bluuebunny/crossref_metadata_2025 huggingface dataset:
Politik Hukum Pengaturan Pendidikan Politik Oleh Partai Politik
Authors: Nurdin Putri Handayani
Published: September 2019

Kehadiran partai politik di alam demokrasi banyak menghadirkan mosi tidak percaya oleh masyarakat luas. Tidak salah, bila ada yang menilai hal ini dampak dari sistem politik Indonesia yang memiliki kecenderungan memposisikan partai politik sebagai aktor utama dalam berdemokrasi. Partisipasi politik merupakan aspek penting dalam sebuah tatanan negara demokrasi substantif. Masyarakat memerlukan pemahaman yang matang mengenai pentingnya sebuah partisipasi politik melalui pendidikan politik. Ada dua isu penting yang menjadi rumusan masalah dalam kajian ini yakni Pertama, bagaimana model pendidikan politik yang ideal dalam mewujudkan partisipasi politik. Kedua, bagaimana sanksi terhadap partai politik yang tidak melakukan pendidikan politik. Selama ini, partai politik lalai dalam menjalankan kewajibannya, partai politik tidak memberikan pendidikan politik kepada masyarakat, namun hanya kepada anggota kader partai politik saja. Oleh karenanya, dalam kajian ini dirumuskan beberapa hal, yakni: Pertama, perlu adanya penguatan dalam merumuskan model pendidikan politik kepada masyarakat dan perlu adanya penguatan terhadap pemberlakuan sanksi yang tegas untuk menekan kepatuhan seluruh partai politik dalam menjalankan kewajibannya untuk memberikan pendidikan politik sehingga mampu mewujudkan demokrasi substantif; Kedua, perlunya evaluasi dana partai politik melalui pelibatan inspektorat dan BPK yang tidak hanya disampaikan kembali pada partai politik akan tetapi menjadi informasi publik secara terbuka. Penulisan ini bersifat preskriptif menggunakan bahan hukum primer dan sekunder. Metode pendekatan yang digunakan yakni pendekatan normatif.
Anotasi Spirit Unable dan Unwilling Terhadap Kejahatan Perang Israel Palestina
Authors: Hadju Zainal Abdul Azis
Published: September 2019

Tujuan dari penelitian ini adalah mengetahui Apa yang menjadi pertimbangan utama suatu entitas diakui sebagai negara oleh hukum internasional dan Bagaimana relasi antara spirit International Criminal Court (ICC) dengan prinsip unable and willing terhadap Palestina menurut hukum internasional.  Jenis penelitian yang digunakan dalam penelitian ini adalah yuridis normatif, dengan pendekatan perundang-undangan, pendekatan kasus, dan pendekatan historis. Hasil penelitian ini menunjukkan bahwa Pasal 1 Konvensi montevidio menyebutkan bahwa ada empat kriteria yang harus dipenuhi oleh sebuah negara baru untuk menjadi sebuah negara berdaulat, yaitu; adanya populasi yang tetap, wilayah, pemerintah, dan kapasitas negara sebagai penunjang dalam melakukan hubungan dengan negara lain. Terdapat pula pengakuan terhadap suatu negara yang terbagi dalam dua bentuk yakni pengakuan secara de jure maupun secara de facto, Palestina telah diakui secara de jure karna dalam praktiknya yang dibuktikan dengan melakukan perjanjian internasional dengan beberapa negara. Bahwa, ICC memiliki empat macam yuridiksi yakni, yuridiksi personal, kriminal, temporal dan territorial. Pasal 17 ayat 2 dan ayat 3 menentukan negara yang dianggap  tidak mau (unwilling). ketidaksediaan (unable). Berkenan dengan hal itu kita dapat kembali ke prinsip otomatis yaitu locus delicti bahwa Israel melakukan kejahatan perang di wilayah palestina dan didukung dengan yurisdiksi dari mahkamah tersebut, maka ICC sudah lebih dari cukup untuk mengadili Israel dengan menggunakan yuridiksi prinsip otomatis yang terkandung dalam statute roma 1998. Kriteria unwilling dan unable dapat diperluas penegakkan melalui Pasal 13 Statuta Roma 1998 yang menyatakan bahwa ICC memiliki tiga kewenangan untuk memeriksa kejahatan internasional,   jika terdapat suatu kenyakinan bahwa salah satu dan atau seluruh pihak melakukan kejahatan internasional sesuai dengan Pasal 5 Statuta Roma 1998.
Dilema Penerapan Sanksi Pelanggaran Lalu Lintas Terhadap Anak
Authors: Ariefulloh Ariefulloh , Asis Abd. , Maskun Maskun
Published: September 2019

