bluuebunny/crossref_metadata_2025 huggingface dataset:
Does the Mass Public Transport System Cover the Social Transport Needs? Targeting SDG 11.2 in Guadalajara, Mexico
Authors: Ochoa-Covarrubias Gabriela , Grindlay Alejandro Luis , Lizarraga Carmen
Published: August 2021

This paper analyses how SITEUR, the Mass Public Transport System (MPTS) in the Guadalajara Metropolitan Area (GMA), covers transport social needs, contributing to achieve Sustainable Development Goals (SDG) 11.2. In order to facilitate this, an Index of Mass Transport Provision (IMTP) was measured through proximity, frequency, and capacity. Then, an Index of Social Transport Needs (ISTN) was calculated by means of transport disadvantage indicators. Finally, the Index of Social Transport Needs Covered (ICSTN) was calculated. The calculations used geographic information systems and principal component analysis in 1834 geographic sections. Findings highlight that 50.3% of the inhabitants have a very high level of social transport needs, while only 6.8% of the population have very low social transport needs. Results show that SITEUR promotes advancement in public transport systems within the GMA relative to quality, security, and reliability and it also contributes to tackling social exclusion in the GMA. A proposal related to transport systems integration is included, to address an important aspect of social exclusion in the city.
Soft Sensor Transferability: A Survey
Authors: Curreri Francesco , Patanè Luca , Xibilia Maria Gabriella
Published: August 2021

Soft Sensors (SSs) are inferential dynamical models employed in industries to perform prediction of process hard-to-measure variables based on their relation with easily accessible ones. They allow implementation of real-time control and monitoring of the plants and present other advantages in terms of costs and efforts. Given the complexity of industrial processes, these models are generally designed with data-driven black-box machine learning (ML) techniques. ML methods work well only if the data on which the prediction is performed share the same distribution with the one on which the model was trained. This is not always possible, since plants can often show new working conditions. Even similar plants show different data distributions, making SSs not scalable between them. Models should then be created from scratch with highly time-consuming procedures. Transfer Learning (TL) is a field of ML that re-uses the knowledge from one task to learn a new different, but related, one. TL techniques are mainly used for classification tasks. Only recently TL techniques have been adopted in the SS field. The proposed survey reports the state of the art of TL techniques for nonlinear dynamical SSs design. Methods and applications are discussed and the new directions of this research field are depicted.
Analysis and Identification of Nonlinear Acoustic Damping in Miniature Loudspeakers
Authors: Huang Jie , Pan Ke-Yu , Feng Xue-Lei , Shen Yong
Published: August 2021

Nonlinear acoustic damping is a key nonlinearity in miniature loudspeakers when the air velocity is at a high amplitude. Measurement of nonlinear acoustic damping is beneficial for predicting and analyzing the performance of miniature loudspeakers. However, the general measuring methods for acoustic impedance, such as the standing-wave tube method or the impedance tube method, are not applicable in this scenario because the nonlinear acoustic damping in miniature loudspeakers is coupled with other system nonlinearities. In this study, a measurement method based on nonlinear system identification was constructed to address this issue. The nonlinear acoustic damping was first theoretically analyzed and then coupled in an equivalent circuit model (ECM) to describe the full dynamics of miniature loudspeakers. Based on the ECM model, the nonlinear acoustic damping was identified using measured electrical data and compared with theoretical calculations. The satisfactory agreement between the identification and theoretical calculations confirms the validity of the proposed identification method.
Deep Learning Applications in Geosciences: Insights into Ichnological Analysis
Authors: Ayranci Korhan , Yildirim Isa E. , Waheed Umair bin , MacEachern James A.
Published: August 2021

Ichnological analysis, particularly assessing bioturbation index, provides critical parameters for characterizing many oil and gas reservoirs. It provides information on reservoir quality, paleodepositional conditions, redox conditions, and more. However, accurately characterizing ichnological characteristics requires long hours of training and practice, and many marine or marginal marine reservoirs require these specialized expertise. This adds more load to geoscientists and may cause distraction, errors, and bias, particularly when continuously logging long sedimentary successions. In order to alleviate this issue, we propose an automated technique to determine the bioturbation index in cores and outcrops by harnessing the capabilities of deep convolutional neural networks (DCNNs) as image classifiers. In order to find a fast and robust solution, we utilize ideas from deep learning. We compiled and labeled a large data set (1303 images) composed of images spanning the full range (BI 0–6) of bioturbation indices. We divided these images into groups based on their bioturbation indices in order to prepare training data for the DCNN. Finally, we analyzed the trained DCNN model on images and obtained high classification accuracies. This is a pioneering work in the field of ichnological analysis, as the current practice is to perform classification tasks manually by experts in the field.
On the Impact of Additive Manufacturing Processes Complexity on Modelling
Authors: Stavropoulos Panagiotis , Foteinopoulos Panagis , Papapacharalampopoulos Alexios
Published: August 2021

