bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial Effects and Nonlinear Analysis of Energy Consumption, Financial Development, and Economic Growth in China
Authors: Zhou Huan , Qu Shaojian , Yuan Qinglu , Wang Shilei
Published: September 2020

Energy consumption is of great significance to the sustainable development of the economy. Due to the spatial heterogeneity of low-carbon growth in regional economies, the relationship between energy consumption and economic growth is complicated. However, a few researches have been published about spatial spillover effects and non-linearity of energy consumption and financial development on regional economic growth in China. Based on the panel data of 30 provinces in China from 2007 to 2017, this paper analyzes the spatial spillover effects and threshold effects of energy consumption and financial development on regional economic growth by using spatial and nonlinear econometric methods. The main conclusions are as follows. Spatial econometric methods show that financial development and energy consumption are two factors of production input to promote China’s economic growth. Meanwhile, energy consumption and financial development have spillover effects on regional economic growth. Additionally, the nonlinear econometric method finds that with increasing financial development, the impact of energy consumption on economic growth is segmented. Therefore, relevant policies should be implemented to enhance the role of finance in energy consumption to promote low-carbon growth of China’s economy.
Aerodynamic Investigation of a Horizontal Axis Wind Turbine with Split Winglet Using Computational Fluid Dynamics
Authors: Sy Miguel Sumait , Abuan Binoe Eugenio , Danao Louis Angelo Macapili
Published: September 2020

Wind energy is one of the fastest growing renewable energy sources, and the most developed energy extraction device that harnesses this energy is the Horizontal Axis Wind Turbine (HAWT). Increasing the efficiency of HAWTs is one important topic in current research with multiple aspects to look at such as blade design and rotor array optimization. This study looked at the effect of wingtip devices, a split winglet, in particular, to reduce the drag induced by the wind vortices at the blade tip, hence increasing performance. Split winglet implementation was done using computational fluid dynamics (CFD) on the National Renewable Energy Lab (NREL) Phase VI sequence H. In total, there are four (4) blade configurations that are simulated, the base NREL Phase VI sequence H blade, an extended version of the previous blade to equalize length of the blades, the base blade with a winglet and the base blade with split winglet. Results at wind speeds of 7 m/s to 15 m/s show that adding a winglet increased the power generation, on an average, by 1.23%, whereas adding a split winglet increased it by 2.53% in comparison to the extended blade. The study also shows that the increase is achieved by reducing the drag at the blade tip and because of the fact that the winglet and split winglet generating lift themselves. This, however, comes at a cost, i.e., an increase in thrust of 0.83% and 2.05% for the blades with winglet and split winglet, respectively, in comparison to the extended blade.
Thermal Viscous Fingering in Thermal Recovery Processes
Authors: Austin-Adigio Maureen , Gates Ian D.
Published: September 2020

Heat and fluid flow at the edge of steam chambers found in thermal recovery processes such as steam-assisted gravity drainage and cyclic steam stimulation remain unresolved. Given the multiple phases present and contrast of thermophysical properties, it remains unclear where instabilities occur within this thin, yet critical, zone of the process. In the research reported here, heat and fluid flow are examined in vertical and horizontal sections of a steam chamber to understand the differences between the two orientations by using detailed and fine-gridded thermal reservoir simulation models. The results show that heat transfer in vertical and horizontal directions are different with greater heat transfer found in the vertical orientation. In the vertical direction, heat transfer occurs with mobilized bitumen draining with subsequent steam moving into the emptied pore space. Conduction beyond the edge of the chamber dominates and heated, low viscosity bitumen fingers into cold, higher viscosity bitumen at the edge of the chamber. Relative permeability effects are observed which can interfere with enhanced oil mobility.
Unsteady Flow Field Characterization of Effusion Cooling Systems with Swirling Main Flow: Comparison Between Cylindrical and Shaped Holes
Authors: Lenzi Tommaso , Picchi Alessio , Bacci Tommaso , Andreini Antonio , Facchini Bruno
Published: September 2020

The presence of injectors with strongly swirled flows, used to promote flame stability in the combustion chambers of gas turbines, influences the behaviour of the effusion cooling jets and consequently of the liner’s cooling capabilities. For this reason, unsteady behaviour of the jets in the presence of swirling flow requires a characterization by means of experimental flow field analyses. The experimental setup of this work consists of a non-reactive single-sector linear combustor test rig, scaled up with respect to the real engine geometry to increase spatial resolution and to reduce the frequencies of the unsteadiness. It is equipped with a radial swirler and multi-perforated effusion plates to simulate the liner cooling system. Two effusion plates were tested and compared: with cylindrical and with laid-back fan-shaped 7-7-7 holes in staggered arrangement. Time resolved Particle Image Velocimetry has been carried out: the unsteady characteristics of the jets, promoted by the intermittent interactions with the turbulent mainstream, have been investigated as their vortex structures and turbulent decay. The results demonstrate how an unsteady analysis is necessary to provide a complete characterization of the coolant behaviour and of its turbulent mixing with mainflow, which affect, in turn, the film cooling capability and liner’s lifetime.
The UK and German Low-Carbon Industry Transitions from a Sectoral Innovation and System Failures Perspective
Authors: Koasidis Konstantinos , Nikas Alexandros , Neofytou Hera , Karamaneas Anastasios , Gambhir Ajay , Wachsmuth Jakob , Doukas Haris
Published: September 2020