Penelitian ini bertujuan untuk mengetahui penerapan sanksi pelanggar lalu lintas oleh anak pasca penerapan e-tilang dan bentuk tindak lanjut oleh aparat penegak hukum terhadap anak yang ditilang. Penelitian ini merupakan penelitian hukum empiris (empirical research). Dalam rangka memperoleh data yang relevan dengan kebutuhan penelitian ini,. Hasil penelitian menunjukkan bahwa penerapan sanksi pelanggar lalu lintas oleh anak dilakukan tidak sesuai dengan ketentuan undang-undang sistem peradilan pidana anak dan peraturan pemerintah tentang Pedoman Pelaksanaan Diversi dan Penanganan Anak Yang Belum Berumur 12 (Dua Belas) Tahun. Penindakan terhadap pelanggar anak, dilakukan dengan meneruskan berkas pelanggaran anak yang bersangkutan ke Pengadilan dan dijatuhi sanksi berupa denda. Penindakan lanjutan oleh aparat penegak hukum terhadap anak yang ditilang di Kab, Konawe adalah dalam bentuk penjatuhan sanksi Pidana Denda. Aparat penegak hukum masih belum menerapkan UU SPPA khususnya dalam penanganan tindak pidana pelanggaran lalu lintas yang dilakukan oleh anak.
What Do Think Tanks Think? Proximity to Power and Foreign Policy Preferences
Authors: Hanania Richard , Abrahms Max
Published: September 2019

We argue that experts are more hawkish the closer they are to power, both figuratively and literally, and show this through the first study to use survey methods to inquire into the foreign policy preferences of think tank analysts and fellows (think tank employees, or TTEs) relative to professors who are experts in international relations. We find that TTEs are 0.47 standard deviations more hawkish than professors as calculated based on a standard survey measuring militant internationalism (MI). Controlling for self-described ideology mitigates this effect although it remains statistically significant. Among professors, those who have worked for the federal government are higher on MI, as are TTEs located closer to Capitol Hill. Differing levels of regional expertise generally cannot explain these differences, except perhaps in the case of Iran.
Use of Prescribed Psychotropics during Pregnancy: A Systematic Review of Pregnancy, Neonatal, and Childhood Outcomes
Authors: Creeley Catherine E. , Denton Lisa K.
Published: September 2019

This paper reviews the findings from preclinical animal and human clinical research investigating maternal/fetal, neonatal, and child neurodevelopmental outcomes following prenatal exposure to psychotropic drugs. Evidence for the risks associated with prenatal exposure was examined, including teratogenicity, neurodevelopmental effects, neonatal toxicity, and long-term neurobehavioral consequences (i.e., behavioral teratogenicity). We conducted a comprehensive review of the recent results and conclusions of original research and reviews, respectively, which have investigated the short- and long-term impact of drugs commonly prescribed to pregnant women for psychological disorders, including mood, anxiety, and sleep disorders. Because mental illness in the mother is not a benign event, and may itself pose significant risks to both mother and child, simply discontinuing or avoiding medication use during pregnancy may not be possible. Therefore, prenatal exposure to psychotropic drugs is a major public health concern. Decisions regarding drug choice, dose, and duration should be made carefully, by balancing severity, chronicity, and co-morbidity of the mental illness, disorder, or condition against the potential risk for adverse outcomes due to drug exposure. Globally, maternal mental health problems are considered as a major public health challenge, which requires a stronger focus on mental health services that will benefit both mother and child. More preclinical and clinical research is needed in order to make well-informed decisions, understanding the risks associated with the use of psychotropic medications during pregnancy.
Preparation and Characterization of Ultrasound Treated Polyvinyl Alcohol/Chitosan/DMC Antimicrobial Films
Authors: Li Rui , Wang Yue , Xu Jie , Ahmed Saeed , Liu Yaowen
Published: September 2019