The interest in additive manufacturing (AM) processes is constantly increasing due to the many advantages they offer. To this end, a variety of modelling techniques for the plethora of the AM mechanisms has been proposed. However, the process modelling complexity, a term that can be used in order to define the level of detail of the simulations, has not been clearly addressed so far. In particular, one important aspect that is common in all the AM processes is the movement of the head, which directly affects part quality and build time. The knowledge of the entire progression of the phenomenon is a key aspect for the optimization of the path as well as the speed evolution in time of the head. In this study, a metamodeling framework for AM is presented, aiming to increase the practicality of simulations that investigate the effect of the movement of the head on part quality. The existing AM process groups have been classified based on three parameters/axes: temperature of the process, complexity, and part size, where the complexity has been modelled using a dedicated heuristic metric, based on entropy. To achieve this, a discretized version of the processes implicated variables has been developed, introducing three types of variable: process parameters, key modeling variables and performance indicators. This can lead to an enhanced roadmap for the significance of the variables and the interpretation and use of the various models. The utilized spectrum of AM processes is discussed with respect to the modelling types, namely theoretical/computational and experimental/empirical.
Candida albicans Antimicrobial and Antibiofilm Activity of Novel Endodontic Solvents
Authors: Ferreira Inês , Rodrigues Maria Elisa , Fernandes Liliana , Henriques Mariana , Pina-Vaz Irene
Published: August 2021

Background: Candida albicans is the most prevalent fungi isolated in endodontic infections. In this study, the ability of C. albicans biofilm to tolerate the novel solvent mixtures methyl ethyl ketone (MEK)/tetrachloroethylene (TCE) and MEK/orange oil (OOil) sequentially to the standard irrigation of sodium hypochlorite (NaOCl) and ethylenediaminetetraacetic (EDTA) was evaluated. Methods: Biofilm cell cultures of C. albicans SC 5314 were treated sequentially with NaOCl and EDTA and exposed to MEK/TCE or MEK/OOil. The effect of the antimicrobial treatment was evaluated using the disk diffusion method for planktonic culture, and the enumeration of colony-forming units (CFUs) and scanning electron microscope (SEM) for biofilm cell culture. Results: C. albicans mature biofilm (24 h) was significantly reduced in biomass and cell viability after solvent mixtures’ exposure, compared with the previous NaOCl and EDTA treatments. MEK/OOil combination caused a total reduction of biofilm, while with MEK/TCE, there was a 3-log (CFU/cm2) reduction compared with the sequence NaOCl and EDTA, and a 4-log (CFU/cm2) reduction compared with the control. Conclusions: The additional exposure of a preformed 24 h C. albicans biofilm to novel solvent mixtures MEK/TCE and MEK/OOil caused a positive antibiofilm impact, overcoming the performance of the conventional endodontic irrigating protocol.
Effects of Resonant Electromagnetic Fields on Biofilm Formation in Pseudomonas aeruginosa
Authors: Haagensen Janus A. J. , Bache Michael , Giuliani Livio , Blom Nikolaj S.
Published: August 2021

The global rise of antimicrobial resistance (AMR) constitutes a future health threat and dictates a need to explore alternative and non-chemical approaches. The aim of this study was to explore the use of weak resonant electromagnetic fields as a method to disrupt biofilm formation of a pathogenic bacterium in cystic fibrosis patients. We developed a bioresonance laboratory setup able to distinguish between changes in planktonic growth and changes in biofilm formation and showed that certain resonant frequencies were able to affect biofilm formation without affecting planktonic growth. In addition, we show that the ambient day-to-day magnetic field affects biofilm formation in a non-consistent manner. Overall, we conclude that our assay is suitable for studying the potential of resonant magnetic fields as a treatment and prevention strategy to prevent biofilm infections, and that certain resonant frequencies may be used as future medical applications to combat antimicrobial resistance.
Opportunities and Challenges of Smartglass-Assisted Interactive Telementoring
Authors: Yoon Hyoseok
Published: August 2021

The widespread adoption of wearables, extended reality, and metaverses has accelerated the diverse configurations of remote collaboration and telementoring systems. This paper explores the opportunities and challenges of interactive telementoring, especially for wearers of smartglasses. In particular, recent relevant studies are reviewed to derive the needs and trends of telementoring technology. Based on this analysis, we define what can be integrated into smartglass-enabled interactive telementoring. To further illustrate this type of special use case for telementoring, we present five illustrative and descriptive scenarios. We expect our specialized use case to support various telementoring applications beyond medical and surgical telementoring, while harmoniously fostering cooperation using the smart devices of mentors and mentees at different scales for collocated, distributed, and remote collaboration.
Enhancing the Output of Climate Models: A Weather Generator for Climate Change Impact Studies
Authors: Croce Pietro , Formichi Paolo , Landi Filippo
Published: August 2021

Evaluation of effects of climate change on climate variable extremes is a key topic in civil and structural engineering, strongly affecting adaptation strategy for resilience. Appropriate procedures to assess the evolution over time of climatic actions are needed to deal with the inherent uncertainty of climate projections, also in view of providing more sound and robust predictions at the local scale. In this paper, an ad hoc weather generator is presented that is able to provide a quantification of climate model inherent uncertainties. Similar to other weather generators, the proposed algorithm allows the virtualization of the climatic data projection process, overcoming the usual limitations due to the restricted number of available climate model runs, requiring huge computational time. However, differently from other weather generation procedures, this new tool directly samples from the output of Regional Climate Models (RCMs), avoiding the introduction of additional hypotheses about the stochastic properties of the distributions of climate variables. Analyzing the ensemble of so-generated series, future changes of climatic actions can be assessed, and the associated uncertainties duly estimated, as a function of considered greenhouse gases emission scenarios. The efficiency of the proposed weather generator is discussed evaluating performance metrics and referring to a relevant case study: the evaluation of extremes of minimum and maximum temperature, precipitation, and ground snow load in a central Eastern region of Italy, which is part of the Mediterranean climatic zone. Starting from the model ensemble of six RCMs, factors of change uncertainty maps for the investigated region are derived concerning extreme daily temperatures, daily precipitation, and ground snow loads, underlying the potentialities of the proposed approach.
Concentrations, Size Distribution, and Community Structure Characteristics of Culturable Airborne Antibiotic-Resistant Bacteria in Xinxiang, Central China
Authors: Yan Xu , Ma Jiahui , Ren Jingyuan , Cui Mengjia , Chen Xinqing , Qiu Dezhi , Lei Miao , Li Tianning , Guo Li , Chen Chun , Han Yunping
Published: August 2021

