bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation Methodology for Physical Radar Perception Sensor Models Based on On-Road Measurements for the Testing and Validation of Automated Driving
Authors: Magosi Zoltan Ferenc , Wellershaus Christoph , Tihanyi Viktor Roland , Luley Patrick , Eichberger Arno
Published: April 2022

In recent years, verification and validation processes of automated driving systems have been increasingly moved to virtual simulation, as this allows for rapid prototyping and the use of a multitude of testing scenarios compared to on-road testing. However, in order to support future approval procedures for automated driving functions with virtual simulations, the models used for this purpose must be sufficiently accurate to be able to test the driving functions implemented in the complete vehicle model. In recent years, the modelling of environment sensor technology has gained particular interest, since it can be used to validate the object detection and fusion algorithms in Model-in-the-Loop testing. In this paper, a practical process is developed to enable a systematic evaluation for perception–sensor models on a low-level data basis. The validation framework includes, first, the execution of test drive runs on a closed highway; secondly, the re-simulation of these test drives in a precise digital twin; and thirdly, the comparison of measured and simulated perception sensor output with statistical metrics. To demonstrate the practical feasibility, a commercial radar-sensor model (the ray-tracing based RSI radar model from IPG) was validated using a real radar sensor (ARS-308 radar sensor from Continental). The simulation was set up in the simulation environment IPG CarMaker® 8.1.1, and the evaluation was then performed using the software package Mathworks MATLAB®. Real and virtual sensor output data on a low-level data basis were used, which thus enables the benchmark. We developed metrics for the evaluation, and these were quantified using statistical analysis.
Predicting Adsorption of Methane and Carbon Dioxide Mixture in Shale Using Simplified Local-Density Model: Implications for Enhanced Gas Recovery and Carbon Dioxide Sequestration
Authors: Pang Yu , Chen Shengnan , Wang Hai
Published: April 2022

Carbon dioxide (CO2) capture and storage have attracted global focus because CO2 emissions are responsible for global warming. Recently, injecting CO2 into shale gas reservoirs is regarded as a promising technique to enhance shale gas (i.e., methane (CH4)) production while permanently storing CO2 underground. This study aims to develop a calculation workflow, which is built on the simplified local-density (SLD) model, to predict excess and absolute adsorption isotherms of gas mixture based on single-component adsorption data. Such a calculation workflow was validated by comparing the measured adsorption of CH4, CO2, and binary CH4/CO2 mixture in shale reported previously in the literature with the predicted results using the calculation workflow. The crucial steps of the calculation workflow are applying the multicomponent SLD model to conduct regression analysis on the measured adsorption isotherm of each component in the gas mixture simultaneously and using the determined key regression parameters to predict the adsorption isotherms of gas mixtures with various feed-gas mole fractions. Through the calculation workflow, the density profiles and mole fractions of the adsorbed gases can be determined, from which the absolute adsorption of the gas mixture is estimated. In addition, the CO2/CH4 adsorption selectivity larger than one is observed, illustrating the preferential adsorption of CO2 over CH4 on shale, which implies that CO2 has enormous potential to enhance CH4 production while sequestering itself in shale. Our findings demonstrate that the proposed calculation workflow depending on the multicomponent SLD model enables us to accurately predict the adsorption of gas mixtures in nanopores based on single-component adsorption results. Following the innovative calculation flow path, we could bypass the experimental difficulties of measuring the multicomponent mole fractions in the gas phase at the equilibrium during the adsorption experiments. This study also provides insight into the CO2/CH4 competitive adsorption behavior in nanopores and gives guidance to CO2-enhanced gas recovery (CO2-EGR) and CO2 sequestration in shale formations.
Gas-Fueled Binary Energy System with Low-Boiling Working Fluid for Enhanced Power Generation
Authors: Morenov Valentin , Leusheva Ekaterina , Lavrik Alexander , Lavrik Anna , Buslaev George
Published: April 2022

This article discusses methods of enhanced power generation using a binary power system with low-boiling fluid as an intermediate energy carrier. The binary power system consists of micro-gas and steam power units and is intended for remote standalone power supply. Trifluotrichloroethane was considered as the working agent of the binary cycle. The developed system was modeled by two parts in MATLAB Simulink and Aspen HYSYS. The model in Aspen HYSYS calculates the energy and material balance of the binary energy system. The model in MATLAB Simulink investigates the operation of power electronics in the energy system for quality power generation. The results of the simulation show that the efficiency of power generation in the range of 100 kW in the developed system with micro-turbine power units reaches 50%.
A Data-Driven Fault Diagnosis Method for Solid Oxide Fuel Cell Systems
Authors: Li Mingfei , Chen Zhengpeng , Dong Jiangbo , Xiong Kai , Chen Chuangting , Rao Mumin , Peng Zhiping , Li Xi , Peng Jingxuan
Published: April 2022

