Elbl Jakub
Published: November 2022

Research of new input raw materials for biogas plants is a very actual topic. There are only a very few studies dealing with the possibility of using silage prepared from the above-ground parts of the Jerusalem artichoke (Helianthus tuberosus L.) and maize (Zea mayse L.) for methane production. This study deals with the determination of methane production and methane content in biogas during the fermentation of maize silage with dissimilar additions of the biomass of the Jerusalem artichoke (JA). Except for the effect of the JA’s addition on the yield of methane, we also studied its potential influence on the inhibition of the process of anaerobic digestion and the bacterial and methanogenic archaeal composition of anaerobic digestate. There were five model silages prepared; two of them contained only maize or JAs, and the remaining three were mixtures of maize and JA silages (30%wt; 50%wt and 70%wt). The fermentation tests showed that the JA addition (from 30 to 70%wt) resulted in the production of biogas decreasing, on average, by 15%. Based on the performed metagenomic analysis, we cannot confirm an essential influence of JA biomass addition on the composition of the community of microorganisms during fermentation.
Smart Agriculture: A Fruit Flower Cluster Detection Strategy in Apple Orchards Using Machine Vision and Learning
Authors: Lee Joseph , Gadsden S. Andrew , Biglarbegian Mohammad , Cline John A.
Published: November 2022

This paper presents the application of machine vision and learning techniques to detect and identify the number of flower clusters on apple trees leading to the ability to predict the potential yield of apples. A new field robot was designed and built to collect and build a dataset of 1500 images of apples trees. The trained model produced a cluster precision of 0.88 or 88% and a percentage error of 14% over 106 trees running the mobile vehicle on both sides of the trees. The detection model was predicting less than the actual amount but the fruit flower count is still significant in that it can give the researcher information on the estimated growth and production of each tree with respect to the actions applied to each fruit tree. A bias could be included to compensate for the average undercount. The resulting F1-Score of the object detection model was 80%, which is similar to other research methods ranging from an F1-Score of 77.3% to 84.1%. This paper helps lay the foundation for future application of machine vision and learning techniques within apple orchards or other fruit tree settings.
Integrated Module Antenna for Automotive UWB Application
Authors: Cha Seung Gook , Yoon Young Joong , Lee Yoon Jin , Hong Seung Take , Mun Hyeon Sik , Park Yong Hee
Published: November 2022

In this paper, an integrated module antenna for automotive UWB application is proposed. The target applications of the proposed antenna are for UWB localization and rear passenger detection. The purpose of this work is to design an antenna with a wide and narrow beamwidth that can be attached to the exterior/interior of a vehicle for simultaneous UWB localization and a rear passenger detection sensor with a single-module substrate in a limited space. For UWB localization, the wide beam coverage is required so the antenna receives the signal from any incident angle in horizontal plane. Meanwhile, the rear passenger detection sensor requires a relatively narrower beamwidth than the localization antenna for accurate detection within the vehicle. To integrate two different antennas into a single compact module substrate, modified ground stubs and parasitic radiators are applied. The size of the entire antenna structure is 35 mm × 65 mm × 1.156 mm. The proposed antenna designed on the multi-layered FR-4 substrate with a dielectric constant of 4.3. The bandwidth of the monopole is 6.14~8.24 GHz, and the patch array is 6.95~8.47 GHz. The isolation between the monopole and the patch array is less than −23 dBi in the target band. The performance of the proposed antenna is verified with simulation and measurement. In addition, a simulation of the proposed antenna with the real vehicle model is also conducted to verify the feasibility on actual vehicle. Based on this work, the proposed antenna can be applied to multi-function antenna for automotive application with low cost.
Usability and Acceptance of Exergames Using Different Types of Training among Older Hypertensive Patients in a Simulated Mixed Reality
Authors: Stamm Oskar , Vorwerg Susan , Haink Michele , Hildebrand Kristian , Buchem Ilona
Published: November 2022

Virtual and augmented reality (VR/AR) exergames are promising tools for increasing training motivation. However, the use of exergames with mixed reality (MR) headsets remains under-researched. Older adults with hypertension could also benefit from the increased training adherence associated with MR. Endurance and strength endurance exercises are recommended for this group to lower blood pressure. The aim of the preliminary study (n = 22) was to compare the usability and acceptance of two exergames, which represent two different training types—strength endurance training (SET) and endurance training (ET). The developed exergame prototypes were applied in “simulated MR” using a VR head-mounted display. We examined the following outcomes: usability (TUI), intention to use (TUI), subjective task load (NASA-TLX), frustration (NASA-TLX), and presence (PQ). The results showed that frustration was significantly greater in the ET than in the SET (p = 0.038). Presence was significantly higher in the SET (p = 0.002). No significant differences in usability and acceptance were found in the exergames. The results indicate that usability and acceptance are not related to the type of training when utilizing MR exergames. Whether the results are transferable with a real MR headset must be determined in further research.
Analysis of Elastic Properties According to the Aspect Ratio of UHMWPE Fibers Added to PP/UHMWPE Composites
Authors: Yun Dong-Han , Yun Jong-Hwan , Jeon Yu-Jae , Kang Min-Soo
Published: November 2022