Antimicrobial resistance is considered an important threat to global health and has recently attracted significant attention from the public. In this study, the concentrations and size distribution characteristics of culturable airborne total bacteria (TB) and four antibiotic-resistant bacteria (tetracycline-resistant bacteria (TRB), ciprofloxacin-resistant bacteria (CRB), erythromycin-resistant bacteria (ERB), and ampicillin-resistant bacteria (ARB)) were investigated for approximately one year to explore their variations under different seasons, diurnal periods, and air quality levels. The concentrations of TB and four antibiotic-resistant bacteria in winter and night were higher than during other seasons and diurnal periods. Their maximum concentrations were detected from air under moderate pollution or heavy pollution. PM2.5, PM10, SO2, and NO2 were positively related to TB and four antibiotic-resistant bacteria (p < 0.01), whereas O3 and wind speed were negatively related to them (p < 0.05). The particle size of TB and four antibiotic-resistant bacteria were mainly distributed in stage V (1.1–2.2 µm). Bacillus was the dominant genus of ARB (75.97%) and CRB (25.67%). Staphylococcus and Macrococcus were the dominant genera of TRB (46.05%) and ERB (47.67%), respectively. The opportunistic pathogens of Micrococcus, Sphingomonas, Enterococcus, Rhodococcus, and Stenotrophomonas were also identified. This study provides important references for understanding the threat of bioaerosols to human health.
Adaptive Crop Management under Climate Uncertainty: Changing the Game for Sustainable Water Use
Authors: Myint Soe W. , Aggarwal Rimjhim , Zheng Baojuan , Wentz Elizabeth A. , Holway Jim , Fan Chao , Selover Nancy J. , Wang Chuyuan , Fischer Heather A.
Published: August 2021

Water supplies are projected to become increasingly scarce, driving farmers, energy producers, and urban dwellers towards an urgent and emerging need to improve the effectiveness and the efficiency of water use. Given that agricultural water use is the largest water consumer throughout the U.S. Southwest, this study sought to answer two specific research questions: (1) How does water consumption vary by crop type on a metropolitan spatial scale? (2) What is the impact of drought on agricultural water consumption? To answer the above research questions, 92 Landsat images were acquired to generate fine-resolution daily evapotranspiration (ET) maps at 30 m spatial resolution for both dry and wet years (a total of 1095 ET maps), and major crop types were identified for the Phoenix Active Management Area. The study area has a subtropical desert climate and relies almost completely on irrigation for farming. Results suggest that there are some factors that farmers and water managers can control. During dry years, crops of all types use more water. Practices that can offset this higher water use include double or multiple cropping practice, drought tolerant crop selection, and optimizing the total farmed area. Double and multiple cropping practices result in water savings because soil moisture is retained from one planting to another. Further water savings occur when drought tolerant crop types are selected, especially in dry years. Finally, disproportionately large area coverage of high water consuming crops can be balanced and/or reduced or replaced with more water efficient crops. This study provides strong evidence that water savings can be achieved through policies that create incentives for adopting smart cropping strategies, thus providing important guidelines for sustainable agriculture management and climate adaptation to improve future food security.
Early-Warning Signals of Drought-Flood State Transition over the Dongting Lake Basin Based on the Critical Slowing Down Theory
Authors: Wu Hao , Hou Wei , Zuo Dongdong , Yan Pengcheng , Zeng Yuxing
Published: August 2021

In this study, the standardized precipitation index (SPI) data in Hunan Province from 1961 to 2020 is adopted. Based on the critical slowing down theory, the moving t-test is firstly used to determine the time of drought-flood state transition in the Dongting Lake basin. Afterwards, by means of the variance and autocorrelation coefficient that characterize the phenomenon of critical slowing down, the early-warning signals indicating the drought-flood state in the Dongting Lake basin are explored. The results show that an obvious drought-to-flood (flood-to-drought) event occurred around 1993 (2003) in the Dongting Lake basin in recent 60 years. The critical slowing down phenomena of the increases in the variance and autocorrelation coefficient, which are detected 5–10 years in advance, can be considered as early-warning signals indicating the drought-flood state transition. Through the studies on the drought-flood state and related early-warning signals for the Dongting Lake basin, the reliabilities of the variance and autocorrelation coefficient-based early-warning signals for abrupt changes are demonstrated. It is expected that the wide application of this method could provide important scientific and technological support for disaster prevention and mitigation in the Dongting Lake basin, and even in the middle and lower reaches of the Yangtze River.
Propagation of a Meteotsunami from the Yellow Sea to the Korea Strait in April 2019
Authors: Kwon Kyungman , Choi Byoung-Ju , Myoung Sung-Gwan , Sim Han-Seul
Published: August 2021

