bluuebunny/crossref_metadata_2025 huggingface dataset:
Analyzing Brexit: Implications for the Electricity System of Great Britain
Authors: Mayer Philip , Ball Christopher Stephen , Vögele Stefan , Kuckshinrichs Wilhelm , Rübbelke Dirk
Published: August 2019

The UK’s exit from the European Union (EU) has potential ramifications for the country’s electricity sector, given its increasing interlinkage with other EU electricity systems. Brexit could hamper the development toward higher market integration and the realization of new interconnector projects. Moreover, a fall in the value of the Pound, resulting from Brexit in the medium term, could also affect the electricity trading structure. Combining a European electricity market model and a multi-criteria decision analysis tool, this study assesses the implications of Brexit for the electricity market of Great Britain (hereafter GB) for 2030, from the perspective of (i) political decision makers, (ii) electricity consumers, and (iii) producers. Results indicate that the implications of Brexit depend on the future development of the GB electricity system and on the objectives of the respective stakeholders. Possible opportunities brought by Brexit under a low-carbon trajectory contrast with greater challenges and tradeoffs between stakeholders under alternative power system development paths. Despite increased British autonomy in energy and climate matters, there remains interdependency between British and EU energy policy.
Mg6MnO8 as a Magnesium-Ion Battery Material: Defects, Dopants and Mg-Ion Transport
Authors: Kuganathan Navaratnarajah , Gkanas Evangelos I. , Chroneos Alexander
Published: August 2019

Rechargeable magnesium ion batteries have recently received considerable attention as an alternative to Li- or Na-ion batteries. Understanding defects and ion transport is a key step in designing high performance electrode materials for Mg-ion batteries. Here we present a classical potential-based atomistic simulation study of defects, dopants and Mg-ion transport in Mg6MnO8. The formation of the Mg–Mn anti-site defect cluster is calculated to be the lowest energy process (1.73 eV/defect). The Mg Frenkel is calculated to be the second most favourable intrinsic defect and its formation energy is 2.84 eV/defect. A three-dimensional long-range Mg-ion migration path with overall activation energy of 0.82 eV is observed, suggesting that the diffusion of Mg-ions in this material is moderate. Substitutional doping of Ga on the Mn site can increase the capacity of this material in the form of Mg interstitials. The most energetically favourable isovalent dopant for Mg is found to be Fe. Interestingly, Si and Ge exhibit exoergic solution enthalpy for doping on the Mn site, requiring experimental verification.
Smart Energy Management Policy in India—A Review
Authors: Yenneti Komali , Rahiman Riya , Panda Adishree , Pignatta Gloria
Published: August 2019

India accounts for six per cent of the world’s primary energy consumption. Rapid urbanization and rapid urban population growth have had a serious impact on energy consumption and subsequent carbon emissions. In particular, cities face a complex and interrelated set of challenges across different sectors (building environment, mobility, water and waste management and public services). Re-examining these challenges by integrating smart energy management (SEM) principles is critical for sustainable and low-carbon urban development. In addition, managing energy footprint is one of the most challenging goals for cities, and as existing cities evolve and transform into smart cities, SEM becomes an integral part of the urban transformation. This article comprehensively reviews the different SEM technologies for different sectors (construction, transportation, public services, water and waste), the policies, and the current challenges and opportunities for SEM policy governance in India. Making urban energy smart can manage a city’s energy footprint and have a positive impact on future carbon emissions.
Load Flow Independent Method for Estimating Neutral Voltage in Three-Phase Power Systems
Authors: Pires Corrêa Henrique , Teles Vieira Flávio Henrique
Published: August 2019

A precise modeling of three-phase power systems is of great importance due to its ability to represent load unbalance and asymmetry in system components. A further enhancement in power system modeling is the computation of neutral voltages, which has been frequently neglected in earlier works. In this Letter, a novel approximate method is proposed for estimating neutral voltages. The method has as its main advantage not requiring the use of load flow algorithms with explicit neutral conductor modeling, thus being applicable to available load flow results in which the neutral voltage was originally omitted.
A Hierarchical Self-Adaptive Method for Post-Disturbance Transient Stability Assessment of Power Systems Using an Integrated CNN-Based Ensemble Classifier
Authors: Zhang Ruoyu , Wu Junyong , Xu Yan , Li Baoqin , Shao Meiyang
Published: August 2019

Data-driven approaches using synchronous phasor measurements are playing an important role in transient stability assessment (TSA). For post-disturbance TSA, there is not a definite conclusion about how long the response time should be. Furthermore, previous studies seldom considered the confidence level of prediction results and specific stability degree. Since transient stability can develop very fast and cause tremendous economic losses, there is an urgent need for faster response speed, credible accurate prediction results, and specific stability degree. This paper proposed a hierarchical self-adaptive method using an integrated convolutional neural network (CNN)-based ensemble classifier to solve these problems. Firstly, a set of classifiers are sequentially organized at different response times to construct different layers of the proposed method. Secondly, the confidence integrated decision-making rules are defined. Those predicted as credible stable/unstable cases are sent into the stable/unstable regression model which is built at the corresponding decision time. The simulation results show that the proposed method can not only balance the accuracy and rapidity of the transient stability prediction, but also predict the stability degree with very low prediction errors, allowing more time and an instructive guide for emergency controls.
A Review of the Hydraulic Transient and Dynamic Behavior of Hydropower Plants with Sloping Ceiling Tailrace Tunnels
Authors: Guo Wencheng
Published: August 2019