Industrial processes are associated with high amounts of energy consumed and greenhouse gases emitted, stressing the urgent need for low-carbon sectoral transitions. This research reviews the energy-intensive iron and steel, cement and chemicals industries of Germany and the United Kingdom, two major emitting countries with significant activity, yet with different recent orientation. Our socio-technical analysis, based on the Sectoral Innovation Systems and the Systems Failure framework, aims to capture existing and potential drivers of or barriers to diffusion of sustainable industrial technologies and extract implications for policy. Results indicate that actor structures and inconsistent policies have limited low-carbon innovation. A critical factor for the successful decarbonisation of German industry lies in overcoming lobbying and resistance to technological innovation caused by strong networks. By contrast, a key to UK industrial decarbonisation is to drive innovation and investment in the context of an industry in decline and in light of Brexit-related uncertainty.
Numerical Investigations on the Propagation of Fire in a Railway Carriage
Authors: Craig Matthew , Asim Taimoor
Published: September 2020

In this study, advanced Computational Fluid Dynamics (CFD)-based numerical simulations have been performed in order to analyse fire propagation in a standard railway compartment. A Fire Dynamics Simulator (FDS) has been employed to mimic real world scenarios associated with fire propagation within railway carriages in order to develop safety guidelines for railway passengers. Comprehensive parametric investigations on the effects of ignition location, intensity and cabin upholstery have been carried out. It has been observed that a fire occurring near the exits of the carriage results in a lower smoke layer height, due to the local carriage geometry, than an identical fire igniting at the center of the carriage. This in turn causes the smoke density along the aisleway to vary by around 30%. Reducing the ignition energy by half has been found to restrict combustion, thus reducing smoke density and carbon exhaust gases, reducing the average temperature from 170 °C to 110 °C. Changing the material lining of the seating has been found to cause the most significant change in output parameters, despite its relative insignificance in bulk mass. A polyester sample produces a peak carbon monoxide concentration of 7500 ppm, which is 27× greater compared with nylon. This difference has been found to be due to the fire spread and propagation between fuels, signifying the polyester’s unsuitability for use in railway carriages.
Spatial Straight-Line Drawing Algorithm Based on Method of Discriminate Regions—A Control Algorithm of Motors
Authors: Wang Jianping , Xiao Shiguang , Song Tao , Yue Junqi , Bian Pingyan , Li Yu
Published: September 2020

A novelty algorithm of spatial straight-line drawing based on a method of discriminate regions is proposed in this paper based on Bresenham’s algorithm. Three-dimensional space is divided into innumerable three-dimensional meshes according to the given rule; the distance between the start and the end points of the three coordinates is Δx, Δy, and Δz, respectively; the distribution types of spatial straight line and the position of the end point are determined by judging the relationship among Δx, Δy, and Δz; then, the active-passive directions can be determined. The plane of the ending point of the straight line in a three-dimensional mesh is divided into four regions; then, the discriminant is obtained; and this discriminant determine which region the point is located in The algorithm is verified and analyzed by the method of contrastive analysis; the results show that: the error of the algorithm is related to the step length L; the maximum theoretical error is 0.7071*L. The discriminants are all integers, so the problem of deviation from the theoretical straight line caused by the retention of decimals of significant digits can be avoided. Finally, the algorithm is applied to the cooperative control of multiple motors, and conversion between unit grid number and pulse number of motors is performed.
Electric Vehicle Aggregate Power Flow Prediction and Smart Charging System for Distributed Renewable Energy Self-Consumption Optimization
Authors: Lo Franco Francesco , Ricco Mattia , Mandrioli Riccardo , Grandi Gabriele
Published: September 2020

In the context of electric vehicle (EV) development and positive energy districts with the growing penetration of non-programmable sources, this paper provides a method to predict and manage the aggregate power flows of charging stations to optimize the self-consumption and load profiles. The prediction method analyzes each charging event belonging to the EV population, and it considers the main factors that influence a charging process, namely the EV’s characteristics, charging ratings, and driver behavior. EV’s characteristics and charging ratings are obtained from the EV model’s and charging stations’ specifications, respectively. The statistical analysis of driver behavior is performed to calculate the daily consumptions and the charging energy request. Then, a model to estimate the parking time of each vehicle is extrapolated from the real collected data of the arrival and departure times in parking lots. A case study was carried out to evaluate the proposed method. This consisted of an industrial area with renewable sources and electrical loads. The obtained results show how EV charging can negatively impact system power flows, causing load peaks and high energy demand. Therefore, a charging management system (CMS) able to operate in the smart charging mode was introduced. Finally, it was demonstrated that the proposed method provides better EV integration and improved performance.
Comparative Analysis of Hybrid Desalination Technologies Powered by SMR
Authors: Ghazaie Seyed Hadi , Sadeghi Khashayar , Sokolova Ekaterina , Fedorovich Evgeniy , Shirani Amirsaeed
Published: September 2020