In this study, a data-driven fault diagnosis method was developed for solid oxide fuel cell (SOFC) systems. First, the complete experimental data was obtained following the design of the SOFC system experiments. Then, principal component analysis (PCA) was performed to reduce the dimensionality of the obtained experimental data. Finally, the fault diagnosis algorithms were designed by support vector machine (SVM) and BP neural network to identify and prevent the reformer carbon deposition and heat exchanger rupture faults, respectively. The research results show that both SVM and BP fault diagnosis algorithms can achieve online fault identification. The PCA + SVM algorithm was compared with the SVM algorithm, BP algorithm, and PCA + BP algorithm, and the results show that the PCA + SVM algorithm is superior in terms of running time and accuracy, the diagnosis accuracy reached more than 99%, and the running time was within 20 s. The corresponding system optimization scheme is also proposed.
Single-Phase Voltage Source Multi-Level Inverter Hysteresis SVPWM Reconfigurable Fault-Tolerant Control Method
Authors: Li Guohua , Wang Liangjun , Li Feng
Published: April 2022

A hysteresis space vector pulse width modulation (SVPWM) reconfigurable fault-tolerant method for single-phase voltage source multi-level inverter with current tracking is proposed. Firstly, the influence of single switch open circuit fault and double switches open circuit fault on the voltage vector of the inverter is analyzed, and on this basis, the equivalent replacement of the voltage vector is obtained by using the topology reconstruction of the inverter, and the redundant voltage vectors with overlapping positions are preferred for equivalent replacement. If there are no coincident non-fault vectors, the other non-fault vectors with the closest position and effect are selected. The fault-tolerant method does not need the switching operation between the main power switching device and spare power switching device of the inverter, and can directly control the on–off process of the inverter reconfiguration unit through the driving signal of insulated gate bipolar translator (IGBT), which is simple and stable. Under the conditions of single switch open circuit and most double switches open circuit, the output current of the inverter can accurately track the reference current.
From Wind to Hybrid: A Contribution to the Optimal Design of Utility-Scale Hybrid Power Plants
Authors: Silva Ana Rita , Estanqueiro Ana
Published: April 2022

When a substantial number of wind parks are approaching the end of their lifespan, and developers of renewables are facing decisions about what to do with their assets, concepts such as hybrid power plants are emerging as a promising solution to enable renewable integration in a cost-effective and robust manner. This work proposes a decision-aid algorithm to perform a comprehensive analysis of hybrid power plants, focusing on the energetic contribution and economic feasibility of converting existing wind power plants into hybrid power plants (i.e., installing photovoltaic panels and a storage system). The analysis was performed by comparing the option of converting existing wind plants into hybrid plants with a pure repowering exercise or overplanting using wind technology only. The obtained results unequivocally demonstrate the added value of hybrid power plants as they promote: (i) a higher installed capacity and yearly capacity factor (up to 50%); (ii) an increased efficiency of existing electric infrastructures; and (iii) a positive contribution to a sustainable energy system with the ability to generate economic value.
Understanding Socio-Economic and Environmental Impacts of Agroforestry on Rural Communities
Authors: Mukhlis Imam , Rizaludin Muhammad Syamsu , Hidayah Isnawati
Published: April 2022

Several studies have highlighted the benefit of implementing agroforestry for rural communities. From the perspective of socio-economic, agroforestry can potentially improve smallholders’ income, increase food security, promote gender equality and stimulate cultural activities in rural areas. Furthermore, agroforestry can enhance ecosystem service through improved soil structure, increased carbon sequestration and higher water retention. Despite having many advantages, the adoption of agroforestry among rural communities, particularly among smallholder farmers in developing countries remains limited. The absence of agroforestry in public policy causes little recognition of this system to tackle the climate crisis as well as to improve rural livelihood. This may be due to, among others, a less comprehensive evidence on impacts that simultaneously touch upon social, economic as well as environmental aspects of agroforestry on the community. This review gives a special emphasis on the current evidence depicting the characteristics of agroforestry adoption, its benefits and potential drawbacks, as well as challenges for the adoption in some developing countries. The outcomes might help related stakeholders to make appropriate decisions to improve rural livelihood.
The Legal Roundwood Market in the Amazon and Its Impact on Deforestation in the Region between 2009–2015
Authors: Andrade Fernando Wallase Carvalho , Pinto Tatiane Inácio , Moreira Letícia da Silva , da Ponte Márcio José Moutinho , Lobato Tarcísio da Costa , de Sousa João Thiago Rodrigues , Moutinho Victor Hugo Pereira
Published: April 2022

Brazil is one of the largest producers of tropical wood in the world. Much of this wood is extracted from the Amazon region, especially in the state of Pará. Despite empirical knowledge, there is little information in the literature about the selectivity of trade and how this production has been behaving in recent years. Is there any relationship between this legal timber trade and deforestation? In this work, we compile data reports from control agencies and analyze the dynamics of the legal timber market in the state of Pará between 2009 and 2015 in terms of species, volume, and monetary value. We also correlate changes in volume m−3 and value m−3 with deforestation increase in the same period and region. We find that only ten groups of species represent almost 50% of the total timber volume marketed in the State, mainly from the Massaranduba (Manilkara) group. According to our models, the supply of a species of wood on the market is defined by its monetary value and not by its availability or characteristics, which hinders the insertion of new species and increases selectivity. Since 2011 the volume of legally traded logs has been decreasing sharply. Traditional forest regions in the state already demonstrate depletion in forested areas. While others, such as the lower Amazon region, have been increasing production, showing that new forestry operations areas are being used for harvesting in the function of the lower availability in traditional areas. Our models show that the legal reduced impact logging timber volume has an inverse relationship with the deforestation increase. Otherwise, preference for a small group of timber types still predominates, which may lead local woods to the danger of extinction.
Pediatric High Grade Glioma Classification Criteria and Molecular Features of a Case Series
Authors: Buccoliero Anna Maria , Giunti Laura , Moscardi Selene , Castiglione Francesca , Provenzano Aldesia , Sardi Iacopo , Scagnet Mirko , Genitori Lorenzo , Caporalini Chiara
Published: April 2022

