bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Deep Learning to Predict the Amount of Chemicals Applied on the Wheel Track for Winter Road Maintenance
Authors: Hatamzad Mahshid , Polanco Pinerez Geanette Cleotilde , Casselgren Johan
Published: March 2022

The decade of big data has emerged in recent years, which has led to entering the era of intelligent transportation. One of the main challenges to deploying intelligent transportation is dealing with winter roads in cold climate countries. Different operations can be used to protect the road from ice and snow, such as spreading chemicals (here salt) on the road surface. Using salt for de-icing and anti-icing increases road safety. However, the excess use of salt must be avoided since it is not cost-efficient and has negative impacts on the environment. Therefore, the accurate and timely prediction of salt quantity for winter road maintenance helps decision support systems to achieve effective and efficient winter road maintenance. Thus, this paper performs exploratory data analysis to determine the relationships among variables to find the best prediction model for this problem. Due to the stochastic nature of variables regarding weather and roads, a deep neural network/deep learning is selected to predict the amount of salt on the wheel track, using historical data measured by sensors and road weather stations. The results show that the proposed model performs perfectly to learn and predict the amount of salt on the wheel track, based on different metrics, including the loss function, scatter plot, mean absolute error, and explained variance.
Hydration Characterization of Two Generations of MTA-Based Root Canal Sealers
Authors: Abu Zeid Sawsan T. , Edrees Hadeel Y.
Published: March 2022

Since the setting characterization of a root canal sealer has an impact on its biological behavior of final obturation, this study evaluated the setting characterization of mineral trioxide aggregate MTA-Fillapex versus MTA-Bioseal compared with epoxy resin (Adseal) root canal sealers. Freshly mixed sealer was inserted into the mold (n = 10). The initial and final setting times were evaluated using a Vicat needle and were then statistically analyzed by one-way ANOVA at p < 0.05. The raw pastes and the stages of the setting reaction were analyzed using Fourier Transform Infrared (FTIR) Spectroscopy. The phase compositions were evaluated using X-ray diffraction (XRD). A significant and fast setting time was recorded by Adseal (4.7 ± 0.46 h) followed by MTA-Bioseal (11.4 ± 1.34 h) at p < 0.001. The MTA-Fillapex did not set completely in three months. The FTIR and XRD of both MTA-Bioseal and Adseal detected bands of the polymerized phases, while those of MTA-Fillapex detected partial polymerization with a low percentage of polymerized silica. MTA-Bioseal and Adseal met the ISO standards for setting times. However, MTA-Fillapex did not fulfill the ideal requirement for the sealer. Although the raw pastes of both MTA-sealers had nearly similar compositions, they behaved differently during the hydration reaction. MTA-Bioseal set completely, while MTA-Fillapex was not completely set.
Multi-Agent Deep Q Network to Enhance the Reinforcement Learning for Delayed Reward System
Authors: Kim Keecheon
Published: March 2022

This study examines various factors and conditions that are related with the performance of reinforcement learning, and defines a multi-agent DQN system (N-DQN) model to improve them. N-DQN model is implemented in this paper with examples of maze finding and ping-pong as examples of delayed reward system, where delayed reward occurs, which makes general DQN learning difficult to apply. The implemented N-DQN shows about 3.5 times higher learning performance compared to the Q-Learning algorithm in the reward-sparse environment in the performance evaluation, and compared to DQN, it shows about 1.1 times faster goal achievement speed. In addition, through the implementation of the prioritized experience replay and the implementation of the reward acquisition section segmentation policy, such a problem as positive-bias of the existing reinforcement learning models seldom or never occurred. However, according to the characteristics of the architecture that uses many numbers of actors in parallel, the need for additional research on light-weighting the system for further performance improvement has raised. This paper describes in detail the structure of the proposed multi-agent N_DQN architecture, the contents of various algorithms used, and the specification for its implementation.
The Use of Graphene and Its Derivatives for the Development of Polymer Matrix Composites by Stereolithographic 3D Printing
Authors: Chiulan Ioana , Voicu Ştefan Ioan , Batalu Dan
Published: March 2022

Significant advances in graphene-based materials have facilitated the development of various composites structures in a diverse range of industry sectors. At present, the preparation of graphene-added materials is mainly developed through traditional methods. However, in recent years, additive manufacturing emerged as a promising approach that enables the printing of complex objects in a layer-by-layer fashion, without the need for moulds or machining equipment. This paper reviews the most recent reports on graphene-based photopolymerizable resins developed for stereolithography (SLA), with particular consideration for medical applications. The characteristics of the SLA technology, the most suitable raw materials and formulations and the properties of final 3D products are described. Throughout, a specific focus is placed on the mechanical properties and biocompatibility of the final 3D-printed object. Finally, remaining challenges and future directions are also discussed.
Evaluation of a Vein Biometric Recognition System on an Ordinary Smartphone
Authors: López-González Paula , Baturone Iluminada , Hinojosa Mercedes , Arjona Rosario
Published: March 2022