Small modular reactors (SMRs) represent a key area of interest to nuclear industry developers, which have been making significant progress during the past few years. Generally, these reactors are promising owing to their improved safety due to passive systems, enhanced containment efficiency, and fewer capital costs in comparison to traditional nuclear reactors. An important advantage of SMRs is their adaptability in being coupled to other energy-consuming systems, such as desalination plants (DPs) to create a cogeneration plant. Considering the serious challenges regarding the freshwater shortage in many regions of the world and the necessity of using low-carbon energy sources, it is advantageous to use SMR for supplying the required heat and electricity of DPs. As a high-performance desalination technology, the hybrid desalination (HD) systems can be exploited, which retain the advantages of both thermal and membrane desalination methods. In this study, several SMR coupling schemes to HD plants have been suggested. In performing a thermodynamic analysis of integrated SMR-DP, the International Atomic Energy Agency (IAEA) Desalination Thermodynamic Optimization Program (DE-TOP) has been utilized. It has been found that the use of relatively hot water from the SMR condenser leads to about 6.5 to 7.5% of total desalination cost reduction, where the produced electricity and hot steam extracted from low-pressure turbine were used to drive the HD system.
Comparison of Profitability of PV Electricity Sharing in Renewable Energy Communities in Selected European Countries
Authors: Radl Johannes , Fleischhacker Andreas , Revheim Frida Huglen , Lettner Georg , Auer Hans
Published: September 2020

The economic value of photovoltaic (PV) systems depends on country-specific conditions. This study investigates the impact of grid fees, solar irradiance and local consumption on the profitability and penetration of PV systems and batteries in renewable energy communities. The linear optimization model calculates the optimal investments into PV and storages applied on a test community, which represents the European housing situation. The comparison of eight countries considers individual heat and cooling demands as well as sector coupling. Results show that renewable energy communities have the potential to reduce electricity costs due to community investments and load aggregation but do not necessarily lead to more distributed PV. Besides full-load hours, the energy component of electricity tariffs has the highest impact on PV distribution. Under current market conditions, battery energy storage systems are rarely profitable for increasing PV self-consumption but there is potential with power pricing. Renewable energy communities enable individuals to be a prosumer without the necessity of owning a PV system. This could lead to more (community) PV investments in the short term. Hence, it hinders investments in a saturated PV market.
An Introduction to Probabilistic Record Linkage with a Focus on Linkage Processing for WTC Registries
Authors: Asher Jana , Resnick Dean , Brite Jennifer , Brackbill Robert , Cone James
Published: September 2020

Since its post-World War II inception, the science of record linkage has grown exponentially and is used across industrial, governmental, and academic agencies. The academic fields that rely on record linkage are diverse, ranging from history to public health to demography. In this paper, we introduce the different types of data linkage and give a historical context to their development. We then introduce the three types of underlying models for probabilistic record linkage: Fellegi-Sunter-based methods, machine learning methods, and Bayesian methods. Practical considerations, such as data standardization and privacy concerns, are then discussed. Finally, recommendations are given for organizations developing or maintaining record linkage programs, with an emphasis on organizations measuring long-term complications of disasters, such as 9/11.
Quality of Life of Cancer Patients Treated with Chemotherapy
Authors: Lewandowska Anna , Rudzki Grzegorz , Lewandowski Tomasz , Próchnicki Michał , Rudzki Sławomir , Laskowska Barbara , Brudniak Joanna
Published: September 2020

Background: Life-quality tests are the basis for assessing the condition of oncological patients. They allow for obtaining valuable information from the patients regarding not only the symptoms of disease and adverse effects of the treatment but also assessment of the psychological, social and spiritual aspects. Taking into account assessment of the quality of life made by the patient in the course of disease has a positive effect on the well-being of patients, their families and their caregivers as well as on satisfaction with the interdisciplinary and holistic oncological care. Methods: A population-based, multi-area cross-sectional study was conducted among patients with cancer in the study in order to assess their life quality. The method used in the study was a clinical interview. Quality of life was measured using the EQ-5D-5L Quality of Life Questionnaire, the Karnofsky Performance Status, our own symptom checklist, Edmonton Symptom Assessment and Visual Analogue Scale. Results: In the subjective assessment of fitness, after using the Karnofsky fitness index, it was shown that 28% (95% CI (confidence interval): 27–30) of patients declared the ability to perform normal physical activity. In the assessment the profile, quality of life and psychometric properties of EQ-5D-5L, it was shown that patients had the most severe problems in terms of self-care (81%, 95% CI: 76–89) and feeling anxious and depressed (63%, 95% CI: 60–68). Conclusions: Cancer undoubtedly has a negative impact on the quality of life of patients, which is related to the disease process itself, the treatment used and the duration of the disease.
User Experiences with a Virtual Alcohol Prevention Simulation for Danish Adolescents
Authors: Guldager Julie Dalgaard , Kjær Satayesh Lavasani , Lyk Patricia , Dietrich Timo , Rundle-Thiele Sharyn , Majgaard Gunver , Stock Christiane
Published: September 2020

