bluuebunny/crossref_metadata_2025 huggingface dataset:
Sárkánykép a magyar népmesekincsben
Authors: Gombos Péter , Németh Csenge Rózsa
Published: January 2020

Kutatásunk során azt szerettük volna megtudni, hogy a magyar népmesékben, illetve általánosabban a magyar néphitben milyen módon jelenik meg a sárkány alakja. Szűkebben arra voltunk kíváncsiak, hogy hogyan, mikor keveredett össze az állatszerű (gyíkszerű), tűzfújó szörnyeteg és a lányrabló (férfiszerű) mesealak figurája. Sejtésünk az volt, hogy eredendően e két sárkánytípus külön (történetekben) létezett, s csak később mehetett végbe az a kontamináció, amelynek eredményeként ma már nem csodálkozunk rá arra, miért is rabol magának feleséget egy repülő, tűzfújó gyíkszörny.

Kutatásunkhoz az első, még 19. századi magyar népmesegyűjtemények közül Arany László, Benedek Elek, Berze Nagy János, Erdélyi János, Ipolyi Arnold, Kriza János, Mailand Oszkár és Merényi László gyűjtéseit tekintettük át. Az ezekben talált sárkányos meséket csoportosítottuk a bennük előforduló sárkányok alakjai szerint, s a kapott eredmények alapján fogalmaztunk meg következtetéseket a keveredés idejét és mikéntjét illetően.
Article 20 of Japan’s Constitution and Regional Integration
Authors: Asgarov Murad
Published: January 2020

Reinterpretation of the Japanese constitution has actual and potential impact on International Relations in the wider North East Asian region.  Most research had been dedicated to the issue of Article 9, which limits Japan’s military capability. The current study is going analyse Article 20 of Japan’s fundamental legal document, which also has an influence on Japan’s role on the international stage. Article 20 de-jure establishes that Japan is a secular state. However, with the current global trend of desecularisation, it is important to consider to what extent Japan is actually secular.Keywords: secularism, Japan, Korea, China, Buzan
Incidence of hypercalcemia and thiazide associated hypercalcemia on an OPD basis biochemical evaluation
Authors: Bhat Moomin Hussain , Khan Mosin Saleem , Masoodi Shariq Rashid , Abass Shuja , Bhat Javaid Rasool , Ahmad Peerzada Ovais , Wangnoo Bisma Rafiq , Dar Taief Ahmad , Andrabi Bathsheeba , Mudassar Syed
Published: January 2020

Background: Hypercalcemia is most of the times diagnosed on routine biochemical evaluation, and concomitant use of thiazide diuretics is common since this group of antihypertensives is frequently prescribed worldwide.

Objective: To determine the incidence of hypercalcemia as well as thiazide-induced hypercalcemia on an OPD basis

Methods: In a prospective hospital-based descriptive study, patients for routine evaluation, attending outpatient clinics.

Results: A total of 373 patients participated in the study, out of which 101(27.1%) were hypertensive. 30 of the 101 hypertensive patients were on thiazides. Hypercalcemia was present in total of 7 (1.9%) patients, primary hyperparathyroidism was seen in 4 patients, out of which 2 patients were on thiazides. 6.7% (2/30) of the patients on thiazides were having hypercalcemia as compared to 1.5% (5/343) patients, not on thiazides (p=0.044).

Conclusion: About every 50 patients evaluated, one patient has hypercalcemia with frequency of hypercalcemia being significantly higher among subjects receiving thiazides than those not receiving thiazide drugs.
Determinants of Bicycle Use among Student Population: Exploratory Research of Social and Infrastructure Factors
Authors: Pogačar Kaja , Dežan Lucija , Lamot Monika , Renčelj Marko
Published: January 2020

By exposing more benefits than shortcomings regarding cycling, this paper focuses on university students as a significant target group that could promote cycling as the main transport mode in cities. The paper addresses a variety of determinants, barriers, and motivation for cycling among the university students within the international context. Furthermore, it exposes the importance of smaller university cities, where students can present a substantial share of the total population. Contextually, we present the research upon the use of bicycles among the students in the university city of Maribor, Slovenia. To examine whether social or infrastructural determinants play a decisive role, a questionnaire was conducted among 382 students. The findings revealed that although the topography of the city and the distances between crucial institutions are, in general, favorable, only 10.7% of students cycle daily, whereby 63.3% do not cycle at all. There were no statistical differences noticed between the impact of infrastructural and social factors; convenience was exposed as a statistically significant determinant, whereas the sustainability aspect proved to be an insignificant factor for students cycling. To conclude, cycling among the student population in smaller cities can represent a common case of potentially high impact of student population regarding sustainable mobility.
Influence of Aluminium and Boron Orthophosphate on the Setting and the Resulting Structure of Alkali Silicate Binders for Refractory Application
Authors: Hopp Vanessa , Masoudi Alavi Ali , Sax Almuth , Quirmbach Peter
Published: January 2020