In this research, chitosan (CS) and poly (vinyl alcohol) (PVA) were adopted as a material, methacryloyloxyethyl trimethyl ammonium chloride (DMC) was added in various concentrations and was treated ultrasonically for the formation of films with the use of the polymer blending method. The influences exerted by the ultrasonication period on PVA/CS/DMC antimicrobial active materials underwent material characteristic tests. The consequences revealed that at the break of the compound films, ultrasonication raised the elongation and tensile strength on the whole. Ultrasonication further or also enhanced the light transmittance performance and composite films’ barrier property. Furthermore, the compound film with a DMC concentration of 2% had good antibacterial properties, the film’s inhibition rates against Staphylococcus aureus and Escherichia coli after ultrasonication were 79.23% ± 1.92% and 72.31% ± 1.35%, respectively.
Phenol Content and Antioxidant and Antiaging Activity of Safflower Seed Oil (Carthamus Tinctorius L.)
Authors: Zemour Kamel , Labdelli Amina , Adda Ahmed , Dellal Abdelkader , Talou Thierry , Merah Othmane
Published: September 2019

The phenol content of vegetable oil and its antioxidant activity are of primary interest for human health. Oilseed species are considered important sources of these compounds with medicinal effects on a large scale. Total phenol content (TPC) and antioxidant activity (AA) of safflower oil were previously studied. Nevertheless, there is no report on genotypic differences and antiaging activity of safflower oil. The aim of this study was to determine the TPC, diphenyl-picrylhydrazyl (DPPH), and antiaging activity on three respective accessions from Syria, France, and Algeria of seed oil of safflower grown under semi-arid conditions during 3 consecutive years (2015, 2016, and 2017). The results showed that phenol content as well as antioxidant and antiaging activity varied according to both genotype and years. In 2017, the mean value of TPC in oil seed was two times higher than in 2015 and 2016. Moreover, accessions presented different TPC values depending on the year. The highest antioxidant activity was observed among accessions in 2017 compared to 2015 and 2016. As expected, a positive correlation was found between TPC and antioxidant activity. The inhibition in the collagenase assay was between 47% and 72.1% compared to the positive control (83.1%), while inhibition in the elastase assay of TPC ranged from 32.2% to 70.3%, with the positive control being 75.8%. These results highlight the interest of safflower oil as a source of phenols with valuable antioxidant and antiaging activity, and uses for cosmetics.
Entropy in Dynamic Systems
Authors: Awrejcewicz Jan , Tenreiro Machado José A.
Published: September 2019

In order to measure and quantify the complex behavior of real-world systems, either novel mathematical approaches or modifications of classical ones are required to precisely predict, monitor and control complicated chaotic and stochastic processes [...]
Use of Cyclic Voltammetry to Describe the Electrochemical Behavior of a Dual-Chamber Microbial Fuel Cell
Authors: López Zavala Miguel Ángel , González Peña Omar Israel , Cabral Ruelas Héctor , Delgado Mena Cristina , Guizani Mokhtar
Published: September 2019