Pediatric high-grade gliomas (pHGGs) encompass a heterogeneous group of tumors. Three main molecular types (H3.3 mutant, IDH mutant, and H3.3/IDH wild-type) and a number of subtypes have been identified. We provide an overview of pHGGs and present a mono-institutional series. We studied eleven non-related pHGG samples through a combined approach of routine diagnostic tools and a gene panel. TP53 and H3F3A were the most mutated genes (six patients each, 54%). The third most mutated gene was EGFR (three patients, 27%), followed by PDGFRA and PTEN (two patients each, 18%). Variants in the EZHIP, MSH2, IDH1, IDH2, TERT, HRAS, NF1, BRAF, ATRX, and PIK3CA genes were relatively infrequent (one patient each, 9%). In one case, gene panel analysis documented the presence of a pathogenic IDH2 variant (c.419G>A, p.Arg140Gln) never described in gliomas. More than one-third of patients carry a variant in a gene associated with tumor-predisposing syndromes. The absence of constitutional DNA did not allow us to identify their constitutional origin.
Factors Affecting Antiretroviral Therapy Adherence among HIV-Positive Pregnant Women in Greece: An Exploratory Study
Authors: Pontiki Georgia , Sarantaki Antigoni , Nikolaidis Petros , Lykeridou Aikaterini
Published: April 2022

The human immunodeficiency virus (HIV) is a major public health problem globally. Each year, approximately 1.4 million women living with HIV get pregnant. This contemporary descriptive study investigates the degree of compliance of HIV-positive women-patients undergoing antiretroviral therapy (ART) during pregnancy. A sample of 200 treated HIV-positive pregnant women (mean age, 32.9 years; Greek nationality, 67.5%; poor educational level, 28.5%) was selected. The data collection occurred in three acquired immunodeficiency syndrome (AIDS) reference centers in Athens, Greece, from November 2019 to September 2021. Patients’ median knowledge score was 50% (IQR: 38.9–61.1%), and their median attitude score was 4.2 (IQR: 3.6–4.4); 13.0% of participants did comply with ART treatment. Specifically, 7.0% of them failed to take their treatment twice when asked about their activities over the preceding 7 days, and 3.0% skipped it three times. Women of Greek nationality had significantly higher compliance with treatment (p < 0.001). Additionally, a higher compared to lower education level was significantly associated with greater compliance (p = 0.001), while women with a low level of social support had significantly lower compliance. Participants who had complied with ART had significantly higher knowledge and attitude scores (p = 0.027). Patient characteristics determine compliance with ART in HIV-positive pregnant women in Greece, while the availability and quality of health system services may modulate this relationship.
Atherogenic Risk, Anthropometry, Diet and Physical Activity in a Sample of Spanish Commercial Airline Pilots
Authors: Alaminos-Torres Ana , Martínez-Álvarez Jesús Román , López-Ejeda Noemi , Marrodán-Serrano Maria Dolores
Published: April 2022

Cardiovascular accidents are the most disabling event for pilots, causing complicated situations during flight and the withdrawal of license. The study aims to assess the modifiable risk factors and the atherogenic index of plasma (AIP) associated with anthropometric, physiometabolic and lifestyle profiles in a sample of Spanish aviation pilots. Data from pilots’ clinical and professional history, anthropometric and bioelectrical impedance assessments of nutritional status, and diet and physical activity questionnaires. The sample comprised 304 men pilots. Up to 53.6% showed excess weight, of which 6.4% were obese, 64.3% presented high relative adiposity and 64.6% showed abdominal obesity. Regarding the physiometabolic profile, 10.0% had hypertension, 42.6% hypercholesterolemia, 9.4% high LDL and 10.6% low HDL, 9.4% hyperglycemia and 8.1% hypertriglyceridemia. The adherence to the Mediterranean diet (MedDiet) was high in 29.7% and low in 14.7%. Most of the sample showed a good physical activity level. The AIP risk increased with higher obesity indicators and LDL cholesterol levels. There was an inverse relationship between the MedDiet adherence and vigorous physical activity and the risk of atherogenicity. Elevated rates of overweight, abdominal obesity and hypercholesterolemia were found, contributing to the atherogenic risk of plasma (AIP). This parameter was significantly associated with all anthropometric indicators and LDL cholesterol. Prevention plans on reducing excess fat and blood cholesterol levels are recommended to reduce cardiovascular risk in Spanish aviation pilots and ensure flight safety.
Measles Vaccination and Outbreaks in Croatia from 2001 to 2019; A Comparative Study to Other European Countries
Authors: Drenjančević Ines , Samardžić Senka , Stupin Ana , Borocz Katalin , Nemeth Peter , Berki Timea
Published: April 2022