Liquid alkali silicates (waterglasses) are used as chemical binders for a wide range of refractory applications, the setting of which can be initiated by the addition of phosphate hardeners. The duration of the setting process is of special interest for an economic lining with short aggregate downtimes. Therefore, in the present work, the influences of two different types of phosphate (aluminium orthophosphate and boron orthophosphate) on the hardening mechanisms of waterglasses are investigated. Time-dependent measurements by dynamic mechanical analysis (DMA) are carried out to observe the setting process. Structural information of the hardened amorphous samples is obtained by means of nuclear magnetic resonance (NMR) spectroscopy. It is shown that the use of different phosphates leads to differences in the setting rate, caused by different modes of network formation. The resultant silicate networks incorporate the aluminium or boron species but differ in the connectivity of those units. In addition, the distribution following the well-known Qn notation of the silicate units is directly influenced by the phosphate type.
Effective Droplet Size Reduction and Excellent Stability of Limonene Nanoemulsion Formed by High-Pressure Homogenizer
Authors: Hidajat Marcel Jonathan , Jo Wantaek , Kim Hyeonhyo , Noh Jongho
Published: January 2020

Limonene as an interesting bioactive material that has great benefits due to its antimicrobial and anti-carcinogen properties. However, it has several limitations such as its oxidative and oily nature. In order to overcome these limitations, a high-pressure homogenizer (HPH) was utilized to produce limonene nanoemulsion, which enhances its dispersibility while preventing oxidation with great stability. Limonene was pre-mixed with soybean oil as carrier oil prior to emulsification. The effect of soybean oil to limonene ratio, number of pass, homogenization pressure, emulsifier concentration and homogenization method were observed. A stability test was also conducted for 28 days at room temperature. The result revealed that soybean oil and limonene demonstrated a certain ratio to produce the most stable nanoemulsion. Meanwhile, emulsion size could be reduced from 327.8 nm to 55.5 nm in five passes at 1000 bar. Increasing the emulsifier concentration could reduce the droplet size to 40 nm. A comparison with other emulsification method showed that HPH was the best emulsification technique due to its intense emulsification power resulted from shear, cavitation, and droplet impacts. This study reveals that HPH is a great and simple way to produce stable limonene nanoemulsion for the cosmetic, pharmaceutical, and food industries.
Approximating Information Measures for Fields
Authors: Dębowski Łukasz
Published: January 2020

We supply corrected proofs of the invariance of completion and the chain rule for the Shannon information measures of arbitrary fields, as stated by Dębowski in 2009. Our corrected proofs rest on a number of auxiliary approximation results for Shannon information measures, which may be of an independent interest. As also discussed briefly in this article, the generalized calculus of Shannon information measures for fields, including the invariance of completion and the chain rule, is useful in particular for studying the ergodic decomposition of stationary processes and its links with statistical modeling of natural language.
Numerical Convergence Analysis of the Frank–Kamenetskii Equation
Authors: Woolway Matthew , Jacobs Byron A. , Momoniat Ebrahim , Harley Charis , Britz Dieter
Published: January 2020

This work investigates the convergence dynamics of a numerical scheme employed for the approximation and solution of the Frank–Kamenetskii partial differential equation. A framework for computing the critical Frank–Kamenetskii parameter to arbitrary accuracy is presented and used in the subsequent numerical simulations. The numerical method employed is a Crank–Nicolson type implicit scheme coupled with a fourth order spatial discretisation as well as a Newton–Raphson update step which allows for the nonlinear source term to be treated implicitly. This numerical implementation allows for the analysis of the convergence of the transient solution toward the steady-state solution. The choice of termination criteria, numerically dictating this convergence, is interrogated and it is found that the traditional choice for termination is insufficient in the case of the Frank–Kamenetskii partial differential equation which exhibits slow transience as the solution approaches the steady-state. Four measures of convergence are proposed, compared and discussed herein.
Sizing and Allocation of Battery Energy Storage Systems in Åland Islands for Large-Scale Integration of Renewables and Electric Ferry Charging Stations
Authors: Kumar Jagdesh , Parthasarathy Chethan , Västi Mikko , Laaksonen Hannu , Shafie-Khah Miadreza , Kauhaniemi Kimmo
Published: January 2020

The stringent emission rules set by international maritime organisation and European Directives force ships and harbours to constrain their environmental pollution within certain targets and enable them to employ renewable energy sources. To this end, harbour grids are shifting towards renewable energy sources to cope with the growing demand for an onshore power supply and battery-charging stations for modern ships. However, it is necessary to accurately size and locate battery energy storage systems for any operational harbour grid to compensate the fluctuating power supply from renewable energy sources as well as meet the predicted maximum load demand without expanding the power capacities of transmission lines. In this paper, the equivalent circuit battery model of nickel–cobalt–manganese-oxide chemistry has been utilised for the sizing of a lithium-ion battery energy storage system, considering all the parameters affecting its performance. A battery cell model has been developed in the Matlab/Simulink platform, and subsequently an algorithm has been developed for the design of an appropriate size of lithium-ion battery energy storage systems. The developed algorithm has been applied by considering real data of a harbour grid in the Åland Islands, and the simulation results validate that the sizes and locations of battery energy storage systems are accurate enough for the harbour grid in the Åland Islands to meet the predicted maximum load demand of multiple new electric ferry charging stations for the years 2022 and 2030. Moreover, integrating battery energy storage systems with renewables helps to increase the reliability and defer capital cost investments of upgrading the ratings of transmission lines and other electrical equipment in the Åland Islands grid.
Optimization and Application for Hydraulic Electric Hybrid Vehicle
Authors: Hwang Hsiu-Ying , Lan Tian-Syung , Chen Jia-Shiun
Published: January 2020