The sloping ceiling tailrace tunnel is a novel tailrace tunnel system for hydropower plants. The design, operation, and maintenance of hydropower plants with sloping ceiling tailrace tunnels are based on the calculation and analysis of hydraulic transients and dynamic behavior. Research achievements have provided guidance and a basis for the safe, stable, and efficient operation of hydropower plants with sloping ceiling tailrace tunnels. Based on research achievements, sloping ceiling tailrace tunnels have been applied to more and more hydropower plants. This review paper gives a systematic literature investigation on the hydraulic transient and dynamic behaviors of hydropower plants with sloping ceiling tailrace tunnels. First, the appearance and development of sloping ceiling tailrace tunnels are stated. Key issues in the hydraulic transient and dynamic behaviors of hydropower plants with sloping ceiling tailrace tunnels are illuminated. Then, research achievements on six issues (i.e., the working principles of sloping ceiling tailrace tunnels, the shape design of sloping ceiling tailrace tunnels, the free surface pressurized flow characteristics in sloping ceiling tailrace tunnels, numerical simulations of transient processes for hydro-turbine governing systems with sloping ceiling tailrace tunnels, the stability of hydro-turbine governing systems with sloping ceiling tailrace tunnels, and the transient process control of hydro-turbine governing systems with sloping ceiling tailrace tunnels) are elaborated. Finally, future research trends are presented. In future research, fluid–solid coupling of the tunnel wall and free surface pressurized flow in sloping ceiling tailrace tunnels is worth studying. For hydropower plants with sloping ceiling tailrace tunnels, a combined operating scheme with thermal power and wind power should be explored.
Robust LFC Strategy for Wind Integrated Time-Delay Power System Using EID Compensation
Authors: Liu Fang , Zhang Kailiang , Zou Runmin
Published: August 2019

This paper presents an active disturbance rejection control (ADRC) technique for load frequency control of a wind integrated power system when communication delays are considered. To improve the stability of frequency control, equivalent input disturbances (EID) compensation is used to eliminate the influence of the load variation. In wind integrated power systems, two area controllers are designed to guarantee the stability of the overall closed-loop system. First, a simplified frequency response model of the wind integrated time-delay power system was established. Then the state-space model of the closed-loop system was built by employing state observers. The system stability conditions and controller parameters can be solved by some linear matrix inequalities (LMIs) forms. Finally, the case studies were tested using MATLAB/SIMULINK software and the simulation results show its robustness and effectiveness to maintain power-system stability.
The Dynamic Partnership of Polycomb and Trithorax in Brain Development and Diseases
Authors: Kuehner Janise N. , Yao Bing
Published: August 2019

Epigenetic mechanisms, including DNA and histone modifications, are pivotal for normal brain development and functions by modulating spatial and temporal gene expression. Dysregulation of the epigenetic machinery can serve as a causal role in numerous brain disorders. Proper mammalian brain development and functions depend on the precise expression of neuronal-specific genes, transcription factors and epigenetic modifications. Antagonistic polycomb and trithorax proteins form multimeric complexes and play important roles in these processes by epigenetically controlling gene repression or activation through various molecular mechanisms. Aberrant expression or disruption of either protein group can contribute to neurodegenerative diseases. This review focus on the current progress of Polycomb and Trithorax complexes in brain development and disease, and provides a future outlook of the field.
Characteristics of VOCs Released from Plywood in Airtight Environments
Authors: Cao Tianyu , Shen Jun , Wang Qifan , Li Huifang , Xu Cong , Dong Huajun
Published: August 2019

In order to explore the emission characteristics of volatile organic compounds (VOCs) and different VOC components in airtight environments, polyvinyl chloride laminated plywood (PVC-P), melamine-impregnated paper laminated plywood (MI-P), water-based paint laminated plywood (WP-P) and unfinished plywood (UF-P) were tested as materials in 15 L small environment cabins. VOCs were collected after being sealed for 2 h, 4 h, 6 h, 8 h, 12 h, 18 h, 24 h and 30 h under different loading ratios (1 m2/m3, 1.5 m2/m3, 2 m2/m3, 2.5 m2/m3) and analyzed using a gas chromatography–mass spectrometer. The results show that VOCs gradually increased and tended to be saturated with the increase of time in an airtight environment. The saturation of veneered plywood was faster than unfinished plywood and the pollution degree of three kinds of veneered plywood from lowest to highest was in order of PVC-P, MI-P, WP-P. Aromatic hydrocarbons account for more than half of VOC concentration, and was most obviously affected by the loading ratios. Surfaced laminated plywood can reduce the emission of aromatic hydrocarbons, but also increases the amount of other compounds released. The concentration of VOC-components shows different characteristic curves at different loading ratios due to the influence of decorative materials.
Evaluation of Stand Biomass Estimation Methods for Major Forest Types in the Eastern Da Xing’an Mountains, Northeast China
Authors: Dong Lihu , Zhang Lianjun , Li Fengri
Published: August 2019