A meteotsunami with a wave height of 0.1–0.9 m and a period of 60 min was observed at tide gauges along the Korea Strait on 7 April 2019, while a train of two to four atmospheric pressure disturbances with disturbance heights of 1.5–3.9 hPa moved eastward from the Yellow Sea to the Korea Strait. Analysis of observational data indicated that isobar lines of the atmospheric pressure disturbances had angles of 75–83° counterclockwise due east and propagated with a velocity of 26.5–31.0 m/s. The generation and propagation process of the meteotsunami was investigated using the Regional Ocean Modeling System. The long ocean waves were amplified due to Proudman resonance in the southwestern Yellow Sea, where the water is deeper than 75 m; here, the long ocean waves were refracted toward the coast on the shallow coastal region of the northern Korea Strait. Refraction and reflection by offshore islands significantly affect the wave heights at the coast. To investigate the effects of an eastward-moving velocity and angle of atmospheric pressure disturbance on the height of a long ocean wave, sensitivity simulations were performed. This result will be useful for the real-time prediction system of meteotsunamis in the Korea Strait.
Global Directed Dynamic Behaviors of a Lotka-Volterra Competition-Diffusion-Advection System
Authors: Chen Lili , Lin Shilei , Zhao Yanfeng
Published: August 2021

This paper investigates the problem of the global directed dynamic behaviors of a Lotka-Volterra competition-diffusion-advection system between two organisms in heterogeneous environments. The two organisms not only compete for different basic resources, but also the advection and diffusion strategies follow the dispersal towards a positive distribution. By virtue of the principal eigenvalue theory, the linear stability of the co-existing steady state is established. Furthermore, the classification of dynamical behaviors is shown by utilizing the monotone dynamical system theory. This work can be seen as a further development of a competition-diffusion system.
An Improved Tikhonov-Regularized Variable Projection Algorithm for Separable Nonlinear Least Squares
Authors: Guo Hua , Liu Guolin , Wang Luyao
Published: August 2021

In this work, we investigate the ill-conditioned problem of a separable, nonlinear least squares model by using the variable projection method. Based on the truncated singular value decomposition method and the Tikhonov regularization method, we propose an improved Tikhonov regularization method, which neither discards small singular values, nor treats all singular value corrections. By fitting the Mackey–Glass time series in an exponential model, we compare the three regularization methods, and the numerically simulated results indicate that the improved regularization method is more effective at reducing the mean square error of the solution and increasing the accuracy of unknowns.
Modulation of Synthetic Tracheal Grafts with Extracellular Matrix Coatings
Authors: Liu Lumei , Dharmadhikari Sayali , Pouliot Robert A. , Li Michael M. , Minneci Peter M. , Tan Zhenghong , Shontz Kimberly , Johnson Jed , Reynolds Susan D. , Breuer Christopher K. , Weiss Daniel J. , Chiang Tendy
Published: August 2021

Synthetic scaffolds for the repair of long-segment tracheal defects are hindered by insufficient biocompatibility and poor graft epithelialization. In this study, we determined if extracellular matrix (ECM) coatings improved the biocompatibility and epithelialization of synthetic tracheal grafts (syn-TG). Porcine and human ECM substrates (pECM and hECM) were created through the decellularization and lyophilization of lung tissue. Four concentrations of pECM and hECM coatings on syn-TG were characterized for their effects on scaffold morphologies and on in vitro cell viability and growth. Uncoated and ECM-coated syn-TG were subsequently evaluated in vivo through the orthotopic implantation of segmental grafts or patches. These studies demonstrated that ECM coatings were not cytotoxic and, enhanced the in vitro cell viability and growth on syn-TG in a dose-dependent manner. Mass spectrometry demonstrated that fibrillin, collagen, laminin, and nephronectin were the predominant ECM components transferred onto scaffolds. The in vivo results exhibited similar robust epithelialization of uncoated and coated syn-TG patches; however, the epithelialization remained poor with either uncoated or coated scaffolds in the segmental replacement models. Overall, these findings demonstrated that ECM coatings improve the seeded cell biocompatibility of synthetic scaffolds in vitro; however, they do not improve graft epithelialization in vivo.
Effect of Extender, Storage Time and Temperature on Kinetic Parameters (CASA) on Bull Semen Samples
Authors: Fernandez-Novo Aitor , Santos-Lopez Sergio , Barrajon-Masa Clara , Mozas Patricia , de Mercado Eduardo , Caceres Elisa , Garrafa Aizic , Gonzalez-Martin Juan V. , Perez-Villalobos Natividad , Oliet Agustín , Astiz Susana , Perez-Garnelo Sonia S.
Published: August 2021