Nowadays, biometrics based on vein patterns as a trait is a promising technique. Vein patterns satisfy universality, distinctiveness, permanence, performance, and protection against circumvention. However, collectability and acceptability are not completely satisfied. These two properties are directly related to acquisition methods. The acquisition of vein images is usually based on the absorption of near-infrared (NIR) light by the hemoglobin inside the veins, which is higher than in the surrounding tissues. Typically, specific devices are designed to improve the quality of the vein images. However, such devices increase collectability costs and reduce acceptability. This paper focuses on using commercial smartphones with ordinary cameras as potential devices to improve collectability and acceptability. In particular, we use smartphone applications (apps), mainly employed for medical purposes, to acquire images with the smartphone camera and improve the contrast of superficial veins, as if using infrared LEDs. A recognition system has been developed that employs the free IRVeinViewer App to acquire images from wrists and dorsal hands and a feature extraction algorithm based on SIFT (scale-invariant feature transform) with adequate pre- and post-processing stages. The recognition performance has been evaluated with a database composed of 1000 vein images associated to five samples from 20 wrists and 20 dorsal hands, acquired at different times of day, from people of different ages and genders, under five different environmental conditions: day outdoor, indoor with natural light, indoor with natural light and dark homogeneous background, indoor with artificial light, and darkness. The variability of the images acquired in different sessions and under different ambient conditions has a large influence on the recognition rates, such that our results are similar to other systems from the literature that employ specific smartphones and additional light sources. Since reported quality assessment algorithms do not help to reject poorly acquired images, we have evaluated a solution at enrollment and matching that acquires several images subsequently, computes their similarity, and accepts only the samples whose similarity is greater than a threshold. This improves the recognition, and it is practical since our implemented system in Android works in real-time and the usability of the acquisition app is high.
Hydrogen Production Possibilities in Slovak Republic
Authors: Durcansky Peter , Nosek Radovan , Lenhard Richard , Zvada Branislav
Published: March 2022

Slovak Republic is a member of the European Union and is a part of the European energy market. Although Slovakia contributes only marginally to global emissions, there is an effort to meet obligations from the Paris climate agreement to reduce greenhouse gases. As in many countries, power industry emissions dominate Slovakia’s emissions output but are partly affected and lowered by the share of nuclear energy. The transition from fossil fuels to renewables is supported by the government, and practical steps have been taken to promote the wide use of renewable resources, such as biomass or solar energy. Another step in this transition process is the support of new technologies that use hydrogen as the primary energy source. The European Union widely supports this effort and is looking for possible sources for hydrogen generation. One of the main renewable resources is hydropower, which is already used in the Slovak Republic. This article presents the current situation of the energy market in Slovakia and possible developments for future hydrogen generation.
Geo-Accumulation Index of Manganese in Soils Due to Flooding in Boac and Mogpog Rivers, Marinduque, Philippines with Mining Disaster Exposure
Authors: Monjardin Cris Edward F. , Senoro Delia B. , Magbanlac Jeffersen James M. , de Jesus Kevin Lawrence M. , Tabelin Carlito B. , Natal Pablito M.
Published: March 2022

This paper presents the effects of flooding on the accumulation of manganese (Mn) in soils within proximity of the Boac and Mogpog rivers in Marinduque of The Philippines. Marinduque, an island province in the Philippines, experienced two catastrophic tailings storage facility (TSF) failures in the 1990s that released sulfide-rich tailings into the two major rivers. The Philippines experiences 21–23 typhoons every year, 11 of which pass thru Marinduque that causing inundation of floodplain areas in the province. A flood hazard map developed using LiDAR DEM was utilized for the Boac and Mogpog rivers for an accurate representation of flooding events. A portable X-ray fluorescence spectrometer (pXRF) and a Hannah multi-parameter device were used for the on-site analyses of Mn concentration and water physico-chemical properties, respectively. Spatial grid mapping with zonal statistics was employed for a comprehensive analysis of all the data collected and processed. Correlation analysis was carried out on Mn concentrations in soil and surface water, electrical conductivity (EC), total dissolved solids (TDS), pH, temperature, curve number (CN), and flood heights. The curve number indicates the runoff response characteristic of the Mogpog-Boac River basin. The results show that 40% of the total floodplain area of Boac and Mogpog were subjected to high hazards with flood heights above 1.5 m. The Mn content of soils had a statistically significant moderate positive correlation with flood height (r = 0.458) and a moderate negative correlation with pH (r = −0.438). This condition suggested that more extensive flooding promotes Mn contamination of floodplain soils in the two rivers, the source of which includes the mobilization of Mn-bearing silt, sediments, and mine drainage from the abandoned mine pits and TSFs. There is also a strong negative correlation between pH and Mn concentrations in surface water, a relationship attributed to the solubilization of Mn-bearing precipitates based on geochemical modeling results. Using Muller’s geo-accumulation index, 77.5% of the total floodplain of the two rivers was identified as “moderately contaminated” with an average Mn soil content of 3.4% by weight (34,000 mg/kg). The Mn contamination map of floodplain soils in the Mogpog and Boac rivers described in this study could guide relevant regional, national, and local government agencies in planning appropriate intervention, mitigation, remediation, and rehabilitation strategies to limit human exposure to highly contaminated areas.
A Study on the Factors Influencing Overall Fatigue and Musculoskeletal Pains in Automobile Manufacturing Production Workers
Authors: Kim Jun Won , Jeong Byung Yong , Park Myoung Hwan
Published: March 2022