Due to the current burden of COVID-19 on public health institutions, increased migration and seasonal touristic traveling, there is an increased risk of epidemic outbreaks of measles, mumps and rubella (MMR). The aim of the present study was to analyze the epidemiological data on MMR immunization coverage and the number of measles cases in 2001–2019 in Croatia and a number of European countries. Results revealed a decreasing trend in vaccination in 2001–2019 throughout Europe. However, Croatia and Hungary still have the highest primary and revaccination coverage, compared to other analyzed countries. The highest number of measles cases was in 2017 in Romania. There was no significant correlation between the percentage of primary vaccination and the number of measles cases (r = −0.0528, p = 0.672), but there was a significant negative correlation between the percentage of revaccination and the number of measles cases (r = −0.445, p < 0.0001). In conclusion, the results of the present study emphasize the necessity to perform a full protocol of vaccination to reach appropriate protection from potential epidemic outbreaks. Furthermore, in the light of present migrations, documenting the migrants’ flow and facilitating vaccination as needed is of utmost importance to prevent future epidemics.
Patient Identification for Serious Illness Conversations: A Scoping Review
Authors: Baxter Rebecca , Fromme Erik K. , Sandgren Anna
Published: April 2022

Serious illness conversations aim to align medical care and treatment with patients’ values, goals, priorities, and preferences. Timely and accurate identification of patients for serious illness conversations is essential; however, existent methods for patient identification in different settings and population groups have not been compared and contrasted. This study aimed to examine the current literature regarding patient identification for serious illness conversations within the context of the Serious Illness Care Program and/or the Serious Illness Conversation Guide. A scoping review was conducted using the Joanna Briggs Institute guidelines. A comprehensive search was undertaken in four databases for literature published between January 2014 and September 2021. In total, 39 articles met the criteria for inclusion. This review found that patients were primarily identified for serious illness conversations using clinical/diagnostic triggers, the ’surprise question’, or a combination of methods. A diverse assortment of clinicians and non-clinical resources were described in the identification process, including physicians, nurses, allied health staff, administrative staff, and automated algorithms. Facilitators and barriers to patient identification are elucidated. Future research should test the efficacy of adapted identification methods and explore how clinicians inform judgements surrounding patient identification.
The New Quadrivalent Adjuvanted Influenza Vaccine for the Italian Elderly: A Health Technology Assessment
Authors: Calabrò Giovanna Elisa , Boccalini Sara , Panatto Donatella , Rizzo Caterina , Di Pietro Maria Luisa , Abreha Fasika Molla , Ajelli Marco , Amicizia Daniela , Bechini Angela , Giacchetta Irene , Lai Piero Luigi , Merler Stefano , Primieri Chiara , Trentini Filippo , Violi Sara , Bonanni Paolo , de Waure Chiara
Published: April 2022

Background. The elderly, commonly defined as subjects aged ≥65 years, are among the at-risk subjects recommended for annual influenza vaccination in European countries. Currently, two new vaccines are available for this population: the MF59-adjuvanted quadrivalent influenza vaccine (aQIV) and the high-dose quadrivalent influenza vaccine (hdQIV). Their multidimensional assessment might maximize the results in terms of achievable health benefits. Therefore, we carried out a Health Technology Assessment (HTA) of the aQIV by adopting a multidisciplinary policy-oriented approach to evaluate clinical, economic, organizational, and ethical implications for the Italian elderly. Methods. A HTA was conducted in 2020 to analyze influenza burden; characteristics, efficacy, and safety of aQIV and other available vaccines for the elderly; cost-effectiveness of aQIV; and related organizational and ethical implications. Comprehensive literature reviews/analyses were performed, and a transmission model was developed in order to address the above issues. Results. In Italy, the influenza burden on the elderly is high and from 77.7% to 96.1% of influenza-related deaths occur in the elderly. All available vaccines are effective and safe; however, aQIV, such as the adjuvanted trivalent influenza vaccine (aTIV), has proved more immunogenic and effective in the elderly. From the third payer’s perspective, but also from the societal one, the use of aQIV in comparison with egg-based standard QIV (eQIV) in the elderly population is cost-effective. The appropriateness of the use of available vaccines as well as citizens’ knowledge and attitudes remain a challenge for a successful vaccination campaign. Conclusions. The results of this project provide decision-makers with important evidence on the aQIV and support with scientific evidence on the appropriate use of vaccines in the elderly.
EU Net-Zero Policy Achievement Assessment in Selected Members through Automated Forecasting Algorithms
Authors: Tudor Cristiana , Sova Robert
Published: April 2022

