bluuebunny/crossref_metadata_2025 huggingface dataset:
Formation and Optimization of Electrical Discharge Coatings Using Conventional Electrodes
Authors: Maddu JagadeeswaraRao , Karrolla Buschaiah , Vuppala Srikanth , Shaik Riyaaz Uddien
Published: September 2021

An emerging topic is electrical discharge (ED) coating with its application on complex shapes and cavities to repair components or act as functional coatings. Because it is a variant process of an electric discharge machine (EDM) with the ability to coat on electrically conductive substrates, there is a possibility that next-generation electrical discharge machining components may exploit the attachment phenomenon to enhance recast layer properties. Previously, researchers have obtained ED coating by mixing the powder in a dielectric medium and/or by using powder metallurgy electrodes. In this work, primarily, an insight in the formation of ED coating on-die sinks electrical discharge machine, using conventional electrode materials viz., bronze on titanium alloy (Ti-6Al-4V) is made. The bronze electrode on the titanium substrate obtained a crack-free copper coating of ~20 microns thickness. In order to perform the experiments, three combinations were made using five parameters: current (Amps), ton (µs), Toff (µs), duty cycle (%), and flushing pressure as constant (bar). After obtaining the coating, a combination of input parameters was selected by optimizing the output performance parameters, viz., the electrical discharge deposition rate, coating thickness, micro-cracks, and elemental coating composition. Secondarily, different optimization techniques viz., grey relational analysis, the technique for order of preferences by similarity to ideal solution, −nD angle method and information divergence method were implemented to find out the suitable combination of parameters where the latter two methods were introduced for the first time in this area of EDM optimization. A study was conducted to check whether the latter two methods are optimization techniques or multi-criteria decision-making techniques. The optimization of existing reactor types and the development of new reactors in wastewater treatment through EDC, by which energy could be saved by replacing the conventional techniques.
A Novel Stator Cooling Structure for Yokeless and Segmented Armature Axial Flux Machine with Heat Pipe
Authors: Le Wei , Lin Mingyao , Lin Keman , Liu Kai , Jia Lun , Yang Anchen , Wang Shuai
Published: September 2021

The yokeless and segmented armature axial flux machine is considered an excellent topology for electric vehicles application. However, its performance is severely limited by the stator cooling system. The heat pipe, as the small size, lightweight, but highly efficient passive phase-change cooling element, has been attracting more and more attention in the thermal management methods of electric motors. Therefore, the relationship between the thermal performance of the heat pipe with temperature is measured in detail through an experimental test platform in this paper. Further, a novel stator cooling structure that combines the heat pipe with the housing water-cooling method is introduced to improve the temperature distribution of the stator. Computational fluid dynamics (CFD) simulation verifies that the proposed cooling structure can accelerate the release of heat from the stator and reduce the temperature of the stator significantly.
A Machine-Learning Approach to Identify the Influence of Temperature on FRA Measurements
Authors: Suassuna de Andrade Ferreira Regelii , Picher Patrick , Ezzaidi Hassan , Fofana Issouf
Published: September 2021

Frequency response analysis (FRA) is a powerful and widely used tool for condition assessment in power transformers. However, interpretation schemes are still challenging. Studies show that FRA data can be influenced by parameters other than winding deformation, including temperature. In this study, a machine-learning approach with temperature as an input attribute was used to objectively identify faults in FRA traces. To the best knowledge of the authors, this has not been reported in the literature. A single-phase transformer model was specifically designed and fabricated for use as a test object for the study. The model is unique in that it allows the non-destructive interchange of healthy and distorted winding sections and, hence, reproducible and repeatable FRA measurements. FRA measurements taken at temperatures ranging from −40 °C to 40 °C were used first to describe the impact of temperature on FRA traces and then to test the ability of the machine learning algorithms to discriminate between fault conditions and temperature variation. The results show that when temperature is not considered in the training dataset, the algorithm may misclassify healthy measurements, taken at different temperatures, as mechanical or electrical faults. However, once the influence of temperature was considered in the training set, the performance of the classifier as studied was restored. The results indicate the feasibility of using the proposed approach to prevent misclassification based on temperature changes.
An Overview of Probabilistic Dimensioning of Frequency Restoration Reserves with a Focus on the Greek Electricity Market
Authors: Papavasiliou Anthony
Published: September 2021

The dynamic dimensioning of frequency restoration reserves based on probabilistic criteria is becoming increasingly relevant in European power grid operations, following the guidelines of European legislation. This article compares dynamic dimensioning based on k-means clustering to static dimensioning on a case study of the Greek electricity market. It presents a model of system imbalances which aims to capture various realistic features of the stochastic behavior of imbalances, including skewed distributions, the dependencies of the imbalance distribution on various imbalance drivers, and the contributions of idiosyncratic noise to system imbalances. The imbalance model was calibrated in order to be consistent with historical reserve requirements in the Greek electricity market. The imbalance model was then employed in order to compare dynamic dimensioning based on probabilistic criteria to static dimensioning. The analysis revealed potential benefits of dynamic dimensioning for the Greek electricity market, which include a reduction in average reserve requirements and the preservation of a constant risk profile due to the adaptive nature of probabilistic dimensioning.
Persistence of Salmonella enterica and Enterococcus faecium NRRL B-2354 on Baby Spinach Subjected to Temperature Abuse after Exposure to Sub-Lethal Stresses
Authors: Chen Zhao , Meng Jianghong
Published: September 2021