In South Korea, the automobile sector is a key industry that occupies a very large proportion of production, employment, and exports in the national economy. However, production workers in the automobile industry are still exposed to a wide range of risk factors. This study aims to investigate the relationships between personal characteristics or occupational hazard exposure and subjective overall fatigue or musculoskeletal pains in the automobile manufacturing industry. We extracted 446 automobile manufacturing production workers as subjects from the data of the 5th Korean Working Conditions Survey. The χ2 test is performed to test whether there are differences in the distribution of complaints of musculoskeletal pains or overall fatigue in view of personal characteristics and exposure to working environment hazards and logistic regression analysis was used to analyze the relationships between them. Results showed that the proportions of the overall fatigue and musculoskeletal pains of the complaining group increase as the hazard exposure time increases. Longer exposure to tobacco smoke shows higher rates of complaints of overall fatigue and musculoskeletal pain. Results of logistic regression show that gender, longer exposure to fumes and dust, manual heavy loads handling, and to repetitive motion were the risk factors for overall fatigue and that gender, work experience, longer working hours, longer exposure to noise, fumes and dust, awkward posture, and high temperature were risk factors for musculoskeletal pains. The results show that there are close relationships between personal characteristics, working environment hazards, overall fatigue, and musculoskeletal pains.
Self-Balancing Power Amplifier with a Minimal DC Offset for Launcher Automation Control Circuits of a Surface-to-Air Missile System
Authors: Żółtowski Piotr , Bużantowicz Witold
Published: March 2022

This paper discusses the design of a new self-balancing amplifier of an AC component power characterized by a minimal output DC offset. The design of the amplifier is based on semiconductor technology and intended for application in low-frequency analog signal processing paths, particularly in surface-to-air missile system launcher automation circuits. The proposed solution has several design and technical-implementation advantages, whereas the primary novelty compared to the commonly used ones is the ability for self-generating a near-zero DC component value of output signal. The design features and technical parameters of the developed amplifier make it suitable for use in a wide range of devices that must ensure the stable, prolonged operation of a low-frequency power amplifier under variable weather conditions and a minimal DC offset of output signal.
A Review on Microfluidic Platforms Applied to Nerve Regeneration
Authors: Dai Chuankai , Liu Xiaoming , Tang Rongyu , He Jiping , Arai Tatsuo
Published: March 2022

In recent decades, microfluidics have significantly advanced nerve regeneration research. Microfluidic devices can provide an accurate simulation of in vivo microenvironment for different research purposes such as analyzing myelin growth inhibitory factors, screening drugs, assessing nerve growth factors, and exploring mechanisms of neural injury and regeneration. The microfluidic platform offers technical supports for nerve regeneration that enable precise spatio-temporal control of cells, such as neuron isolation, single-cell manipulation, neural patterning, and axon guidance. In this paper, we review the development and recent advances of microfluidic platforms for nerve regeneration research.
Alkali-Activated Materials with Pre-Treated Municipal Solid Waste Incinerator Bottom Ash
Authors: Avila Yoleimy , Silva Rui Vasco , de Brito Jorge
Published: March 2022

This study presents the results of an experimental campaign on the use of municipal solid waste incinerator bottom ash (MIBA) and fly ash (FA) as precursors for the production of alkali-activated materials. MIBA was subjected to a pre-treatment stage in response to two issues: high metallic aluminum content, which reacts in a high pH solution, releasing hydrogen; and low amorphous content of silica-, aluminum- and calcium-bearing phases, which translates into a limited formation of reaction products. The proposed pre-treatment stage oxidizes most of the metallic aluminum fraction and compensates for the low reactivity of the material via the formation of additional reactants. Different combinations of MIBA and FA were tried—mass-based ratios of 0/100, 25/75, 50/50, 75/25, and 100/0 for MIBA/FA. Two mix designs of the alkaline activator with sodium hydroxide and sodium silicate were evaluated by varying the Na2O/binder and SiO2/Na2O ratios. These mortars were tested in the fresh and hardened state. The results showed that the pre-treatment stage was effective at stabilizing the dimensional variation of MIBA. Despite the lower reactivity of MIBA, mortars with 50/50 of MIBA/FA presented a maximum 28-day compressive strength of 25.2 MPa, higher than the 5.7 MPa of mortars made with MIBA only.
200 Gbps/λ PON Downstream C-Band Direct-Detection Links with ≥29 dB Power Budget
Authors: Wang Haoyi , Torres-Ferrera Pablo , Rizzelli Giuseppe , Mercinelli Roberto , Ferrero Valter , Gaudino Roberto
Published: March 2022

In this paper we present the simulative analysis of a 200 Gbps per wavelength (λ) 8-level pulse amplitude modulation (PAM-8) downstream communication over up to 20 km single mode fiber (SMF) in C-band based on direct detection (DD) achieving at least a 29 dB link power budget in a PON environment. We use chromatic dispersion digital pre-compensation (CD-DPC) and a dual-arm in-phase and quadrature Mach–Zehnder modulator (IQ-MZM) at the optical line termination (OLT) side, while preserving DD in the optical network unit (ONU). Three receiver digital-signal-processing (DSP) options are analyzed and compared: square-root-like technique (SQRT) in combination with a feed forward equalizer (FFE) and a decision feedback equalizer (DFE), the Volterra nonlinear equalizer (VNLE), and the SQRT in combination with the VNLE. The SQRT can be applied in combination with the VNLE to decrease the receiver DSP complexity while maintaining the required system performance. We show that PAM-8 with CD-DPC and the SQRT in combination with the VNLE is a feasible solution for 200 Gbps per λ downstream C-band transmission for PON.
Fabrication of a Stainless-Steel Pump Impeller by Integrated 3D Sand Printing and Casting: Mechanical Characterization and Performance Study in a Chemical Plant
Authors: Hernández Felix , Fragoso Alex
Published: March 2022