The European Union (EU) has positioned itself as a frontrunner in the worldwide battle against climate change and has set increasingly ambitious pollution mitigation targets for its members. The burden is heavier for the more vulnerable economies in Central and Eastern Europe (CEE), who must juggle meeting strict greenhouse gas emission (GHG) reduction goals, significant fossil-fuel reliance, and pressure to respond to current pandemic concerns that require an increasing share of limited public resources, while facing severe repercussions for non-compliance. Thus, the main goals of this research are: (i) to generate reliable aggregate GHG projections for CEE countries; (ii) to assess whether these economies are on track to meet their binding pollution reduction targets; (iii) to pin-point countries where more in-depth analysis using spatial inventories of GHGs at a finer resolution is further needed to uncover specific areas that should be targeted by additional measures; and (iv) to perform geo-spatial analysis for the most at-risk country, Poland. Seven statistical and machine-learning models are fitted through automated forecasting algorithms to predict the aggregate GHGs in nine CEE countries for the 2019–2050 horizon. Estimations show that CEE countries (except Romania and Bulgaria) will not meet the set pollution reduction targets for 2030 and will unanimously miss the 2050 carbon neutrality target without resorting to carbon credits or offsets. Austria and Slovenia are the least likely to meet the 2030 emissions reduction targets, whereas Poland (in absolute terms) and Slovenia (in relative terms) are the farthest from meeting the EU’s 2050 net-zero policy targets. The findings thus stress the need for additional measures that go beyond the status quo, particularly in Poland, Austria, and Slovenia. Geospatial analysis for Poland uncovers that Krakow is the city where pollution is the most concentrated with several air pollutants surpassing EU standards. Short-term projections of PM2.5 levels indicate that the air quality in Krakow will remain below EU and WHO standards, highlighting the urgency of policy interventions. Further geospatial data analysis can provide valuable insights into other geo-locations that require the most additional efforts, thereby, assisting in the achievement of EU climate goals with targeted measures and minimum socio-economic costs. The study concludes that statistical and geo-spatial data, and consequently research based on these data, complement and enhance each other. An integrated framework would consequently support sustainable development through bettering policy and decision-making processes.
Progesterone Can Directly Inhibit the Life Activities of Toxoplasma gondii In Vitro through the Progesterone Receptor Membrane Component (PGRMC)
Authors: Wu Yihan , Zhang Xiao , Fu Yong , Liu Jing , Xue Yangfei , Liu Qun
Published: April 2022

Toxoplasma gondii (T. gondii), as an opportunistic pathogen, has special pathogenic effects on pregnant animals and humans. Progesterone (P4) is a critical hormone that supports pregnancy, and its levels fluctuate naturally during early pregnancy. However, little is known about the association of host P4 levels with the infectivity and pathogenicity of T. gondii. Our study showed that P4 significantly inhibited the invasion and proliferation of tachyzoites, resulting in abnormal cytoskeletal daughter budding and subsequent autophagy in vitro. To investigate the underlying mechanism, we identified a Toxoplasma gondii progesterone membrane receptor protein (TgPGRMC) that was localized to the mitochondrion and closely related to the effect of P4 on tachyzoites. The knockout of the pgrmc gene conferred resistance to P4 inhibitory effects. Our results prove the direct relationship between P4 single factors and T. gondii in vitro and demonstrate that TgPGRMC is an important link between T. gondii and P4, providing a new direction for research on T. gondii infection during pregnancy.
Enhancing Post-Stroke Rehabilitation and Preventing Exo-Focal Dopaminergic Degeneration in Rats—A Role for Substance P
Authors: Frase Sibylle , Löffler Franziska , Hosp Jonas A.
Published: April 2022

Dopaminergic signaling is a prerequisite for motor learning. Delayed degeneration of dopaminergic neurons after stroke is linked to motor learning deficits impairing motor rehabilitation. This study investigates safety and efficacy of substance P (SP) treatment on post-stroke rehabilitation, as this neuropeptide combines neuroprotective and plasticity-promoting properties. Male Sprague Dawley rats received a photothrombotic stroke within the primary motor cortex (M1) after which a previously acquired skilled reaching task was rehabilitated. Rats were treated with intraperitoneal saline (control group, n = 7) or SP-injections (250 µg/kg) 30 min before (SP-pre; n = 7) or 16 h (SP-post; n = 6) after rehabilitation training. Dopaminergic neurodegeneration, microglial activation and substance P-immunoreactivity (IR) were analyzed immunohistochemically. Systemic SP significantly facilitated motor rehabilitation. This effect was more pronounced in SP-pre compared to SP-post animals. SP prevented dopaminergic cell loss after stroke, particularly in the SP-pre condition. Despite its proinflammatory propensity, SP administration did not increase stroke volumes, post-stroke deficits or activation of microglia in the midbrain. Finally, SP administration prevented ipsilesional hypertrophy of striatal SPergic innervation, particularly in the SP-post condition. Mechanistically, SP-pre likely involved plasticity-promoting effects in the early phase of rehabilitation, whereas preservation of dopaminergic signaling may have ameliorated rehabilitative success in both SP groups during later stages of training. Our results demonstrate the facilitating effect of SP treatment on motor rehabilitation after stroke, especially if administered prior to training. SP furthermore prevented delayed dopaminergic degeneration and preserved physiological endogenous SPergic innervation.
ABA Speeds Up the Progress of Color in Developing F. chiloensis Fruit through the Activation of PAL, CHS and ANS, Key Genes of the Phenylpropanoid/Flavonoid and Anthocyanin Pathways
Authors: Mattus-Araya Elena , Guajardo Joselin , Herrera Raúl , Moya-León María A.
Published: April 2022