This pilot study explores 31 Danish adolescent user experiences for the newly developed virtual party simulation app—Virtual Reality (VR) FestLab. The main objective of this study was to investigate usability for VR FestLab, which aims to improve alcohol resistance skills for Danish adolescents. A secondary objective was to understand gameplay experiences. The study is a mixed method study that draws on questionnaire data (n = 31) and focus group interviews (n = 10) of boarding school students participating in the pilot study. Descriptive statistics were used to examine quantitative data, and qualitative data were analyzed thematically. Quantitative findings indicated that gameplay experiences of the VR simulation were positive, and all User Experience Questionnaire (UEQ) items were answered positively. The focus group interviews showed that adolescents found the simulation to be realistic. Feedback indicated that the group pressure experienced in the simulation was regarded to be less than in real life. Adolescents had varying approaches to playing the VR simulation, they thought the quality of the simulation was good, and only a few users experienced technical difficulties. These initial study findings indicate that VR FestLab is a promising tool for the prevention of alcohol use among adolescents.
What Motivates Volunteers to Engage in Health-Related Citizen Science Initiatives? A Case Study of Our Outdoors
Authors: Lehman Elizabeth , Jepson Ruth , McAteer John , Archibald Daryll
Published: September 2020

Citizen science is increasing in popularity but remains largely located in the disciplines of environmental and natural sciences. However, it has the potential to be a useful tool in other disciplines such as health. The aim of this study was to identify the factors for involvement (or non-involvement) in health-related citizen science projects using the Our Outdoors citizen science initiative as an example. Our Outdoors aims to understand how urban and rural shared outdoors spaces (e.g., parks, lakes, rivers, beaches) can affect human health and well-being (both positively and negatively). Understanding the motivations for involvement in such a program is likely to be useful for increasing participation rates and involvement. Qualitative research methods were used in this study in which semi-structured interviews were conducted with 12 participants from two community projects in Scotland, United Kingdom. A thematic analysis revealed five key themes pertaining to the factors that motivated engagement with health-related citizen science projects such as Our Outdoors. These include enhancing social connectedness; personal learning development; making a difference in the community; gaining health and well-being benefits; and finally, demotivating factors relating to time constraints and the term “citizen science”. This study concludes that emphasising motivating factors in the promotional material for health-related citizen science projects may increase recruitment and the active involvement of participants. Similarly, reducing the presence of demotivating factors and considering the use of the term “citizen science” is likely to encourage participation
Kriging-Based Land-Use Regression Models That Use Machine Learning Algorithms to Estimate the Monthly BTEX Concentration
Authors: Hsu Chin-Yu , Zeng Yu-Ting , Chen Yu-Cheng , Chen Mu-Jean , Lung Shih-Chun Candice , Wu Chih-Da
Published: September 2020

This paper uses machine learning to refine a Land-use Regression (LUR) model and to estimate the spatial–temporal variation in BTEX concentrations in Kaohsiung, Taiwan. Using the Taiwanese Environmental Protection Agency (EPA) data of BTEX (benzene, toluene, ethylbenzene, and xylenes) concentrations from 2015 to 2018, which includes local emission sources as a result of Asian cultural characteristics, a new LUR model is developed. The 2019 data was then used as external data to verify the reliability of the model. We used hybrid Kriging-land-use regression (Hybrid Kriging-LUR) models, geographically weighted regression (GWR), and two machine learning algorithms—random forest (RF) and extreme gradient boosting (XGBoost)—for model development. Initially, the proposed Hybrid Kriging-LUR models explained each variation in BTEX from 37% to 52%. Using machine learning algorithms (XGBoost) increased the explanatory power of the models for each BTEX, between 61% and 79%. This study compared each combination of the Hybrid Kriging-LUR model and (i) GWR, (ii) RF, and (iii) XGBoost algorithm to estimate the spatiotemporal variation in BTEX concentration. It is shown that a combination of Hybrid Kriging-LUR and the XGBoost algorithm gives better performance than other integrated methods.
Fatherhood and Smoking Problems in Indonesia: Exploration of Potential Protective Factors for Men Aged 18–49 Years from the United Nations Multi-Country Study on Men and Violence
Authors: Kodriati Nurul , Hayati Elli Nur , Santosa Ailiana , Pursell Lisa
Published: September 2020

Background: Despite the sustained high prevalence of smoking among Indonesian adult men, little is known about possible protective factors in this group. This study examined the relationship between key characteristics of masculinity (e.g., fatherhood status, being the main breadwinner or sole provider for the family) and current smoking behaviours (smoking status and cigarettes smoked per day (CPD)) among Indonesian men aged 18–49 years. Methods: In total, 2540 Indonesian men aged 18–49 participated in the United Nations Multi-Country Study on Men and Violence, 2012. Fatherhood status was categorised into three groups: nonfathers, new fathers and more experienced fathers. The association between fatherhood status and current smoking, as well as fatherhood status and cigarettes smoked per day (CPD), was estimated by employing logistic and zero-inflated negative binomial regressions, respectively. Results: Socioeconomic factors were associated with smoking behaviour among Indonesian adult men. The odds of smoking among new fathers and more experienced fathers were 2.3 (95% CI: 1.09–4.79) and 1.5 times (95% CI: 1.08–2.17) higher compared with nonfathers, respectively. Men who had a shared income with their partner or received income from their parents smoked 13% (95% CI 0.79–0.95) and 11% fewer CPD (95% CI 0.79–0.99) compared with men who were the main breadwinner, respectively. Conclusions: In this study, fatherhood represents an aspect of traditionally masculine roles, offering a new perspective for looking at smoking problems in Indonesia. Other key aspects of traditional masculinity characteristics, the breadwinner role, occupation and sources of family income had significant associations with smoking status and CPD. Men smoked fewer CPD as fathers and when sharing the financial responsibility for their family equally with their spouse.
Promoting Sustainable Wellbeing: Integrating Positive Psychology and Environmental Sustainability in Education
Authors: Ronen Tammie , Kerret Dorit
Published: September 2020