This study comparatively analyzed the behavior of elastic properties by aspect ratio of the ultra-high molecular weight polyethylene (UHMWPE) fibers that are added when creating a composite material of polypropylene and UHMWPE. The volume fraction (VF) of UHMWPE fibers added to polypropylene was fixed at 5%. The elastic properties were lumped for analysis according to the aspect ratio of the UHMWPE fibers oriented on the polypropylene matrix; they were analyzed using the Halpin–Tsai model, which involves a theoretical approach and finite element analysis based on the homogenization method. Finite element analysis was performed for fiber aspect ratios of 0.2 to 30 UHMWPE via the homogenization technique using the ANSYS Material Designer. For theoretical comparison, UHMWPE fiber aspect ratios of 0.2 to 100 were comparatively analyzed using the Halpin–Tsai model. When the aspect ratio of UHMWPE fiber was 0.2, it was calculated as 1518 MPa, and when the aspect ratio was 30, it was 2365 MPa, and it increased by 55.8%. As the aspect ratio increased, E22 and G12 converged to a constant value (1550 MPa). In the future, when the volume fraction of UHMWPE changes from 0 to 50%, a study must be conducted to analyze the predicted behavior of the elastic properties when the aspect ratio of the UHMWPE fiber changes.
Accelerating Electromagnetic Field Simulations Based on Memory-Optimized CPML-FDTD with OpenACC
Authors: Padilla-Perez Diego , Medina-Sanchez Isaac , Hernández Jorge , Couder-Castañeda Carlos
Published: November 2022

Although GPUs can offer higher computing power at low power consumption, their low-level programming can be relatively complex and consume programming time. For this reason, directive-based alternatives such as OpenACC could be used to specify high-level parallelism without original code modification, giving very accurate results. Nevertheless, in the FDTD method, absorbing boundary conditions are commonly used. The key to successful performance is correctly implementing the boundary conditions that play an essential role in memory use. This work accelerates the simulations of electromagnetic wave propagation that solve the Maxwell curl equations by FDTD using CMPL boundary in TE mode using OpenACC directives. A gain of acceleration optimizing the use of memory is shows, checking the loops intensities, and the use of single precision to improve the performance is also analyzed, producing an acceleration of around 5X for double precision and 11X for single precision respectively, comparing with the serial vectorized version, without introducing errors in long-term simulations. The scenarios of simulation established are common of interest and are solved at different frequencies supported by a Mid-range cards GeForce RTX 3060 and Titan RTX.
Use of a DNN in Recording and Analysis of Operator Attention in Advanced HMI Systems
Authors: Gomolka Zbigniew , Zeslawska Ewa , Twarog Boguslaw , Kordos Damian , Rzucidlo Pawel
Published: November 2022

The main objective of this research was to propose a smart technology to record and analyse the attention of operators of transportation devices where human–machine interaction occurs. Four simulators were used in this study: General Aviation (GA), Remotely Piloted Aircraft System (RPAS), AS 1600, and Czajka, in which a spatio-temporal trajectory of system operator attention describing the histogram distribution of cockpit instrument observations was sought. Detection of the position of individual instruments in the video stream recorded by the eyetracker was accomplished using a pre-trained Fast R-CNN deep neural network. The training set for the network was constructed using a modified Kanade–Lucas–Tomasi (KLT) algorithm, which was applied to optimise the labelling of the cockpit instruments of each simulator. A deep neural network allows for sustained instrument tracking in situations where classical algorithms stop their work due to introduced noise. A mechanism for the flexible selection of Area Of Interest (AOI) objects that can be tracked in the recorded video stream was used to analyse the recorded attention using a mobile eyetracker. The obtained data allow for further analysis of key skills in the education of operators of such systems. The use of deep neural networks as a detector for selected instrument types has made it possible to universalise the use of this technology for observer attention analysis when applied to a different objects-sets of monitoring and control instruments.
Selection of Listeria monocytogenes InlA-Binding Peptides Using Phage Display—Novel Compounds for Diagnostic Applications?
Authors: Kenzel Julia , Brüggemann Dagmar Adeline , Funke Susanne Aileen
Published: November 2022

Listeria monocytogenes is a pathogenic, gram-positive bacterium causing foodborne infections and listeriosis, an infection responsible for serious medical conditions, especially for pregnant women, newborns, or people with a weak immune system. Even after antibiotic treatment, 30% of clinical infections result in death. L. monocytogenes is able to enter and multiply in mammalian cells. Invasion into epithelial cells in the human intestine is mediated by the interaction of the bacterial surface protein internalin A (InlA) with the host cell receptor E-cadherin (E-cad). We have used phage display to select InlA-specific peptides consisting of 12 amino acids using a randomized, recombinant peptide library. We could demonstrate that the selected peptides bound to recombinant InlA protein as well as to L. monocytogenes cells. In vitro, some of the peptides inhibited the interaction between recombinant InlA and human E-cad. As far as we know, this is the first publication on the development of InlA-specific peptide ligands. In the future, our peptides might be used for the development of innovative diagnostic tools or even therapeutic approaches.
A Malware Propagation Model Considering Conformity Psychology in Social Networks
Authors: Zhu Qingyi , Liu Yuhang , Luo Xuhang , Cheng Kefei
Published: November 2022