The exposure of foodborne pathogens such as Salmonella enterica to a sub-lethal stress may protect bacterial cells against distinct stresses during the production of leafy greens, which can constitute potential health hazards to consumers. In this study, we evaluated how the prior exposure of S. enterica to sub-lethal food processing-related stresses influenced its subsequent persistence on baby spinach under cold (4 °C for 7 days) and temperature abuse (37 °C for 2 h + 4 °C for 7 days) conditions. We also compared the survival characteristics of pre-stressed S. enterica and Enterococcus faecium NRRL B-2354 as its surrogate on baby spinach. A cocktail of three S. enterica serovars, as well as S. Typhimurium ATCC 14028 wild type and its ΔrpoS mutant, and E. faecium NRRL B-2354, was first exposed to sub-lethal desiccation, oxidation, heat shock, and acid stresses. Afterward, baby spinach was inoculated with unstressed or pre-stressed cells at 7.0 log CFU/sample unit, followed by 7-day storage under cold and temperature abuse conditions. The unstressed S. enterica (fresh cells in sterile 0.85% saline) decreased rapidly within the first day and thereafter persisted around 5.5 log CFU/sample unit under both conditions. The desiccation-stressed S. enterica showed the highest bacterial counts (p < 0.05) compared to other conditions. The unstressed S. enterica survived better (p < 0.05) than the oxidation- and acid-stressed S. enterica, while there were no significant differences (p > 0.05) between the unstressed and heat-shocked S. enterica. Unlike the wild type, temperature abuse did not lead to the enhanced survival of the ΔrpoS mutant after exposure to desiccation stress, indicating that the rpoS gene could play a critical role in the persistence of desiccation-stressed S. enterica subjected to temperature abuse. E. faecium NRRL B-2354 was more persistent (p < 0.05) than the pre-stressed S. enterica under both conditions, suggesting its use as a suitable surrogate for pre-stressed S. enterica by providing a sufficient safety margin. Our results demonstrate the merit of considering the prior exposure of foodborne pathogens to sub-lethal stresses when validating the storage conditions for leafy greens.
Composting of Olive Mill Pomace, Agro-Industrial Sewage Sludge and Other Residues: Process Monitoring and Agronomic Use of the Resulting Composts
Authors: Leone Alessandro , Romaniello Roberto , Tamborrino Antonia , Beneduce Luciano , Gagliardi Anna , Giuliani Marcella , Gatta Giuseppe
Published: September 2021

The viability of co-composting of olive mill pomace added to sewage sludge with other organic residues was evaluated and the agronomic use of the final composts was investigated. Two composting piles at different carbon-nitrogen ratios were performed, in which olive mill pomace (OMP), sewage sludge from vegetable processing (SS), fresh residues from artichoke processing residues (AR), and wheat straw (WS) were used. The two composting piles were placed inside a specially built greenhouse and a turning machine pulled by a tractor was used for turning and shredding the organic matrix (every 6 days) during the process. The humidity and temperature of organic matrices have been monitored and controlled during the entire composting process, which lasted 90 days. The process was also monitored to evaluate the microbiological safety of the final compost. The humidity of both piles was always kept just above 50% until the end of the thermophilic phase and the maximum temperature was about 50 °C during the thermophilic phase. The carbon-nitrogen ratio decreased from 21.4 and 28.2, respectively (initial value at day 1 in Pile A and B), to values ranging from 12.9 to 15.1, both composts that originated from the two different piles were microbiologically safe. During a two-year period, the effects of different types of compost on the main qualitative parameters of processing tomato and durum wheat was evaluated. Five fertilization treatments were evaluated for tomato and durum wheat crops: unfertilized control (TR1); compost A (TR2); compost B (TR3); ½ mineral and ½ compost A (TR4); and mineral fertilizer commonly used for the two crops (TR5). Concerning the processing tomato yield, TR5 and TR4 showed the best results (2.73 and 2.51 kg, respectively). The same trend was observed considering the marketable yield per plant. The only difference was related to the treatments that included the compost (2.32, 1.77, and 1.73 kg/plant for TR4, TR3, and TR2, respectively). As regards the qualitative parameters of tomato, the highest average weight of the fruits was found in the TR5, TR4, and TR3 treatments (respectively, 73.67 g, 70.34 g, and 68.10 g). For durum wheat, only the protein component was differentiated between treatments. Furthermore, wheat grain yield parameters generally increased by combined application of mineral fertilizer and compost.
Improved Gel Properties of Whey Protein-Stabilized Emulsions by Ultrasound and Enzymatic Cross-Linking
Authors: Zhao Yanli , Xue Shiqi , Zhang Xinyue , Zhang Tiehua , Shen Xue
Published: September 2021