This article proposes an integrative policy approach to defining and promoting wellbeing through the joint lenses of positive psychology and environmental sustainability. The study suggests that while both positive education and environmental education address various aspects of wellbeing, a common definition is still absent. The study proposes a framework for advancing a mutual concept of wellbeing: “sustainable wellbeing”, integrating aspects of individual wellbeing and the wellbeing of the environment. Sustainable wellbeing is achieved when improving individual wellbeing is correlated with improving the wellbeing of other members of society and the natural environment. It suggests a framework for integrating the benefits of positive education and environmental education into a coherent approach for exploring, discussing, and experiencing sustainable wellbeing. The paper mainly develops, explores, and demonstrates ten rules for implementing sustainable wellbeing literacy in schools, based on cognitive behavioral therapy and positive psychology insights. It contributes to the development and understanding of wellbeing, highlights the benefits of parallel developments of two distinct educational fields, and offers practical guidelines for implementing educational programs. Furthermore, the paper contributes to developing 21st century educational systems and further develops the emerging field of positive sustainability.
A Novel Cis-Acting RNA Structural Element Embedded in the Core Coding Region of the Hepatitis C Virus Genome Directs Internal Translation Initiation of the Overlapping Core+1 ORF
Authors: Vassilaki Niki , Frakolaki Efseveia , Kalliampakou Katerina I. , Sakellariou Panagiotis , Kotta-Loizou Ioly , Bartenschlager Ralf , Mavromara Penelope
Published: September 2020

Hepatitis C virus (HCV) genome translation is initiated via an internal ribosome entry site (IRES) embedded in the 5′-untranslated region (5′UTR). We have earlier shown that the conserved RNA stem-loops (SL) SL47 and SL87 of the HCV core-encoding region are important for viral genome translation in cell culture and in vivo. Moreover, we have reported that an open reading frame overlapping the core gene in the +1 frame (core+1 ORF) encodes alternative translation products, including a protein initiated at the internal AUG codons 85/87 of this frame (nt 597–599 and 603–605), downstream of SL87, which is designated core+1/Short (core+1/S). Here, we provide evidence for SL47 and SL87 possessing a novel cis-acting element that directs the internal translation initiation of core+1/S. Firstly, using a bicistronic dual luciferase reporter system and RNA-transfection experiments, we found that nucleotides 344–596 of the HCV genotype-1a and -2a genomes support translation initiation at the core+1 frame AUG codons 85/87, when present in the sense but not the opposite orientation. Secondly, site-directed mutagenesis combined with an analysis of ribosome–HCV RNA association elucidated that SL47 and SL87 are essential for this alternative translation mechanism. Finally, experiments using cells transfected with JFH1 replicons or infected with virus-like particles showed that core+1/S expression is independent from the 5′UTR IRES and does not utilize the polyprotein initiation codon, but it requires intact SL47 and SL87 structures. Thus, SL47 and SL87, apart from their role in viral polyprotein translation, are necessary elements for mediating the internal translation initiation of the alternative core+1/S ORF.
Role of miRNA-mRNA Interaction in Neural Stem Cell Differentiation of Induced Pluripotent Stem Cells
Authors: Kumar Satish , Curran Joanne E. , DeLeon Erica , Leandro Ana C. , Howard Tom E. , Lehman Donna M. , Williams-Blangero Sarah , Glahn David C. , Blangero John
Published: September 2020

miRNA regulates the expression of protein coding genes and plays a regulatory role in human development and disease. The human iPSCs and their differentiated progenies provide a unique opportunity to identify these miRNA-mediated regulatory mechanisms. To identify miRNA–mRNA regulatory interactions in human nervous system development, well characterized NSCs were differentiated from six validated iPSC lines and analyzed for differentially expressed (DE) miRNome and transcriptome by RNA sequencing. Following the criteria, moderated t statistics, FDR-corrected p-value ≤ 0.05 and fold change—absolute (FC-abs) ≥2.0, 51 miRNAs and 4033 mRNAs were found to be significantly DE between iPSCs and NSCs. The miRNA target prediction analysis identified 513 interactions between 30 miRNA families (mapped to 51 DE miRNAs) and 456 DE mRNAs that were paradoxically oppositely expressed. These 513 interactions were highly enriched in nervous system development functions (154 mRNAs; FDR-adjusted p-value range: 8.06 × 10−15–1.44 × 10−4). Furthermore, we have shown that the upregulated miR-10a-5p, miR-30c-5p, miR23-3p, miR130a-3p and miR-17-5p miRNA families were predicted to down-regulate several genes associated with the differentiation of neurons, neurite outgrowth and synapse formation, suggesting their role in promoting the self-renewal of undifferentiated NSCs. This study also provides a comprehensive characterization of iPSC-generated NSCs as dorsal neuroepithelium, important for their potential use in in vitro modeling of human brain development and disease.
What Role Does COA6 Play in Cytochrome C Oxidase Biogenesis: A Metallochaperone or Thiol Oxidoreductase, or Both?
Authors: Maghool Shadi , Ryan Michael T. , Maher Megan J.
Published: September 2020