CASA kinetic parameters are often evaluated in a diagnostic centre. How storage conditions affect ejaculates up to evaluation is unclear. We assessed, in 25 commercial bulls electroejaculated in the field, the impact of time until evaluation (0–2 h, 4–6 h, and 24 h post-ejaculation), holding temperature (5 °C vs. room temperature), and extender (AndroMed®, BIOXcell® or INRA96®) on CASA kinetic parameters. Total and progressive motility, VCL, VAP, VCL, ALH, BCF, STR, LIN, and WOB were assessed. CASA kinetic parameters were preserved for up to 4–6 h post-ejaculation, except for AndroMed®. Regardless of extender or temperature, motility decreased from 4–6 h up to 24 h, with the best values obtained with BIOXcell® at 5 °C. Our results suggest that BIOXcell® can preserve sperm motility for up to 6 h, either at 5 °C or room temperature, and also INRA96® at room temperature, with motility assessments and the percentage of the most rapid sperms being the lowest with INRA96® at 5 °C. The kinetic parameters decreased when analyses were performed at 24 h. Therefore, we suggest evaluating seminal quality as soon as possible, before 6 h after collection. These results help to fix adequate protocols for the short-term storage and shipment of bovine semen collected under field conditions.
Overview of Poultry Management as a Key Factor for Solving Food and Nutritional Security with a Special Focus on Chicken Breeding in East African Countries
Authors: Pius Lenox Omondi , Strausz Péter , Kusza Szilvia
Published: August 2021

The focus of this review is to offer an overview of food and nutritional security, to identify associated constraints, and propose possible alternative solutions for improving the East African poultry sub-sector in the pursuit of food security, focusing on chicken breeding. To better understand the prospects of the poultry industry, we highlighted and combined confirming evidence of the phenotypic variability and genetic diversity of East African chicken genetic resources using both morphological and molecular tools, as well as performance traits. Furthermore, this work gives a detailed indication of what would be lost if indigenous chicken populations are left to suffer the ongoing massive genetic erosions due to various factors, not limited to indiscriminate crossbreeding. Previous and recent attempts to improve the productivity of indigenous chicken are highlighted, and possible future breeding plans and areas of immediate research are suggested as well. This review concludes that under the prevailing conditions, the village chicken production system appears to be the most imperious production system that needs to be extensively developed ; however, for the sustainability of the industry, the proposed improvement strategies should create a permanent balance between the competing needs of genetic improvement and the genetic diversity of the indigenous chicken genetic resource.
The Role of Methionine Residues in the Regulation of Liquid-Liquid Phase Separation
Authors: Aledo Juan Carlos
Published: August 2021

Membraneless organelles are non-stoichiometric supramolecular structures in the micron scale. These structures can be quickly assembled/disassembled in a regulated fashion in response to specific stimuli. Membraneless organelles contribute to the spatiotemporal compartmentalization of the cell, and they are involved in diverse cellular processes often, but not exclusively, related to RNA metabolism. Liquid-liquid phase separation, a reversible event involving demixing into two distinct liquid phases, provides a physical framework to gain insights concerning the molecular forces underlying the process and how they can be tuned according to the cellular needs. Proteins able to undergo phase separation usually present a modular architecture, which favors a multivalency-driven demixing. We discuss the role of low complexity regions in establishing networks of intra- and intermolecular interactions that collectively control the phase regime. Post-translational modifications of the residues present in these domains provide a convenient strategy to reshape the residue–residue interaction networks that determine the dynamics of phase separation. Focus will be placed on those proteins with low complexity domains exhibiting a biased composition towards the amino acid methionine and the prominent role that reversible methionine sulfoxidation plays in the assembly/disassembly of biomolecular condensates.
Computational Insights into the Structural Dynamics of MDA5 Variants Associated with Aicardi–Goutières Syndrome and Singleton–Merten Syndrome
Authors: Gosu Vijayakumar , Sasidharan Santanu , Saudagar Prakash , Lee Hak-Kyo , Shin Donghyun
Published: August 2021

Melanoma differentiation-associated protein 5 (MDA5) is a crucial RIG-I-like receptor RNA helicase enzyme encoded by IFIH1 in humans. Single nucleotide polymorphisms in the IFIH1 results in fatal genetic disorders such as Aicardi–Goutières syndrome and Singleton–Merten syndrome, and in increased risk of type I diabetes in humans. In this study, we chose four different amino acid substitutions of the MDA5 protein responsible for genetic disorders: MDA5L372F, MDA5A452T, MDA5R779H, and MDA5R822Q and analyzed their structural and functional relationships using molecular dynamic simulations. Our results suggest that the mutated complexes are relatively more stable than the wild-type MDA5. The radius of gyration, interaction energies, and intra-hydrogen bond analysis indicated the stability of mutated complexes over the wild type, especially MDA5L372F and MDA5R822Q. The dominant motions exhibited by the wild-type and mutant complexes varied significantly. Moreover, the betweenness centrality of the wild-type and mutant complexes showed shared residues for intra-signal propagation. The observed results indicate that the mutations lead to a gain of function, as reported in previous studies, due to increased interaction energies and stability between RNA and MDA5 in mutated complexes. These findings are expected to deepen our understanding of MDA5 variants and may assist in the development of relevant therapeutics against the disorders.
A Novel Bispecific Antibody Targeting CD3 and Lewis Y with Potent Therapeutic Efficacy against Gastric Cancer
Authors: Chen Jie , Pan Zhidi , Han Lei , Zhou Yuexian , Zong Huifang , Wang Lei , Sun Rui , Jiang Hua , Xie Yueqing , Yuan Yunsheng , Wu Mingyuan , Bian Yanling , Zhang Baohong , Zhu Jianwei
Published: August 2021