This study investigated the effects of high-intensity ultrasound (HUS) and transglutaminase pretreatment on the gelation behavior of whey protein soluble aggregate (WPISA) emulsions. HUS pretreatment and TGase-mediated cross-linking delayed the onset of gelation but significantly increased (p < 0.05) the gel firmness (G′) both after gel formation at 25 °C and during storage at 4 °C. The frequency sweep test indicated that all gels had a similar frequency dependence at 4 and 25 °C, and the elasticity and viscosity of the WPISA-stabilized emulsion gel were significantly enhanced by HUS pretreatment and TGase-mediated cross-linking (p < 0.05). HUS and TGase-mediated cross-linking greatly improved the textural properties of WPISA-stabilized emulsion gels, as revealed by their increases in gel hardness, cohesiveness, resilience, and chewiness. HUS pretreatment and TGase-mediated cross-linking significantly increased the water-holding capacity but decreased the swelling ratios of the gels (p < 0.05). Interactive force analysis confirmed that noncovalent interactions, disulfide bonds, and TGase-induced covalent cross-links were all involved in the formation of gel networks. In conclusion, the combination of HUS and TGase-mediated cross-linking were beneficial for improving the gelation properties of WPISA-stabilized emulsion as a controlled release vehicle for potential food industrial applications.
Psychometric Properties of the Taiwanese Version of the Tilburg Frailty Indicator for Community-Dwelling Older Adults
Authors: Lin Chia-Hui , Liu Chieh-Yu , Rong Jiin-Ru
Published: September 2021

Screening the frailty level of older adults is essential to avoid morbidity, prevent falls and disability, and maintain quality of life. The Tilburg Frailty Indicator (TFI) is a self-report instrument developed to assess frailty for community-dwelling older adults. The aim of this study was to explore the psychometric properties of the Taiwanese version of TFI (TFI-T). The sample consisted of 210 elderly participants living in the community. The scale was implemented to conduct a confirmatory factor analysis (CFA) test for validity. The models were evaluated through sensitivity, specificity, area under the curve, and receiving operating characteristic (ROC) curve. CFA was performed to evaluate construct validity, and the TFI-T has a goodness of fit with the three-factor structure of the TFI. Totally, the 15 items of TFI-T have acceptable internal consistency (Cronbach’s alpha = 0.78), and test–retest reliability (r = 0.88, p < 0.001). The criterion-related validity was examined, the TFI-T correlation with the Kihon Checklist (KCL) score (r = 0.74; p < 0.001). The cutoff of 5.5 based on the Youden index was considered optimal. The area under the ROC curve analysis indicated that the TFI-T has good accuracy in frailty screening. The TFI-T exhibits good reliability and validity and can be used as a sensitive and accurate instrument, which is highly applicable to screen frailty in Taiwan among older adults.
Neutralizing a Springboard for Inflammation: Physical Activity to Control the Immune Network
Authors: Kallen Victor , Scherder Rogier , Cramer Maarten J. , Stam Jacqueline , Johnson Bruce , Scherder Erik
Published: September 2021

The severe consequences of the present Corona Virus Disease 2019 COVID-19 pandemic seem to be closely related to an already ongoing (‘first’) pandemic, directly associated with a sedentary lifestyle. It seems evident that the prognosis after infection is substantially worse for individuals suffering from, for example, (visceral) obesity, cardiovascular disease, and diabetes type 2. Consequently, it may be considered highly relevant to gain insight into the potential beneficial effects of exercise interventions to strengthen the immune system, particularly in high-risk populations. For this reason, the exercise protocols that are suggested to strengthen the immune system, which can be executed by all ages and almost all physical conditions, were reviewed and evaluated. Previously published protocols range from interrupting prolonged sitting, to regular low-to-moderate exercise activities, to high intensity, typically interval, sports formats. Reported positive effects on immune functioning appear to be induced either directly or via beneficial metabolic and/or psychological effects and become measurable after 3 weeks to 3 months. Based in these findings, it appeared possible to design an optimal exercise protocol to maximize effects on immune functioning that should be executable for all, even under restricted (‘lockdown’) circumstances.
The Impact of ESG Management on Investment Decision: Institutional Investors’ Perceptions of Country-Specific ESG Criteria
Authors: Park So Ra , Jang Jae Young
Published: September 2021

Existing global ESG models are limited in terms of applicability and predictability, especially in countries with an unstable environment. On the other hand, utilizing internally made or privately sourced ESG models have caused issues relating to generalizability, comparability, and continuity. In our research, we present an ESG framework that is specific to South Korea, which has both global and country-specific factors in all three categories. The AHP model is used to determine how the three categories’ materiality would be viewed by institutional investors as well as how country-specific factors rank against global factors. The results of this study show that institutional investors place more importance on environmental and governance factors compared to social factors. Factors including shareholders’ rights, pollution and waste, greenhouse gas emissions, and risk and opportunity management are found to have greater influences on investors’ investment decisions. In addition, it was confirmed that both of the country-specific variables for South Korea, partnership with subcontractor and CEO reputation, have a significant influence on investment decisions. By having the ESG model validated by institutional investors, who are the main users of ESG disclosures of corporations, our methodology of presenting a country-specific model can be benchmarked by studies on other emerging markets with a variety of country-level specificities.
GIS Models for Vulnerability of Coastal Erosion Assessment in a Tropical Protected Area
Authors: Vieira Luís Russo , Vieira José Guilherme , Silva Isabel Marques da , Barbieri Edison , Morgado Fernando
Published: September 2021