Targeting the application of medium and heavy vehicles, a hydraulic electric hybrid vehicle (HEHV) was designed, and its energy management control strategy is discussed in this paper. Matlab/Simulink was applied to establish the pure electric vehicle and HEHV models, and backward simulation was adopted for the simulation, to get the variation of torque and battery state of charge (SOC) through New York City Cycle of the US Environmental Protection Agency (EPA NYCC). Based on the simulation, the energy management strategy was designed. In this research, the rule-based control strategy was implemented as the energy distribution management strategy first, and then the genetic algorithm was utilized to conduct global optimization strategy analysis. The results from the genetic algorithm were employed to modify the rule-based control strategy to improve the electricity economic performance of the vehicle. The simulation results show that the electricity economic performance of the designed hydraulic hybrid vehicle was improved by 36.51% compared to that of a pure electric vehicle. The performance of energy consumption after genetic algorithm optimization was improved by 43.65%.
Improvement of RVM Test Interpretation Using a Debye Equivalent Circuit
Authors: Martínez Miguel , Pleite Jorge
Published: January 2020

The aim of this document is to present how the interpretation of the RVM (Recovery Voltage Measurement) test can be improved through the use of a Debye equivalent circuit. As it is described in the literature, the interpretation of the RVM test requires expertise and if the transformer presents a high interfacial polarization it is not possible to diagnose it in detail. The Debye model is proposed in this work for enhancing RVM interpretation. This model is based on an electrical circuit that includes basic R-C components, that allows two interesting features: on one hand, insulation physical effects can be separately represented and, on the other, the values of the R-C components can be calculated from the RVM response. A method is proposed in which using a sweep with a constant number of predefined time constants branches allows us to determine the areas of influence of the different compounds present in the dielectric. Finally, several case studies are presented, in which it is correlated a dielectric oil treatment carried out and the equivalent circuit changes using a sweep allows us to analyze different branches’ sensitivity and to identify the areas of influence of each compound.
Experimental Study on a Flue Gas Waste Heat Cascade Recovery System under Variable Working Conditions
Authors: Liu Jiayou , Gong Xiaoyun , Zhang Wenhua , Sun Fengzhong , Wang Qingbiao
Published: January 2020

Recovering flue gas waste heat is beneficial to improving the unit efficiency in power plants. To obtain the change rules of performance parameters of a flue gas waste heat cascade recovery system (FWCRS) under variable working conditions, an experiment bench was designed and built. The variation laws of the inlet temperature and exhaust flue gas temperature of a low temperature economizer (LTE), the inlet and outlet air temperature of an air preheater (AP), the heat exchange quantities of the AP, LTE, and front-located air heater and an additional economizer (AE), as well as the waste heat recovery efficiency, the system exergy efficiency, and the energy grade replacement coefficient were obtained as the flue gas flow, flue gas temperature, bypass flue gas ratio, air temperature, and circulating water flow in AE changed. Using an orthogonal test, the flue gas temperature, bypass flue gas ratio and air temperature were proved to be the significant factors affecting the performance parameters of FWCRS, and the bypass flue gas ratio was suggested as an adjusting parameter of FWCRS under variable working conditions.
Representative Days for Expansion Decisions in Power Systems
Authors: García-Cerezo Álvaro , Baringo Luis , García-Bertrand Raquel
Published: January 2020

Short-term uncertainty needs to be properly modeled when analyzing a planning problem in a power system. Since the use of all available historical data may lead to problems of computational intractability, clustering algorithms may be applied in order to reduce the computational effort without compromising accurate representation of historical data. In this paper, we propose a modified version of the traditional K-means method, seeking to represent the maximum and minimum values of input data, namely, electricity demand and renewable production in several locations of a power system. Extreme values of these parameters must be represented as they are high-impact decisions that are taken with respect to expansion and operation. The method proposed is based on the K-means algorithm, which represents the correlation between demand and wind-power production. The chronology of historical data, which influences the performance of some technologies, is characterized through representative days, each made up of 24 operating conditions. A realistic case study, applying representative days, analyzes the generation and transmission expansion planning of the IEEE 24-bus Reliability Test System. Results show that the proposed method is preferable to the traditional K-means technique.
Reduced Bipolar Conduction in Bandgap-Engineered n-Type Cu0.008Bi2(Te,Se)3 by Sulfur Doping
Authors: Shin Weon Ho , Kim Hyun-Sik , Kim Se Yun , Choo Sung-sil , Hong Seok-won , Oh Yeseong , Yang Yerim , Kim Yoona , Park Hee Jung , Kim Sang-il
Published: January 2020

Significant bipolar conduction of the carriers in Bi2Te3-based alloys occurs at high temperatures due to their narrow bandgaps. Therefore, at high temperatures, their Seebeck coefficients decrease, the bipolar thermal conductivities rapidly increase, and the thermoelectric figure of merit, zT, rapidly decreases. In this study, band modification of n-type Cu0.008Bi2(Te,Se)3 alloys by sulfur (S) doping, which could widen the bandgap, is investigated regarding carrier transport properties and bipolar thermal conductivity. The increase in bandgap by S doping is demonstrated by the Goldsmid–Sharp estimation. The bipolar conduction reduction is shown in the carrier transport characteristics and thermal conductivity. In addition, S doping induces an additional point-defect scattering of phonons, which decreases the lattice thermal conductivity. Thus, the total thermal conductivity of the S-doped sample is reduced. Despite the reduced power factor due to the unfavorable change in the conduction band, zT at high temperatures is increased by S doping with simultaneous reductions in bipolar and lattice thermal conductivity.
Zero-Vector-Injection Based Current Sharing Control of Interleaved Full-Bridge LLC Resonant Converters
Authors: Wu Xuanlyu , Luo Dejie , Wu Panpan , Zhao Xin , Kang Zhen , Wu Xiaohua
Published: January 2020