Lewis Y antigen, a glycan highly expressed on most epithelial cancers, was targeted for cancer treatment but lacked satisfactory results in some intractable and refractory cancers. Thus, it is highly desirable to develop an effective therapy against these cancers, hopefully based on this target. In this work, we constructed a novel T cell-engaging bispecific antibody targeting Lewis Y and CD3 (m3s193 BsAb) with the IgG-[L]-scfv format. In vitro activity of m3s193 BsAb was evaluated by affinity assay to target cells, cytotoxicity assay, cytokines releasing assay, and T cells proliferation and recruiting assays. Anti-tumor activity against gastric cancer was evaluated in vivo by subcutaneous huPBMCs/tumor cells co-grafting model and huPBMCs intravenous injecting model. In vitro, m3s193 BsAb appeared to have a high binding affinity to Lewis Y positive cells and Jurkat cells. The BsAb showed stronger activity than its parent mAb in T cell recruiting, activation, proliferation, cytokine release, and cytotoxicity. In vivo, m3s193 BsAb not only demonstrated higher therapeutic efficacy in the huPBMCs/tumor co-grafting gastric carcinoma model than the parent mAb but also eliminated tumors in the model of intravenous injection with huPBMCs. Strong anti-tumor activity of m3s193 BsAb revealed that Lewis Y could be targeted in T cell-engaging BsAb for gastric cancer therapy.
Oviductal Telocytes in Patients with Uterine Myoma
Authors: Aleksandrovych Veronika , Wrona Anna , Bereza Tomasz , Pityński Kazimierz , Gil Krzysztof
Published: August 2021

Tubal factor infertility occurs in 30–35% of infertile pairs and may be caused by impaired muscular contractility and ciliary beating as well as immunological imbalance and chronic inflammation. Newly discovered telocytes (TCs) have a wide palette of features, which play a role in oviduct physiology. We have observed tissue samples from human fallopian tubes in patients with and without uterine myoma by immunolabelling. According to the immunohistochemical co-expression of markers, it has been determined that TCs are engaged in a wide range of physiological processes, including local innervation, sensitivity to hypoxia, regulation of calcium, and sex steroid hormones balances. Due to the proximity of NOS- and ChAT-positive nerve fibers and the expression of ion channels markers, tubal TCs might be considered conductor cells. Additionally, their integration in contractions and cilia physiology in the context of fertility has been revealed. We have observed the difference in telocytes expression in the human oviduct between groups of patients and attempted to describe this population of cells specifically in the case of infertility development, a clinically relevant avenue for further studies.
Exosomes: Potential Disease Biomarkers and New Therapeutic Targets
Authors: Mosquera-Heredia Maria I. , Morales Luis C. , Vidal Oscar M. , Barceló Ernesto , Silvera-Redondo Carlos , Vélez Jorge I. , Garavito-Galofre Pilar
Published: August 2021

Exosomes are extracellular vesicles released by cells, both constitutively and after cell activation, and are present in different types of biological fluid. Exosomes are involved in the pathogenesis of diseases, such as cancer, neurodegenerative diseases, pregnancy disorders and cardiovascular diseases, and have emerged as potential non-invasive biomarkers for the detection, prognosis and therapeutics of a myriad of diseases. In this review, we describe recent advances related to the regulatory mechanisms of exosome biogenesis, release and molecular composition, as well as their role in health and disease, and their potential use as disease biomarkers and therapeutic targets. In addition, the advantages and disadvantages of their main isolation methods, characterization and cargo analysis, as well as the experimental methods used for exosome-mediated drug delivery, are discussed. Finally, we present potential perspectives for the use of exosomes in future clinical practice.
Clot Retraction: Cellular Mechanisms and Inhibitors, Measuring Methods, and Clinical Implications
Authors: Jansen Ellen E. , Hartmann Matthias
Published: August 2021

Platelets have important functions in hemostasis. Best investigated is the aggregation of platelets for primary hemostasis and their role as the surface for coagulation leading to fibrin- and clot-formation. Importantly, the function of platelets does not end with clot formation. Instead, platelets are responsible for clot retraction through the concerted action of the activated αIIbβ3 receptors on the surface of filopodia and the platelet’s contractile apparatus binding and pulling at the fibrin strands. Meanwhile, the signal transduction events leading to clot retraction have been investigated thoroughly, and several targets to inhibit clot retraction have been demonstrated. Clot retraction is a physiologically important mechanism allowing: (1) the close contact of platelets in primary hemostasis, easing platelet aggregation and intercellular communication, (2) the reduction of wound size, (3) the compaction of red blood cells to a polyhedrocyte infection-barrier, and (4) reperfusion in case of thrombosis. Several methods have been developed to measure clot retraction that have been based on either the measurement of clot volume or platelet forces. Concerning the importance of clot retraction in inborn diseases, the failure of clot retraction in Glanzmann thrombasthenia is characterized by a bleeding phenotype. Concerning acquired diseases, altered clot retraction has been demonstrated in patients with coronary heart disease, stroke, bronchial asthma, uremia, lupus erythematodes, and other diseases. However, more studies on the diagnostic and prognostic value of clot retraction with methods that have to be standardized are necessary.
Hydrolysable Tannins Exhibit Acetylcholinesterase Inhibitory and Anti-Glycation Activities In Vitro and Learning and Memory Function Improvements in Scopolamine-Induced Amnesiac Mice
Authors: Chen Lih-Geeng , Lin Shyr-Yi , Lee Yi-Shan , Wang Ching-Chiung , Hou Wen-Chi
Published: August 2021