Coastal erosion is considered a major worldwide challenge. The vulnerability assessment of coastal areas, in relation to climate change, is a key topic of worldwide increasing interest. The integration of methodologies supported by Remote Sensing, Geographical Information Systems (GIS) and in situ monitoring has allowed a viable identification of vulnerable areas to erosion. In the present study, a model was proposed to the assessment of the estuarine system of Cananéia-Iguape (Brazil), by applying the evaluation and prediction of vulnerability models for the conservation and preservation of mangroves. Approximately 1221 Km2 were classified, with 16% of the total presenting high and very high vulnerability to erosion. Other relevant aspects, were the identification and georeferencing sites that showed strong evidence of erosion and, thus, having a huge influence on the final vulnerability scores. The obtained results led to the development of a multidisciplinary approach through the application of a prediction and description model that resulted from the adaptation of the study system from a set of implemented models for coastal regions, in order to contribute to the erosion vulnerability assessment in the mangroves ecosystems (and associated localities, municipalities and communities).
Possible Steps of the Carboxylation of Ribulose-1,5-biphosphate from Intermediates: 2,3-Enediol versus 1,2-Enol
Authors: Fedunov Roman G. , Sokolov Victor A.
Published: September 2021

Ribulose 1,5-bisphosphate (RuBP) undergoes enolization to initiate fixation of atmospheric carbon dioxide in the plant carbon cycle. The known model assumes the binding of RuBP to the Rubisco active site with the subsequent formation of 2,3-enediol (2,3,4-trihydroxypent-2-ene-1,5-diyl diphosphate). In the present study, it is assumed that 1,2-enol (2,3,4-trihydroxypent-1-ene-1,5-diyl diphosphate) can be formed in the enolization step to initiate the carboxylation reaction. We have used Kohn–Sham density functional theory on WB97X-D3/Def2-TZVP levels to compare the reaction barriers in the two ways. We considered the pathways of carboxylation of 1/2-ene (mono/di)ol via the C1 and C2 carbons without taking into account the binding of RuBP to the magnesium ion. Calculations of Gibbs free energies confirm the equal probability of the formation of 2,3-enediol and 1,2-enol. Quantum–chemical modeling of enolization and carboxylation reactions supports the important role of the bridging water molecule and diphosphate groups, which provide proton transfer and lower reaction barriers. The results show that carbon dioxide fixation can occur without a magnesium ion, and binding with C1 can have a lower barrier (~12 kcal/mol) than with C2 (~23 kcal/mol).
FAK Shutdown: Consequences on Epithelial Morphogenesis and Biomarker Expression Involving an Innovative Biomaterial for Tissue Regeneration
Authors: Wang Xiaoling , Steinberg Thorsten , Dieterle Martin P. , Ramminger Imke , Husari Ayman , Tomakidi Pascal
Published: September 2021

By employing an innovative biohybrid membrane, the present study aimed at elucidating the mechanistic role of the focal adhesion kinase (FAK) in epithelial morphogenesis in vitro over 4, 7, and 10 days. The consequences of siRNA-mediated FAK knockdown on epithelial morphogenesis were monitored by quantifying cell layers and detecting the expression of biomarkers of epithelial differentiation and homeostasis. Histologic examination of FAK-depleted samples showed a significant increase in cell layers resembling epithelial hyperplasia. Semiquantitative fluorescence imaging (SQFI) revealed tissue homeostatic disturbances by significantly increased involucrin expression over time, persistence of yes-associated protein (YAP) and an increase of keratin (K) 1 at day 4. The dysbalanced involucrin pattern was underscored by ROCK-IISer1366 activity at day 7 and 10. SQFI data were confirmed by quantitative PCR and Western blot analysis, thereby corroborating the FAK shutdown-related expression changes. The artificial FAK shutdown was also associated with a significantly higher expression of filaggrin at day 10, sustained keratinocyte proliferation, and the dysregulated expression of K19 and vimentin. These siRNA-induced consequences indicate the mechanistic role of FAK in epithelial morphogenesis by simultaneously considering prospective biomaterial-based epithelial regenerative approaches.
Expression of the Malus sieversii NF-YB21 Encoded Gene Confers Tolerance to Osmotic Stresses in Arabidopsis thaliana
Authors: Feng Chen , Wang Yanyan , Sun Yueting , Peng Xiang , Zhang Xiang , Zhou Xin , Jiao Jiale , Zhai Zefeng , Xiao Yuqin , Wang Weili , Liu Yang , Li Tianhong
Published: September 2021

Drought is the main environmental factor that limits the yield and quality of apples (Malus × domestica) grown in arid and semi-arid regions. Nuclear factor Ys (NF-Ys) are important transcription factors involved in the regulation of plant growth, development, and various stress responses. However, the function of NF-Y genes is poorly understood in apples. Here, we identified 43 NF-Y genes in the genome of apples and conducted an initial functional characterization of the apple NF-Y. Expression analysis of NF-Y members in M. sieversii revealed that a large number of NF-Ys were highly expressed in the roots compared with the leaves, and a large proportion of NF-Y genes responded to drought treatment. Furthermore, heterologous expression of MsNF-YB21, which was significantly upregulated by drought, led to a longer root length and, thus, conferred improved osmotic and salt tolerance in Arabidopsis. Moreover, the physiological analysis of MsNF-YB21 overexpression revealed enhanced antioxidant systems, including antioxidant enzymes and compatible solutes. In addition, genes encoding catalase (AtCAT2, AtCAT3), superoxide dismutase (AtFSD1, AtFSD3, AtCSD1), and peroxidase (AtPER12, AtPER42, AtPER47, AtPER51) showed upregulated expression in the MsNF-YB21 overexpression lines. These results for the MsNF-Y gene family provide useful information for future studies on NF-Ys in apples, and the functional analysis of MsNF-YB21 supports it as a potential target in the improvement of apple drought tolerance via biotechnological strategies.
Drugs Interfering with Insulin Resistance and Their Influence on the Associated Hypermetabolic State in Severe Burns: A Narrative Review
Authors: Greabu Maria , Badoiu Silviu Constantin , Stanescu-Spinu Iulia-Ioana , Miricescu Daniela , Totan Alexandra Ripszky , Badoiu Silvia Elena , Costagliola Michel , Jinga Viorel
Published: September 2021