Cyclic voltammetry (CV) was used in this work to describe the electrochemical behavior of a dual-chamber microbial fuel cell (MFC). The system performance was evaluated under vacuum and non-pressurized conditions, different reaction times, two sweep potentials, 25 and 50 mVs−1 and under different analyte solutions, such as distilled water and domestic wastewater. CV experiments were conducted by using a potentiostat with three different configurations to collect the measurements. A dual-chamber MFC system was equipped with a DupontTM Nafion® 117 proton exchange membrane (PEM), graphite electrodes (8.0 cm × 2.5 cm × 0.2 cm) and an external electric circuit with a 100-Ω resistor. An electrolyte (0.1 M HCl, pH ≈ 1.8) was used in the cathode chamber. It was found that the proton exchange membrane plays a major role on the electrochemical behavior of the MFC when CV measurements allow observing the conductivity performance in the MFC in the absence of a reference electrode; under this potentiostat setting, less current density values are obtained on the scanned window potentials. Therefore, potentiostat setting is essential to obtain information in complex electrochemical processes present in biological systems, such as it is the case in the MFCs. Results of the study showed that wastewater constituents and the biomass suspended or attached (biofilm) over the electrode limited the electron charge transfer through the interface electrode-biofilm-liquor. This limitation can be overcome by: (i) Enhancing the conductivity of the liquor, which is a reduction of the ohmic drop, (ii) reducing the activation losses by a better catalysis, and (iii) by limiting the diffusional gradients in the bulk liquor, for instance, by forced convection. The use of the electrolyte (0.1 M HCl, pH ≈ 1.8) and its diffusion from the cathode to the anode chamber reduces the resistance to the flow of ions through the PEM and the flow of electrons through the anodic and cathodic electrolytes. Also reduces the activation losses during the electron transfer from the substrate to the electrode surface due to the electrode catalysis improvement. On the other hand, vacuum also demonstrated that it enhances the electrochemical performance of the dual-chamber MFC due to the fact that higher current densities in the system are favored.
Finite Element Modeling and Analysis of High Power, Low-loss Flux-Pipe Resonant Coils for Static Bidirectional Wireless Power Transfer
Authors: Olukotun Babatunde , Partridge Julius , Bucknall Richard
Published: September 2019

This paper presents the optimal modeling and finite element analysis of strong-coupled, high-power and low-loss flux-pipe resonant coils for bidirectional wireless power transfer (WPT), applicable to electric vehicles (EVs) using series-series compensation topology. The initial design involves the modeling of strong-coupled flux-pipe coils with a fixed number of wire-turns. The ohmic and core loss reduction for the optimized coil model was implemented by creating two separate coils that are electrically parallel but magnetically coupled in order to achieve maximum flux linkage between the secondary and primary coils. Reduction in the magnitude of eddy current losses was realized by design modification of the ferrite core geometry and optimized selection of shielding material. The ferrite core geometry was modified to create a C-shape that enabled the boosting and linkage of useful magnetic flux. In addition, an alternative copper shielding methodology was selected with the advantage of having fewer eddy current power losses per unit mass when compared with aluminum of the same physical dimension. From the simulation results obtained, the proposed flux-pipe model offers higher coil-to-coil efficiency and a significant increase in power level when compared with equivalent circular, rectangular and traditional flux-pipe models over a range of load resistance. The proposed model design is capable of transferring over 11 kW of power across an airgap of 200 mm with a coil-to-coil efficiency of over 99% at a load resistance of 60 Ω.
An Integrated Methodology for Rule Extraction from ELM-Based Vacuum Tank Degasser Multiclassifier for Decision-Making
Authors: Wang Senhui , Li Haifeng , Zhang Yongjie , Zou Zongshu
Published: September 2019