At present, malware is still a major security threat to computer networks. However, only a fraction of users with some security consciousness take security measures to protect computers on their own initiative, and others who know the current situation through social networks usually follow suit. This phenomenon is referred to as conformity psychology. It is obvious that more users will take countermeasures to prevent computers from being infected if the malware spreads to a certain extent. This paper proposes a deterministic nonlinear SEIQR propagation model to investigate the impact of conformity psychology on malware propagation. Both the local and global stabilities of malware-free equilibrium are proven while the existence and local stability of endemic equilibrium is proven by using the central manifold theory. Additionally, some numerical examples and simulation experiments based on two network datasets are performed to verify the theoretical analysis results. Finally, the sensitivity analysis of system parameters is carried out.
Solving Biharmonic Equations with Tri-Cubic C1 Splines on Unstructured Hex Meshes
Authors: Youngquist Jeremy , Peters Jörg
Published: November 2022

Unstructured hex meshes are partitions of three spaces into boxes that can include irregular edges, where n≠4 boxes meet along an edge, and irregular points, where the box arrangement is not consistent with a tensor-product grid. A new class of tri-cubic C1 splines is evaluated as a tool for solving elliptic higher-order partial differential equations over unstructured hex meshes. Convergence rates for four levels of refinement are computed for an implementation of the isogeometric Galerkin approach applied to Poisson’s equation and the biharmonic equation. The ratios of error are contrasted and superior to an implementation of Catmull-Clark solids. For the trivariate Poisson problem on irregularly partitioned domains, the reduction by 24 in the L2 norm is consistent with the optimal convergence on a regular grid, whereas the convergence rate for Catmull-Clark solids is measured as O(h3). The tri-cubic splines in the isogeometric framework correctly solve the trivariate biharmonic equation, but the convergence rate in the irregular case is lower than O(h4). An optimal reduction of 24 is observed when the functions on the C1 geometry are relaxed to be C0.
Multiterm Impulsive Caputo–Hadamard Type Differential Equations of Fractional Variable Order
Authors: Benkerrouche Amar , Souid Mohammed Said , Stamov Gani , Stamova Ivanka
Published: November 2022

In this study, we deal with an impulsive boundary value problem (BVP) for differential equations of variable fractional order involving the Caputo–Hadamard fractional derivative. The fundamental problems of existence and uniqueness of solutions are studied, and new existence and uniqueness results are established in the form of two fixed point theorems. In addition, Ulam–Hyers stability sufficient conditions are proved illustrating the suitability of the derived fundamental results. The obtained results are supported also by an example. Finally, the conclusion notes are highlighted.
Strong Players and Stable Coalition Structures in PMAS Profit Game
Authors: Meca Ana , Sošić Greys
Published: November 2022

In a non-negative profit game that possesses a Population Monotonic Allocation Scheme (PMAS), being a member of a larger coalition implies that your profit cannot decrease. In this paper, we refer to such games as PMAS profit games. As population monotonicity is a nice and desirable property that encourages formation of larger coalitions and implies stability of the grand coalition, we explore if this special feature of PMAS games can help in identifying additional stable coalition structures under different stability concepts in cooperative games—namely, core partitions, the von Neumann–Morgenstern (vNM) stable set, the largest consistent set, and the equilibrium process of coalition formation (EPCF)—and in developing relationships between coalition structures that are stable under these different stability concepts. We first define two special classes of players for PMAS profit games—extreme and strong players—and use them to develop an algorithm for construction of stable (core) partitions. We also use extreme players to identify absorbing states for equilibrium processes of coalition formation with high level of farsightedness. We then explore the impact of population monotonicity on the relationship between stable coalition structures under abovementioned stability concepts. While we are able to obtain some results related to stability of the grand coalition and to establish relationships between stable coalition structures under different stability notions that are consistent with the existing body of knowledge, population monotonicity in general does not add enough for strengthening of the existing results. However, we are able to show a couple of more general result that hold for arbitrary cooperative TU profit games. That is, we show that the members of vNM farsighted stable sets are core partitions, and that core partitions are members of a vNM stable sets. Moreover, we show that the members of vNM farsighted stable sets are EPCF-stable partitions.
High-Performance and Low-Cost Membranes Based on Poly(vinylpyrrolidone) and Cardo-Poly(etherketone) Blends for Vanadium Redox Flow Battery Applications
Authors: Mu Tong , Leng Shifan , Tang Weiqin , Shi Ning , Wang Guorui , Yang Jingshuai
Published: November 2022