The emergence of additive manufacturing is renovating the landscape of available production technologies. In this paper, we describe the fabrication of a closed vane pump impeller (ϕ 206 mm, height 68 mm, weight 4 kg) by binder jetting 3D printing of a sand mould followed by casting using stainless steel 316 to create an identical copy of a part in service in a chemical plant in Tarragona, Spain. The original part was reverse engineered and used to create a sand mould by binder jetting 3D printing on which new impellers were fabricated by casting. Metallographic studies showed an austenitic matrix with 6.3% of ferritic phase and 40 μm × 8 μm ferrite grains without precipitated carbides. The impeller was put into operation in a centrifugal pump at a polyol/polyglycol plant belonging to Dow Chemical Ibérica SL from October 2020 to April 2021. Process variables related to the pump behaviour were compared with the same variables obtained in previous cycles with the original impeller for three different product viscosities (30, 180, and 500 cSt). At 500 cSt, the average current consumption was 9.34 A as compared with the 9.41 A measured with the original impeller. Similarly, the pump pressure remained essentially constant during process operation with both impellers (3.97 bar with the new impeller vs. 3.99 bar with the old). Other monitored parameters (product flow, tank level) were similar in both cases, validating the fabrication strategy from an operational point of view. This work further demonstrated that the implementation of additive manufacturing technologies in chemical process engineering is a useful solution to fabricate spare parts that are difficult to replicate with other technologies, providing consequent economic benefits.
Influence of Anomalies on the Models for Nitrogen Oxides and Ozone Series
Authors: Bărbulescu Alina , Dumitriu Cristian Stefan , Ilie Iulia , Barbeş Sebastian-Barbu
Published: March 2022

Nowadays, observing, recording, and modeling the dynamics of atmospheric pollutants represent actual study areas given the effects of pollution on the population and ecosystems. The existence of aberrant values may influence reports on air quality when they are based on average values over a period. This may also influence the quality of models, which are further used in forecasting. Therefore, correct data collection and analysis is necessary before modeling. This study aimed to detect aberrant values in a nitrogen oxide concentration series recorded in the interval 1 January–8 June 2016 in Timisoara, Romania, and retrieved from the official reports of the National Network for Monitoring the Air Quality, Romania. Four methods were utilized, including the interquartile range (IQR), isolation forest, local outlier factor (LOF) methods, and the generalized extreme studentized deviate (GESD) test. Autoregressive integrated moving average (ARIMA), Generalized Regression Neural Networks (GRNN), and hybrid ARIMA-GRNN models were built for the series before and after the removal of aberrant values. The results show that the first approach provided a good model (from a statistical viewpoint) for the series after the anomalies removal. The best model was obtained by the hybrid ARIMA-GRNN. For example, for the raw NO2 series, the ARIMA model was not statistically validated, whereas, for the series without outliers, the ARIMA(1,1,1) was validated. The GRNN model for the raw series was able to learn the data well: R2 = 76.135%, the correlation between the actual and predicted values (rap) was 0.8778, the mean standard errors (MSE) = 0.177, the mean absolute error MAE = 0.2839, and the mean absolute percentage error MAPE = 9.9786. Still, on the test set, the results were worse: MSE = 1.5101, MAE = 0.8175, rap = 0.4482. For the series without outliers, the model was able to learn the data in the training set better than for the raw series (R2 = 0.996), whereas, on the test set, the results were not very good (R2 = 0.473). The performances of the hybrid ARIMA–GRNN on the initial series were not satisfactory on the test (the pattern of the computed values was almost linear) but were very good on the series without outliers (the correlation between the predicted values on the test set was very close to 1). The same was true for the models built for O3.
Recent Developments in Biological Processing Technology for Palm Oil Mill Effluent Treatment—A Review
Authors: Dominic Debbie , Baidurah Siti
Published: March 2022

POME is the most voluminous waste generated from palm oil milling activities. The discharge of POME into the environment without any treatment processing could inflict an undesirable hazard to humans and the environment due to its high amount of toxins, organic, and inorganic materials. The treatment of POME prior to discharge into the environment is utmost required to protect the liability for human health and the environment. Biological treatments are preferable due to eco-friendly attributes that are technically and economically feasible. The goal of this review article is to highlight the current state of development in the biological processing technologies for POME treatment. These biological processing technologies are conducted in the presence of fungi, bacteria, microalgae, and a consortium of microorganisms. Numerous microbes are listed to identify the most efficient strain by monitoring the BOD, COD, working volume of the reactor, and treatment time. The most effective processing technology for POME treatment uses an upflow anaerobic sludge blanket reactor with the COD value of 99%, hydraulic retention time of 7.2 days, and a working volume of 4.7 litres. Biological processing technologies are mooted as an efficient and sustainable management practice of POME waste.
Effect of Motility Factors D-Penicillamine, Hypotaurine and Epinephrine on the Performance of Spermatozoa from Five Hamster Species
Authors: Tourmente Maximiliano , Sanchez-Rodriguez Ana , Roldan Eduardo R. S.
Published: March 2022

