bluuebunny/crossref_metadata_2025 huggingface dataset:
Closed Endotracheal Suctioning Impact on Ventilator-Related Parameters in Obstructive and Restrictive Respiratory Systems: A Bench Study
Authors: Jung Fang , Chou Shang-Shing P. , Yang Shih-Hsing , Lin Jau-Chen , Jow Guey-Mei
Published: June 2021

A closed suctioning system (CSS) in patients with coronavirus disease 2019 (COVID-19) prevents spraying respiratory secretions into the environment during suction. However, it is not clear whether ventilation is maintained during the suction procedure, especially in patients with compromised pulmonary mechanics. This paper determines the effects of endotracheal tube (ETT) size, suction catheter size, and two lung mechanics (resistance and compliance) on ventilator-related parameters measured during suction. Suction was performed on an adult training lung, ventilated with either volume-controlled (VC-CMV) or pressure-controlled mandatory ventilation (PC-CMV), using ETT sizes of 6.5–8.0 mm paired with suction catheter sizes of 8–14 French (Fr). Peak inspiratory pressure (PIP) increased by 50% when the ETT’s ventilation area was less than 25 mm2 in size, especially in patients with high airway resistance ventilated with VC-CMV. Positive end-expiratory pressure (PEEP) levels significantly decreased when using 14 Fr SC during VC-CMV and fewer effects during PC-CMV. Change of expiratory minute volume increased with higher outer diameter of suction catheters and decreased with severe lung compliance during PC-CMV. The change in ventilator-related parameters were intently monitored in the patient whose pulmonary mechanic was compromised through the CSS endotracheal tube suctioning procedures in clinical airway management.
Study on the Mechanical Characteristics of the Sleeper Slab Track on a Long-Span Steel Truss Bridge
Authors: Zeng Zhiping , Huang Xiangdong , Wang Weidong , Zhu Bin , Zhang Zheng , Wang Di
Published: June 2021

This paper uses the long-span steel truss slab track as its research subject to analyze the new type of sleeper slab track structure with an experimental method. Firstly, a full-scale model was established in the laboratory to form a “rail–sleeper slab–self-compacting concrete cushion–steel beam” composite structure, and a fatigue test was performed on the track structure. The cyclic load was set up as a sine form with a range between 75 and 375 kN at a 5 Hz interval and 3 × 106 cycles. Based on the test, the performance of the track structure under cyclic train load was studied. Secondly, after every 106 loading cycles, the vertical static loading test and horizontal resistance test of the track structure were carried out to obtain the strain and displacement under different loading cycles. Finally, after 3 × 106 cycles of sine cyclic loading, the horizontal ultimate resistance test of the track structure was carried out to study its horizontal failure mode. The aims of this paper were to verify the applicability of the sleeper slab track, identify the mechanical properties, and determine the unfavorable position. The findings can provide an important reference for the practical use of the sleeper slab track structure.
School of the Future: A Comprehensive Study on the Effectiveness of Augmented Reality as a Tool for Primary School Children’s Education
Authors: Afnan  , Muhammad Khan , Khan Noman , Lee Mi-Young , Imran Ali , Sajjad Muhammad
Published: June 2021

With the emerging technologies of augmented reality (AR) and virtual reality (VR), the learning process in today’s classroom is much more effective and motivational. Overlaying virtual content into the real world makes learning methods attractive and entertaining for students while performing activities. AR techniques make the learning process easy, and fun as compared to traditional methods. These methods lack focused learning and interactivity between the educational content. To make learning effective, we propose to use handheld marker-based AR technology for primary school students. We developed a set of four applications based on students’ academic course of primary school level for learning purposes of the English alphabet, decimal numbers, animals and birds, and an AR Globe for knowing about different countries around the world. These applications can be played wherever and whenever a user wants without Internet connectivity, subject to the availability of a tablet or mobile device and the required target images. These applications have performance evaluation quizzes (PEQs) for testing students’ learning progress. Our study investigates the effectiveness of AR-based learning materials in terms of learning performance, motivation, attitude, and behavior towards different methods of learning. Our activity results favor AR-based learning techniques where students’ learning motivation and performance are enhanced compared to the non-AR learning methods.
Evaluation of ACL Graft Remodeling and Prediction of Graft Insufficiency in Sequenced MRI—Two-Year Follow-Up
Authors: Zdanowicz Urszula , Ciszkowska-Łysoń Beata , Paśnik Marcin , Drwięga Michał , Ratajczak Karol , Fulawka Kamil , Lee Yoojin C. , Śmigielski Robert
Published: June 2021