Agricultural waste from the hulls of water caltrop (Trapa taiwanesis Nakai, TT-hull) was extracted by either steeping them in cold 95% ethanol (C95E), refluxing 95E, refluxing 50E, or refluxing hot water (HW) to obtain C95EE, 95EE, 50EE, and HWE, respectively. These four extracts showed acetylcholinesterase (AChE) inhibitory activities and free radical scavenging activities, as well as anti-non-enzymatic protein glycation in vitro. Eight compounds were isolated from TT-hull-50EE and were used to plot the chromatographic fingerprints of the TT-hull extracts, among which tellimagrandin-I, tellimagrandin-II, and 1,2,3,6-tetra-galloylglucose showed the strongest AChE inhibitory activities, and they also exhibited anti-amyloid β peptide aggregations. The scopolamine-induced amnesiac ICR mice that were fed with TT-hull-50EE or TT-hull-HWE (100 and 200 mg/kg) or tellimagrandin-II (100 and 200 mg/kg) showed improved learning behavior when evaluated using passive avoidance or water maze evaluation, and they showed significant differences (p < 0.05) compared to those in the control group. The enriched hydrolysable tannins of the recycled TT-hull may be developed as functional foods for the treatment of degenerative disorders.
Spectrophotometric Assays for Sensing Tyrosinase Activity and Their Applications
Authors: Fan Yu-Fan , Zhu Si-Xing , Hou Fan-Bin , Zhao Dong-Fang , Pan Qiu-Sha , Xiang Yan-Wei , Qian Xing-Kai , Ge Guang-Bo , Wang Ping
Published: August 2021

Tyrosinase (TYR, E.C. 1.14.18.1), a critical enzyme participating in melanogenesis, catalyzes the first two steps in melanin biosynthesis including the ortho-hydroxylation of L-tyrosine and the oxidation of L-DOPA. Previous pharmacological investigations have revealed that an abnormal level of TYR is tightly associated with various dermatoses, including albinism, age spots, and malignant melanoma. TYR inhibitors can partially block the formation of pigment, which are always used for improving skin tone and treating dermatoses. The practical and reliable assays for monitoring TYR activity levels are very useful for both disease diagnosis and drug discovery. This review comprehensively summarizes structural and enzymatic characteristics, catalytic mechanism and substrate preference of TYR, as well as the recent advances in biochemical assays for sensing TYR activity and their biomedical applications. The design strategies of various TYR substrates, alongside with several lists of all reported biochemical assays for sensing TYR including analytical conditions and kinetic parameters, are presented for the first time. Additionally, the biomedical applications and future perspectives of these optical assays are also highlighted. The information and knowledge presented in this review offer a group of practical and reliable assays and imaging tools for sensing TYR activities in complex biological systems, which strongly facilitates high-throughput screening TYR inhibitors and further investigations on the relevance of TYR to human diseases.
Gender Perspective in Dual Diagnosis
Authors: Torrens-Melich Marta , Orengo Teresa , Rodríguez de Fonseca Fernando , Almodóvar Isabel , Baquero Abel , Benito Ana
Published: August 2021

Little data are available for women diagnosed with a dual diagnosis. However, dual diagnosis in women presents increased stigma, social penalties, and barriers to access to treatment than it does for men. Indeed, it increases the probability of suffering physical or sexual abuse, violent victimization, gender-based violence, unemployment, social exclusion, social-role problems, and physical and psychiatric comorbidities. Thus, a transversal sex and gender-based perspective is required to adequately study and treat dual diagnosis. For this, sex and gender factors should be included in every scientific analysis; professionals should review their own prejudices and stereotypes and train themselves specifically from a gender perspective; administrations should design and provide specific treatment resources for women; and we could all contribute to a structural social transformation that goes beyond gender mandates and norms and reduces the risk of abuse and violence inflicted on women.
Impact of Glucocorticoid on a Cellular Model of Parkinson’s Disease: Oxidative Stress and Mitochondrial Function
Authors: Claros Silvia , Gil Antonio , Martinelli Mauro , Valverde Nadia , Lara Estrella , Boraldi Federica , Pavia Jose , Martín-Montañez Elisa , Garcia-Fernandez María
Published: August 2021

Stress seems to contribute to the neuropathology of Parkinson’s disease (PD), possibly by dysregulation of the hypothalamic–pituitary–adrenal axis. Oxidative distress and mitochondrial dysfunction are key factors involved in the pathophysiology of PD and neuronal glucocorticoid-induced toxicity. Animal PD models have been generated to study the effects of hormonal stress, but no in vitro model has yet been developed. Our aim was to examine the impact of corticosterone (CORT) administration on a dopaminergic neuronal cell model of PD induced by the neurotoxin MPP+, as a new combined PD model based on the marker of endocrine response to stress, CORT, and oxidative-mitochondrial damage. We determined the impact of CORT, MPP+ and their co-incubation on reactive oxygen species production (O2−•), oxidative stress cellular markers (advanced-oxidation protein products and total antioxidant status), mitochondrial function (mitochondrial membrane potential and mitochondrial oxygen consumption rate) and neurodegeneration (Fluoro-Jade staining). Accordingly, the administration of MPP+ or CORT individually led to cell damage compared to controls (p < 0.05), as determined by several methods, whereas their co-incubation produced strong cell damage (p < 0.05). The combined model described here could be appropriate for investigating neuropathological hallmarks and for evaluating potential new therapeutic tools for PD patients suffering mild to moderate emotional stress.
The Reduced-Degree-of-Freedom Model for Seismic Analysis of Predominantly Plan-Symmetric Reinforced Concrete Wall–Frame Building
Authors: Jamšek Aleš , Dolšek Matjaž
Published: August 2021