Phenolic compounds with antioxidant properties have risen in interest due to their benefits for human health. Fragaria chiloensis is a native wild berry species from Chile that develops a white/pink receptacle and white flesh at the ripe stage. Changes in color parameters, anthocyanins, secondary metabolites (phenolics, flavonoids), and total antioxidant capacity were followed during the development and ripening of F. chiloensis fruit. The increment in color ‘a’ index takes place in parallel with anthocyanins rise and the reduction in phenolics, flavonoids, and antioxidant capacity. Good correlations were determined between color development, anthocyanins, and the expression of key phenylpropanoid/flavonoid and anthocyanin pathway genes. To investigate the role of ABA on color development, detached immature fruit (C2 stage) were treated with exogenous ABA and stored at 20 °C. Fruit color development was accelerated by ABA treatment compared to non-treated fruit, and consistent with that, the increment in the accumulation of anthocyanins and transcripts of phenylpropanoid/flavonoid, and anthocyanin pathways genes such as FcPAL, FcCHS, and FcANS were observed. This suggests that ABA promotes transcriptional changes that lead to the color formation on this non-climacteric fruit.
Identification of Novel GSK-3β Hits Using Competitive Biophysical Assays
Authors: Balboni Beatrice , Tripathi Shailesh Kumar , Veronesi Marina , Russo Debora , Penna Ilaria , Giabbai Barbara , Bandiera Tiziano , Storici Paola , Girotto Stefania , Cavalli Andrea
Published: April 2022

Glycogen synthase kinase 3 beta (GSK-3β) is an evolutionarily conserved serine-threonine kinase dysregulated in numerous pathologies, such as Alzheimer’s disease and cancer. Even though GSK-3β is a validated pharmacological target most of its inhibitors have two main limitations: the lack of selectivity due to the high homology that characterizes the ATP binding site of most kinases, and the toxicity that emerges from GSK-3β complete inhibition which translates into the impairment of the plethora of pathways GSK-3β is involved in. Starting from a 1D 19F NMR fragment screening, we set up several biophysical assays for the identification of GSK-3β inhibitors capable of binding protein hotspots other than the ATP binding pocket or to the ATP binding pocket, but with an affinity able of competing with a reference binder. A phosphorylation activity assay on a panel of several kinases provided selectivity data that were further rationalized and corroborated by structural information on GSK-3β in complex with the hit compounds. In this study, we identified promising fragments, inhibitors of GSK-3β, while proposing an alternative screening workflow that allows facing the flaws that characterize the most common GSK-3β inhibitors through the identification of selective inhibitors and/or inhibitors able to modulate GSK-3β activity without leading to its complete inhibition.
The Apoptotic Effect of Caffeic or Chlorogenic Acid on the C32 Cells That Have Simultaneously Been Exposed to a Static Magnetic Field
Authors: Kimsa-Dudek Magdalena , Synowiec-Wojtarowicz Agnieszka , Krawczyk Agata , Kosowska Agnieszka , Kimsa-Furdzik Małgorzata , Francuz Tomasz
Published: April 2022

The induction of apoptosis is one of the main goals of the designed anti-cancer therapies. In recent years, increased attention has been paid to the physical factors such as magnetic fields and to the natural bioactive compounds and the possibilities using them in medicine. Hence, the aim of this study was to evaluate the anti-tumor effect of caffeic or chlorogenic acid in combination with a moderate-strength static magnetic field on C32 melanoma cells by assessing the effect of both factors on the apoptotic process. The apoptosis of the C32 cells was evaluated using a flow cytometry analysis. The expression of the apoptosis-associated genes was determined using the RT-qPCR technique. The caspase activity and the concentration of the oxidative damage markers were also measured. It was found that phenolic acids and a static magnetic field trigger the apoptosis of the C32 cells and also affect the expression of the genes encoding the apoptosis regulatory proteins. In conclusion, our study indicated that both of the phenolic acids and a static magnetic field can be used supportively in the treatment of melanoma and that caffeic acid is more pro-apoptotic than chlorogenic acid.
Autism Spectrum Disorder: Focus on Glutamatergic Neurotransmission
Authors: Montanari Martina , Martella Giuseppina , Bonsi Paola , Meringolo Maria
Published: April 2022

Disturbances in the glutamatergic system have been increasingly documented in several neuropsychiatric disorders, including autism spectrum disorder (ASD). Glutamate-centered theories of ASD are based on evidence from patient samples and postmortem studies, as well as from studies documenting abnormalities in glutamatergic gene expression and metabolic pathways, including changes in the gut microbiota glutamate metabolism in patients with ASD. In addition, preclinical studies on animal models have demonstrated glutamatergic neurotransmission deficits and altered expression of glutamate synaptic proteins. At present, there are no approved glutamatergic drugs for ASD, but several ongoing clinical trials are currently focusing on evaluating in autistic patients glutamatergic pharmaceuticals already approved for other conditions. In this review, we provide an overview of the literature concerning the role of glutamatergic neurotransmission in the pathophysiology of ASD and as a potential target for novel treatments.
Molecular Characterization of Three Tandemly Located Flagellin Genes of Stenotrophomonas maltophilia
Authors: Wu Cheng-Mu , Huang Hsin-Hui , Li Li-Hua , Lin Yi-Tsung , Yang Tsuey-Ching
Published: April 2022