Background: Postoperative magnetic resonance imaging (MRI) evaluation of anterior cruciate ligament (ACL) graft maturity is a useful and practical tool that allows for assessment of graft status and remodeling stage. The purpose of this study was to evaluate and compare previously described methods of graft evaluation in MRI. We identify factors influencing the maturation and correlating graft appearance in MRI with indirect symptoms of graft insufficiency to identify patients at risk. Methods: Retrospective evaluation was performed in 44 patients who received bone patellar tendon bone (BPTB) ACL reconstruction with nine consecutive postoperative MRIs at 2, 6, 12, 18, 24, 36, 48, 72, and 96 weeks. Graft status was evaluated using signal-to-noise quotient (SNQ) methods in both sagittal and axial planes. We also assessed the homogeneity of the graft by standard deviation (SD) of signal intensity. SNQ was correlated with patient’s age, sex, postoperative weight-bearing, as well as indirect signs of graft insufficiency by MRI including graft appearance, posterior cruciate ligament (PCL) buckling, and measurement of anterior tibia subluxation. Results: We observed that the results of modelling SNQs from both sagittal and axial planes were similar. For both SNQs, the change over weeks quotient was nonlinear where the clinical parameter increased at week 36 and subsequently decreased. The SNQ at week 96 does not reach the levels from week 2. We observed that the model incorporating SNQ and relative SD (rSD) in the sagittal plane predicted the tibia anterior subluxation proportions better than the model with clinical parameters measured in the axial plane. Our results demonstrate that greater SD is associated with less graft homogeneity, which could indicate that this model is a good predictor of graft insufficiency. In addition, the proportion of PCL buckling increased over the course of the study. Conclusions: MRI graft evaluation is very useful for assessing graft ligamentization stage and to predict graft insufficiency.
Barrier-Free Wheelchair with a Mechanical Transmission
Authors: Lee Jongseok , Jeong Wonhyeong , Han Jaeoh , Kim Taesu , Oh Sehoon
Published: June 2021

Wheelchairs are an important means of transportation for the elderly and disabled. However, the movement of wheelchairs on long curbs and stairs is restricted. In this study, a wheelchair for climbing stairs was developed based on a mechanical transmission system that rotates the entire driving part through a link structure and an actuator to change the speed. The first mode drives the caterpillar, and the second mode drives the wheels. When driving on flat ground, it uses landing gears and wheels, and when climbing stairs, it uses the caterpillar; accordingly, a stable driving is possible. The stability of the transmission is confirmed through stress analysis. The method used in our study makes it is possible to manufacture lightweight wheelchairs because a single motor drives both the wheel and caterpillar through the transmission system.
Combustion and Performance Evaluation of a Spark Ignition Engine Operating with Acetone–Butanol–Ethanol and Hydroxy
Authors: Guillin-Estrada Wilson , Maestre-Cambronel Daniel , Bula-Silvera Antonio , Gonzalez-Quiroga Arturo , Duarte-Forero Jorge
Published: June 2021

Alternative fuels for internal combustion engines (ICE) emerge as a promising solution for a more sustainable operation. This work assesses combustion and performance of the dual-fuel operation in the spark ignition (SI) engine that simultaneously integrates acetone–butanol–ethanol (ABE) and hydroxy (HHO) doping. The study evaluates four fuel blends that combine ABE 5, ABE 10, and an HHO volumetric flow rate of 0.4 LPM. The standalone gasoline operation served as the baseline for comparison. We constructed an experimental test bench to assess operation conditions, fuel mode, and emissions characteristics of a 3.5 kW-YAMAHA engine coupled to an alkaline electrolyzer. The study proposes thermodynamic and combustion models to evaluate the performance of the dual-fuel operation based on in-cylinder pressure, heat release rate, combustion temperature, fuel properties, energy distribution, and emissions levels. Results indicate that ABE in the fuel blends reduces in-cylinder pressure by 10–15% compared to the baseline fuel. In contrast, HHO boosted in-cylinder pressure up to 20%. The heat release rate and combustion temperature follow the same trend, corroborating that oxygen enrichment enhances gasoline combustion. The standalone ABE operation raises fuel consumption by around 10–25 g∙kWh−1 compared to gasoline depending on the load, whereas HHO decreases fuel consumption by around 25%. The dual-fuel operation shows potential for mitigating CO, HC, and smoke emissions, although NOx emissions increased. The implementation of dual-fuel operation in SI engines represents a valuable tool for controlling emissions and reducing fuel consumption while maintaining combustion performance and thermal efficiency.
Light-Induced Ring Pattern in a Dye-Doped Nematic Liquid Crystal
Authors: Clerc Marcel G. , González-Cortés Gregorio , Hidalgo Paulina I. , Letelier Lucciano A. , Morel Mauricio J. , Vergara Jorge
Published: June 2021

The use of dye-doped liquid crystals allows the amplification of the coupling of light and liquid crystals. Light can induce the self-organization of the molecular order. The appearance of ring patterns has been observed, which has been associated with phase modulation. However, the morphology and dynamics of the ring patterns are not consistent with self-modulation. Based on an experimental setup with two parallel coherence beams orthogonal to a liquid crystal cell, one of which induces photo-isomerization and the other causes illumination, the formation of ring patterns is studied. To use these two coherent beams, we synthesize methylred methyl ester as a dye-dopant, which is photosensitive only to one of the light beams, and a commercial E7 liquid crystal as a matrix. Based on a mathematical model that accounts for the coupling between the concentration of the cis-state and the order parameter, we elucidate the emergence of the rings as forming patterns in an inhomogeneous medium. The bifurcation diagram is analytically characterized. The emergence, propagation of the rings, and the establishment of the ring patterns are in fair agreement with the experimental observations.
Indoor Positioning Systems Can Revolutionise Digital Lean
Authors: Tran Tuan-Anh , Ruppert Tamás , Abonyi János
Published: June 2021