It has become widely accepted that insulin resistance and glucose hypermetabolism can be linked to acute pathologies, such as burn injury, severe trauma, or sepsis. Severe burns can determine a significant increase in catabolism, having an important effect on glucose metabolism and on muscle protein metabolism. It is imperative to acknowledge that these alterations can lead to increased mortality through organ failure, even when the patients survive the initial trauma caused by the burn. By limiting the peripheral use of glucose with consequent hyperglycemia, insulin resistance determines compensatory increased levels of insulin in plasma. However, the significant alterations in cellular metabolism lead to a lack of response to insulin’s anabolic functions, as well as to a decrease in its cytoprotective role. In the end, via pathological insulin signaling associated with increased liver gluconeogenesis, elevated levels of glucose are detected in the blood. Several cellular mechanisms have been incriminated in the development of insulin resistance in burns. In this context, the main aim of this review article is to summarize some of the drugs that might interfere with insulin resistance in burns, taking into consideration that such an approach can significantly improve the prognosis of the burned patient.
RNA-Seq-Based Profiling of pl Mutant Reveals Transcriptional Regulation of Anthocyanin Biosynthesis in Rice (Oryza sativa L.)
Authors: Xu Ruonan , Pan Ronghui , Zhang Yuchan , Feng Yanlei , Nath Ujjal Kumar , Gan Yinbo , Shi Chunhai , Akhter Delara
Published: September 2021

Purple-colored leaves in plants attain much interest for their important biological functions and could be a potential source of phenotypic marker in selecting individuals in breeding. The transcriptional profiling helps to precisely identify mechanisms of leaf pigmentation in crop plants. In this study, two genetically unlike rice genotypes, the mutant purple leaf (pl) and wild (WT) were selected for RNA-sequencing and identifying the differentially expressed genes (DEGs) that are regulating purple leaf color. In total, 609 DEGs were identified, of which 513 and 96 genes were up- and down-regulated, respectively. The identified DEGs are categorized into metabolic process, carboxylic acid biosynthesis, phenylpropanoids, and phenylpropanoid biosynthesis process enrichment by GO analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) confirmed their association with phenylpropanoid synthesis, flavonoid synthesis, and phenylalanine metabolism. To explore molecular mechanism of purple leaf color, a set of anthocyanin biosynthetic and regulatory gene expression patterns were checked by qPCR. We found that OsPAL (Os02g0626100, Os02g0626400, Os04g0518400, Os05g0427400 and Os02g0627100), OsF3H (Os03g0122300), OsC4HL (Os05g0320700), and Os4CL5 (Os08g0448000) are associated with anthocyanin biosynthesis, and they were up-regulated in pl leaves. Two members of regulatory MYB genes (OsMYB55; Os05g0553400 and Os08g0428200), two bHLH genes (Os01g0196300 and Os04g0300600), and two WD40 genes (Os11g0132700 and Os11g0610700) also showed up-regulation in pl mutant. These genes might have significant and vital roles in pl leaf coloration and could provide reference materials for further experimentation to confirm the molecular mechanisms of anthocyanin biosynthesis in rice.
Nitrosative Stress and Human Disease: Therapeutic Potential of Denitrosylation
Authors: Yoon Somy , Eom Gwang Hyeon , Kang Gaeun
Published: September 2021

Proteins dynamically contribute towards maintaining cellular homeostasis. Posttranslational modification regulates the function of target proteins through their immediate activation, sudden inhibition, or permanent degradation. Among numerous protein modifications, protein nitrosation and its functional relevance have emerged. Nitrosation generally initiates nitric oxide (NO) production in association with NO synthase. NO is conjugated to free thiol in the cysteine side chain (S-nitrosylation) and is propagated via the transnitrosylation mechanism. S-nitrosylation is a signaling pathway frequently involved in physiologic regulation. NO forms peroxynitrite in excessive oxidation conditions and induces tyrosine nitration, which is quite stable and is considered irreversible. Two main reducing systems are attributed to denitrosylation: glutathione and thioredoxin (TRX). Glutathione captures NO from S-nitrosylated protein and forms S-nitrosoglutathione (GSNO). The intracellular reducing system catalyzes GSNO into GSH again. TRX can remove NO-like glutathione and break down the disulfide bridge. Although NO is usually beneficial in the basal context, cumulative stress from chronic inflammation or oxidative insult produces a large amount of NO, which induces atypical protein nitrosation. Herein, we (1) provide a brief introduction to the nitrosation and denitrosylation processes, (2) discuss nitrosation-associated human diseases, and (3) discuss a possible denitrosylation strategy and its therapeutic applications.
Isolation and Functional Characterization of Two SHORT VEGETATIVE PHASE Homologous Genes from Mango
Authors: Mo Xiao , Luo Cong , Yu Haixia , Chen Jinwen , Liu Yuan , Xie Xiaojie , Fan Zhiyi , He Xinhua
Published: September 2021