Complex IV (cytochrome c oxidase; COX) is the terminal complex of the mitochondrial electron transport chain. Copper is essential for COX assembly, activity, and stability, and is incorporated into the dinuclear CuA and mononuclear CuB sites. Multiple assembly factors play roles in the biogenesis of these sites within COX and the failure of this intricate process, such as through mutations to these factors, disrupts COX assembly and activity. Various studies over the last ten years have revealed that the assembly factor COA6, a small intermembrane space-located protein with a twin CX9C motif, plays a role in the biogenesis of the CuA site. However, how COA6 and its copper binding properties contribute to the assembly of this site has been a controversial area of research. In this review, we summarize our current understanding of the molecular mechanisms by which COA6 participates in COX biogenesis.
Two Alternative Splicing Variants of AtERF73/HRE1, HRE1α and HRE1β, Have Differential Transactivation Activities in Arabidopsis
Authors: Seok Hye-Yeon , Ha Jimin , Lee Sun-Young , Bae Hyoungjoon , Moon Yong-Hwan
Published: September 2020

AtERF73/HRE1 is an AP2/ERF transcription factor in Arabidopsis and has two distinct alternative splicing variants, HRE1α and HRE1β. In this study, we examined the differences between the molecular functions of HRE1α and HRE1β. We found that HRE1α and HRE1β are both involved in hypoxia response and root development and have transactivation activity. Two conserved motifs in the C-terminal region of HRE1α and HRE1β, EELL and LWSY-like, contributed to their transactivation activity, specifically the four E residues in the EELL motif and the MGLWS amino acid sequence at the end of the LWSY-like motif. The N-terminal region of HRE1β also showed transactivation activity, mediated by the VDDG motif, whereas that of HRE1α did not. The transactivation activity of HRE1β was stronger than that of HRE1α in Arabidopsis protoplasts. Both transcription factors transactivated downstream genes via the GCC box. RNA-sequencing analysis further supported that both HRE1α and HRE1β might regulate gene expression associated with the hypoxia stress response, although they may transactivate different subsets of genes in downstream pathways. Our results, together with previous studies, suggested that HRE1α and HRE1β differentially transactivate downstream genes in hypoxia response and root development in Arabidopsis.
Bone Microenvironment and Osteosarcoma Metastasis
Authors: Yang Chaofei , Tian Ye , Zhao Fan , Chen Zhihao , Su Peihong , Li Yu , Qian Airong
Published: September 2020

The bone microenvironment is an ideal fertile soil for both primary and secondary tumors to seed. The occurrence and development of osteosarcoma, as a primary bone tumor, is closely related to the bone microenvironment. Especially, the metastasis of osteosarcoma is the remaining challenge of therapy and poor prognosis. Increasing evidence focuses on the relationship between the bone microenvironment and osteosarcoma metastasis. Many elements exist in the bone microenvironment, such as acids, hypoxia, and chemokines, which have been verified to affect the progression and malignance of osteosarcoma through various signaling pathways. We thoroughly summarized all these regulators in the bone microenvironment and the transmission cascades, accordingly, attempting to furnish hints for inhibiting osteosarcoma metastasis via the amelioration of the bone microenvironment. In addition, analysis of the cross-talk between the bone microenvironment and osteosarcoma will help us to deeply understand the development of osteosarcoma. The cellular and molecular protagonists presented in the bone microenvironment promoting osteosarcoma metastasis will accelerate the exploration of novel therapeutic strategies towards osteosarcoma.
Different Conditions for the Modification of Polycaprolactone Films with L-Arginine
Authors: Nashchekina Yuliya , Chabina Alina , Nashchekin Alexey , Mikhailova Natalia
Published: September 2020

Poly-ε-caprolactone (PCL) is a biodegradable polymer used in regenerative medicine. Mesenchymal stem cells (MSCs) play an important role in the regeneration of different tissues. The hydrophobicity and neutrality of a PCL surface reduce MSCs’ adhesion and proliferation. In this study, PCL films were treated with arginine to improve surface hydrophilicity. The influences of arginine concentration, temperature, and solvent on PCL surface properties were investigated. PCL films treated with a solution of arginine in isopropyl alcohol were found to have the maximum number of amino groups. The greatest number of cells, 2 h after seeding, adhered to such films. It was shown that amino groups affect the interaction of cells with a modified surface and the hydrolysis reaction after treatment with isopropyl alcohol promotes the formation of adhesive focal contacts. Hence, our results illustrate that functional groups on the PCL surface after arginine solution treatment regulate MSC adhesion and focal contact formation.
Inorganic Phosphate (Pi) Signaling in Endothelial Cells: A Molecular Basis for Generation of Endothelial Microvesicles in Uraemic Cardiovascular Disease
Authors: Abbasian Nima , Bevington Alan , Burton James O. , Herbert Karl E. , Goodall Alison H. , Brunskill Nigel J.
Published: September 2020