The powerful combination of lean principles and digital technologies accelerates waste identification and mitigation faster than traditional lean methods. The new digital lean (also referred to as Lean 4.0) solutions incorporate sensors and digital equipment, yielding innovative solutions that extend the reach of traditional lean tools. The tracking of flexible and configurable production systems is not as straightforward as in a simple conveyor. This paper examines how the information provided by indoor positioning systems (IPS) can be utilised in the digital transformation of flexible manufacturing. The proposed IPS-based method enriches the information sources of value stream mapping and transforms positional data into key-performance indicators used in Lean Manufacturing. The challenges of flexible and reconfigurable manufacturing require a dynamic value stream mapping. To handle this problem, a process mining-based solution has been proposed. A case study is provided to show how the proposed method can be employed for monitoring and improving manufacturing efficiency.
Crawling Magnetic Robot to Perform a Biopsy in Tubular Environments by Controlling a Magnetic Field
Authors: Jung Eunsoo , Nam Jaekwang , Lee Wonseo , Kim Jongyul , Jang Gunhee
Published: June 2021

We developed a crawling magnetic robot (CMR), which can stably navigate and perform biopsies remotely in tubular environments by controlling a magnetic field. The CMR is composed of a crawling part and a biopsy part. The crawling part allows the CMR to crawl forward and backward via an asymmetric friction force generated by an external precessional magnetic field. The biopsy part closes or opens the cover of a needle to use the biopsy needle selectively with the control of the external precessional magnetic field. The cover of the biopsy part prevents damage to the tubular environments because the biopsy needle is inside the cover while the CMR is navigating. We developed the design of the proposed CMR using magnetic torque constraints and a magnetic force constraint, and then we fabricated the CMR with three-dimensional printing technology. Finally, we conducted an experiment to measure the CMR’s puncturing force with a load cell and conducted an experiment in a Y-shaped watery glass tube with pseudo-tissue to verify the crawling motion, the uncovering and covering motion of the biopsy needle, and the CMR’s ability to extract tissue with the biopsy needle.
Optimal Fall Protection System Selection Using a Fuzzy Multi-Criteria Decision-Making Approach for Construction Sites
Authors: Jin Haifeng , Goodrum Paul M.
Published: June 2021

Construction falls are a leading cause of fatalities in almost every construction industry around the globe, and fall protection systems are the key measures to ensure the safety of labor crews. This study develops a fuzzy multi-criteria decision-making model integrating analytical hierarchy process, fuzzy set theory and Technique for Order Preference by Similarity to Ideal Solution approach to analyze the overall performance of various fall protection plans for construction projects, which focuses on evaluation and selection of the appropriate protection plan considering the most influential safety, productivity, and economy factors. Results show that the optimal plan can be effectively identified and determined among all potential alternatives. Besides, the model overcomes the shortcoming of weight value uncertainty and ambiguous decision information through membership function calculations. As a result, it provides guidance for the improvement of construction performance, intending to minimize fall risks, improve labor productivity, and save economical cost on the jobsites.
Micro-Landscape Dependent Changes in Arbuscular Mycorrhizal Fungal Community Structure
Authors: Veresoglou Stavros D , Grünfeld Leonie , Mola Magkdi
Published: June 2021

The roots of most plants host diverse assemblages of arbuscular mycorrhizal fungi (AMF), which benefit the plant hosts in diverse ways. Even though we understand that such AMF assemblages are non-random, we do not fully appreciate whether and how environmental settings can make them more or less predictable in time and space. Here we present results from three controlled experiments, where we manipulated two environmental parameters, habitat connectance and habitat quality, to address the degree to which plant roots in archipelagos of high connectance and invariable habitats are colonized with (i) less diverse and (ii) easier to predict AMF assemblages. We observed no differences in diversity across our manipulations. We show, however, that mixing habitats and varying connectance render AMF assemblages less predictable, which we could only detect within and not between our experimental units. We also demonstrate that none of our manipulations favoured any specific AMF taxa. We present here evidence that the community structure of AMF is less responsive to spatio-temporal manipulations than root colonization rates which is a facet of the symbiosis which we currently poorly understand.
In Vitro Cytotoxic Effects of Secondary Metabolites Present in Sarcopoterium Spinosum L.
Authors: Hudec Jozef , Mojzis Jan , Habanova Marta , Saraiva Jorge A. , Hradil Pavel , Liptaj Tibor , Kobida Lubomir , Haban Miroslav , Holovicova Maria , Zvercova Dominika
Published: June 2021