Energy storage systems have aroused public interest because of the blooming development of intermittent renewable energy sources. Vanadium redox flow batteries (VRFBs) are the typical candidates owing to their flexible operation and good cycle durability. However, due to the usage of perfluorinated separator membranes, VRFBs suffer from both high cost and serious vanadium ions cross penetration. Herein, we fabricate a series of low-budget and high-performance blend membranes from polyvinylpyrrolidone (PVP) and cardo-poly(etherketone) (PEKC) for VFRB. A PEKC network gives the membrane excellent mechanical rigidity, while PVP endows the blend membranes with superior sulfonic acid uptake owing to the present N-heterocycle and carbonyl group in PVP, resulting in low area resistance. Meanwhile, blend membranes also display low vanadium ion permeability resulting from the electrostatic repulsion effect of protonated PVP polymer chains towards vanadium ions. Consequently, the 50%PVP-PEKC membrane has a high ionic selectivity of 1.03 × 106 S min cm−3, while that of Nafion 115 is nearly 17 times lower (6.03 × 104 S min cm−3). The VRFB equipped with 50%PVP-PEKC membrane has high coulombic efficiencies (99.3–99.7%), voltage efficiencies (84.6–67.0%) and energy efficiencies (83.9–66.8%) at current densities of 80–180 mA cm−2, and possesses excellent cycle constancy, indicating that low-cost x%PVP-PEKC blend membranes have a great application potentiality for VRFBs.
Functional Blockage of S100A8/A9 Ameliorates Ischemia–Reperfusion Injury in the Lung
Authors: Nakata Kentaro , Okazaki Mikio , Sakaue Tomohisa , Kinoshita Rie , Komoda Yuhei , Shimizu Dai , Yamamoto Haruchika , Tanaka Shin , Suzawa Ken , Shien Kazuhiko , Miyoshi Kentaroh , Yamamoto Hiromasa , Ohara Toshiaki , Sugimoto Seiichiro , Yamane Masaomi , Matsukawa Akihiro , Sakaguchi Masakiyo , Toyooka Shinichi
Published: November 2022

(1) Background: Lung ischemia–reperfusion (IR) injury increases the mortality and morbidity of patients undergoing lung transplantation. The objective of this study was to identify the key initiator of lung IR injury and to evaluate pharmacological therapeutic approaches using a functional inhibitor against the identified molecule. (2) Methods: Using a mouse hilar clamp model, the combination of RNA sequencing and histological investigations revealed that neutrophil-derived S100A8/A9 plays a central role in inflammatory reactions during lung IR injury. Mice were assigned to sham and IR groups with or without the injection of anti-S100A8/A9 neutralizing monoclonal antibody (mAb). (3) Results: Anti-S100A8/A9 mAb treatment significantly attenuated plasma S100A8/A9 levels compared with control IgG. As evaluated by oxygenation capacity and neutrophil infiltration, the antibody treatment dramatically ameliorated the IR injury. The gene expression levels of cytokines and chemokines induced by IR injury were significantly reduced by the neutralizing antibody. Furthermore, the antibody treatment significantly reduced TUNEL-positive cells, indicating the presence of apoptotic cells. (4) Conclusions: We identified S100A8/A9 as a novel therapeutic target against lung IR injury.
Experimental Study to Evaluate the Wear Performance of UHMWPE and XLPE Material for Orthopedics Application
Authors: Bhoi Sandeep , Prasad Arbind , Kumar Ashwani , Sarkar Rudra Bubai , Mahto Bidyanand , Meena Chandan Swaroop , Pandey Chandan
Published: November 2022

The main objective of this study is to perform an abrasive wear resistance study of UMHWPE and XLPE by using different grades of abrasive paper (grade 100 (190 µm), grade 220 (50 µm), and grade 400 (40 µm)) with minor (10 N) and major (15 N) loading conditions. In this article, wear performance of the UMHWPE and XLPE materials compared to the bio-tribological data as reported earlier in the clinical studies has been investigated. The experimental result shows that the loss of materials for the XLPE was much higher than the UHMWPE under similar loading conditions. UHMWPE shows a 34% reduction in wear at minor loading conditions and a 53% reduction in wear at major loading conditions. From experimental results it was concluded that Cross-link PE has better wear resistance than UHMWPE in minor wear conditions, whereas UHMWPE shows better wear resistance under major loading conditions. Based upon these results, UHMWPE and XLPE have been recommended for use as bearing materials in orthopedics. The experimental results of this study were validated using results from the available literature.
Changes in Muscular Activity in Different Stable and Unstable Conditions on Aquatic Platforms
Authors: Conceição Ana , Fernandes Orlando , Baia Miguel , Parraca Jose A. , Gonçalves Bruno , Batalha Nuno
Published: November 2022