Stenotrophomonas maltophilia is a motile, opportunistic pathogen. The flagellum, which is involved in swimming, swarming, adhesion, and biofilm formation, is considered a virulence factor for motile pathogens. Three flagellin genes, fliC1, fliC2, and fliC3, were identified from the sequenced S. maltophilia genome. FliC1, fliC2, and fliC3 formed an operon, and their encoding proteins shared 67–82% identity. Members of the fliC1C2C3 operon were deleted individually or in combination to generate single mutants, double mutants, and a triple mutant. The contributions of the three flagellins to swimming, swarming, flagellum morphology, adhesion, and biofilm formation were assessed. The single mutants generally had a compromise in swimming and no significant defects in swarming, adhesion on biotic surfaces, and biofilm formation on abiotic surfaces. The double mutants displayed obvious defects in swimming and adhesion on abiotic and biotic surfaces. The flagellin-null mutant lost swimming ability and was compromised in adhesion and biofilm formation. All tested mutants demonstrated substantial but different flagellar morphologies, supporting that flagellin composition affects filament morphology. Bacterial swimming motility was significantly compromised under an oxidative stress condition, irrespective of flagellin composition. Collectively, the utilization of these three flagellins for filament assembly equips S. maltophilia with flagella adapted to provide better ability in swimming, adhesion, and biofilm formation for its pathogenesis.
Prediction of Metabolic Profiles from Transcriptomics Data in Human Cancer Cell Lines
Authors: Cavicchioli Maria Vittoria , Santorsola Mariangela , Balboni Nicola , Mercatelli Daniele , Giorgi Federico Manuel
Published: April 2022

The Metabolome and Transcriptome are mutually communicating within cancer cells, and this interplay is translated into the existence of quantifiable correlation structures between gene expression and metabolite abundance levels. Studying these correlations could provide a novel venue of understanding cancer and the discovery of novel biomarkers and pharmacological strategies, as well as laying the foundation for the prediction of metabolite quantities by leveraging information from the more widespread transcriptomics data. In the current paper, we investigate the correlation between gene expression and metabolite levels in the Cancer Cell Line Encyclopedia dataset, building a direct correlation network between the two molecular ensembles. We show that a metabolite/transcript correlation network can be used to predict metabolite levels in different samples and datasets, such as the NCI-60 cancer cell line dataset, both on a sample-by-sample basis and in differential contrasts. We also show that metabolite levels can be predicted in principle on any sample and dataset for which transcriptomics data are available, such as the Cancer Genome Atlas (TCGA).
Integration of Neighbor Topologies Based on Meta-Paths and Node Attributes for Predicting Drug-Related Diseases
Authors: Xuan Ping , Lu Zixuan , Zhang Tiangang , Liu Yong , Nakaguchi Toshiya
Published: April 2022

Identifying new disease indications for existing drugs can help facilitate drug development and reduce development cost. The previous drug–disease association prediction methods focused on data about drugs and diseases from multiple sources. However, they did not deeply integrate the neighbor topological information of drug and disease nodes from various meta-path perspectives. We propose a prediction method called NAPred to encode and integrate meta-path-level neighbor topologies, multiple kinds of drug attributes, and drug-related and disease-related similarities and associations. The multiple kinds of similarities between drugs reflect the degrees of similarity between two drugs from different perspectives. Therefore, we constructed three drug–disease heterogeneous networks according to these drug similarities, respectively. A learning framework based on fully connected neural networks and a convolutional neural network with an attention mechanism is proposed to learn information of the neighbor nodes of a pair of drug and disease nodes. The multiple neighbor sets composed of different kinds of nodes were formed respectively based on meta-paths with different semantics and different scales. We established the attention mechanisms at the neighbor-scale level and at the neighbor topology level to learn enhanced neighbor feature representations and enhanced neighbor topological representations. A convolutional-autoencoder-based module is proposed to encode the attributes of the drug–disease pair in three heterogeneous networks. Extensive experimental results indicated that NAPred outperformed several state-of-the-art methods for drug–disease association prediction, and the improved recall rates demonstrated that NAPred was able to retrieve more actual drug–disease associations from the top-ranked candidates. Case studies on five drugs further demonstrated the ability of NAPred to identify potential drug-related disease candidates.
Rotamers in Crystal Structures of Xylitol, D-Arabitol and L-Arabitol
Authors: Wanat Monika , Malinska Maura , Kucia Malgorzata , Sicinski Rafal R. , Woźniak Krzysztof
Published: April 2022

Rotamers are stereoisomers produced by rotation (twisting) about σ bonds and are often rapidly interconverting at room temperature. Xylitol—massively produced sweetener—(2R,3r,4S)-pentane-1,2,3,4,5-pentol) forms rotamers from the linear conformer by rotation of a xylitol fragment around the C2–C3 bond (rotamer 1) or the C3–C4 bond (rotamer 2). The rotamers form two distinguishable structures. Small differences in geometry of rotamers of the main carbon chain were confirmed by theoretical calculations; however, they were beyond the capabilities of the X-ray powder diffraction technique due to the almost identical unit cell parameters. In the case of rotamers of similar compounds, the rotations occurred mostly within hydroxyl groups likewise rotations in L-arabitol and D-arabitol, which are discussed in this work. Our results, supported by theoretical calculations, showed that energetic differences are slightly higher for rotamers with rotations within hydroxyl groups instead of a carbon chain.
Physiological Electric Field: A Potential Construction Regulator of Human Brain Organoids
Authors: Yu Xiyao , Meng Xiaoting , Pei Zhe , Wang Guoqiang , Liu Rongrong , Qi Mingran , Zhou Jiaying , Wang Fang
Published: April 2022