Interleaved LLC resonant converters are widely used in various fields. However, interleaved LLC converters under Pulse Frequency Modulation (PFM) will lose the regulation of individual phases, causing a load sharing problem. Existing load sharing solutions have limitations; for example, phase shedding and current sharing cannot be realized at the same time. This paper proposed a novel current sharing method for interleaved full-bridge LLC resonant converters. Based on Zero-Vector-Injection, the voltage applied to the resonant tank is controlled to compensate for the difference in gain caused by component tolerance. The modulation strategy is proposed to maintain soft switching after Zero-Vector-Injection, and the phase shedding technique is also used to improve the efficiency at a light load. The detailed theoretical analysis and implementation method are proposed and validated using simulations. Experiments are also carried out to verify the feasibility of the proposed strategy based on a 2-phase 1.8 kW prototype.
Numerical and Experimental Study on Convective Heat Transfer Characteristics in Foam Materials
Authors: Lu Hongyan , Yang Lixin , Wu Zhiyong , Xu Siqi
Published: January 2020

Foam materials are widely used in heat exchange because of their high porosity and large specific surface area. Correctly characterizing heat transfer characteristics is the key to ensuring efficient heat transfer. In this paper, single-blow transient test technology is used to experimentally measure the temperature. Silicon carbide ceramics with various thicknesses ranging from 30 to 105 mm and different pore structures were used in the experiments. The test was carried out at the velocity ranging from 0.5 to 1.8 m/s. The air temperature distributions of the inlet and outlet were obtained by processing the experimental data, and the regularity of the average volumetric heat transfer coefficient was obtained and analyzed. Subsequently, the simplified tetrakaidecahedron models with a porosity of 0.85 and 0.75 were used to analyze the heat transfer characteristics. The local thermal equilibrium and local thermal non-equilibrium at the pore scale were analyzed. By comparing the simulation with the experiment, it shows that the larger thickness affects local thermal equilibrium and leads to a decrease in the volumetric heat transfer coefficient. The conclusion can be used to guide the optimization of the design of foam material-mediated heat exchange equipment.
Mathematical Modeling and Performance Analysis of a New Hybrid Solar Dryer of Lemon Slices for Controlling Drying Temperature
Authors: Hao Wengang , Liu Shuonan , Mi Baoqi , Lai Yanhua
Published: January 2020

A new hybrid solar dryer was designed and constructed in this study, which consisted of a flat-plate solar collector with dual-function (DF-FPSC), drying chamber with glass, fan etc. The DF-FPSC was firstly applied in drying agricultural products. The innovative application of hybrid solar dryer can control the drying chamber air temperature within a suitable range by different operation strategies. Drying experiments for lemon slices in the hybrid solar dryer were conducted by comparing open sun drying (OSD). Eight mathematical models of drying characteristics were employed to select the most suitable model for describing the drying curves of lemon slices. Furthermore, energy, exergy economic and environment (4E) analysis were also adopted to analyze the drying process of lemon slices. The results show that under the same experimental condition, the drying capability of the hybrid solar dryer was stronger than that of OSD. Meanwhile, it was found that the Two term and Wang and Singh models were the most suitable for fitting the lemon slices’ drying characteristics inside the hybrid solar dryer. The drying chamber air temperature can be controlled under about 60 °C during the process of lemon slices’ drying. The experimental results show the feasibility and validity of the proposed hybrid solar dryer.
Extraction Behaviors of Lignin and Hemicellulose-Derived Sugars During Organosolv Fractionation of Agricultural Residues Using a Bench-Scale Ball Milling Reactor
Authors: Kim Tae Hoon , Kwak Hyun , Kim Tae Hyun , Oh Kyeong Keun
Published: January 2020

Ethanol organosolv fractionation combined with ball milling was conducted on three major agricultural residues: Rice husk (RH), rice straw (RS), and barley straw (BS). The highest lignin extraction yields of RH, RS, and BS were 55.2%, 53.1%, and 59.4% and the purity of lignin recovered was 99.5% for RH and RS, and 96.8% for BS, with similar chemical characteristics, i.e., low molecular weight distributions (1453–1817 g/mol) and poly dispersity index (1.15–1.28). However, considering the simultaneous production of hemicellulose-derived sugars, distinctive fractionation behaviors were shown for the three agricultural residues. The highest hemicellulose-derived sugar yield was 73.8% when RH was fractionated at 170 °C for 30 min. Meanwhile, very low sugar yields of 31.9% and 35.7% were obtained from RS and BS, respectively. The highest glucan-to-glucose conversion yield from enzymatic hydrolysis of fractionated RH reached 85.2%. Meanwhile, the enzymatic digestibility of the fractionated RS and BS was 60.0% and 70.5%, respectively. Consequently, the fractionation efficiency for RH can be improved with fine refinement. For the case of RS, other fractionation process should be applied to achieve effective fractionation performance.
Influence and Impact of Data Averaging and Temporal Resolution on the Assessment of Energetic, Economic and Technical Issues of Hybrid Photovoltaic-Battery Systems
Authors: Burgio Alessandro , Menniti Daniele , Sorrentino Nicola , Pinnarelli Anna , Leonowicz Zbigniew
Published: January 2020