The present study aimed to analyse and compare the muscle activity of twelve participants (seven men and five women) (age 20.1 ± 0.9 years; height 170.5 ± 10 cm; body mass: 64.86 ± 8.3 kg) in two exercises, each with two variants: squat (dynamic and static) and plank (hands and elbows) in a stable environment on land and an unstable environment on an aquatic platform. The erector spinae, biceps femoris, rectus femoris, external oblique, and rectus abdominis muscles were evaluated using surface electromyography. The dynamic squat increases the recruitment of the biceps femoris and external oblique, while the static squat demands greater activation of the rectus femoris. The elbow plank exercise increases the recruitment of erector spinae muscles, and the hand plank exercise increases the recruitment of the erector spinae and external oblique. In conclusion, performing exercises in unstable conditions on an aquatic platform slightly increases muscle recruitment.
Efficacy of Single and Multi-Strain Probiotics on In Vitro Strain Compatibility, Pathogen Inhibition, Biofilm Formation Capability, and Stress Tolerance
Authors: Puvanasundram Puvaneswari , Chong Chou Min , Sabri Suriana , Yusoff Md Sabri Mohd , Lim Keng Chin , Karim Murni
Published: November 2022

Compatibility of each strain in a multi-strain probiotic (MSP), along with its properties, becomes a strong base for its formulation. In this study, single-strain probiotics (SSPs) and multi-strain probiotics (MSPs) were evaluated in vitro for strain compatibility, microbial antagonism, biofilm formation capacity, and stress tolerance. Bacillus amyloliquefaciens L11, Enterococcus hirae LAB3, and Lysinibacillus fusiformis SPS11 were chosen as MSP1 candidates because they showed much stronger antagonism to Aeromonas hydrophila and Streptococcus agalactiae than a single probiotic. MSP 2 candidates were Lysinibacillus fusiformis strains SPS11, A1, and Lysinibacillus sphaericus strain NAS32 because the inhibition zone produced by MSP 2 against Vibrio harveyi and Vibrio parahaemolyticus was much higher than that produced by its constituent SSPs. MSP1 in the co-culture assay reduced (p < 0.05) A. hydrophila count from 9.89 ± 0.1 CFU mL−1 to 2.14 ± 0.2 CFU mL−1. The biofilm formation of both MSPs were significantly higher (p < 0.05) than its constituent SSPs and the pathogens. The SSPs in both MSPs generally showed resistance to high temperatures (80, 90, and 100 °C) and a wide range of pH (2 to 9). This in vitro assessment study demonstrates that MSP1 and 2 have the potential to be further explored as multi-strain probiotics on selected aquatic species.
Mitigating the Mistletoe Menace: Biotechnological and Smart Management Approaches
Authors: Mudgal Gaurav , Kaur Jaspreet , Chand Kartar , Parashar Manisha , Dhar Sanjoy K. , Singh Gajendra B. , Gururani Mayank A.
Published: November 2022

Mistletoes have been considered a keystone resource for biodiversity, as well as a remarkable source of medicinal attributes that attract pharmacologists. Due to their hemiparasitic nature, mistletoes leach water and nutrients, including primary and secondary metabolites, through the vascular systems of their plant hosts, primarily trees. As a result of intense mistletoe infection, the hosts suffer various growth and physiological detriments, which often lead to tree mortality. Because of their easy dispersal and widespread tropism, mistletoes have become serious pests for commercial fruit and timber plantations. A variety of physical and chemical treatment methods, along with silvicultural practices, have shaped conventional mistletoe management. Others, however, have either failed to circumvent the growing range and tropism of these parasitic plants or present significant environmental and public health risks. A biocontrol approach that could sidestep these issues has never achieved full proof of concept in real-field applications. Our review discusses the downsides of conventional mistletoe control techniques and explores the possibilities of biotechnological approaches using biocontrol agents and transgenic technologies. It is possible that smart management options will pave the way for technologically advanced solutions to mitigate mistletoes that are yet to be exploited.
In Silico Protein Folding Prediction of COVID-19 Mutations and Variants
Authors: Bhowmick Sumana , Jing Tim , Wang Wei , Zhang Elena Y. , Zhang Frank , Yang Yanmin
Published: November 2022

With its fast-paced mutagenesis, the SARS-CoV-2 Omicron variant has threatened many societies worldwide. Strategies for predicting mutagenesis such as the computational prediction of SARS-CoV-2 structural diversity and its interaction with the human receptor will greatly benefit our understanding of the virus and help develop therapeutics against it. We aim to use protein structure prediction algorithms along with molecular docking to study the effects of various mutations in the Receptor Binding Domain (RBD) of the SARS-CoV-2 and its key interactions with the angiotensin-converting enzyme 2 (ACE-2) receptor. The RBD structures of the naturally occurring variants of SARS-CoV-2 were generated from the WUHAN-Hu-1 using the trRosetta algorithm. Docking (HADDOCK) and binding analysis (PRODIGY) between the predicted RBD sequences and ACE-2 highlighted key interactions at the Receptor-Binding Motif (RBM). Further mutagenesis at conserved residues in the Original, Delta, and Omicron variants (P499S and T500R) demonstrated stronger binding and interactions with the ACE-2 receptor. The predicted T500R mutation underwent some preliminary tests in vitro for its binding and transmissibility in cells; the results correlate with the in-silico analysis. In summary, we suggest conserved residues P499 and T500 as potential mutation sites that could increase the binding affinity and yet do not exist in nature. This work demonstrates the use of the trRosetta algorithm to predict protein structure and future mutations at the RBM of SARS-CoV-2, followed by experimental testing for further efficacy verification. It is important to understand the protein structure and folding to help develop potential therapeutics.
Quantitative Sensory Testing in Late-Onset ATTRv Presymptomatic Subjects: A Single Center Experience
Authors: Tozza Stefano , Severi Daniele , Palumbo Giovanni , Provitera Vincenzo , Ruggiero Lucia , Dubbioso Raffaele , Iodice Rosa , Nolano Maria , Manganelli Fiore
Published: November 2022