Brain organoids can reproduce the regional three-dimensional (3D) tissue structure of human brains, following the in vivo developmental trajectory at the cellular level; therefore, they are considered to present one of the best brain simulation model systems. By briefly summarizing the latest research concerning brain organoid construction methods, the basic principles, and challenges, this review intends to identify the potential role of the physiological electric field (EF) in the construction of brain organoids because of its important regulatory function in neurogenesis. EFs could initiate neural tissue formation, inducing the neuronal differentiation of NSCs, both of which capabilities make it an important element of the in vitro construction of brain organoids. More importantly, by adjusting the stimulation protocol and special/temporal distributions of EFs, neural organoids might be created following a predesigned 3D framework, particularly a specific neural network, because this promotes the orderly growth of neural processes, coordinate neuronal migration and maturation, and stimulate synapse and myelin sheath formation. Thus, the application of EF for constructing brain organoids in a3D matrix could be a promising future direction in neural tissue engineering.
Interdependence of Angiogenesis and Arteriogenesis in Development and Disease
Authors: le Noble Ferdinand , Kupatt Christian
Published: April 2022

The structure of arterial networks is optimized to allow efficient flow delivery to metabolically active tissues. Optimization of flow delivery is a continuous process involving synchronization of the structure and function of the microcirculation with the upstream arterial network. Risk factors for ischemic cardiovascular diseases, such as diabetes mellitus and hyperlipidemia, adversely affect endothelial function, induce capillary regression, and disrupt the micro- to macrocirculation cross-talk. We provide evidence showing that this loss of synchronization reduces arterial collateral network recruitment upon arterial stenosis, and the long-term clinical outcome of current revascularization strategies in these patient cohorts. We describe mechanisms and signals contributing to synchronized growth of micro- and macrocirculation in development and upon ischemic challenges in the adult organism and identify potential therapeutic targets. We conclude that a long-term successful revascularization strategy should aim at both removing obstructions in the proximal part of the arterial tree and restoring “bottom-up” vascular communication.
Dexamethasone Attenuates the Expression of MMP-13 in Chondrocytes through MKP-1
Authors: Lehtola Tiina , Nummenmaa Elina , Tuure Lauri , Hämäläinen Mari , Nieminen Riina M. , Moilanen Teemu , Pemmari Antti , Moilanen Eeva
Published: April 2022

Mitogen-activated protein kinase phosphatase-1 (MKP-1) is upregulated in inflammation and reduces the activity of proinflammatory mitogen-activated protein kinases (MAP kinases) by dephosphorylation. MAP kinases are intracellular signaling pathways that mediate the cellular effects of proinflammatory cytokines. In the present study, we investigated the effects of the glucocorticoid dexamethasone on the expression of catabolic enzymes in chondrocytes and tested the hypothesis that these effects are mediated through MKP-1. Dexamethasone was found to significantly attenuate the expression of matrix metalloproteinase (MMP)-13 in human OA chondrocytes as well as in chondrocytes from MKP-1 WT mice, but not in chondrocytes from MKP-1 KO mice. Dexamethasone also increased the expression of MKP-1 in murine and human OA chondrocytes. Furthermore, p38 MAP kinase inhibitors significantly attenuated MMP-13 expression in human OA chondrocytes, while JNK MAP kinase inhibitors had no effect. The results indicate that the effect of dexamethasone on MMP-13 expression in chondrocytes was mediated by an MKP-1 and p38 MAP kinase-dependent manner. These findings, together with previous results, support the concept of MKP-1 as a protective factor in articular chondrocytes in inflammatory conditions and as a potential drug target to treat OA.
Leaf Photosynthesis and Its Temperature Response Are Different between Growth Stages and N Supplies in Rice Plants
Authors: Ye Miao , Zhang Zhengcan , Huang Guanjun , Li Yong
Published: April 2022

Leaf photosynthesis is highly correlated with CO2-diffusion capacities, which are determined by both leaf anatomical traits and environmental stimuli. In the present study, leaf photosynthetic rate (A), stomatal conductance (gs), mesophyll conductance (gm) and the related leaf anatomical traits were studied on rice plants at two growth stages and with two different N supplies, and the response of photosynthesis to temperature (T) was also studied. We found that gm was significantly higher at mid-tillering stage and at high N treatment. The larger gm was related to a larger chloroplast surface area facing intercellular air spaces and a thinner cell wall in comparison with booting stage and zero N treatment. At mid-tillering stage and at high N treatment, gm showed a stronger temperature response. The modelling of the gm-T relationships suggested that, in comparison with booting stage and zero N treatment, the stronger temperature response of gm was related to the higher activation energy of the membrane at mid-tillering stage and at high N treatment. The findings in the present study can enhance our knowledge on the physiological and environmental determinants of photosynthesis.