The SHORT VEGETATIVE PHASE (SVP) gene is a transcription factor that integrates flowering signals and plays an important role in the regulation of flowering time in many plants. In this study, two full-length cDNA sequences of SVP homologous genes—MiSVP1 and MiSVP2—were obtained from ‘SiJiMi’ mango. Sequence analysis showed that the MiSVPs had typical MADS-box domains and were highly conserved between each other. The analysis of expression patterns showed that the MiSVPs were expressed during flower development and highly expressed in vegetative tissues, with low expression in flowers/buds. The MiSVPs could responded to low temperature, NaCl, and PEG treatment. Subcellular localization revealed that MiSVP1 and MiSVP2 were localized in the nucleus. Transformation of Arabidopsis revealed that overexpression of MiSVP1 delayed flowering time, overexpression of MiSVP2 accelerated flowering time, and neither MiSVP1 nor MiSVP2 had an effect on the number of rosette leaves. Overexpression of MiSVP1 increased the expression of AtFLC and decreased the expression of AtFT and AtSOC1, and overexpression of MiSVP2 increased the expression levels of AtSOC1 and AtFT and decreased the expression levels of AtFLC. Point-to-point and bimolecular fluorescence complementation (BiFC) assays showed that MiSVP1 and MiSVP2 could interact with SEP1-1, SOC1D, and AP1-2. These results suggest that MiSVP1 and MiSVP2 may play a significant roles in the flowering process of mango.
Chemokine-Directed Tumor Microenvironment Modulation in Cancer Immunotherapy
Authors: Bule Pedro , Aguiar Sandra Isabel , Aires-Da-Silva Frederico , Dias Joana Nunes Ribeiro
Published: September 2021

Chemokines are a large family of small chemotactic cytokines that coordinates immune cell trafficking. In cancer, they have a pivotal role in the migration pattern of immune cells into the tumor, thereby shaping the tumor microenvironment immune profile, often towards a pro-tumorigenic state. Furthermore, chemokines can directly target non-immune cells in the tumor microenvironment, including cancer, stromal and vascular endothelial cells. As such, chemokines participate in several cancer development processes such as angiogenesis, metastasis, cancer cell proliferation, stemness and invasiveness, and are therefore key determinants of disease progression, with a strong influence in patient prognosis and response to therapy. Due to their multifaceted role in the tumor immune response and tumor biology, the chemokine network has emerged as a potential immunotherapy target. Under the present review, we provide a general overview of chemokine effects on several tumoral processes, as well as a description of the currently available chemokine-directed therapies, highlighting their potential both as monotherapy or in combination with standard chemotherapy or other immunotherapies. Finally, we discuss the most critical challenges and prospects of developing targeted chemokines as therapeutic options.
Teriflunomide Inhibits JCPyV Infection and Spread in Glial Cells and Choroid Plexus Epithelial Cells
Authors: O’Hara Bethany A. , Gee Gretchen V. , Haley Sheila A. , Morris-Love Jenna , Nyblade Charlotte , Nieves Chris , Hanson Barbara A. , Dang Xin , Turner Timothy J. , Chavin Jeffrey M. , Lublin Alex , Koralnik Igor J. , Atwood Walter J.
Published: September 2021

Several classes of immunomodulators are used for treating relapsing-remitting multiple sclerosis (RRMS). Most of these disease-modifying therapies, except teriflunomide, carry the risk of progressive multifocal leukoencephalopathy (PML), a severely debilitating, often fatal virus-induced demyelinating disease. Because teriflunomide has been shown to have antiviral activity against DNA viruses, we investigated whether treatment of cells with teriflunomide inhibits infection and spread of JC polyomavirus (JCPyV), the causative agent of PML. Treatment of choroid plexus epithelial cells and astrocytes with teriflunomide reduced JCPyV infection and spread. We also used droplet digital PCR to quantify JCPyV DNA associated with extracellular vesicles isolated from RRMS patients. We detected JCPyV DNA in all patients with confirmed PML diagnosis (n = 2), and in six natalizumab-treated (n = 12), two teriflunomide-treated (n = 7), and two nonimmunomodulated (n = 2) patients. Of the 21 patients, 12 (57%) had detectable JCPyV in either plasma or serum. CSF was uniformly negative for JCPyV. Isolation of extracellular vesicles did not increase the level of detection of JCPyV DNA versus bulk unprocessed biofluid. Overall, our study demonstrated an effect of teriflunomide inhibiting JCPyV infection and spread in glial and choroid plexus epithelial cells. Larger studies using patient samples are needed to correlate these in vitro findings with patient data.
Model Bridge Span Traversed by a Heavy Mass: Analysis and Experimental Verification
Authors: Dadoulis Georgios I. , Manolis George D.
Published: September 2021