Assessments of sperm performance are valuable tools for the analysis of sperm fertilizing potential and to understand determinants of male fertility. Hamster species constitute important animal models because they produce sperm cells in high quantities and of high quality. Sexual selection over evolutionary time in these species seems to have resulted in the largest mammalian spermatozoa, and high swimming and bioenergetic performances. Earlier studies showed that golden hamster sperm requires motility factors such as D-penicillamine, hypotaurine and epinephrine (PHE) to sustain survival over time, but it is unknown how they affect swimming kinetics or ATP levels and if other hamster species also require them. The objective of the present study was to examine the effect of PHE on spermatozoa of five hamster species (Mesocricetus auratus, Cricetulus griseus, Phodopus campbelli, P. sungorus, P. roborovskii). In sperm incubated for up to 4 h without or with PHE, we assessed motility, viability, acrosome integrity, sperm velocity and trajectory, and ATP content. The results showed differences in the effect of PHE among species. They had a significant positive effect on the maintenance of sperm quality in M. auratus and C. griseus, whereas there was no consistent effect on spermatozoa of the Phodopus species. Differences between species may be the result of varying underlying regulatory mechanisms of sperm performance and may be important to understand how they relate to successful fertilization.
Induction of Stem-Cell-Derived Cardiomyogenesis by Fibroblast Growth Factor 10 (FGF10) and Its Interplay with Cardiotrophin-1 (CT-1)
Authors: Khosravi Farhad , Ahmadvand Negah , Wartenberg Maria , Sauer Heinrich
Published: March 2022

For heart regeneration purposes, embryonic stem cell (ES)-based strategies have been developed to induce the proliferation of cardiac progenitor cells towards cardiomyocytes. Fibroblast growth factor 10 (FGF10) contributes to cardiac development and induces cardiomyocyte differentiation in vitro. Yet, among pro-cardiogenic factors, including cardiotrophin-1 (CT-1), the hyperplastic function of FGF10 in cardiomyocyte turnover remains to be further characterized. We investigated the proliferative effects of FGF10 on ES-derived cardiac progenitor cells in the intermediate developmental stage and examined the putative interplay between FGF10 and CT-1 in cardiomyocyte proliferation. Mouse ES cells were treated with FGF10 and/or CT-1. Differential expression of cardiomyocyte-specific gene markers was analyzed at transcript and protein levels. Substantial upregulation of sarcomeric α-actinin was detected by qPCR, flow cytometry, Western blot and immunocytochemistry. FGF10 enhanced the expression of other structural proteins (MLC-2a, MLC-2v and TNNT2), transcriptional factors (NKX2-5 and GATA4), and proliferation markers (Aurora B and YAP-1). FGF10/CT-1 co-administration led to an upregulation of proliferation markers, suggesting the synergistic potential of FGF10 + CT-1 on cardiomyogenesis. In summary, we provided evidence that FGF10 and CT-1 induce cardiomyocyte structural proteins, associated transcription factors, and cardiac cell proliferation, which could be applicable in therapies to replenish damaged cardiomyocytes.
Enhancement of Antiviral T-Cell Responses by Vitamin C Suggests New Strategies to Improve Manufacturing of Virus-Specific T Cells for Adoptive Immunotherapy
Authors: Laubert Miriam , Bonifacius Agnes , Dragon Anna , Mangare Caroline , Blasczyk Rainer , Huehn Jochen , Eiz-Vesper Britta
Published: March 2022

Allogeneic and autologous transplantation of hematopoietic stem cells (HSCT) are being routinely used to treat patients with leukemia and lymphoma. Due to the required immunosuppression after stem cell transplantation, infection and reactivation by viruses are life-threatening complications. In recent years, adoptive transfer using virus-specific T cells (VSTs) has emerged as alternative to conventional therapies. Since vitamins are described to influence the immune system and its cellular components, the aim of this study was to examine whether vitamins modulate VST function and thereby enable an improvement of therapy. For that, we investigated the impact of vitamin C and D on the functionality of cytomegalovirus (CMV)-specific T cells isolated from CMV-seropositive healthy donors. We were able to show that vitamin C increases the expansion and activation state of CMV-specific T cells, and an increased influence of vitamin C was observed on cells isolated from male donors and donors above 40 years of age. A higher frequency of the terminally differentiated effector memory CD8+ T-cell population in these donors indicates a connection between these cells and the enhanced response to vitamin C. Thus, here we provide insights into the impact of vitamin C on cytotoxic T cells as well as possible additional selection criteria and strategies to improve VST functionality.
Sequential Biotherapy Targeting IL-5 and IL-4/13 in Patients with Eosinophilic Asthma with Sinusitis and Otitis Media
Authors: Chikumoto Ayumi , Oishi Keiji , Hamada Kazuki , Hirano Tsunahiko , Kakugawa Tomoyuki , Kanesada Keiko , Matsunaga Kazuto
Published: March 2022