The present work proposes an integrated methodology for rule extraction in a vacuum tank degasser (VTD) for decision-making purposes. An extreme learning machine (ELM) algorithm is established for a three-class classification problem according to an end temperature of liquid steel that is higher than its operating restriction, within the operation restriction and lower than the operating restriction. Based on these black-box model results, an integrated three-step approach for rule extraction is constructed to interpret the understandability of the proposed ELM classifier. First, the irrelevant attributes are pruned without decreasing the classification accuracy. Second, fuzzy rules are generated in the form of discrete input attributes and the target classification. Last but not the least, the rules are refined by generating rules with continuous attributes. The novelty of the proposed rule extraction approach lies in the generation of rules using the discrete and continuous attributes at different stages. The proposed method is analyzed and validated on actual production data derived from a No.2 steelmaking workshop in Baosteel. The experimental results revealed that the extracted rules are effective for the VTD system in classifying the end temperature of liquid steel into high, normal, and low ranges. In addition, much fewer input attributes are needed to implement the rules for the manufacturing process of VTD. The extracted rules serve explicit instructions for decision-making for the VTD operators.
Enhancement of Fault Feature Extraction from Displacement Signals by Suppressing Severe End Distortions via Sinusoidal Wave Reduction
Authors: Chen Binqiang , Lan Qixin , Li Yang , Zhuang Shiqiang , Cao Xincheng
Published: September 2019

Displacement signals, acquired by eddy current sensors, are extensively used in condition monitoring and health prognosis of electromechanical equipment. Owing to its sensitivity to low frequency components, the displacement signal often contains sinusoidal waves of high amplitudes. If the digitization of the sinusoidal wave does not satisfy the condition of full period sampling, an effect of severe end distortion (SED), in the form of impulsive features, is likely to occur because of boundary extensions in discrete wavelet decompositions. The SED effect will complicate the extraction of weak fault features if it is left untreated. In this paper, we investigate the mechanism of the SED effect using theories based on Fourier analysis and wavelet analysis. To enhance feature extraction performance from displacement signals in the presence of strong sinusoidal waves, a novel method, based on the Fourier basis and a compound wavelet dictionary, is proposed. In the procedure, ratio-based spectrum correction methods, using the rectangle window as well as the Hanning window, are employed to obtain an optimized reduction of strong sinusoidal waves. The residual signal is further decomposed by the compound wavelet dictionary which consists of dyadic wavelet packets and implicit wavelet packets. It was verified through numerical simulations that the reconstructed signal in each wavelet subspace can avoid severe end distortions. The proposed method was applied to case studies of an experimental test with rub impact fault and an engineering test with blade crack fault. The analysis results demonstrate the proposed method can effectively suppress the SED effect in displacement signal analysis, and therefore enhance the performance of wavelet analysis in extracting weak fault features.
Energetic and Exergetic Analysis of Low Global Warming Potential Refrigerants as Substitutes for R410A in Ground Source Heat Pumps
Authors: Bobbo Sergio , Fedele Laura , Curcio Marco , Bet Anna , De Carli Michele , Emmi Giuseppe , Poletto Fabio , Tarabotti Andrea , Mendrinos Dimitris , Mezzasalma Giulia , Bernardi Adriana
Published: September 2019

In the European Union (EU), buildings are responsible for about 40% of the total final energy consumption, and 36% of the European global CO2 emissions. The European Commission released directives to push for the enhancement of the buildings energy performance and identified, beside the retrofit of the current building stock, Heating, Ventilation, and Air Conditioning (HVAC) systems as the other main way to increase renewable energy sharing and overall building energy efficiency. For this purpose, Ground Source Heat Pumps (GSHPs) represent one of the most interesting technologies to provide energy for heating, cooling, and domestic water production in residential applications, ensuring a significant reduction (e.g., up to 44% compared with air-source heat pumps) of energy consumption and the corresponding emissions. At present, GSHPs mainly employ the refrigerant R410A as the working fluid, which has a Global Warming Potential (GWP) of 2087. However, following the EU Regulation No. 517/2014 on fluorinated greenhouse gases, this high GWP refrigerant will have to be substituted for residential applications in the next years. Thus, to increase the sustainability of GSHPs, it is necessary to identify short time alternative fluids with lower GWP, before finding medium-long term solutions characterized by very low GWP. This is one of the tasks of the UE project "Most Easy, Efficient, and Low-Cost Geothermal Systems for Retrofitting Civil and Historical Buildings" (acronym GEO4CIVHIC). Here, a thorough thermodynamic analysis, based on both energy and exergy analysis, will be presented to perform a comparison between different fluids as substitutes for R410A, considered as the benchmark for GSHP applications. These fluids have been selected considering their lower flammability with respect to hydrocarbons (mainly R290), that is one of the main concerns for the companies. A parametric analysis has been performed, for a reversible GSHP cycle, at various heat source and sink conditions, with the aim to identify the fluid giving the best energetic performance and to evaluate the distribution of the irreversibilities along the cycle. Considering all these factors, R454B turned out to be the most suitable fluid to use in a ground source heat pump, working at given conditions. Special attention has been paid to the compression phase and the heat transfer in evaporator and condenser.
NAFLD and Extra-Hepatic Comorbidities: Current Evidence on a Multi-Organ Metabolic Syndrome
Authors: Rosato Valerio , Masarone Mario , Dallio Marcello , Federico Alessandro , Aglitti Andrea , Persico Marcello
Published: September 2019