Backgrounds Hereditary transthyretin amyloidosis (ATTRv) presymptomatic subjects undergo multidisciplinary evaluation to detect, as early as possible, a subclinical involvement of multisystem disease. Quantitative sensory testing (QST) that investigates and discriminates the function of C, Aδ and Aβ fibers is included as an instrumental test to monitor nerve fiber function. The purpose of this study was to evaluate the role of QST in the context of the multidisciplinary evaluation in late onset carriers. Methods Four-teen presymptomatic (namely carriers) were enrolled. Subjects underwent thermal [cold and warm detection threshold (CDT, WDT), cold and heat pain (CP and HP)] and tactile QST in four body sites: foot dorsum, distal lateral leg, distal thigh, hand dorsum. Results Overall, presymptomatic subject showed a significant difference in all thermal QST findings compared to the control group. All subjects had at least one altered thermal QST finding; the sites more frequently altered were foot and leg, whilst the thermal modalities which were more frequently abnormal were CDT, WDT and CP. Conclusions Our study highlights the importance of performing thermal QST in subjects carrying TTR mutation, given the high frequency of abnormal findings. Notably, performing both innocuous and painful stimulation in foot and/or leg increases the chance of detecting nerve fiber dysfunction. Moreover, the investigation of the hand may provide useful information in monitoring disease progression before the Predicted Age of Disease Onset (PADO).
Adenovirus-Inspired Virus-like-Particles Displaying Melanoma Tumor Antigen Specifically Target Human DC Subsets and Trigger Antigen-Specific Immune Responses
Authors: Besson Solène , Laurin David , Chauvière Cyrielle , Thépaut Michel , Kleman Jean-Philippe , Pezet Mylène , Manches Olivier , Fieschi Franck , Aspord Caroline , Fender Pascal
Published: November 2022

Virus-like particles constitute versatile vectors that can be used as vaccine platforms in many fields from infectiology and more recently to oncology. We previously designed non-infectious adenovirus-inspired 60-mer dodecahedric virus-like particles named ADDomers displaying on their surface either a short epitope or a large tumor/viral antigen. In this work, we explored for the first time the immunogenicity of ADDomers exhibiting melanoma-derived tumor antigen/epitope and their impact on the features of human dendritic cell (DC) subsets. We first demonstrated that ADDomers displaying tumor epitope/antigen elicit a strong immune-stimulating potential of human DC subsets (cDC2s, cDC1s, pDCs), which were able to internalize and cross-present tumor antigen, and subsequently cross-prime antigen-specific T-cell responses. To further limit off-target effects and enhance DC targeting, we engineered specific motifs to de-target epithelial cells and improve DCs’ addressing. The improved engineered platform making it possible to display large antigen represents a tool to overcome the barrier of immune allele restriction, broadening the immune response, and paving the way to its potential utilization in humans as an off-the-shelf vaccine.
Individualization of Mycophenolic Acid Therapy through Pharmacogenetic, Pharmacokinetic and Pharmacodynamic Testing
Authors: Winnicki Wolfgang , Fichtenbaum Andreas , Mitulovič Goran , Herkner Harald , Regele Florina , Baier Michael , Zelzer Sieglinde , Wagner Ludwig , Sengoelge Guerkan
Published: November 2022

Mycophenolic acid (MPA) is a widely used immunosuppressive agent and exerts its effect by inhibiting inosine 5′-monophosphate dehydrogenase (IMPDH), the main regulating enzyme of purine metabolism. However, significant unexplained differences in the efficacy and tolerability of MPA therapy pose a clinical challenge. Therefore, broad pharmacogenetic, pharmacokinetic, and pharmacodynamic approaches are needed to individualize MPA therapy. In this prospective cohort study including 277 renal transplant recipients, IMPDH2 rs11706052 SNP status was assessed by genetic sequencing, and plasma MPA trough levels were determined by HPLC and IMPDH enzyme activity in peripheral blood mononuclear cells (PBMCs) by liquid chromatography–mass spectrometry. Among the 277 patients, 84 were identified with episodes of biopsy-proven rejection (BPR). No association was found between rs11706052 SNP status and graft rejection (OR 1.808, and 95% CI, 0.939 to 3.479; p = 0.076). Furthermore, there was no association between MPA plasma levels and BPR (p = 0.69). However, the patients with graft rejection had a significantly higher predose IMPDH activity in PBMCs compared to the controls without rejection at the time of biopsy (110.1 ± 50.2 vs. 95.2 ± 45.4 pmol/h; p = 0.001), and relative to the baseline IMPDH activity before transplantation (p = 0.042). Our results suggest that individualization of MPA therapy, particularly through pharmacodynamic monitoring of IMPDH activity in PBMCs, has the potential to improve the clinical outcomes of transplant patients.
Endothelium-Derived Relaxing Factors and Endothelial Function: A Systematic Review
Authors: Nappi Francesco , Fiore Antonio , Masiglat Joyce , Cavuoti Teresa , Romandini Michela , Nappi Pierluigi , Avtaar Singh Sanjeet Singh , Couetil Jean-Paul
Published: November 2022