In this work, we investigate the transient response of a model bridge traversed by a heavy mass moving with constant velocity. Two response regimes are identified, namely forced vibrations followed by free vibrations as the moving mass goes past the far support of the simply supported span of the bridge. Despite this being a classical problem in structural dynamics, there is an implicit assumption in the literature that moving loads possess masses that are at least an order of magnitude smaller than the mass of the bridge span that they traverse. This alludes to interaction problems involving secondary systems, whose presence does not alter the basic characteristics of the primary system. In our case, the dynamic properties of the bridge span during the passage of a heavy mass change continuously over time, leading to an eigenvalue problem that is time dependent. During the free vibration regime, however, the bridge recovers the expected dynamic properties corresponding to its original configuration. Therefore, the aim here is the development of a mathematical model whose numerical solution is validated by comparison with experimental results recovered from an experiment involving a scaled bridge span traversed by a rolling mass. Following that, the target is to identify regions in the transient response of the bridge span that can be used for recovering the bridge’s dynamic properties and subsequently trace the development of structural damage. In closing, the present work has ramifications in the development of structural health monitoring systems applicable to critical civil engineering infrastructure, such as railway and highway bridges.
Role of Advanced Glycation End-Products and Other Ligands for AGE Receptors in Thyroid Cancer Progression
Authors: Bronowicka-Szydełko Agnieszka , Kotyra Łukasz , Lewandowski Łukasz , Gamian Andrzej , Kustrzeba-Wójcicka Irena
Published: September 2021

To date, thyroid cancers (TCs) remain a clinical challenge owing to their heterogeneous nature. The etiopathology of TCs is associated not only with genetic mutations or chromosomal rearrangements, but also non-genetic factors, such as oxidative-, nitrosative-, and carbonyl stress-related alterations in tumor environment. These factors, through leading to the activation of intracellular signaling pathways, induce tumor tissue proliferation. Interestingly, the incidence of TCs is often coexistent with various simultaneous mutations. Advanced glycation end-products (AGEs), their precursors and receptors (RAGEs), and other ligands for RAGEs are reported to have significant influence on carcinogenesis and TCs progression, inducing gene mutations, disturbances in histone methylation, and disorders in important carcinogenesis-related pathways, such as PI3K/AKT/NF-kB, p21/MEK/MPAK, or JAK/STAT, RAS/ERK/p53, which induce synthesis of interleukins, growth factors, and cytokines, thus influencing metastasis, angiogenesis, and cancer proliferation. Precursors of AGE (such as methylglyoxal (MG)) and selected ligands for RAGEs: AS1004, AS1008, and HMGB1 may, in the future, become potential targets for TCs treatment, as low MG concentration is associated with less aggressive anaplastic thyroid cancer, whereas the administration of anti-RAGE antibodies inhibits the progression of papillary thyroid cancer and anaplastic thyroid cancer. This review is aimed at collecting the information on the role of compounds, engaged in glycation process, in the pathogenesis of TCs. Moreover, the utility of these compounds in the diagnosis and treatment of TCs is thoroughly discussed. Understanding the mechanism of action of these compounds on TCs pathogenesis and progression may potentially be the grounds for the development of new treatment strategies, aiming at quality-of-life improvements.
BCMA in Multiple Myeloma—A Promising Key to Therapy
Authors: Kleber Martina , Ntanasis-Stathopoulos Ioannis , Terpos Evangelos
Published: September 2021

Despite the discoveries of numerous agents including next generation proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, multiple myeloma (MM) remains an incurable disease. The field of myeloma treatment in refractory or relapsed patients after standard therapy entered a new era due to the B-cell maturation antigen (BMCA) targeted approach. BCMA is a member of the tumor necrosis factor receptor family with high expression in mature B-lymphocytes and plasma cells. Given the understanding of BCMA mechanism of action in MM, BCMA plays a promising role as a therapeutic target. Several clinical trials are underway to evolve the current BCMA targeted treatment concept such as antibody-drug conjugates (ADCs), bispecific T cell engagers (BITEs) and chimeric antigen receptor (CAR) T cell therapy. Current results of representative BCMA trials may close the gap of the unmet clinical need to further improve the outcome of heavily pretreated MM patients with the potency to change the paradigm in newly diagnosed and refractory MM. This comprehensive review will give an update on various BMCA targeted treatment modalities (ADCs, BITEs, CAR T cell therapy) and its existing results on efficacy and safety from preclinical and clinical trials.
A Novel Diagnostic Score Integrating Atrial Dimensions to Differentiate between the Athlete’s Heart and Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Rossi Valentina A. , Niederseer David , Sokolska Justyna M. , Kovacs Boldizsar , Costa Sarah , Gasperetti Alessio , Brunckhorst Corinna , Akdis Deniz , Tanner Felix C. , Duru Firat , Schmied Christian M. , Saguner Ardan M.
Published: September 2021