The temporal resolution of the demand and generation profiles may have a significant impact on the estimation of self-sufficiency and self-consumption for consumers and prosumers. As an example, measuring the load profile, with a low temporal resolution, may lead to the under-estimation of energy consumption, while measuring solar irradiation with a low temporal resolution may lead to the over-estimation of on-site energy generation. Storage systems may reduce errors due to the lower temporal resolution by 8–10 times or even more, depending on the capacity of the batteries. Besides self-generation and self-consumption, there are other indicators that can be influenced by temporal resolution that deserve to be investigated. This is a detailed study of the influence of temporal resolution and the time averaging on a hybrid photovoltaic-battery system; this study encompasses both economic and technical aspects, from the calculation of savings on the electricity bill to the estimation of the equivalent cycles of battery storage system. To this end, the three-minute load profile of a real case study is used to obtain other three load profiles with temporal resolution equal to 15, 30, and 60 min via data averaging. Therefore, the authors analyze the influence and the impact of temporal resolution and data averaging in terms of: The size of the photovoltaic generator and the capacity of the storage system; the savings in the electricity bill and the balance between costs and savings; the peak values and the average values of power flows during high generation and low generation; the profile of the storage system over the year; the utilization rate of the storage system and the rated power of the electronic converter that regulates the charge and the discharge; the profile of the state of charge of the storage system and the life-time estimation of batteries through the calculation of the equivalent number of cycles.
Energy End-Use Categorization and Performance Indicators for Energy Management in the Engineering Industry
Authors: Kanchiralla Fayas , Jalo Noor , Johnsson Simon , Thollander Patrik , Andersson Maria
Published: January 2020

Energy efficiency (EE) improvement is one of the most crucial elements in the decarbonization of industry. EE potential within industries largely remains untapped due to the lack of information regarding potential EE measures (EEM), knowledge regarding energy use, and due to the existence of some inconsistencies in the evaluation of energy use. Classification of energy end-using processes would increase the understanding of energy use, which in turn would increase the detection and deployment of EEMs. The study presents a novel taxonomy with hierarchical levels for energy end-use in manufacturing operations for the engineering industry, analyzes processes in terms of energy end-use (EEU) and CO2 emissions, and scrutinizes energy performance indicators (EnPIs), as well as proposing potential new EnPIs that are suitable for the engineering industry. Even though the study has been conducted with a focus on the Swedish engineering industry, the study may be generalizable to the engineering industry beyond Sweden.
Emission of Volatile Organic Compounds from Heartwood and Sapwood of Selected Coniferous Species
Authors: Czajka Magdalena , Fabisiak Beata , Fabisiak Ewa
Published: January 2020

The qualitative and quantitative composition of volatile organic compounds (VOC) emitted from furnishings from solid wood and all kinds of wood derivative materials depends on many factors, of which the most important is the wood species. The intraspecies and interspecies differences in VOC emission result from the differences in the chemical composition and anatomical structure of heartwood and sapwood of different species. VOC composition analysis was performed separately for heartwood and sapwood of Scots pine (Pinus sylvestris L.), Norway spruce (Picea abies (L.) Karst.) and European larch (Larix decidua Mill.) trees. The studies were conducted in a glass climatic chamber of 0.025 m3, equipped with a system for the monitoring and control of climatic conditions. Samples of air for analyses were collected after 3, 7, 14 and 28 days of exposure. The results provided evidence for interspecies and intraspecies differences in the qualitative and quantitative compositions of VOC. The concentration of total VOC (TVOC) released from heartwood of Scots pine was higher than that released from sapwood. For European larch and Norway spruce, the opposite relations were observed. The VOC emission from Scots pine heartwood was about 17 times higher than the emission from European larch and Norway spruce heartwood. The differences in TVOC emitted from the sapwood of samples from different species were smaller. For each of the species, the highest percentage contribution to TVOC was made by terpenes. The second highest percentage contribution in TVOC was made by compounds containing a carbonyl group, mainly aldehydes, while aromatic compounds made the third highest contribution.
Oral Delivery of a Tetrameric Tripeptide Inhibitor of VEGFR1 Suppresses Pathological Choroid Neovascularization
Authors: Tarallo Valeria , Iaccarino Emanuela , Cicatiello Valeria , Sanna Riccardo , Ruvo Menotti , De Falco Sandro
Published: January 2020