Background: The endothelium plays a pivotal role in homeostatic mechanisms. It specifically modulates vascular tone by releasing vasodilatory mediators, which act on the vascular smooth muscle. Large amounts of work have been dedicated towards identifying mediators of vasodilation and vasoconstriction alongside the deleterious effects of reactive oxygen species on the endothelium. We conducted a systematic review to study the role of the factors released by the endothelium and the effects on the vessels alongside its role in atherosclerosis. Methods: A search was conducted with appropriate search terms. Specific attention was offered to the effects of emerging modulators of endothelial functions focusing the analysis on studies that investigated the role of reactive oxygen species (ROS), perivascular adipose tissue, shear stress, AMP-activated protein kinase, potassium channels, bone morphogenic protein 4, and P2Y2 receptor. Results: 530 citations were reviewed, with 35 studies included in the final systematic review. The endpoints were evaluated in these studies which offered an extensive discussion on emerging modulators of endothelial functions. Specific factors such as reactive oxygen species had deleterious effects, especially in the obese and elderly. Another important finding included the shear stress-induced endothelial nitric oxide (NO), which may delay development of atherosclerosis. Perivascular Adipose Tissue (PVAT) also contributes to reparative measures against atherosclerosis, although this may turn pathological in obese subjects. Some of these factors may be targets for pharmaceutical agents in the near future. Conclusion: The complex role and function of the endothelium is vital for regular homeostasis. Dysregulation may drive atherogenesis; thus, efforts should be placed at considering therapeutic options by targeting some of the factors noted.
An Innovative PTD-IVT-mRNA Delivery Platform for CAR Immunotherapy of ErbB(+) Solid Tumor Neoplastic Cells
Authors: Georgiou-Siafis Sofia K. , Miliotou Androulla N. , Ntenti Charikleia , Pappas Ioannis S. , Papadopoulou Lefkothea C.
Published: November 2022

Chimeric antigen receptor (CAR) immunotherapy includes the genetic modification of immune cells to carry such a receptor and, thus, recognize cancer cell surface antigens. Viral transfection is currently the preferred method, but it carries the risk of off-target mutagenicity. Other transfection platforms have thus been proposed, such the in vitro transcribed (IVT)-mRNAs. In this study, we exploited our innovative, patented delivery platform to produce protein transduction domain (PTD)-IVT-mRNAs for the expression of CAR on NK-92 cells. CAR T1E-engineered NK-92 cells, harboring the sequence of T1E single-chain fragment variant (scFv) to recognize the ErbB receptor, bearing either CD28 or 4-1BB as co-stimulatory signaling domains, were prepared and assessed for their effectiveness in two different ErbB(+) cancer cell lines. Our results showed that the PTD-IVT-mRNA of CAR was safely transduced and expressed into NK-92 cells. CAR T1E-engineered NK-92 cells provoked high levels of cell death (25–33%) as effector cells against both HSC-3 (oral squamous carcinoma) and MCF-7 (breast metastatic adenocarcinoma) human cells in the co-incubation assays. In conclusion, the application of our novel PTD-IVT-mRNA delivery platform to NK-92 cells gave promising results towards future CAR immunotherapy approaches.
The Efficacy of an N-Acetylcysteine–Antibiotic Combination Therapy on Achromobacter xylosoxidans in a Cystic Fibrosis Sputum/Lung Cell Model
Authors: Aiyer Aditi , Das Theerthankar , Whiteley Gregory S. , Glasbey Trevor , Kriel Frederik H. , Farrell Jessica , Manos Jim
Published: November 2022

Cystic fibrosis (CF) is a disorder causing dysfunctional ion transport resulting in the accumulation of viscous mucus. This environment fosters a chronic bacterial biofilm-associated infection in the airways. Achromobacter xylosoxidans, a gram-negative aerobic bacillus, has been increasingly associated with antibiotic resistance and chronic colonisation in CF. In this study, we aimed to create a reproducible model of CF infection using an artificial sputum medium (ASMDM-1) with bronchial (BEAS-2B) and macrophage (THP-1) cells to test A. xylosoxidans infection and treatment toxicity. This study was conducted in three distinct stages. First, the tolerance of BEAS-2B cell lines and two A. xylosoxidans strains against ASMDM-1 was optimised. Secondly, the cytotoxicity of combined therapy (CT) comprising N-acetylcysteine (NAC) and the antibiotics colistin or ciprofloxacin was tested on cells alone in the sputum model in both BEAS-2B and THP-1 cells. Third, the efficacy of CT was assessed in the context of a bacterial infection within the live cell/sputum model. We found that a model using 20% ASMDM-1 in both cell populations tolerated a colistin–NAC-based CT and could significantly reduce bacterial loads in vitro (~2 log10 CFU/mL compared to untreated controls). This pilot study provides the foundation to study other bacterial opportunists that infect the CF lung to observe infection and CT kinetics. This model also acts as a springboard for more complex co-culture models.
Sorafenib versus Lenvatinib Causes Stronger Oxidative Damage to Membrane Lipids in Noncancerous Tissues of the Thyroid, Liver, and Kidney: Effective Protection by Melatonin and Indole-3-Propionic Acid
Authors: Stępniak Jan , Krawczyk-Lipiec Joanna , Lewiński Andrzej , Karbownik-Lewińska Małgorzata
Published: November 2022