Currently, forest biomass estimation methods at the regional scale have attracted the greatest attention from researchers, and the development of stand biomass models has become popular a trend. In this study, a total of 5074 measurements on 1053 permanent sample plots were obtained in the Eastern Da Xing’an Mountains, and three additive systems of stand biomass equations were developed. The first additive system (M-1) used stand variables as the predictors (i.e., stand basal area and average height), the second additive system (M-2) utilized stand volume as the sole predictor, and the third additive system (M-3) included both stand volume and biomass expansion and conversion factors (BCEFs) as the predictors. The coefficients of the three model systems were estimated with nonlinear seemingly unrelated regression (NSUR), while the heteroscedasticity of the model residuals was solved with the weight function. The jackknifing technique was used on the residuals, and several statistics were used to assess the prediction performance of each model. We comprehensively evaluated four stand biomass estimation methods (i.e., M-1, M-2, M-3 and a constant BCEF (M-4)). Here, we showed that the (1) three additive systems of stand biomass equations showed good model fitting and prediction performance, (2) M-3 significantly improved the model fitting and performance and provided the most accurate predictions for most stand biomass components, and (3) the ranking of the four stand biomass estimation methods followed the order of M-3 > M-2 > M-4 > M-1. Our results demonstrated these additive stand biomass models could be used to estimate the stand aboveground and belowground biomass for the major forest types in the Eastern Da Xing’an Mountains, although the most appropriate method depends on the available data and forest type.
Assessment of Arundo donax Fibers for Oil Spill Recovery Applications
Authors: Fiore Vincenzo , Piperopoulos Elpida , Calabrese Luigi
Published: August 2019

In the last years, natural fibers are increasingly investigated as an oil recovery system in order to overcome the oil spillage phenomena, thus preserving environment and aquatic life. In particular, lignocellulose-based fibers have recently been employed with promising results. In such a context, the aim of this paper is to assess the oil sorption capability of natural fibers extracted from the stem of the giant reed Arundo donax L., a perennial rhizomatous grass belonging to the Poaceae family that grows naturally all around the world thanks to its ability to tolerate different climatic conditions. Sorption tests in several pollutants and water as a reference were carried out. The fibers have absorption capacities that are about five to six times their weight. Depending on the high absorption kinetics, possible applicative interests can be identified. Eventually, depending on the fiber size, adsorption properties were related to the microstructure and morphology of Arundo donax fibers.
Identifying Freshness of Spinach Leaves Stored at Different Temperatures Using Hyperspectral Imaging
Authors: Zhu Susu , Feng Lei , Zhang Chu , Bao Yidan , He Yong
Published: August 2019

Spinach is prone to spoilage in the course of preservation. Spinach leaves stored at different temperatures for different durations will have varying degrees of freshness. In order to monitor the freshness of spinach leaves during storage, a rapid and non-destructive method—hyperspectral imaging technology—was applied in this study. Visible near-infrared reflectance (Vis-NIR) (380–1030 nm) and near-infrared reflectance (NIR) (874–1734 nm) hyperspectral imaging systems were used. Spinach leaves preserved at different temperatures with different durations (0, 3, 6, 9 days at 4 °C and 0, 1, 2 days at 20 °C) were studied. Principal component analysis (PCA) was adopted as a qualitative analysis method. The second-order derivative spectra were utilized to select effective wavelengths. Partial least squares discriminant analysis (PLS-DA), support vector machine (SVM), and extreme learning machine (ELM) were used to build models based on full spectra and effective wavelengths. All three models achieved good results, with accuracies above 92% for both Vis-NIR spectra and NIR spectra. ELM obtained the best results, with all accuracies reaching 100%. The overall results indicate the possibility of the freshness identification of spinach preserved at different temperatures for different durations using two kinds of hyperspectral imaging systems.
Population Genetic Analysis of the Estonian Native Horse Suggests Diverse and Distinct Genetics, Ancient Origin and Contribution from Unique Patrilines
Authors: Castaneda Caitlin , Juras Rytis , Khanshour Anas , Randlaht Ingrid , Wallner Barbara , Rigler Doris , Lindgren Gabriella , Raudsepp Terje , Cothran E. Gus
Published: August 2019

The Estonian Native Horse (ENH) is a medium-size pony found mainly in the western islands of Estonia and is well-adapted to the harsh northern climate and poor pastures. The ancestry of the ENH is debated, including alleged claims about direct descendance from the extinct Tarpan. Here we conducted a detailed analysis of the genetic makeup and relationships of the ENH based on the genotypes of 15 autosomal short tandem repeats (STRs), 18 Y chromosomal single nucleotide polymorphisms (SNPs), mitochondrial D-loop sequence and lateral gait allele in DMRT3. The study encompassed 2890 horses of 61 breeds, including 33 ENHs. We show that the expected and observed genetic diversities of the ENH are among the highest within 52 global breeds, and the highest among 8 related Northern European ponies. The genetically closest breeds to the ENH are the Finn Horse, and the geographically more distant primitive Hucul and Konik. ENH matrilines are diverse and relate to draught and Pontic-Caspian breeds. ENH patrilines relate to draught breeds, and to a unique haplogroup not described before. None of the 33 ENHs carried the “gait” mutation, but the mutation was found in 2 Huculs. The study demonstrates that the ENH is a genetically distinct and diverse breed of ancient origin with no notable pressure of selective breeding.
Prediction and Analysis of Electrical Accidents and Risk Due to Climate Change
Authors: Jeong Min-Chang , Kim Jaehyuck
Published: August 2019