Age-related macular degeneration (AMD) is the primary cause of blindness in advanced countries. Repeated intravitreal delivery of anti-vascular endothelial growth factor (VEGF) agents has represented an important advancement for the therapy of wet AMD with significative results in terms of blindness prevention and partial vision restore. Nonetheless, some patients are not responsive or do not attain significant visual improvement, intravitreal injection may cause serious complications and important side effects have been reported for the prolonged block of VEGF-A. In order to evaluate new anti-angiogenic strategies, we focused our attention on VEGF receptor 1 (VEGFR1) developing a specific VEGFR-1 antagonist, a tetrameric tripeptide named inhibitor of VEGFR 1 (iVR1). We have evaluated its anti-angiogenic activity in the preclinical model of AMD, the laser-induced choroid neovascularization (CNV). iVR1 is able to potently inhibit CNV when delivered by intravitreal injection. Surprisingly, it is able to significantly reduce CNV also when delivered by gavage. Our data show that the specific block of VEGFR1 in vivo represents a valid alternative to the block of VEGF-A and that the inhibition of the pathological neovascularization at ocular level is also possible by systemic delivery of compounds not targeting VEGF-A.
The Anti-Inflammatory Effects of Angiogenin in an Endotoxin Induced Uveitis in Rats
Authors: Park Jihae , Kim Jee Taek , Lee Soo Jin , Kim Jae Chan
Published: January 2020

Angiogenin (ANG) is involved in the innate immune system and inflammatory disease. The aim of this study is to evaluate the anti-inflammatory effects of ANG in an endotoxin induced uveitis (EIU) rat model and the pathways involved. EIU rats were treated with balanced salt solution (BSS), a non-functional mutant ANG (mANG), or wild-type ANG (ANG). The integrity of the blood-aqueous barrier was evaluated by the infiltrating cell and protein concentrations in aqueous humor. Histopathology, Western blot, and real-time qRT-PCR of aqueous humor and ocular tissue were performed to analyze inflammatory cytokines and transcription factors. EIU treated with ANG had decreased inflammatory cells and protein concentrations in the anterior chamber. Compared to BSS and mANG, ANG treatment showed reduced expression of IL-1β, IL-8, TNF-α, and Myd88, while the expression of IL-4 and IL-10 was increased. Western blot of ANG treatment showed decreased expression of IL-6, inducible nitric oxide synthase (iNOS), IL-1β, TNF-α, and phosphorylated NF-κB and increased expression of IL-10. In conclusion, ANG seems to reduce effectively immune mediated inflammation in the EIU rat model by reducing the expression of proinflammatory cytokines, while increasing the expression of anti-inflammatory cytokines through pathways related to NF-κB. Therefore, ANG shows potential for effectively suppressing immune-inflammatory responses in vivo.
A New Cold-Adapted and Salt-Tolerant Glutathione Reductase from Antarctic Psychrophilic Bacterium Psychrobacter sp. and Its Resistance to Oxidation
Authors: Wang Yatong , Wang Quanfu , Hou Yanhua
Published: January 2020

A new glutathione reductase gene (psgr) coding for glutathione reductase (GR) from an Antarctic bacterium was cloned and overexpressed into Escherichia coli (E. coli). A sequence analysis revealed that PsGR is a protein consisting of 451 amino acids, and homology modeling demonstrated that PsGR has fewer hydrogen bonds and salt bridges, which might lead to improved conformational flexibility at low temperatures. PsGR possesses the flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide phosphate (NADPH) binding motifs. Recombinant PsGR (rPsGR) was purified using Ni-NTA affinity chromatography and was found to have a molecular mass of approximately 53.5 kDa. rPsGR was found to be optimally active at 25 °C and a pH of 7.5. It was found to be a cold-adapted enzyme, with approximately 42% of its optimal activity remaining at 0 °C. Moreover, rPsGR was most active in 1.0 M NaCl and 62.5% of its full activity remained in 3.0 M NaCl, demonstrating its high salt tolerance. Furthermore, rPsGR was found to have a higher substrate affinity for NADPH than for GSSG (oxidized glutathione). rPsGR provided protection against peroxide (H2O2)-induced oxidative stress in recombinant cells, and displayed potential application as an antioxidant protein. The results of the present study provide a sound basis for the study of the structural characteristics and catalytic characterization of cold-adapted GR.
Crocetin Extracted from Saffron Shows Antitumor Effects in Models of Human Glioblastoma
Authors: Colapietro Alessandro , Mancini Andrea , Vitale Flora , Martellucci Stefano , Angelucci Adriano , Llorens Silvia , Mattei Vincenzo , Gravina Giovanni Luca , Alonso Gonzalo Luis , Festuccia Claudio
Published: January 2020