Sorafenib and lenvatinib are multi-targeted tyrosine kinase inhibitors which are currently approved to treat advanced hepatocellular carcinoma, renal cell carcinoma and radioiodine-refractory differentiated thyroid carcinoma. However this treatment is often limited due to common adverse events which may occur via oxidative stress. The study aims to compare sorafenib- and lenvatinib-induced oxidative damage to membrane lipids (lipid peroxidation, LPO) in homogenates of porcine noncancerous tissues of the thyroid, the liver, and the kidney and to check if it can be prevented by antioxidants melatonin and indole-3-propionic acid (IPA). Homogenates of individual tissues were incubated in the presence of sorafenib or lenvatinib (1 mM, 100 µM, 10 µM, 1 µM, 100 nM, 10 nM, 1 nM, 100 pM) together with/without melatonin (5.0 mM) or IPA (5.0 mM). The concentration of malondialdehyde + 4-hydroxyalkenals, as the LPO index, was measured spectrophotometrically. The incubation of tissue homogenates with sorafenib resulted in a concentration-dependent increase in LPO (statistically significant for concentrations of 1mM and 100 µM in the thyroid and the liver, and of 1 mM, 100 µM, and 10 µM in the kidney). The incubation of thyroid homogenates with lenvatinib did not change LPO level. In case of the liver and the kidney, lenvatinib increased LPO but only in its highest concentration of 1 mM. Melatonin and IPA reduced completely (to the level of control) sorafenib- and lenvatinib-induced LPO in all examined tissues regardless of the drug concentration. In conclusion, sorafenib comparing to lenvatinib is a stronger damaging agent of membrane lipids in noncancerous tissues of the thyroid, the liver, and the kidney. The antioxidants melatonin and IPA can be considered to be used in co-treatment with sorafenib and lenvatinib to prevent their undesirable toxicity occurring via oxidative stress.
Cervical Cell Image Classification-Based Knowledge Distillation
Authors: Gao Wenjian , Xu Chuanyun , Li Gang , Zhang Yang , Bai Nanlan , Li Mengwei
Published: November 2022

Current deep-learning-based cervical cell classification methods suffer from parameter redundancy and poor model generalization performance, which creates challenges for the intelligent classification of cervical cytology smear images. In this paper, we establish a method for such classification that combines transfer learning and knowledge distillation. This new method not only transfers common features between different source domain data, but also realizes model-to-model knowledge transfer using the unnormalized probability output between models as knowledge. A multi-exit classification network is then introduced as the student network, where a global context module is embedded in each exit branch. A self-distillation method is then proposed to fuse contextual information; deep classifiers in the student network guide shallow classifiers to learn, and multiple classifier outputs are fused using an average integration strategy to form a classifier with strong generalization performance. The experimental results show that the developed method achieves good results using the SIPaKMeD dataset. The accuracy, sensitivity, specificity, and F-measure of the five classifications are 98.52%, 98.53%, 98.68%, 98.59%, respectively. The effectiveness of the method is further verified on a natural image dataset.
Life Cycle Assessment of Embodied Carbon in Buildings: Background, Approaches and Advancements
Authors: Khan Sahil Ali , Alam Tabish , Khan Mohammad Saaim , Blecich Paolo , Kamal Mohammad Arif , Gupta Naveen Kumar , Yadav Anil Singh
Published: November 2022

The environment demands a reduction in greenhouse gas (GHG) emissions, as building and construction are responsible for more than 40% of the energy consumed worldwide and 30% of the world’s GHG emissions. Many countries have aligned themselves with the Paris agreement, following its target of achieving net zero carbon emissions, although some governments are focused on the operational energy efficiency part of the equation instead of the whole equation. This study emphasizes the significance of incorporating the minimization of embodied emissions into all parts of the building, with a focus on the measurement of embodied carbon, concepts of its management and strategies proposed and enacted for mitigation. As estimate is an important part of any debate, the measurement approach covers the uncertainty analysis from diverse points of view through a novel approach; management covers the early design tools, and the significance of the lifecycle stages; mitigation covers the reduction strategies of embodied carbon, although reduction in embodied carbon is a subjective topic and depends on region. The analysis covers the ideal approaches for mitigation irrespective of the region.