The industrial development and the increase in the use of fossil fuels have been accelerating global warming and climate change, thereby causing more frequent and intense natural disasters than ever before. Since electrical facilities are generally installed outdoors, they are greatly affected by natural disasters, thus accidents related to electrical equipment has been on the rise. In this paper, we present the risk rating associated with climate change by analyzing the statistics of electrical fires, electric shock accidents and electrical equipment accidents caused by domestic climate change. Further, we present a risk rating analysis model for electrical fires on a monthly basis through the data analysis of electrical hazards associated with various regional (metropolitan city) climatic conditions (temperature, humidity), and analyze the accident risk rating for natural disasters related to low and high voltage equipment. Through this risk analysis model for each region and type of equipment, we presented a basic prediction model for electrical hazards. Therefore, it is possible to provide electrical safety services in the future by displaying a risk prediction map of electrical hazards for each region and type of electrical equipment through web sites or smart phone apps using the presented analysis data. Further, efforts should be made to increase the robustness or reliability of electrical equipment in order to prevent electrical accidents caused by natural disasters due to climate change in advance.
Social Organization Participation, Government Governance and the Equalization of Basic Public Services: Evidence from China
Authors: Yang Gangqiang , Xue Yongyu , Ma Yuxi
Published: August 2019

This paper uses the methods of System Generalized method of moments (SYS-GMM), mediation effect and linkage effect to investigate the relationship among social organization participation, government governance and the equalization of basic public services from 2007 to 2017 in China. The empirical results show that the participation of social organizations and improvement in the government governance can promote the equalization of basic public services. The government has a greater capacity to drive the equalization of basic public services, but the density of social organizations can serve as a mediator in the equalization of basic public services. The government governance and social organization density have a strong linkage effect, but the link with social organization quality is weak. Furthermore, a linkage effect is evident in medical and health care, public education, environmental protection, and public culture but not in public science and social welfare.
Occurrence, Distribution and Risk Assessment of Mercury in Multimedia of Soil-Dust-Plants in Shanghai, China
Authors: Liu Yanzhuo , Song Shanshan , Bi Chunjuan , Zhao Junli , Xi Di , Su Ziqi
Published: August 2019

The urban environment is a complex ecosystem influenced by strong human disturbances in multi-environmental media, so it is necessary to analyze urban environmental pollutants through the comprehensive analysis of different media. Soil, road dust, foliar dust, and camphor leaves from 32 sample sites in Shanghai were collected for the analysis of mercury contamination in soil–road dust–leaves–foliar dust systems. Mercury concentrations in surface soils in Shanghai were the highest, followed by road dust, foliar dust, and leaves, successively. The spatial distribution of mercury in the four environmental media presented different distribution patterns. Except for the significant correlation between mercury concentrations in road dust and mercury concentrations in leaves (r = 0.56, p < 0.001), there was no significant correlation between the other groups in the four media. Besides this, there was no significant correlation between mercury concentrations and land types. The LUR (Land use regression) model was used to assess the impact of urbanization factors on mercury distribution in the environment. The results showed that soil mercury was affected by factories and residential areas. Foliar dust mercury was affected by road density and power plants. Leaf mercury was affected by power plants and road dust mercury was affected by public service areas. The highest average HI (Hazard index) value of mercury in Shanghai was found in road dust, followed by surface soil and foliar dust. The HI values for children were much higher than those for adults. However, the HI values of mercury exposure in all sampling sites were less than one, suggesting a lower health risk level. The microscopic mechanism of mercury in different environmental media was suggested to be studied further in order to learn the quantitative effects of urbanization factors on mercury concentrations.
A Systematic Review of Sexual Minority Women’s Experiences of Health Care in the UK
Authors: Meads Catherine , Hunt Ros , Martin Adam , Varney Justin
Published: August 2019

Sexual minority women (SMW) experience worse health and disproportionate behavioural risks to health than heterosexual women. This mixed-methods systematic review evaluated recent studies on health experiences of UK SMW, published 2010–2018. Analysis was through narrative thematic description and synthesis. Identified were 23,103 citations, 26 studies included, of which 22 provided qualitative and nine quantitative results. SMW had worse health experiences that might impact negatively on access, service uptake and health outcomes. Findings highlighted significant barriers facing SMW, including heteronormative assumptions, perceptions and experiences of negative responses to coming out, ignorance and prejudice from healthcare professionals, and barriers to raising concerns or complaints. Little information was available about bisexual and trans women’s issues. Findings highlighted the need for explicit and consistent education for healthcare professionals on SMW issues, and stronger application of non-discrimination policies in clinical settings.
User Evaluation of Map-Based Visual Analytic Tools
Authors: Popelka Stanislav , Herman Lukáš , Řezník Tomas , Pařilová Michaela , Jedlička Karel , Bouchal Jiří , Kepka Michal , Charvát Karel
Published: August 2019