Sarcopoterium spinosum (L.) is a medicinal plant traditionally used for the treatment of various diseases including cancer in the Near- and Middle East. The fractions and constituents of the ethanol extract of S. spinosum were screened for in vitro cytotoxic activities on Jurkat (acute T-lymphoblastic leukemia), HeLa (cervical adenocarcinoma), MCF-7 (mammary gland adenocarcinoma), Caco-2 (human colorectal adenocarcinoma), and MDA-MB-231 (mammary gland adenocarcinoma) cell lines using the MTT (3-(dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The ethanol extract was subsequently re-extracted with ethyl acetate and in its sub-fraction obtained by column chromatography three compounds (stachydrine, benzalkonium chloride and rutine) were the first time identified by nuclear magnetic resonance (NMR) analyses. The most active subfraction showed cytotoxic activity against HeLa, MCF-7, and Caco-2 cell lines. The three compounds mentioned, as standards of high-performance liquid chromatography (HPLC) quality, were studied individually and in combination. Cytotoxic activity observed might be due to the presence of benzalkonium chloride and rutin. Benzalkonium chloride showed the strongest growth suppression effect against HeLa cells (IC50 8.10−7 M) and MCF-7 cells (IC50 5.10−6 M). The mixture of stachydrine and benzalkonium chloride allowed a synergistic cytotoxic effect against all tested cancer and normal cells to be obtained. Anti-cancer activity of the plant extract of S. spinosum remains under-investigated, so this research describes how the three major compounds identified in the ethyl acetate extract can exert a significant dose dependent in vitro cytotoxicity.
Can Sustainable Packaging Help to Reduce Food Waste? A Status Quo Focusing Plant-Derived Polymers and Additives
Authors: Korte Imke , Kreyenschmidt Judith , Wensing Joana , Bröring Stefanie , Frase Jan Niklas , Pude Ralf , Konow Christopher , Havelt Thomas , Rumpf Jessica , Schmitz Michaela , Schulze Margit
Published: June 2021

The promotion of sustainable packaging is part of the European Green Deal and plays a key role in the EU’s social and political strategy. One option is the use of renewable resources and biomass waste as raw materials for polymer production. Lignocellulose biomass from annual and perennial industrial crops and agricultural residues are a major source of polysaccharides, proteins, and lignin and can also be used to obtain plant-based extracts and essential oils. Therefore, these biomasses are considered as potential substitute for fossil-based resources. Here, the status quo of bio-based polymers is discussed and evaluated in terms of properties related to packaging applications such as gas and water vapor permeability as well as mechanical properties. So far, their practical use is still restricted due to lower performance in fundamental packaging functions that directly influence food quality and safety, the length of shelf life, and thus the amount of food waste. Besides bio-based polymers, this review focuses on plant extracts as active packaging agents. Incorporating extracts of herbs, flowers, trees, and their fruits is inevitable to achieve desired material properties that are capable to prolong the food shelf life. Finally, the adoption potential of packaging based on polymers from renewable resources is discussed from a bioeconomy perspective.
Variable Neighborhood Strategy Adaptive Search to Solve Parallel-Machine Scheduling to Minimize Energy Consumption While Considering Job Priority and Control Makespan
Authors: Nanthapodej Rujapa , Liu Cheng-Hsiang , Nitisiri Krisanarach , Pattanapairoj Sirorat
Published: June 2021

Environmental concerns and rising energy prices put great pressure on the manufacturing industry to reduce pollution and save energy. Electricity is one of the main machinery energy sources in a plant; thus, reducing energy consumption both saves energy costs and protects our planet. This paper proposes the novel method called variable neighborhood strategy adaptive search (VaNSAS) in order to minimize energy consumption while also considering job priority and makespan control for parallel-machine scheduling problems. The newly presented neighborhood strategies of (1) solution destroy and repair (SDR), (2) track-transition method (TTM), and (3) multiplier factor (MF) were proposed and tested against the original differential evaluation (DE), current practice procedure (CU), SDR, TTM, and MF for three groups of test instances, namely small, medium, and large. Experimental results revealed that VaNSAS outperformed DE, CU, SDR, TTM, and MF, as it could find the optimal solution and the mathematical model in the small test instance, while the DE could only find 25%, and the others could not. In the remaining test instances, VaNSAS performed 16.35–19.55% better than the best solution obtained from Lingo, followed by DE, CU, SDR, TTM, and MF, which performed 7.89–14.59% better. Unfortunately, the CU failed to improve the solution and had worse performance than that of Lingo, including all proposed methods.
ECLand: The ECMWF Land Surface Modelling System
Authors: Boussetta Souhail , Balsamo Gianpaolo , Arduini Gabriele , Dutra Emanuel , McNorton Joe , Choulga Margarita , Agustí-Panareda Anna , Beljaars Anton , Wedi Nils , Munõz-Sabater Joaquín , de Rosnay Patricia , Sandu Irina , Hadade Ioan , Carver Glenn , Mazzetti Cinzia , Prudhomme Christel , Yamazaki Dai , Zsoter Ervin
Published: June 2021

The land-surface developments of the European Centre for Medium-range Weather Forecasts (ECMWF) are based on the Carbon-Hydrology Tiled Scheme for Surface Exchanges over Land (CHTESSEL) and form an integral part of the Integrated Forecasting System (IFS), supporting a wide range of global weather, climate and environmental applications. In order to structure, coordinate and focus future developments and benefit from international collaboration in new areas, a flexible system named ECLand, which would facilitate modular extensions to support numerical weather prediction (NWP) and society-relevant operational services, for example, Copernicus, is presented. This paper introduces recent examples of novel ECLand developments on (i) vegetation; (ii) snow; (iii) soil; (iv) open water/lake; (v) river/inundation; and (vi) urban areas. The developments are evaluated separately with long-range, atmosphere-forced surface offline simulations and coupled land-atmosphere-ocean experiments. This illustrates the benchmark criteria for assessing both process fidelity with regards to land surface fluxes and reservoirs of the water-energy-carbon exchange on the one hand, and on the other hand the requirements of ECMWF’s NWP, climate and atmospheric composition monitoring services using an Earth system assimilation and prediction framework.
Effect of Biochar and Straw Application on Nitrous Oxide and Methane Emissions from Eutric Regosols with Different pH in Sichuan Basin: A Mesocosm Study
Authors: Ntacyabukura Tite , Uwiringiyimana Ernest , Zhou Minghua , Zhang Bowen , Zhu Bo , Harerimana Barthelemy , Nambajimana Jean de Dieu , Nsabimana Gratien , Nsengumuremyi Pascal
Published: June 2021