Over recent years, many authors discussed the effects of different natural compounds on glioblastoma (GBM). Due to its capacity to impair survival and progression of different cancer types, saffron extract (SE), named crocetin (CCT), is particularly noteworthy. In this work, we elucidated the antitumor properties of crocetin in glioma in vivo and in vitro models for the first time. The in vitro results showed that the four tumor cell lines observed in this study (U251, U87, U138, and U373), which were treated with increasing doses of crocetin, showed antiproliferative and pro-differentiative effects as demonstrated by a significant reduction in the number of viable cells, deep changes in cell morphology, and the modulation of mesenchymal and neuronal markers. Indeed, crocetin decreased the expression of Cluster of Differentiation CD44, CD90, CXCR4, and OCT3/4 mesenchymal markers, but increased the expression of βIII-Tubulin and neurofilaments (NFH) neuronal linage-related markers. Epigenetic mechanisms may modulate these changes, since Histone Deacetylase, HDAC1 and HDAC3 were downmodulated in U251 and U87 cells, whereas HDAC1 expression was downmodulated in U138 and U373 cells. Western blotting analyses of Fatty Acid Synthase, FASN, and CD44 resulted in effective inhibition of these markers after CCT treatment, which was associated with important activation of the apoptosis program and reduced glioma cell movement and wound repair. The in vivo studies aligned with the results obtained in vitro. Indeed, crocetin was demonstrated to inhibit the growth of U251 and U87 cells that were subcutaneously injected into animal models. In particular, the Tumor To Progression or TTP values and Kaplan–Meier curves indicated that crocetin had more major effects than radiotherapy alone, but similar effects to temozolomide (TMZ). An intra-brain cell inoculation of a small number of luciferase-transfected U251 cells provided a model that was able to recapitulate recurrence after surgical tumor removal. The results obtained from the orthotopic intra-brain model indicated that CCT treatment increased the disease-free survival (DFS) and overall survival (OS) rates, inducing a delay in appearance of a detectable bioluminescent lesion. CCT showed greater efficacy than Radio Therapy (RT) but comparable efficacy to temozolomide in xenograft models. Therefore, we aimed to continue the study of crocetin’s effects in glioma disease, focusing our attention on the radiosensitizing properties of the natural compound and highlighting the ways in which this was realized.
Impact of the Different Preparation Methods to Obtain Autologous Non-Activated Platelet-Rich Plasma (A-PRP) and Activated Platelet-Rich Plasma (AA-PRP) in Plastic Surgery: Wound Healing and Hair Regrowth Evaluation
Authors: Gentile Pietro , Calabrese Claudio , De Angelis Barbara , Dionisi Laura , Pizzicannella Jacopo , Kothari Ashutosh , De Fazio Domenico , Garcovich Simone
Published: January 2020

Autologous therapies using platelet-rich plasma (PRP) need meticulous preparation—currently, no standardised preparation technique exists. Processing Quantitative Standards (PQSs) define manufacturing quantitative variables (such as time, volume and pressure). Processing Qualitative Standards (PQLSs) define the quality of the materials and methods of manufacturing. The aim of this review is to use existing PQSs and PQLs to report the in vivo/in vitro results obtained by using different Kits, that utilise different procedures (classified as Closed-Technique and Opened-Technique) to isolate autologous human activated (AA-PRP) or non-activated PRP (A-PRP). PQSs included the volumes of blood collected as well as the reagents used, the time/gravity of centrifugation, and the duration, temperature and tilt level/speed of centrifugation. PQLSs included the use of Calcium Chloride CaCl2, Kit weight, transparency of Kit components, the maintenance of a closed sterile processing environment and the use of a small centrifuge. Eight CE marked devices for PRP extraction were evaluated: Angel®, Biomed®, Cascade® and Selphyl®, Mag-18®, i-Stem®, MyCells® and Regenlab®. Using a Kit with the PQSs and PQLSs described in this study enables the isolation of A-PRP, thereby meeting consensus quality criteria. As our understanding of Critical Quality Attributes (CQAs) of A-PRP continues to evolve, especially with respect to purity and potency, adjustments to these benchmark PQSs and PQLs will hopefully help isolate A-PRP of desired CQAs with greater reproducibility, quality, and safety. Confirmatory studies will no doubt need to be completed.
Immune Checkpoint Inhibitors in Pre-Treated Gastric Cancer Patients: Results from a Literature-Based Meta-Analysis
Authors: Roviello Giandomenico , Corona Silvia Paola , D’Angelo Alberto , Rosellini Pietro , Nobili Stefania , Mini Enrico
Published: January 2020

Immunotherapy has recently changed the treatment of several cancers. We performed a literature-based meta-analysis of randomised controlled trials to assess the efficacy of the novel immune checkpoint inhibitors (ICIs) in metastatic gastric cancer. The main outcome was overall survival. Based on age (cut-off agreed at 65 years), tumour location (gastric vs. gastro-oesophageal junction), programmed death-ligand 1 (PD-L1) status, sex and Eastern Cooperative Oncology Group (ECOG) status (1 vs. 0), we scheduled a subgroup analysis for the overall survival. Three studies were included in the analysis for a total of 1456 cases (811 cases were in the experimental group and 645 cases in the control group). The pooled analysis showed improved overall survival in the experimental arm in the absence of statistical significance (hazard ratio (HR) = 0.87, 95% CI: 0.64–1.18; p = 0.37). The subgroup of patients with PD-L1-positive tumours (HR = 0.82 vs. 1.04) and gastro-oesophageal junction cancer (HR = 0.82 vs. 1.04) showed a statistically significant advantage of overall survival. This study supports the efficacy of immune checkpoint inhibitors in the subgroup of patients with metastatic gastric cancer with PD-L1-positive and gastro-oesophageal junction tumour location. Future studies are needed with the aim of identifying reliable predictive biomarkers of ICI efficacy.
Conflicting Actions of Inhalational Anesthetics, Neurotoxicity and Neuroprotection, Mediated by the Unfolded Protein Response
Authors: Kokubun Hiroshi , Jin Hisayo , Komita Mari , Aoe Tomohiko
Published: January 2020