Type 2 (T2) inflammation plays an important role in the pathogenesis of allergic diseases such as asthma, eosinophilic chronic rhinosinusitis (ECRS), or eosinophilic otitis media (EOM). Currently, in severe asthma with the T2 phenotype, biologics targeting mediators of T2 inflammation dramatically improve the management of severe asthma. While treatment with a single biologic is common, little is known about cases of the sequential use of two biologics. Here, we report a case of severe asthma with refractory ECRS and EOM in which total control of these allergic diseases could not be achieved with a single biologic but could be achieved via the sequential use of the anti-IL-5 receptor antibody and human anti-IL-4/13 receptor monoclonal antibody. It is suggested that it is necessary to control multiple T2 inflammatory pathways to achieve total control of severe allergic diseases. Sequential biotherapy may help solve the clinical challenges associated with single-agent molecular-targeted therapies.
Membrane Activity of LL-37 Derived Antimicrobial Peptides against Enterococcus hirae: Superiority of SAAP-148 over OP-145
Authors: Piller Paulina , Wolinski Heimo , Cordfunke Robert A. , Drijfhout Jan Wouter , Keller Sandro , Lohner Karl , Malanovic Nermina
Published: March 2022

The development of antimicrobial agents against multidrug-resistant bacteria is an important medical challenge. Antimicrobial peptides (AMPs), human cathelicidin LL-37 and its derivative OP-145, possess a potent antimicrobial activity and were under consideration for clinical trials. In order to overcome some of the challenges to their therapeutic potential, a very promising AMP, SAAP-148 was designed. Here, we studied the mode of action of highly cationic SAAP-148 in comparison with OP-145 on membranes of Enterococcus hirae at both cellular and molecular levels using model membranes composed of major constituents of enterococcal membranes, that is, anionic phosphatidylglycerol (PG) and cardiolipin (CL). In all assays used, SAAP-148 was consistently more efficient than OP-145, but both peptides displayed pronounced time and concentration dependences in killing bacteria and performing at the membrane. At cellular level, Nile Red-staining of enterococcal membranes showed abnormalities and cell shrinkage, which is also reflected in depolarization and permeabilization of E. hirae membranes. At the molecular level, both peptides abolished the thermotropic phase transition and induced disruption of PG/CL. Interestingly, the membrane was disrupted before the peptides neutralized the negative surface charge of PG/CL. Our results demonstrate that SAAP-148, which kills bacteria at a significantly lower concentration than OP-145, shows stronger effects on membranes at the cellular and molecular levels.
Bioactive Peptides and Proteins from Wasp Venoms
Authors: Luo Lei , Kamau Peter Muiruri , Lai Ren
Published: March 2022

Wasps, members of the order Hymenoptera, use their venom for predation and defense. Accordingly, their venoms contain various constituents acting on the circulatory, immune and nervous systems. Wasp venom possesses many allergens, enzymes, bioactive peptides, amino acids, biogenic amines, and volatile matters. In particular, some peptides show potent antimicrobial, anti-inflammatory, antitumor, and anticoagulant activity. Additionally, proteinous components from wasp venoms can cause tissue damage or allergic reactions in organisms. These bioactive peptides and proteins involved in wasp predation and defense may be potential sources of lead pharmaceutically active molecules. In this review, we focus on the advances in bioactive peptides and protein from the venom of wasps and their biological effects, as well as the allergic reactions and immunotherapy induced by the wasp venom.
CAR-T Cells/-NK Cells in Cancer Immunotherapy and the Potential of MSC to Enhance Its Efficacy: A Review
Authors: Chan Ler Yie , Dass Sylvia Annabel , Tye Gee Jun , Imran Siti A. M. , Wan Kamarul Zaman Wan Safwani , Nordin Fazlina
Published: March 2022

The chimeric antigen receptor (CAR) plays a dynamic role in targeting tumour-associated antigens in cancer cells. This novel therapeutic discovery combines fragments of monoclonal antibodies with the signalling and co-stimulatory domains that have been modified to its current fourth generation. CAR has been widely implemented in T-cells and natural killer (NK) cells immunotherapy. The significant advancement in CAR technology is evident based on numerous ongoing clinical trials on CAR-T/-NK cells and successful CAR-related products such as Kymriah (Novartis) and Yescarta (Kite Pharma, Gilead). Another important cell-based therapy is the engineering of mesenchymal stem cells (MSC). Researchers have been exploring MSCs and their innate homing abilities to tumour sites and secretion cytokines that bridge both CAR and MSC technologies as a therapeutic agent. This combination allows for both therapies to overcome each one’s flaw as an immunotherapy intervention. Herein, we have provided a concise review on the background of CAR and its applications in different cancers, as well as MSCs’ unique ability as delivery vectors for cancer therapy and the possibility of enhancing the CAR-immune cells’ activity. Hence, we have highlighted throughout this review the synergistic effects of both interventions.
Oncolytic Vaccinia Virus Augments T Cell Factor 1-Positive Stem-like CD8+ T Cells, Which Underlies the Efficacy of Anti-PD-1 Combination Immunotherapy
Authors: Jeon Yun-Hui , Lee Namhee , Yoo Jiyoon , Won Solchan , Shin Suk-kyung , Kim Kyu-Hwan , Park Jun-Gyu , Kim Min-Gang , Kim Hang-Rae , Oh Keunhee , Lee Dong-Sup
Published: March 2022