Big data have also become a big challenge for cartographers, as the majority of big data may be localized. The use of visual analytics tools, as well as comprising interactive maps, stimulates inter-disciplinary actors to explore new ideas and decision-making methods. This paper deals with the evaluation of three map-based visual analytics tools by means of the eye-tracking method. The conceptual part of the paper begins with an analysis of the state-of-the-art and ends with the design of proof-of-concept experiments. The verification part consists of the design, composition, and realization of the conducted eye-tracking experiment, in which three map-based visual analytics tools were tested in terms of user-friendliness. A set of recommendations on GUI (graphical user interface) design and interactive functionality for map makers is formulated on the basis of the discovered errors and shortcomings in the assessed stimuli. The results of the verification were used as inputs for improving the three tested map-based visual analytics tools and might serve as a best practice for map-based visual analytics tools in general, as well as for improving the policy making cycle as elaborated by the European project PoliVisu (Policy Development based on Advanced Geospatial Data Analytics and Visualization).
Comparative Analysis of miRNA Abundance Revealed the Function of Vvi-miR828 in Fruit Coloring in Root Restriction Cultivation Grapevine (Vitis vinifera L.)
Authors: Chen Qiuju , Deng Bohan , Gao Jie , Zhao Zhongyang , Chen Zili , Song Shiren , Wang Lei , Zhao Liping , Xu Wenping , Zhang Caixi , Wang Shiping , Ma Chao
Published: August 2019

Root restriction cultivation leads to early maturation and quality improvement, especially in the anthocyanin content in grapevine. However, the molecular mechanisms that underlie these changes have not been thoroughly elucidated. In this study, four small RNA libraries were constructed, which included the green soft stage (GS) and ripe stage (RS) of ‘Muscat’ (Vitis vinifera L.) grape berries that were grown under root restriction (RR) and in traditional cultivation (no root restriction, CK). A total of 162 known miRNAs and 14 putative novel miRNAs were detected from the four small RNA libraries by high-throughput sequencing. An analysis of differentially expressed miRNAs (DEMs) revealed that 13 miRNAs exhibited significant differences in expression between RR and CK at the GS and RS stages, respectively. For different developmental stages of fruit, 23 and 34 miRNAs showed expression differences between the GS and RS stages in RR and CK, respectively. The expression patterns of the eight DEMs and their targets were verified by qRT-PCR, and the expression profiles of target genes were confirmed to be complementary to the corresponding miRNAs in RR and CK. The function of Vvi-miR828, which showed the down regulated expression in the RS stage under root restriction, was identified by gene transformation in Arabidopsis. The anthocyanin content significantly decreased in transgenic lines, which indicates the regulatory capacity of Vvi-miR828 in fruit coloration. The miRNA expression pattern comparison between RR and CK might provide a means of unraveling the miRNA-mediated molecular process regulating grape berry development under root restricted cultivation.
Insights into the Phylogeny and Evolution of Cold Shock Proteins: From Enteropathogenic Yersinia and Escherichia coli to Eubacteria
Authors: Yu Tao , Keto-Timonen Riikka , Jiang Xiaojie , Virtanen Jussa-Pekka , Korkeala Hannu
Published: August 2019

Psychrotrophic foodborne pathogens, such as enteropathogenic Yersinia, which are able to survive and multiply at low temperatures, require cold shock proteins (Csps). The Csp superfamily consists of a diverse group of homologous proteins, which have been found throughout the eubacteria. They are related to cold shock tolerance and other cellular processes. Csps are mainly named following the convention of those in Escherichia coli. However, the nomenclature of certain Csps reflects neither their sequences nor functions, which can be confusing. Here, we performed phylogenetic analyses on Csp sequences in psychrotrophic enteropathogenic Yersinia and E. coli. We found that representative Csps in enteropathogenic Yersinia and E. coli can be clustered into six phylogenetic groups. When we extended the analysis to cover Enterobacteriales, the same major groups formed. Moreover, we investigated the evolutionary and structural relationships and the origin time of Csp superfamily members in eubacteria using nucleotide-level comparisons. Csps in eubacteria were classified into five clades and 12 subclades. The most recent common ancestor of Csp genes was estimated to have existed 3585 million years ago, indicating that Csps have been important since the beginning of evolution and have enabled bacterial growth in unfavorable conditions.
MicroRNA-15a Regulates the Differentiation of Intramuscular Preadipocytes by Targeting ACAA1, ACOX1 and SCP2 in Chickens
Authors: Li Guoxi , Fu Shouyi , Chen Yi , Jin Wenjiao , Zhai Bin , Li Yuanfang , Sun Guirong , Han Ruili , Wang Yanbin , Tian Yadong , Li Hong , Kang Xiangtao
Published: August 2019

Our previous studies showed that microRNA-15a (miR-15a) was closely related to intramuscular fat (IMF) deposition in chickens; however, its regulatory mechanism remains unclear. Here, we evaluated the expression characteristics of miR-15a and its relationship with the expression of acetyl-CoA acyltransferase 1 (ACAA1), acyl-CoA oxidase 1 (ACOX1) and sterol carrier protein 2 (SCP2) by qPCR analysis in Gushi chicken breast muscle at 6, 14, 22, and 30 weeks old, where we performed transfection tests of miR-15a mimics in intramuscular preadipocytes and verified the target gene of miR-15a in chicken fibroblasts (DF1). The miR-15a expression level at 30 weeks increased 13.5, 4.5, and 2.7-fold compared with the expression levels at 6, 14, and 22 weeks, respectively. After 6 days of induction, miR-15a over-expression significantly promoted intramuscular adipogenic differentiation and increased cholesterol and triglyceride accumulation in adipocytes. Meanwhile, 48 h after transfection with miR-15a mimics, the expression levels of ACAA1, ACOX1 and SCP2 genes decreased by 56.52%, 31.18% and 37.14% at the mRNA level in intramuscular preadipocytes. In addition, the co-transfection of miR-15a mimics and ACAA1, ACOX1 and SCP2 3′UTR (untranslated region) dual-luciferase vector significantly inhibited dual-luciferase activity in DF1 cells. Taken together, our data demonstrate that miR-15a can reduce fatty acid oxidation by targeting ACAA1, ACOX1, and SCP2, which subsequently indirectly promotes the differentiation of chicken intramuscular preadipocytes.
Circulating miRNAs as Potential Biomarkers Associated with Cardiac Remodeling and Fibrosis in Chagas Disease Cardiomyopathy
Authors: Nonaka Carolina Kymie Vasques , Macêdo Carolina Thé , Cavalcante Bruno Raphael Ribeiro , Alcântara Adriano Costa de , Silva Daniela Nascimento , Bezerra Milena da Rocha , Caria Alex Cleber Improta , Tavora Fábio Rocha Fernandes , Neto João David de Souza , Noya-Rabelo Márcia Maria , Rogatto Silvia Regina , Ribeiro dos Santos Ricardo , Souza Bruno Solano de Freitas , Soares Milena Botelho Pereira
Published: August 2019