Preclinical studies have shown that exposure of the developing brain to inhalational anesthetics can cause neurotoxicity. However, other studies have claimed that anesthetics can exert neuroprotective effects. We investigated the mechanisms associated with the neurotoxic and neuroprotective effects exerted by inhalational anesthetics. Neuroblastoma cells were exposed to sevoflurane and then cultured in 1% oxygen. We evaluated the expression of proteins related to the unfolded protein response (UPR). Next, we exposed adult mice in which binding immunoglobulin protein (BiP) had been mutated, and wild-type mice, to sevoflurane, and evaluated their cognitive function. We compared our results to those from our previous study in which mice were exposed to sevoflurane at the fetal stage. Pre-exposure to sevoflurane reduced the expression of CHOP in neuroblastoma cells exposed to hypoxia. Anesthetic pre-exposure also significantly improved the cognitive function of adult wild-type mice, but not the mutant mice. In contrast, mice exposed to anesthetics during the fetal stage showed cognitive impairment. Our data indicate that exposure to inhalational anesthetics causes endoplasmic reticulum (ER) stress, and subsequently leads to an adaptive response, the UPR. This response may enhance the capacity of cells to adapt to injuries and improve neuronal function in adult mice, but not in developing mice.
Subchromosome-Scale Nuclear and Complete Mitochondrial Genome Characteristics of Morchella crassipes
Authors: Liu Wei , Cai Yingli , Zhang Qianqian , Shu Fang , Chen Lianfu , Ma Xiaolong , Bian Yinbing
Published: January 2020

Morchella crassipes (Vent.) Pers., a typical yellow morel species with high economic value, is mainly distributed in the low altitude plains of Eurasia. However, rare research has been performed on its genomics and polarity, thus limiting its research and development. Here, we reported a fine physical map of the nuclear genome at the subchromosomal-scale and the complete mitochondrial genome of M. crassipes. The complete size of the nuclear genome was 56.7 Mb, and 23 scaffolds were assembled, with eight of them being complete chromosomes. A total of 11,565 encoding proteins were predicted. The divergence time analysis showed that M. crassipes representing yellow morels differentiated with black morels at ~33.98 Mya (million years), with 150 gene families contracted and expanded in M. crassipes versus the two black morels (M. snyderi and M. importuna). Furthermore, 409 CAZYme genes were annotated in M. crassipes, containing almost all plant cell wall degrading enzymes compared with the mycorrhizal fungi (truffles). Genomic annotation of mating type loci and amplification of the mating genes in the monospore population was conducted, the results indicated that M. crassipes is a heterothallic fungus. Additionally, a complete circular mitochondrial genome of M. crassipes was assembled, the size reached as large as 531,195 bp. It can be observed that the strikingly large size was the biggest up till now, coupled with 14 core conserved mitochondrial protein-coding genes, two rRNAs, 31 tRNAs, 51 introns, and 412 ncORFs. The total length of intron sequences accounted for 53.67% of the mitochondrial genome, with 19 introns having a length over 5 kb. Particularly, 221 of 412 ncORFs were distributed within 51 introns, and the total length of the ncORFs sequence accounted for 40.83% of the mitochondrial genome, and 297 ncORFs had expression activity in the mycelium stage, suggesting their potential functions in M. crassipes. Meanwhile, there was a high degree of repetition (51.31%) in the mitochondria of M. crassipes. Thus, the large number of introns, ncORFs and internal repeat sequences may contribute jointly to the largest fungal mitochondrial genome to date. The fine physical maps of nuclear genome and mitochondrial genome obtained in this study will open a new door for better understanding of the mysterious species of M. crassipes.
Is Newborn Screening the Ultimate Strategy to Reduce Diagnostic Delays in Pompe Disease? The Parent and Patient Perspective
Authors: Saich Raymond , Brown Renee , Collicoat Maddy , Jenner Catherine , Primmer Jenna , Clancy Beverley , Holland Tarryn , Krinks Steven
Published: January 2020

Pompe disease (PD) is a rare, autosomal-recessively inherited deficiency in the enzyme acid α-glucosidase. It is a spectrum disorder; age at symptom onset and rate of deterioration can vary considerably. In affected infants prognosis is poor, such that without treatment most infants die within the first year of life. To lose a baby in their first year of life to a rare disease causes much regret, guilt, and loneliness to parents, family, and friends. To lose a baby needlessly when there is an effective treatment amplifies this sadness. With so little experience of rare disease in the community, once a baby transfers to their home they are subject to a very uncertain and unyielding diagnostic journey while their symptomology progresses and their health deteriorates. With a rare disease like PD, the best opportunity to diagnose a baby is at birth. PD is not yet included in the current newborn screening (NBS) panel in Australia. Should it be? In late 2018 the Australian Pompe Association applied to the Australian Standing committee on Newborn Screening to have PD included. The application was not upheld. Here we provide an overview of the rationale for NBS, drawing on the scientific literature and perspectives from The Australian Pompe Association, its patients and their families. In doing so, we hope to bring a new voice to this very important debate.
Anionic Polymerization of ε-Caprolactam under the Influence of Water: 2. Kinetic Model
Authors: Wendel Rainer , Rosenberg Philipp , Wilhelm Michael , Henning Frank
Published: January 2020

The reaction kinetics of anionic polymerization for the production of anionic polyamide 6 (aPA6) are widely understood. It is also known that this reaction is very sensitive to external influences such as water. This paper analyzes and quantifies the influence of water on the reaction of ε-caprolactam to anionic polyamide 6. A kinetic model is developed in which the reactive molecules of the activator and catalyst are defined as variables and the concentrations of activator and catalyst as well as water content are considered. A model for the calculation of the reaction kinetics is established and validated with experimental data. The developed model can be used to predict the influence and compensation of water by addition of surplus activator and catalyst during the polymerization of ε-caprolactam.