Adoption of crop residue amendments has been increasingly recommended as an effective management practice for mitigating greenhouse gas emissions while enhancing soil fertility, thereby increasing crop production. However, the effect of biochar and straw on nitrous oxide (N2O) and methane (CH4) emissions in soils of differing pH remains poorly understood. Three treatments (control (i.e., no amendment), maize straw, and biochar derived from maize straw) were therefore established separately in soils with different pH levels, classified as follows: acidic, neutral, and alkaline. N2O and CH4 were investigated using a static chamber–gas chromatography system during 57 days of a mesocosm study. The results showed that cumulative N2O emissions were significantly higher in acidic soils than in other experimental soils, with the values ranging from 7.48 to 11.3 kg N ha−1, while CH4 fluxes ranged from 0.060 to 0.089 kg C ha−1, with inconclusive results. However, a weak negative correlation was observed between log N2O and log NO3-N in acidic soil with either biochar or straw, while the same parameters with CH4 showed a moderate negative correlation, suggesting a likelihood that these amendments could mitigate GHGs as a result of the NO3-N increase in acidic soils. It is also possible, given the alkaline nature of the biochar, that incorporation had a significant buffer effect on soil acidity, effectively increasing soil pH by >0.5 pH units. Our findings suggest that for the rates of application for biochar and straw used in this study, the magnitude of reductions in the emissions of N2O and CH4 are dependent in part on initial soil pH.
Numerical Solution of an Interval-Based Uncertain SIR (Susceptible–Infected–Recovered) Epidemic Model by Homotopy Analysis Method
Authors: Bakare Emmanuel A. , Chakraverty Snehashish , Potucek Radovan
Published: June 2021

This work proposes an interval-based uncertain Susceptible–Infected–Recovered (SIR) epidemic model. The interval model has been numerically solved by the homotopy analysis method (HAM). The SIR epidemic model is proposed and solved under different uncertain intervals by the HAM to obtain the numerical solution of the model. Furthermore, the SIR ODE model was transformed into a stochastic differential equation (SDE) model and the results of the stochastic and deterministic models were compared using numerical simulations. The results obtained were compared with the numerical solution and found to be in good agreement. Finally, various simulations were done to discuss the solution.
A New Application in Biology Education: Development and Implementation of Arduino-Supported STEM Activities
Authors: Görgülü Arı Aslı , Meço Gülsüm
Published: June 2021

Considering that generations that have grown up in the 21st-century have grown alongside technology, it is thought that integrating technology into lessons helps students learn the subject. This study aims to develop five STEM activities for the lesson of the human body systems by integrating the coding-based Arduino into STEM education. The activities were implemented to 6th-grade students for seven weeks and the effects on students’ skills of establishing a cause-effect relationship. The study method was pre-test-post-test quasi-experimental design, and the cause-effect relationship scale and semi-structured view form were used as data collection tools. As a result of the study, a significant difference was found between the Arduino-supported STEM activities developed and the students’ skills of establishing a cause-effect relationship. The students who received the Arduino-supported STEM education found the course to be entertaining and educational, and the future goals of these students were affected. In order to bring individuals who love their profession into the future, Arduino-supported STEM education should be applied and expanded in other branches and class levels.
Nucleoside Analogues Are Potent Inducers of Pol V-mediated Mutagenesis
Authors: Sumabe Balagra Kasim , Ræder Synnøve Brandt , Røst Lisa Marie , Sharma Animesh , Donkor Eric S. , Mosi Lydia , Duodu Samuel , Bruheim Per , Otterlei Marit
Published: June 2021

Drugs targeting DNA and RNA in mammalian cells or viruses can also affect bacteria present in the host and thereby induce the bacterial SOS system. This has the potential to increase mutagenesis and the development of antimicrobial resistance (AMR). Here, we have examined nucleoside analogues (NAs) commonly used in anti-viral and anti-cancer therapies for potential effects on mutagenesis in Escherichia coli, using the rifampicin mutagenicity assay. To further explore the mode of action of the NAs, we applied E. coli deletion mutants, a peptide inhibiting Pol V (APIM-peptide) and metabolome and proteome analyses. Five out of the thirteen NAs examined, including three nucleoside reverse transcriptase inhibitors (NRTIs) and two anti-cancer drugs, increased the mutation frequency in E. coli by more than 25-fold at doses that were within reported plasma concentration range (Pl.CR), but that did not affect bacterial growth. We show that the SOS response is induced and that the increase in mutation frequency is mediated by the TLS polymerase Pol V. Quantitative mass spectrometry-based metabolite profiling did not reveal large changes in nucleoside phosphate or other central carbon metabolite pools, which suggests that the SOS induction is an effect of increased replicative stress. Our results suggest that NAs/NRTIs can contribute to the development of AMR and that drugs inhibiting Pol V can reverse this mutagenesis.
Chemokines in Severe Cutaneous Adverse Reactions (SCARs)
Authors: Miyagawa Fumi , Asada Hideo
Published: June 2021