Chagas disease (CD) affects approximately 6–7 million people worldwide, from which 30% develop chronic Chagas cardiomyopathy (CCC), usually after being asymptomatic for years. Currently available diagnostic methods are capable of adequately identifying infected patients, but do not provide information regarding the individual risk of developing the most severe form of the disease. The identification of biomarkers that predict the progression from asymptomatic or indeterminate form to CCC, may guide early implementation of pharmacological therapy. Here, six circulating microRNAs (miR-19a-3p, miR-21-5p, miR-29b-3p, miR-30a-5p, miR-199b-5p and miR-208a-3p) were evaluated and compared among patients with CCC (n = 28), CD indeterminate form (n = 10) and healthy controls (n = 10). MiR-19a-3p, miR-21-5p, and miR-29b-3p were differentially expressed in CCC patients when compared to indeterminate form, showing a positive correlation with cardiac dysfunction, functional class, and fibrosis, and a negative correlation with ejection fraction and left ventricular strain. Cardiac tissue analysis confirmed increased expression of microRNAs in CCC patients. In vitro studies using human cells indicated the involvement of these microRNAs in the processes of cardiac hypertrophy and fibrosis. Our study suggests that miRNAs are involved in the process of cardiac fibrosis and remodeling presented in CD and indicate a group of miRNAs as potential biomarkers of disease progression in CCC.
Integrated Analysis of miRNA and mRNA Endorses a Twenty miRNAs Signature for Colorectal Carcinoma
Authors: Angius Andrea , Uva Paolo , Pira Giovanna , Muroni Maria Rosaria , Sotgiu Giovanni , Saderi Laura , Uleri Elena , Caocci Maurizio , Ibba Gabriele , Cesaraccio Maria Rosaria , Serra Caterina , Carru Ciriaco , Manca Alessandra , Sanges Francesca , Porcu Alberto , Dolei Antonia , Scanu Antonio Mario , Cossu Rocca Paolo , De Miglio Maria Rosaria
Published: August 2019

Colorectal cancer (CRC) ranks as the most frequent carcinoma worldwide. CRC patients show strong prognostic differences and responses to treatment, and 20% have incurable metastatic disease at diagnosis. We considered it essential to investigate mechanisms that control cellular regulatory networks, such as the miRNA–mRNA interaction, known to be involved in cancer pathogenesis. We conducted a human miRNome analysis by TaqMan low density array, comparing CRC to normal colon tissue (NCT, and experimentally identified gene targets of miRNAs deregulated, by anti-correlation analysis, with the CRC whole-transcriptome profile obtained from RNASeq experiments. We identified an integrated signature of 20 deregulated miRNAs in CRC. Enrichment analyses of the gene targets controlled by these miRNAs brought to light 25 genes, members of pathways known to lead to cell growth and death (CCND1, NKD1, FZD3, MAD2L1, etc.), such as cell metabolism (ACSL6, PRPS1-2). A screening of prognosis-mediated miRNAs underlined that the overexpression of miR-224 promotes CRC metastasis, and is associated with high stage and poor survival. These findings suggest that the biology and progression of CRC depend on deregulation of multiple miRNAs that cause a complex dysfunction of cellular molecular networks. Our results have further established miRNA–mRNA interactions and defined multiple pathways involved in CRC pathogenesis.
Developing Regenerative Treatments for Developmental Defects, Injuries, and Diseases Using Extracellular Matrix Collagen-Targeting Peptides
Authors: Goldbloom-Helzner Leora , Hao Dake , Wang Aijun
Published: August 2019

Collagen is the most widespread extracellular matrix (ECM) protein in the body and is important in maintaining the functionality of organs and tissues. Studies have explored interventions using collagen-targeting tissue engineered techniques, using collagen hybridizing or collagen binding peptides, to target or treat dysregulated or injured collagen in developmental defects, injuries, and diseases. Researchers have used collagen-targeting peptides to deliver growth factors, drugs, and genetic materials, to develop bioactive surfaces, and to detect the distribution and status of collagen. All of these approaches have been used for various regenerative medicine applications, including neovascularization, wound healing, and tissue regeneration. In this review, we describe in depth the collagen-targeting approaches for regenerative therapeutics and compare the benefits of using the different molecules for various present and future applications.
Microtubules: A Key to Understand and Correct Neuronal Defects in CDKL5 Deficiency Disorder?
Authors: Barbiero Isabella , De Rosa Roberta , Kilstrup-Nielsen Charlotte
Published: August 2019