Hyperphosphataemia increases cardiovascular mortality in patients with kidney disease. Direct effects of high inorganic phosphate (Pi) concentrations have previously been demonstrated on endothelial cells (ECs), including generation of procoagulant endothelial microvesicles (MVs). However, no mechanism directly sensing elevated intracellular Pi has ever been described in mammalian cells. Here, we investigated the hypothesis that direct inhibition by Pi of the phosphoprotein phosphatase PP2A fulfils this sensing role in ECs, culminating in cytoskeleton disruption and MV generation. ECs were treated with control (1 mM [Pi]) vs. high (2.5 mM [Pi]), a condition that drives actin stress fibre depletion and MV generation demonstrated by confocal microscopy of F-actin and NanoSight Nanoparticle tracking, respectively. Immuno-blotting demonstrated that high Pi increased p-Src, p-PP2A-C and p-DAPK-1 and decreased p-TPM-3. Pi at 100 μM directly inhibited PP2A catalytic activity. Inhibition of PP2A enhanced inhibitory phosphorylation of DAPK-1, leading to hypophosphorylation of Tropomyosin-3 at S284 and MV generation. p-Src is known to perform inhibitory phosphorylation on DAPK-1 but also on PP2A-C. However, PP2A-C can itself dephosphorylate (and therefore inhibit) p-Src. The direct inhibition of PP2A-C by Pi is, therefore, amplified by the feedback loop between PP2A-C and p-Src, resulting in further PP2A-C inhibition. These data demonstrated that PP2A/Src acts as a potent sensor and amplifier of Pi signals which can further signal through DAPK-1/Tropomyosin-3 to generate cytoskeleton disruption and generation of potentially pathological MVs.
Transcriptome Sequencing Revealed an Inhibitory Mechanism of Aspergillus flavus Asexual Development and Aflatoxin Metabolism by Soy-Fermenting Non-Aflatoxigenic Aspergillus
Authors: Yang Kunlong , Geng Qingru , Song Fengqin , He Xiaona , Hu Tianran , Wang Shihua , Tian Jun
Published: September 2020

Aflatoxins (AFs) have always been regarded as the most effective carcinogens, posing a great threat to agriculture, food safety, and human health. Aspergillus flavus is the major producer of aflatoxin contamination in crops. The prevention and control of A. flavus and aflatoxin continues to be a global problem. In this study, we demonstrated that the cell-free culture filtrate of Aspergillus oryzae and a non-aflatoxigenic A. flavus can effectively inhibit the production of AFB1 and the growth and reproduction of A. flavus, indicating that both of the non-aflatoxigenic Aspergillus strains secrete inhibitory compounds. Further transcriptome sequencing was performed to analyze the inhibitory mechanism of A. flavus treated with fermenting cultures, and the results revealed that genes involved in the AF biosynthesis pathway and other biosynthetic gene clusters were significantly downregulated, which might be caused by the reduced expression of specific regulators, such as AflS, FarB, and MtfA. The WGCNA results further revealed that genes involved in the TCA cycle and glycolysis were potentially involved in aflatoxin biosynthesis. Our comparative transcriptomics also revealed that two conidia transcriptional factors, brlA and abaA, were found to be significantly downregulated, which might lead to the downregulation of conidiation-specific genes, such as the conidial hydrophobins genes rodA and rodB. In summary, our research provides new insights for the molecular mechanism of controlling AF synthesis to control the proliferation of A. flavus and AF pollution.
Molecular and Structural Effects of Percutaneous Interventions in Chronic Achilles Tendinopathy
Authors: Darrieutort-Laffite Christelle , Soslowsky Louis J. , Le Goff Benoit
Published: September 2020

Achilles tendinopathy (AT) is a common problem, especially in people of working age, as well as in the elderly. Although the pathogenesis of tendinopathy is better known, therapeutic management of AT remains challenging. Various percutaneous treatments have been applied to tendon lesions: e.g., injectable treatments, platelet-rich plasma (PRP), corticosteroids, stem cells, MMP inhibitors, and anti-angiogenic agents), as well as percutaneous procedures without any injection (percutaneous soft tissue release and dry needling). In this review, we will describe and comment on data about the molecular and structural effects of these treatments obtained in vitro and in vivo and report their efficacy in clinical trials. Local treatments have some impact on neovascularization, inflammation or tissue remodeling in animal models, but evidence from clinical trials remains too weak to establish an accurate management plan, and further studies will be necessary to evaluate their value.
Non-Coding RNAs in Brain Tumors, the Contribution of lncRNAs, circRNAs, and snoRNAs to Cancer Development—Their Diagnostic and Therapeutic Potential
Authors: Latowska Julia , Grabowska Adriana , Zarębska Żaneta , Kuczyński Konrad , Kuczyńska Bogna , Rolle Katarzyna
Published: September 2020