Although the incidence of severe cutaneous adverse reactions (SCARs) to medications is very low, SCARs can result in disability or even death if they are not diagnosed and treated properly. As the rapid recognition of SCARs is essential, it is necessary to develop diagnostic markers for them that can also be used to assess severity and predict outcomes in the early phase. In addition, it is important to identify novel therapeutic targets for SCARs. Chemokines are chemotactic cytokines that control the migratory patterns and locations of immune cells and usually exhibit markedly specific associations with certain human diseases. In Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), the Th1-associated chemokines chemokine (C-X-C motif) ligand 9 (CXCL9) and CXCL10 predominate, while in drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS), the levels of the Th2-associated chemokines chemokine (C-C motif) ligand 17 (CCL17) and CCL22 are markedly elevated. We suggest that the distinct chemokine profiles of SJS/TEN and DIHS/DRESS can be used to aid their differential diagnosis. CXCL10 has also been reported to be associated with the development of long-term sequelae in DIHS/DRESS. This review focuses on the chemokines involved in the pathogenesis and adjuvant diagnosis of SCARs, particularly SJS/TEN and DIHS/DRESS, but also provides a brief overview of SCARs and the chemokine superfamily. As it is being increasingly recognized that an association exists between human herpesvirus 6 (HHV-6) and DIHS/DRESS, the possible roles of the chemokine/chemokine receptor homologs encoded by HHV-6 in the pathogenesis of DIHS/DRESS are also discussed.
Micro-Aqueous Organic System: A Neglected Model in Computational Lipase Design?
Authors: Wang Shang , Xu Yan , Yu Xiao-Wei
Published: June 2021

Water content is an important factor in lipase-catalyzed reactions in organic media but is frequently ignored in the study of lipases by molecular dynamics (MD) simulation. In this study, Candida antarctica lipase B, Candida rugosa lipase and Rhizopus chinensis lipase were used as research models to explore the mechanisms of lipase in micro-aqueous organic solvent (MAOS) media. MD simulations indicated that lipases in MAOS systems showed unique conformations distinguished from those seen in non-aqueous organic solvent systems. The position of water molecules aggregated on the protein surface in MAOS media is the major determinant of the unique conformations of lipases and particularly impacts the distribution of hydrophilic and hydrophobic amino acids on the lipase surface. Additionally, two maxima were observed in the water-lipase radial distribution function in MAOS systems, implying the formation of two water shells around lipase in these systems. The energy landscapes of lipases along solvent accessible areas of catalytic residues and the minimum energy path indicated the dynamic open states of lipases in MAOS systems differ from those in other solvent environments. This study confirmed the necessity of considering the influence of the microenvironment on MD simulations of lipase-catalyzed reactions in organic media.
To Be, or Notch to Be: Mediating Cell Fate from Embryogenesis to Lymphopoiesis
Authors: Ng Han Leng , Quail Elizabeth , Cruickshank Mark N. , Ulgiati Daniela
Published: June 2021

Notch signaling forms an evolutionarily conserved juxtacrine pathway crucial for cellular development. Initially identified in Drosophila wing morphogenesis, Notch signaling has since been demonstrated to play pivotal roles in governing mammalian cellular development in a large variety of cell types. Indeed, abolishing Notch constituents in mouse models result in embryonic lethality, demonstrating that Notch signaling is critical for development and differentiation. In this review, we focus on the crucial role of Notch signaling in governing embryogenesis and differentiation of multiple progenitor cell types. Using hematopoiesis as a diverse cellular model, we highlight the role of Notch in regulating the cell fate of common lymphoid progenitors. Additionally, the influence of Notch through microenvironment interplay with lymphoid cells and how dysregulation influences disease processes is explored. Furthermore, bi-directional and lateral Notch signaling between ligand expressing source cells and target cells are investigated, indicating potentially novel therapeutic options for treatment of Notch-mediated diseases. Finally, we discuss the role of cis-inhibition in regulating Notch signaling in mammalian development.
Optimization of High-Density Fe-Au Nano-Arrays for Surface-Enhanced Raman Spectroscopy of Biological Samples
Authors: Marinaro Giovanni , Coluccio Maria Laura , Gentile Francesco
Published: June 2021

The method of realizing nanostructures using porous alumina templates has attracted interest due to the precise geometry and cheap cost of nanofabrication. In this work, nanoporous alumina membranes were utilized to realize a forest of nanowires, providing a bottom-up nanofabrication method suitable for surface-enhanced Raman spectroscopy (SERS). Gold and iron were electroplated through the straight channels of the membrane. The resulting nanowires are, indeed, made of an active element for plasmonic resonance and SERS as the hexagonal distribution of the nanowires and the extreme high density of the nanowires allows to excite the plasmon and detect the Raman signal. The method to reduce the distance between pores and, consequently, the distance of the nanowires after electrodeposition is optimized here. Indeed, it has been predicted that the light intensity enhancement factor is up to 1012 when the gap is small than 10 nm. Measurements of Raman signal of thiol groups drying on the gold nanowires show that the performance of the device is improved. As the thiol group can be linked to proteins, the device has the potential of a biosensor for the detection of a few biomolecules. To assess the performance of the device and demonstrate its ability to analyze biological solutions, we used it as SERS substrates to examine solutions of IgG in low abundance ranges. The results of the test indicate that the sensor can convincingly detect biomolecules in physiologically relevant ranges.
An Ultrasensitive Biosensor for Detection of Femtogram Levels of the Cancer Antigen AGR2 Using Monoclonal Antibody Modified Screen-Printed Gold Electrodes
Authors: Białobrzeska Wioleta , Dziąbowska Karolina , Lisowska Małgorzata , Mohtar M. Aiman , Muller Petr , Vojtesek Borivoj , Krejcir Radovan , O’Neill Robert , Hupp Ted R. , Malinowska Natalia , Bięga Ewelina , Bigus Daniel , Cebula Zofia , Pala Katarzyna , Czaczyk Elżbieta , Żołędowska Sabina , Nidzworski Dawid
Published: June 2021