CDKL5 deficiency disorder (CDD) is a severe neurodevelopmental encephalopathy caused by mutations in the X-linked CDKL5 gene that encodes a serine/threonine kinase. CDD is characterised by the early onset of seizures and impaired cognitive and motor skills. Loss of CDKL5 in vitro and in vivo affects neuronal morphology at early and late stages of maturation, suggesting a link between CDKL5 and the neuronal cytoskeleton. Recently, various microtubule (MT)-binding proteins have been identified as interactors of CDKL5, indicating that its roles converge on regulating MT functioning. MTs are dynamic structures that are important for neuronal morphology, migration and polarity. The delicate control of MT dynamics is fundamental for proper neuronal functions, as evidenced by the fact that aberrant MT dynamics are involved in various neurological disorders. In this review, we highlight the link between CDKL5 and MTs, discussing how CDKL5 deficiency may lead to deranged neuronal functions through aberrant MT dynamics. Finally, we discuss whether the regulation of MT dynamics through microtubule-targeting agents may represent a novel strategy for future pharmacological approaches in the CDD field.
Plakophilin-2 Haploinsufficiency Causes Calcium Handling Deficits and Modulates the Cardiac Response Towards Stress
Authors: van Opbergen Chantal J.M. , Noorman Maartje , Pfenniger Anna , Copier Jaël S. , Vermij Sarah H. , Li Zhen , van der Nagel Roel , Zhang Mingliang , de Bakker Jacques M.T. , Glass Aaron M. , Mohler Peter J. , Taffet Steven M. , Vos Marc A. , van Rijen Harold V.M. , Delmar Mario , van Veen Toon A.B.
Published: August 2019

Human variants in plakophilin-2 (PKP2) associate with most cases of familial arrhythmogenic cardiomyopathy (ACM). Recent studies show that PKP2 not only maintains intercellular coupling, but also regulates transcription of genes involved in Ca2+ cycling and cardiac rhythm. ACM penetrance is low and it remains uncertain, which genetic and environmental modifiers are crucial for developing the cardiomyopathy. In this study, heterozygous PKP2 knock-out mice (PKP2-Hz) were used to investigate the influence of exercise, pressure overload, and inflammation on a PKP2-related disease progression. In PKP2-Hz mice, protein levels of Ca2+-handling proteins were reduced compared to wildtype (WT). PKP2-Hz hearts exposed to voluntary exercise training showed right ventricular lateral connexin43 expression, right ventricular conduction slowing, and a higher susceptibility towards arrhythmias. Pressure overload increased levels of fibrosis in PKP2-Hz hearts, without affecting the susceptibility towards arrhythmias. Experimental autoimmune myocarditis caused more severe subepicardial fibrosis, cell death, and inflammatory infiltrates in PKP2-Hz hearts than in WT. To conclude, PKP2 haploinsufficiency in the murine heart modulates the cardiac response to environmental modifiers via different mechanisms. Exercise upon PKP2 deficiency induces a pro-arrhythmic cardiac remodeling, likely based on impaired Ca2+ cycling and electrical conduction, versus structural remodeling. Pathophysiological stimuli mainly exaggerate the fibrotic and inflammatory response.
Different Dynamics in 6aJL2 Proteins Associated with AL Amyloidosis, a Conformational Disease
Authors: Maya-Martinez Roberto , French-Pacheco Leidys , Valdés-García Gilberto , Pastor Nina , Amero Carlos
Published: August 2019

Light-chain amyloidosis (AL) is the most common systemic amyloidosis and is caused by the deposition of mainly insoluble immunoglobulin light chain amyloid fibrils in multiple organs, causing organ failure and eventually death. The germ-line λ6a has been implicated in AL, where a single point mutant at amino acid 24 (6aJL2-R24G) has been observed in around 25% of patient samples. Structural analysis has shown only subtle differences between both proteins; nevertheless, 6aJL2-R24G is more prone to form amyloid fibrils. To improve our understanding of the role of protein flexibility in amyloid fibril formation, we have used a combination of solution nuclear magnetic resonance spectroscopy and molecular dynamics simulations to complement the structural insight with dynamic knowledge. Fast timescale dynamics (ps–ns) were equivalent for both proteins, but suggested exchange events for some residues. Even though most of the intermediate dynamics (μs–ms) occurred at a similar region for both proteins, the specific characteristics are very different. A minor population detected in the dispersion experiments could be associated with the formation of an off-pathway intermediate that protects from fiber formation more efficiently in the germ-line protein. Moreover, we found that the hydrogen bond patterns for both proteins are similar, but the lifetime for the mutant is significantly reduced; as a consequence, there is a decrease in the stability of the tertiary structure that extends throughout the protein and leads to an increase in the propensity to form amyloid fibers.
Absorption and Emission Spectroscopic Investigation of the Thermal Dynamics of the Archaerhodopsin 3 Based Fluorescent Voltage Sensor QuasAr1
Authors: Penzkofer Alfons , Silapetere Arita , Hegemann Peter
Published: August 2019