Objective: The 2010 Task Force Criteria (TFC) have not been tested to differentiate ARVC from the athlete’s heart. Moreover, some criteria are not available (myocardial biopsy, genetic testing, morphology of ventricular tachycardia) or subject to interobserver variability (right ventricular regional wall motion abnormalities) in clinical practice. We hypothesized that atrial dimensions are useful and robust to differentiate between both entities and proposed a new diagnostic score based upon readily available parameters including echocardiographic atrial dimensions. Methods: In this observational study, 21 patients with definite ARVC were matched for age, gender and body mass index to 42 athletes. Based on ROC analysis, the following parameters were included in the score: indexed right/left atrial volumes ratio (RAVI/LAVI ratio), NT-proBNP, RVOT measurements (PLAX and PSAX BSA-corrected), tricuspid annular motion (TAM), precordial TWI and depolarization abnormalities according to TFC. Results: ARVC patients had a higher RAVI/LAVI ratio (1.76 ± 1.5 vs. 0.87 ± 0.2, p < 0.001), lower right ventricular function (fac: 29 ± 10.1 vs. 42.2 ± 5%, p < 0.001; TAM: 19.8 ± 5.4 vs. 23.8 ± 3.8 mm, p = 0.001) and higher serum NT-proBNP levels (345 ± 612 vs. 48 ± 57 ng/L, p < 0.001). Our score showed a good performance, which is comparable to the 2010 TFC using those parameters, which are available in routine clinical practice (AUC93%, p < 0.001 (95%CI 0.874–0.995) vs. AUC97%, p < 0.001 (95%CI 0.93–1.00). A score of 6/12 points yielded a specificity of 91% and an improved sensitivity of 67% for ARVC diagnosis as compared to a sensitivity of 41% for the abovementioned readily available 2010 TFC. Conclusions: ARVC patients present with significantly larger RA compared to athletes, resulting in a greater RAVI/LAVI ratio. Our novel diagnostic score includes readily available clinical parameters and has a high diagnostic accuracy to differentiate between ARVC and the athlete’s heart.
Biological Mechanism(s) Underpinning the Association between Antipsychotic Drugs and Weight Gain
Authors: Panizzutti Bruna , Bortolasci Chiara C. , Spolding Briana , Kidnapillai Srisaiyini , Connor Timothy , Richardson Mark F. , Truong Trang T. T. , Liu Zoe S. J. , Gray Laura , Kim Jee Hyun , Dean Olivia M. , Berk Michael , Walder Ken
Published: September 2021

Weight gain and consequent metabolic alterations are common side-effects of many antipsychotic drugs. Interestingly, several studies have suggested that improvement in symptoms and adverse metabolic effects are correlated. We used next generation sequencing data from NT-2 (human neuronal) cells treated with aripiprazole, amisulpride, risperidone, quetiapine, clozapine, or vehicle control, and compared with the Pillinger P-score (ranked from 0 to 1, indicating greater increase in weight gain and related metabolic parameters) to identify the genes most associated with the drugs’ propensity to cause weight gain. The top 500 genes ranked for their correlation with the drugs’ propensity to cause weight gain were subjected to pathway analysis using DAVID (NIH). We further investigated transcription factors (TFs) that are more likely to regulate the genes involved in these processes using the prediction tool of key TFs from TRRUST. The results suggest an enrichment for genes involved in lipid biosynthesis and metabolism, which are of interest for mechanisms underpinning weight-gain. The list of genes involved in the lipid pathways that correlated with weight gain was enriched for genes transcriptionally regulated by SREBF1 and SREBF2. Furthermore, quetiapine significantly increased the expression of SREBF1 and SREBF2 in NT-2 cells. Our results suggest that the effects of these antipsychotic drugs on lipid metabolism may be mediated, at least in part, via regulation of SREBF1/SREBF2 expression, with evidence of a direct effect of quetiapine on the expression of SREBF1/2. The effects of antipsychotic drugs on lipid metabolism may influence white matter structure (therapeutic effect) and the risk of weight gain, lipid disturbances, and, consequently, metabolic syndrome (adverse effects). Understanding the different molecular effects of these drugs could inform a personalized medicine approach in treating patients with schizophrenia.
Revealing Hidden Features in Multilayered Artworks by Means of an Epi-Illumination Photoacoustic Imaging System
Authors: Tserevelakis George J. , Chaban Antonina , Klironomou Evgenia , Melessanaki Kristalia , Striova Jana , Zacharakis Giannis
Published: September 2021

Photoacoustic imaging is a novel, rapidly expanding technique, which has recently found several applications in artwork diagnostics, including the uncovering of hidden layers in paintings and multilayered documents, as well as the thickness measurement of optically turbid paint layers with high accuracy. However, thus far, all the presented photoacoustic-based imaging technologies dedicated to such measurements have been strictly limited to thin objects due to the detection of signals in transmission geometry. Unavoidably, this issue restricts seriously the applicability of the imaging method, hindering investigations over a wide range of cultural heritage objects with diverse geometrical and structural features. Here, we present an epi-illumination photoacoustic apparatus for diagnosis in heritage science, which integrates laser excitation and respective signal detection on one side, aiming to provide universal information in objects of arbitrary thickness and shape. To evaluate the capabilities of the developed system, we imaged thickly painted mock-ups, in an attempt to reveal hidden graphite layers covered by various optically turbid paints, and compared the measurements with standard near-infrared (NIR) imaging. The obtained results prove that photoacoustic signals reveal underlying sketches with up to 8 times improved contrast, thus paving the way for more relevant applications in the field.
Online Prediction of Ship Coupled Heave-Pitch Motions in Irregular Waves Based on a Coarse-and-Fine Tuning Fixed-Grid Wavelet Network
Authors: Huang Baigang , Jiang Jianjun , Zou Zaojian
Published: September 2021

A method based on a coarse- and fine-tuning fixed-grid wavelet networks is presented for online prediction of the coupled heave-pitch motions of a ship in irregular waves. The online modeling method contains two processes, i.e., coarse tuning and fine tuning. The coarse tuning is used to select the important wavelet terms, while the fine tuning is only used to compute the related coefficients of the selected wavelet terms. The Givens transformation algorithm is applied to realize the fine-tuning process. Due to the continuous fine-tuning process, the computational efficiency is improved significantly. Both simulation data and experimental data are used to verify the modeling method. The prediction results illustrate that the method has the ability to online predict the coupled heave-pitch motions of a ship in irregular waves.