Brain tumors are one of the most frightening ailments that afflict human beings worldwide. They are among the most lethal of all adult and pediatric solid tumors. The unique cell-intrinsic and microenvironmental properties of neural tissues are some of the most critical obstacles that researchers face in the diagnosis and treatment of brain tumors. Intensifying the search for potential new molecular markers in order to develop new effective treatments for patients might resolve this issue. Recently, the world of non-coding RNAs (ncRNAs) has become a field of intensive research since the discovery of their essential impact on carcinogenesis. Some of the most promising diagnostic and therapeutic regulatory RNAs are long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and small nucleolar RNAs (snoRNAs). Many recent reports indicate the important role of these molecules in brain tumor development, as well as their implications in metastasis. In the following review, we summarize the current state of knowledge about regulatory RNAs, namely lncRNA, circRNAs, and snoRNAs, and their impact on the development of brain tumors in children and adults with particular emphasis on malignant primary brain tumors—gliomas and medulloblastomas (MB). We also provide an overview of how these different ncRNAs may act as biomarkers in these tumors and we present their potential clinical implications.
Cytotoxic and Senolytic Effects of Methadone in Combination with Temozolomide in Glioblastoma Cells
Authors: Kaina Bernd , Beltzig Lea , Piee-Staffa Andrea , Haas Bodo
Published: September 2020

Methadone is an analgesic drug used for pain treatment and heroin substitution. Recently, methadone has been proposed to be useful also for cancer therapy, including glioblastoma multiforme (GBM), the most severe form of brain cancer, because experiments on cultured glioma cells treated with doxorubicin showed promising results. Doxorubicin, however, is not used first-line in GBM therapy. Therefore, we analyzed the cytotoxic effect of methadone alone and in combination with temozolomide, a DNA-alkylating drug that is first-line used in GBM treatment, utilizing GBM-derived cell lines and a human fibroblast cell line. We show that methadone is cytotoxic on its own, inducing apoptosis and necrosis, which was observed at a concentration above 20 µg/mL. Methadone was similar toxic in isogenic MGMT expressing and non-expressing cells, and in LN229 glioblastoma and VH10T human fibroblasts. The apoptosis-inducing activity of methadone is not bound on the opioid receptor (OR), since naloxone, a competitive inhibitor of OR, did not attenuate methadone-induced apoptosis/necrosis. Administrating methadone and temozolomide together, temozolomide had no impact on methadone-induced apoptosis (which occurred 3 days after treatment), while temozolomide-induced apoptosis (which occurred 5 days after treatment) was unaffected at low (non-toxic) methadone concentration (5 µg/mL), and at high (toxic) methadone concentration (20 µg/mL) the cytotoxic effects of methadone and temozolomide were additive. Methadone is not genotoxic, as revealed by comet and γH2AX assay, and did not ameliorate the genotoxic effect of temozolomide. Further, methadone did not induce cellular senescence and had no effect on temozolomide-induced senescence. Although methadone was toxic on senescent cells, it cannot be considered a senolytic drug since cytotoxicity was not specific for senescent cells. Finally, we show that methadone had no impact on the MGMT promoter methylation. Overall, the data show that methadone on glioblastoma cells in vitro is cytotoxic and induces apoptosis/necrosis at doses that are above the level that can be achieved in vivo. It is not genotoxic, and does not ameliorate the cell killing or the senescence-inducing effect of temozolomide (no synergistic effect), indicating it has no impact on temozolomide-induced signaling pathways. The data do not support the notion that concomitant methadone treatment supports temozolomide-based chemotherapy.
Role of Muscle-Specific Histone Methyltransferase (Smyd1) in Exercise-Induced Cardioprotection against Pathological Remodeling after Myocardial Infarction
Authors: Liang Qiaoqin , Cai Mengxin , Zhang Jiaqi , Song Wei , Zhu Wanyu , Xi Lei , Tian Zhenjun
Published: September 2020

Pathological remodeling is the main detrimental complication after myocardial infarction (MI). Overproduction of reactive oxygen species (ROS) in infarcted myocardium may contribute to this process. Adequate exercise training after MI may reduce oxidative stress-induced cardiac tissue damage and remodeling. SET and MYND domain containing 1 (Smyd1) is a muscle-specific histone methyltransferase which is upregulated by resistance training, may strengthen sarcomere assembly and myofiber folding, and may promote skeletal muscles growth and hypertrophy. However, it remains elusive if Smyd1 has similar functions in post-MI cardiac muscle and participates in exercise-induced cardioprotection. Accordingly, we investigated the effects of interval treadmill exercise on cardiac function, ROS generation, Smyd1 expression, and sarcomere assembly of F-actin in normal and infarcted hearts. Adult male rats were randomly divided into five groups (n = 10/group): control (C), exercise alone (EX), sham-operated (S), MI induced by permanent ligation of left anterior descending coronary artery (MI), and MI with interval exercise training (MI + EX). Exercise training significantly improved post-MI cardiac function and sarcomere assembly of F-actin. The cardioprotective effects were associated with increased Smyd1, Trx1, cTnI, and α-actinin expression as well as upregulated ratio of phosphorylated AMP-activated protein kinase (AMPK)/AMPK, whereas Hsp90, MuRF1, brain natriuretic peptide (BNP) expression, ROS generation, and myocardial fibrosis were attenuated. The improved post-MI cardiac function was associated with increased Smyd1 expression. In cultured H9C2 cardiomyoblasts, in vitro treatment with H2O2 (50 µmol/L) or AMP-activated protein kinase (AMPK) agonist (AICAR, 1 mmol/L) or their combination for 4 h simulated the effects of exercise on levels of ROS and Smyd1. In conclusion, we demonstrated a novel role of Smyd1 in association with post-MI exercise-induced cardioprotection. The moderate level of ROS-induced upregulation of Smyd1 may be an important target for modulating post-MI cardiac function and remodeling.