Oncolytic virotherapy has garnered attention as an antigen-agnostic therapeutic cancer vaccine that induces cancer-specific T cell responses without additional antigen loading. As anticancer immune responses are compromised by a lack of antigenicity and chronic immunosuppressive microenvironments, an effective immuno-oncology modality that converts cold tumors into hot tumors is crucial. To evaluate the immune-activating characteristics of oncolytic vaccinia virus (VACV; JX-594, pexastimogene devacirepvec), diverse murine syngeneic cancer models with different tissue types and immune microenvironments were used. Intratumorally administered mJX-594, a murine variant of JX-594, potently increased CD8+ T cells, including antigen-specific cancer CD8+ T cells, and decreased immunosuppressive cells irrespective of tissue type or therapeutic efficacy. Remodeling of tumors into inflamed ones by mJX-594 led to a response to combined anti-PD-1 treatment, but not to mJX-594 or anti-PD-1 monotherapy. mJX-594 treatment increased T cell factor 1-positive stem-like T cells among cancer-specific CD8+ T cells, and anti-PD-1 combination treatment further increased proliferation of these cells, which was important for therapeutic efficacy. The presence of functional cancer-specific CD8+ T cells in the spleen and bone marrow for an extended period, which proliferated upon encountering cancer antigen-loaded splenic dendritic cells, further indicated that long-term durable anticancer immunity was elicited by oncolytic VACV.
Reward System Dysfunction and the Motoric-Cognitive Risk Syndrome in Older Persons
Authors: Lauretani Fulvio , Testa Crescenzo , Salvi Marco , Zucchini Irene , Lorenzi Beatrice , Tagliaferri Sara , Cattabiani Chiara , Maggio Marcello
Published: March 2022

During aging, many physiological systems spontaneously change independent of the presence of chronic diseases. The reward system is not an exception and its dysfunction generally includes a reduction in dopamine and glutamate activities and the loss of neurons of the ventral tegmental area (VTA). These impairments are even more pronounced in older persons who have neurodegenerative diseases and/or are affected by cognitive and motoric frailty. All these changes may result in the occurrence of cognitive and motoric frailty and accelerated progression of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. In particular, the loss of neurons in VTA may determine an acceleration of depressive symptoms and cognitive and motor frailty trajectory, producing an increased risk of disability and mortality. Thus, we hypothesize the existence of a loop between reward system dysfunction, depression, and neurodegenerative diseases in older persons. Longitudinal studies are needed to evaluate the determinant role of the reward system in the onset of motoric-cognitive risk syndrome.
Animal Models of Chorioamnionitis: Considerations for Translational Medicine
Authors: Raia-Barjat Tiphaine , Digonnet Margaux , Giraud Antoine , Ayash Taghreed , Vancolen Seline , Benharouga Mohamed , Chauleur Céline , Alfaidy Nadia , Sébire Guillaume
Published: March 2022

Preterm birth is defined as any birth occurring before 37 completed weeks of gestation by the World Health Organization. Preterm birth is responsible for perinatal mortality and long-term neurological morbidity. Acute chorioamnionitis is observed in 70% of premature labor and is associated with a heavy burden of multiorgan morbidities in the offspring. Unfortunately, chorioamnionitis is still missing effective biomarkers and early placento- as well as feto-protective and curative treatments. This review summarizes recent advances in the understanding of the underlying mechanisms of chorioamnionitis and subsequent impacts on the pregnancy outcome, both during and beyond gestation. This review also describes relevant and current animal models of chorioamnionitis used to decipher associated mechanisms and develop much needed therapies. Improved knowledge of the pathophysiological mechanisms underpinning chorioamnionitis based on preclinical models is a mandatory step to identify early in utero diagnostic biomarkers and design novel anti-inflammatory interventions to improve both maternal and fetal outcomes.
Structural Insights from Molecular Modeling of Isoindolin-1-One Derivatives as PI3Kγ Inhibitors against Gastric Carcinoma
Authors: Ghosh Suparna , Cho Seung Joo
Published: March 2022

The upregulation of phosphoinositol-3-kinase γ (PI3Kγ) is deemed to be positively correlated with tumor-associated-macrophage (TAM)-mediated gastric carcinoma (GC). PI3Kγ suppresses tumor necrosis factor-alpha (TNF-α) and interleukin-12 (IL-12) through activation of the AKT/mTOR pathway, which promotes the immunosuppressant phenotype of TAM. Unlike α and β isoforms, δ and γ isoforms are primarily distributed in leucocytes and macrophages. Dual inhibitors against PI3Kδ and PI3Kγ have been proven to have merits in targeting solid tumors. Furthermore, it has been found that PI3Kδ is activated by cytokines, while PI3Kγ is activated by G-protein-coupled receptors (GPCRs). This facilitates determining the functional difference between these two isoforms. For this goal, selective inhibitors would be immensely helpful. In the current manuscript, we conducted various molecular modeling studies with a series of isoindolin-1-one derivatives as potent PI3Kγ inhibitors by combining molecular docking, molecular dynamics (MD), molecular mechanics, Poisson–Boltzmann/generalized Born surface area (MM-PB/GBSA) binding free energy calculation, and three-dimensional structure–activity relationship (3D-QSAR) study. To evaluate the selectivity of γ isoform over δ, the molecular modeling studies of idelalisib analogs reported as PI3Kδ inhibitors were also investigated. The contour polyhedrons were generated from the comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) around the ligand-bound active site for both isoforms, which could emphasize plausible explanations for the physicochemical factors that affect selective ligand recognition. The binding modalities of the two isoforms using CoMFA and MD models were compared, which suggested some key differences in the molecular interactions with the ligands and could be summarized as three subsites (one affinity subsite near the C-helix and DFG and two hydrophobic subsites). In the context of the structure–activity relationship (SAR), several new compounds were designed using a fragment-substitution strategy with the aim of selectively targeting PI3Kγ. The pIC50 values of the designed compounds were predicted by the 3D-QSAR models, followed by the MM-PB/GBSA binding energy estimation. The overall findings suggest that the designed compounds have the potential to be used as PI3Kγ inhibitors with a higher binding affinity and selectivity.
Dual-Layered Approach of Ovine Collagen-Gelatin/Cellulose Hybrid Biomatrix Containing Graphene Oxide-Silver Nanoparticles for Cutaneous Wound Healing: Fabrication, Physicochemical, Cytotoxicity and Antibacterial Characterisation
Authors: Salleh Atiqah , Mustafa Norlaila , Teow Yeit Haan , Fatimah Mohd Nor , Khairudin Fauzul Azim , Ahmad Ishak , Fauzi Mh Busra
Published: March 2022