The detection of cancer antigens is a major aim of cancer research in order to develop better patient management through early disease detection. Many cancers including prostate, lung, and ovarian secrete a protein disulfide isomerase protein named AGR2 that has been previously detected in urine and plasma using mass spectrometry. Here we determine whether a previously developed monoclonal antibody targeting AGR2 can be adapted from an indirect two-site ELISA format into a direct detector using solid-phase printed gold electrodes. The screen-printed gold electrode was surface functionalized with the anti-AGR2 specific monoclonal antibody. The interaction of the recombinant AGR2 protein and the anti-AGR2 monoclonal antibody functionalized electrode changed its electrochemical impedance spectra. Nyquist diagrams were obtained after incubation in an increasing concentration of purified AGR2 protein with a range of concentrations from 0.01 fg/mL to 10 fg/mL. In addition, detection of the AGR2 antigen can be achieved from cell lysates in medium or artificial buffer. These data highlight the utility of an AGR2-specific monoclonal antibody that can be functionalized onto a gold printed electrode for a one-step capture and quantitation of the target antigen. These platforms have the potential for supporting methodologies using more complex bodily fluids including plasma and urine for improved cancer diagnostics.
Disruptions in Effective Connectivity within and between Default Mode Network and Anterior Forebrain Mesocircuit in Prolonged Disorders of Consciousness
Authors: Coulborn Sean , Taylor Chris , Naci Lorina , Owen Adrian M. , Fernández-Espejo Davinia
Published: June 2021

Recent research indicates prolonged disorders of consciousness (PDOC) result from structural and functional impairments to key cortical and subcortical networks, including the default mode network (DMN) and the anterior forebrain mesocircuit (AFM). However, the specific mechanisms which underpin such impairments remain unknown. It is known that disruptions in the striatal-pallidal pathway can result in the over inhibition of the thalamus and lack of excitation to the cortex that characterizes PDOC. Here, we used spectral dynamic causal modelling and parametric empirical Bayes on rs-fMRI data to assess whether DMN changes in PDOC are caused by disruptions in the AFM. PDOC patients displayed overall reduced coupling within the AFM, and specifically, decreased self-inhibition of the striatum, paired with reduced coupling from striatum to thalamus. This led to loss of inhibition from AFM to DMN, mostly driven by posterior areas including the precuneus and inferior parietal cortex. In turn, the DMN showed disruptions in self-inhibition of the precuneus and medial prefrontal cortex. Our results provide support for the anterior mesocircuit model at the subcortical level but highlight an inhibitory role for the AFM over the DMN, which is disrupted in PDOC.
Differential Epigenetic Signature of Corticospinal Motor Neurons in ALS
Authors: Ozyurt Tunch , Gautam Mukesh
Published: June 2021

Corticospinal motor neurons (CSMN) are an indispensable neuron population for the motor neuron circuitry. They are excitatory projection neurons, which collect information from different regions of the brain and transmit it to spinal cord targets, initiating and controlling motor function. CSMN degeneration is pronounced cellular event in motor neurons diseases, such as amyotrophic lateral sclerosis (ALS). Genetic mutations contribute to only about ten percent of ALS. Thus understanding the involvement of other factors, such as epigenetic controls, is immensely valuable. Here, we investigated epigenomic signature of CSMN that become diseased due to misfolded SOD1 toxicity and TDP-43 pathology, by performing quantitative analysis of 5-methylcytosine (5mC) and 5-hydroxymethycytosine (5hmC) expression profiles during end-stage of the disease in hSOD1G93A, and prpTDP-43A315T mice. Our analysis revealed that expression of 5mC was specifically reduced in CSMN of both hSOD1G93A and prpTDP-43A315T mice. However, 5hmC expression was increased in the CSMN that becomes diseased due to misfolded SOD1 and decreased in CSMN that degenerates due to TDP-43 pathology. These results suggest the presence of a distinct difference between different underlying causes. These differential epigenetic events might modulate the expression profiles of select genes, and ultimately contribute to the different paths that lead to CSMN vulnerability in ALS.
Sex Differences in Spatial Memory: Comparison of Three Tasks Using the Same Virtual Context
Authors: Tascón Laura , Di Cicco Carmen , Piccardi Laura , Palmiero Massimiliano , Bocchi Alessia , Cimadevilla José Manuel
Published: June 2021