A reduced-degree-of-freedom (RDOF) model for seismic analysis of predominantly plan-symmetric reinforced concrete (RC) wall–frame buildings is introduced. The RDOF model of the wall–frame building consists of elastic beam–column elements with concentrated plasticity used for simulating cantilever walls and predominantly plan-symmetric RC frame buildings that are represented by the improved fish-bone (IFB) model. In this paper, the capability of the RDOF model is demonstrated for two frame buildings and two wall–frame buildings. The RDOF models were defined directly from the building information model. This is an advantage of RDOF models with respect to single-degree-of-freedom (SDOF) models, while the computational robustness of the RDOF models also makes them attractive for the seismic analysis of building stock. The imposed cyclic displacement analyses conducted for the investigated buildings proved that the condensation of the degrees of freedom for RDOF models was appropriate. Consequently, only minor differences were observed for maximum storey drift IDA curves, maximum storey acceleration IDA curves, and seismic fragility functions for different limit states. However, development is needed to make RDOF models appropriate for preliminary seismic performance assessment of plan-irregular buildings.
Novel Insights into the Molecular Regulation of Ribonucleotide Reductase in Adrenocortical Carcinoma Treatment
Authors: Bothou Christina , Sharma Ashish , Oo Adrian , Kim Baek , Perge Pal , Igaz Peter , Ronchi Cristina L. , Shapiro Igor , Hantel Constanze
Published: August 2021

Current systemic treatment options for patients with adrenocortical carcinomas (ACCs) are far from being satisfactory. DNA damage/repair mechanisms, which involve, e.g., ataxia-telangiectasia-mutated (ATM) and ataxia-telangiectasia/Rad3-related (ATR) protein signaling or ribonucleotide reductase subunits M1/M2 (RRM1/RRM2)-encoded ribonucleotide reductase (RNR) activation, commonly contribute to drug resistance. Moreover, the regulation of RRM2b, the p53-induced alternative to RRM2, is of unclear importance for ACC. Upon extensive drug screening, including a large panel of chemotherapies and molecular targeted inhibitors, we provide strong evidence for the anti-tumoral efficacy of combined gemcitabine (G) and cisplatin (C) treatment against the adrenocortical cell lines NCI-H295R and MUC-1. However, accompanying induction of RRM1, RRM2, and RRM2b expression also indicated developing G resistance, a frequent side effect in clinical patient care. Interestingly, this effect was partially reversed upon addition of C. We confirmed our findings for RRM2 protein, RNR-dependent dATP levels, and modulations of related ATM/ATR signaling. Finally, we screened for complementing inhibitors of the DNA damage/repair system targeting RNR, Wee1, CHK1/2, ATR, and ATM. Notably, the combination of G, C, and the dual RRM1/RRM2 inhibitor COH29 resulted in previously unreached total cell killing. In summary, we provide evidence that RNR-modulating therapies might represent a new therapeutic option for ACC.
Mapping Epitopes Recognised by Autoantibodies Shows Potential for the Diagnosis of High-Grade Serous Ovarian Cancer and Monitoring Response to Therapy for This Malignancy
Authors: Moody Rhiane , Wilson Kirsty , Kampan Nirmala Chandralega , McNally Orla M. , Jobling Thomas W. , Jaworowski Anthony , Stephens Andrew N. , Plebanski Magdalena
Published: August 2021

Autoantibodies recognising phosphorylated heat shock factor 1 (HSF1-PO4) protein are suggested as potential new diagnostic biomarkers for early-stage high-grade serous ovarian cancer (HGSOC). We predicted in silico B-cell epitopes in human and murine HSF1. Three epitope regions were synthesised as peptides. Circulating immunoglobulin A (cIgA) against the predicted peptide epitopes or HSF1-PO4 was measured using ELISA, across two small human clinical trials of HGSOC patients at diagnosis. To determine whether chemotherapy would promote changes in reactivity to either HSF1-PO4 or the HSF-1 peptide epitopes, IgA responses were further assessed in a sample of patients after a full cycle of chemotherapy. Anti-HSF1-PO4 responses correlated with antibody responses to the three selected epitope regions, regardless of phosphorylation, with substantial cross-recognition of the corresponding human and murine peptide epitope variants. Assessing reactivity to individual peptide epitopes, compared to HSF1-PO4, improved assay sensitivity. IgA responses to HSF1-PO4 further increased significantly post treatment, indicating that HSF1-PO4 is a target for immunity in response to chemotherapy. Although performed in a small cohort, these results offer potential insights into the interplay between autoimmunity and ovarian cancer and offer new peptide biomarkers for early-stage HGSOC diagnosis, to monitor responses to chemotherapy, and widely for pre-clinical HGSOC research.