Tissue engineering products have grown rapidly as an alternative solution available for chronic wound and burn treatment. However, some drawbacks include additional procedures and a lack of antibacterial properties that can impair wound healing, which are issues that need to be tackled effectively for better wound recovery. This study aimed to develop a functionalized dual-layered hybrid biomatrix composed of collagen sponge (bottom layer) to facilitate cell proliferation and adhesion and gelatin/cellulose hydrogel (outer layer) incorporated with graphene oxide and silver nanoparticles (GC-GO/AgNP) to prevent possible external infections post-implantation. The bilayer hybrid scaffold was crosslinked with 0.1% (w/v) genipin for 6 h followed by advanced freeze-drying technology. Various characterisation parameters were employed to investigate the microstructure, biodegradability, surface wettability, nanoparticles antibacterial activity, mechanical strength, and biocompatibility of the bilayer bioscaffold towards human skin cells. The bilayer bioscaffold exhibited favourable results for wound healing applications as it demonstrated good water uptake (1702.12 ± 161.11%), slow rate of biodegradation (0.13 ± 0.12 mg/h), and reasonable water vapour transmission rate (800.00 ± 65.85 gm−2 h−1) due to its porosity (84.83 ± 4.48%). The biomatrix was also found to possess hydrophobic properties (48.97 ± 3.68°), ideal for cell attachment and high mechanical strength. Moreover, the hybrid GO-AgNP promoted antibacterial properties via the disk diffusion method. Finally, biomatrix unravelled good cellular compatibility with human dermal fibroblasts (>90%). Therefore, the fabricated bilayer scaffold could be a potential candidate for skin wound healing application.
Biomimicry as a Sustainable Design Methodology—Introducing the ‘Biomimicry for Sustainability’ Framework
Authors: Ilieva Lazaara , Ursano Isabella , Traista Lamiita , Hoffmann Birgitte , Dahy Hanaa
Published: March 2022

Biomimicry is an interdisciplinary approach to study and transfer principles or mechanisms from nature to solve design challenges, frequently differentiated from other design disciplines by its particular focus on and promise of sustainability. However, in the biomimicry and biologically inspired design literature, there are varying interpretations of how and whether biomimetic designs lead to sustainable outcomes and how sustainability, nature, and mimesis are conceptualised and engaged in practice. This paper takes a particular focus on the built environment and presents a theoretical overview of biomimicry literature spanning across specific fields, namely architecture, philosophy, sustainability and design. We develop upon conceptual considerations in an effort to contribute to the growing calls in the literature for more reflective discussions about the nuanced relationship between biomimicry and sustainability. We further develop a ‘Biomimicry for Sustainability’ framework that synthesises recent reflective deliberations, as a possible direction for further theorisation of biomimicry, aiming to elaborate on the role of biomimicry as a sustainable design methodology and its potential to cultivate more sustainable human–nature relations. The framework is used as a tool for retrospective analysis, based on literature of completed designs, and as a catalyst for biomimetic design thinking. The objective of this paper is to serve as a point of departure for more active and deeper discussions regarding future biomimetic practice in the context of sustainability and transformational change, particularly within the built environment.
Brief Strategy Training in Aging: Near Transfer Effects and Mediation of Gains by Improved Self-Regulation
Authors: Strickland-Hughes Carla M. , West Robin L.
Published: March 2022

A common approach to cognitive intervention for adults is memory strategy training, but limited work of this type has examined intervention effects in relation to self-regulation (e.g., strategy usage, memory beliefs) and few have established near transfer (training-related performance gain on untrained tasks related to the target task). The present research, Everyday Memory Clinic—Revised (EMC-R), examined whether relatively brief face-name association training, offering elements focused on self-regulation, can improve name recall, enhance memory self-regulation, and lead to near transfer. Participants were 122 healthy, well-educated middle-aged and older adults (51–90 years old) randomly assigned to a strategy training program (SO), a comparable program with a theoretical self-regulatory boost (SB), or a waitlist control group. Compared to the waitlist group, both groups of trainees demonstrated higher pretest-posttest improvements in name recall (target task), memory self-efficacy, and effective strategy use, as well as the near transfer of gains to nontrained associative tasks, a rare finding in strategy training research. Furthermore, changes in memory self-efficacy and strategy use fully mediated the effect of training on name recall. This innovative approach for brief memory intervention offers a model for successful training that can be easily disseminated via community centers and lifelong learning programs.