Spatial memory has been studied through different instruments and tools with different modalities of administration. The cognitive load varies depending on the measure used and it should be taken into account to correctly interpret results. The aim of this research was to analyze how men and women perform three different spatial memory tasks with the same spatial context but with different cognitive demands. A total of 287 undergraduate students from the University of Almeria (Spain) and the University of L’Aquila (Italy) participated in the study. They were divided into three groups balanced by sex according to the spatial memory test they performed: the Walking Space Boxes Room Task (WSBRT), the Almeria Spatial Memory Recognition Test (ASMRT) and the Non-Walking Space Boxes Room Task (NWSBRT). Time spent and number of errors/correct answers were registered for analysis. In relation to the WSBRT and the ASMRT, men were faster and reached the optimal level of performance before women. In the three tests, familiarity with the spatial context helped to reduce the number of errors, regardless of the level of difficulty. In conclusion, sex differences were determined by the familiarity with the spatial context, the difficulty level of the task, the active or passive role of the participant and the amount of visual information provided in each screen shot.
Masonry Dome Behavior under Gravity Loads Based on the Support Condition by Considering Variable Curves and Thicknesses
Authors: Sharbaf Asem , Bemanian Mohammadreza , Daneshjoo Khosro , Shakib Hamzeh
Published: June 2021

It is necessary to recognize masonry domes’ behavior under gravity loads in order to strengthen, restore, and conserve them. The neutral hoop plays a crucial role in identifying the masonry dome’s behavior to distinguish between its tensile and compressive regions. When it comes to determining the neutral hoop position in a dome with the same brick material, in addition to determining the dome’s curve and thickness, the support condition located on the boundary line is a significant parameter that has received less attention in the past. Therefore, this research aims to comprehensively define masonry dome behaviors based on the support condition’s effect on the masonry dome’s behavior, in addition to thickness and curve parameters, by determining neutral hoop(s). The method is a graphical and numerical analysis to define the sign-changing positioning in the first principal stress (hoop stress), based on the shell theory and extracted from a finite element method (FEM) Karamba3D analysis of a macro-model. The case studies are in four types of supports: condition fixed, free in the X- and Y-axes, free in all axes (domes placed on a drum), and free in all axes (domes placed on a pendentive and a drum). For each support condition, twelve curves and four varied thicknesses for each curve are considered. Results based on the dome’s variables show that, in general, four types of masonry domes behavior can be identified: single-masonry dome behavior with no neutral hoop; double-masonry dome behavior where all hoops are compressive with a single neutral hoop; double-masonry dome behavior where hoops are compressive and tensile with a single neutral hoop; and treble-masonry dome behavior with double neutral hoops.
Evaluating the Connection between Thermal Comfort and Productivity in Buildings: A Systematic Literature Review
Authors: Bueno Ana , de Paula Xavier Antonio , Broday Evandro
Published: June 2021

The thermal environment is one of the main factors that influence thermal comfort and, consequently, the productivity of occupants inside buildings. Throughout the years, research has described the connection between thermal comfort and productivity. Mathematical models have been established in the attempt to predict changes in productivity according to thermal variations in the environment. Some of these models have failed for a number of reasons, including the understanding of the effect that several environment variables have had on performance. From this context, a systematic literature review was carried out with the aim of verifying the connection between thermal comfort and productivity and the combinations of different thermal and personal factors that can have an effect on productivity. A hundred and twenty-eight articles were found which show a connection between productivity and some thermal comfort variables. By means of specific inclusion and exclusion criteria, 60 articles were selected for a final analysis. The main conclusions found in this study were: (i) the vast majority of research uses subjective measures and/or a combination of methods to evaluate productivity; (ii) performance/productivity can be attained within an ampler temperature range; (iii) few studies present ways of calculating productivity.
Loss of Nitric Oxide Induces Fibrogenic Response in Organotypic 3D Co-Culture of Mammary Epithelia and Fibroblasts—An Indicator for Breast Carcinogenesis
Authors: Ren Gang , Zheng Xunzhen , Sharma Vandana , Letson Joshua , Nestor-Kalinoski Andrea L. , Furuta Saori
Published: June 2021

Excessive myofibroblast activation, which leads to dysregulated collagen deposition and the stiffening of the extracellular matrix (ECM), plays pivotal roles in cancer initiation and progression. Cumulative evidence attests to the cancer-causing effects of a number of fibrogenic factors found in the environment, diseases and drugs. While identifying such factors largely depends on epidemiological studies, it would be of great importance to develop a robust in vitro method to demonstrate the causal relationship between fibrosis and cancer. Here, we tested whether our recently developed organotypic three-dimensional (3D) co-culture would be suitable for that purpose. This co-culture system utilizes the discontinuous ECM to separately culture mammary epithelia and fibroblasts in the discrete matrices to model the complexity of the mammary gland. We observed that pharmaceutical deprivation of nitric oxide (NO) in 3D co-cultures induced myofibroblast differentiation of the stroma as well as the occurrence of epithelial–mesenchymal transition (EMT) of the parenchyma. Such in vitro response to NO deprivation was unique to co-cultures and closely mimicked the phenotype of NO-depleted mammary glands exhibiting stromal desmoplasia and precancerous lesions undergoing EMT. These results suggest that this novel 3D co-culture system could be utilized in the deep mechanistic studies of the linkage between fibrosis and cancer.