QuasAr1 is a fluorescent voltage sensor derived from Archaerhodopsin 3 (Arch) of Halorubrum sodomense by directed evolution. Here we report absorption and emission spectroscopic studies of QuasAr1 in Tris buffer at pH 8. Absorption cross-section spectra, fluorescence quantum distributions, fluorescence quantum yields, and fluorescence excitation spectra were determined. The thermal stability of QuasAr1 was studied by long-time attenuation coefficient measurements at room temperature (23 ± 2 °C) and at 2.5 ± 0.5 °C. The apparent melting temperature was determined by stepwise sample heating up and cooling down (obtained apparent melting temperature: 65 ± 3 °C). In the protein melting process the originally present protonated retinal Schiff base (PRSB) with absorption maximum at 580 nm converted to de-protonated retinal Schiff base (RSB) with absorption maximum at 380 nm. Long-time storage of QuasAr1 at temperatures around 2.5 °C and around 23 °C caused gradual protonated retinal Schiff base isomer changes to other isomer conformations, de-protonation to retinal Schiff base isomers, and apoprotein structure changes showing up in ultraviolet absorption increase. Reaction coordinate schemes are presented for the thermal protonated retinal Schiff base isomerizations and deprotonations in parallel with the dynamic apoprotein restructurings.
Isolation of a Novel Metalloproteinase from Agkistrodon Venom and Its Antithrombotic Activity Analysis
Authors: Huang Jin , Fan Hui , Yin Xiaojian , Huang Fang
Published: August 2019

Snake venom contains large amounts of active proteins and peptides. In this study, a novel snake protein, metalloproteinase SP, was successfully isolated from the venom of Agkistrodon acutus by multi-gel chromatography. The isolated protein exhibits anti-platelet aggregation activity. Animal experiments showed that it exhibited defibration, anticoagulation, and antithrombotic effects and contributes to improved blood rheology and antiplatelet aggregation. In vivo experiments demonstrated that it prolonged clotting time, partial thromboplastin time, prothrombin time, thrombin time, fibrinogen time and reduced fibrinogen content of mice. Also, metalloproteinase SP inhibited carrageenan-induced tail thrombosis, ADP-induced acute pulmonary embolism, and ADP, Arachidonic acid (AA), or collagen-induced platelet aggregation. In vitro experiments showed that the protein cleaved the α, β, and γ chains of fibrinogen. Metabolomic analysis upon metalloproteinase SP treatment revealed that 14 metabolites, which are mainly involved in phenylalanine, tyrosine, and tryptophan biosynthesis, responded to metalloproteinase SP treatment. In summary, the isolated snake venom protein inhibits formation of acute pulmonary embolism probably through regulating and restoring perturbed energy, lipid, and amino acid metabolism.
Discovery of New Inhibitors of Transforming Growth Factor-Beta Type 1 Receptor by Utilizing Docking and Structure-Activity Relationship Analysis
Authors: Jiang Jun-Hao , Deng Ping
Published: August 2019

The transforming growth factor-beta (TGF-β) plays an important role in pathological fibrosis and cancer transformation. Therefore, the inhibition of the TGF-β signaling pathway has therapeutic potential in the treatment of cancer. In this study, the binding modes between 47 molecules with a pyrrolotriazine-like backbone structure and transforming growth factor-beta type 1 receptor (TβR1) were simulated by molecular docking using Discovery Studio software, and their structure–activity relationships were analyzed. On the basis of the analysis of the binding modes of ligands in the active site and the structure–activity relationships, 29,254 new compounds were designed for virtual screening. According to the aforementioned analyses and Lipinski’s rule of five, five new compounds (CQMU1901–1905) with potential activity were screened through molecular docking. Among them, CQMU1905 is an attractive molecule composed of 5-fluorouracil (5-FU), 6-mercaptopurine (6-MP), and 5-azacytosine. Interestingly, 5-FU, 6-MP, and 5-azacytidine are often used as anti-metabolic agents in cancer treatment. Compared with existing compounds, CQMU1901–1905 can interact with target proteins more effectively and have good potential for modification, making them worthy of further study.
Reducing Secondary Flow Losses in Low-Pressure Turbines: The “Snaked” Blade
Authors: Giovannini Matteo , Rubechini Filippo , Marconcini Michele , Arnone Andrea , Bertini Francesco
Published: August 2019

This paper presents an innovative design for reducing the impact of secondary flows on the aerodynamics of low-pressure turbine (LPT) stages. Starting from a state-of-the-art LPT stage, a local reshaping of the stator blade was introduced in the end-wall region in order to oppose the flow turning deviation. This resulted in an optimal stator shape, able to provide a more uniform exit flow angle. The detailed comparison between the baseline stator and the redesigned one allowed for pointing out that the rotor row performance increased thanks to the more uniform inlet flow, while the stator losses were not significantly affected. Moreover, it was possible to derive some design rules and to devise a general blade shape, named ‘snaked’, able to ensure such results. This generalization translated in an effective parametric description of the ‘snaked’ shape, in which few parameters are sufficient to describe the optimal shape modification starting from a conventional design. The “snaked” blade concept and its design have been patented by Avio Aero. The stator redesign was then applied to a whole LPT module in order to evaluate the potential benefit of the ‘snaked’ design on the overall turbine performance. Finally, the design was validated by means of an experimental campaign concerning the stator blade. The spanwise distributions of the flow angle and pressure loss coefficient at the stator exit proved the effectiveness of the redesign in providing a more uniform flow to the successive row, while preserving the original stator losses.