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and its incidence is definitely increasing. NAFLD is a metabolic disease with extensive multi-organ involvement, whose extra-hepatic manifestations include type 2 diabetes mellitus, cardiovascular disease, obstructive sleep apnea, chronic kidney disease, osteoporosis, and polycystic ovarian syndrome. Recently, further evidence has given attention to pathological correlations not strictly related to metabolic disease, also incorporating in this broad spectrum of systemic involvement hypothyroidism, psoriasis, male sexual dysfunction, periodontitis, and urolithiasis. The most common cause of mortality in NAFLD is represented by cardiovascular disease, followed by liver-related complications. Therefore, clinicians should learn to screen and initiate treatment for these extra-hepatic manifestations, in order to provide appropriate multidisciplinary assessments and rigorous surveillance. This review evaluates the current evidence regarding extra-hepatic associations of NAFLD, focusing on the pathogenic hypothesis and the clinical implications.
Internal and External Demands in Basketball Referees during the U-16 European Women’s Championship
Authors: García-Santos David , Pino-Ortega José , García-Rubio Javier , Vaquera Alejandro , Ibáñez Sergio J.
Published: September 2019

(1) Background: The use of advanced technology to study the energy demands of sport participants during actual sport competition is an important current research direction. The purpose of this study was to identify the physiological, internal, and external demands placed on basketball referees using ultra-wideband (UWB) technology, in relation to the period of the game. (2) Methods: The sample was comprised of nine international referees, and the data collection took place during the Women’s EuroBasket Sub-16 championship. Internal and external load were assessed through the inertial device WIMU PROTM, using UWB technology in order to quantify the effort exerted by each referee. The internal load was examined in relation to each individual’s heart rate (HR). The external load included the kinematic variables accelerations (Acc), decelerations (Dec), Acc/min, Dec/min, distance covered, steps, maximum speed (Vmax), average speed (Vavg), and speed zones, as well as the neuromuscular variables impacts (Imp), PlayerLoadTM (PLTM), PLTM/min, Metabolic Power (PMet), and PMet/min. (3) Results: The results exposed that referees work around 62% HRmax and spend more than 80% of the match at intensities between 0–12 km/h. The first period was the period in which the greatest work demand was experienced in relation to these neuromuscular outcomes (11.92 PL; 3.61 Met; 277 Impacts). The results revealed a diminishment of internal and external demands on the referees over the course of the game. (4) Conclusions: The results highlight the importance of monitoring and quantifying the workload of basketball officials, because doing so would allow for the establishment of individualized performance profiles that could be designed with the purpose of benefiting referee performance during games. The use of inertial devices allows for the objective quantification of referee workload under competitive circumstances.
Time Trends in the Co-use of Cannabis and the Misuse of Tranquilizers, Sedatives and Sleeping Pills among Young Adults in Spain between 2009 and 2015
Authors: Palacios-Ceña Domingo , Jiménez-Trujillo Isabel , Hernández-Barrera Valentín , Lima Florencio Lidiane , Carrasco-Garrido Pilar
Published: September 2019

The aims of this study were: (a) to estimate time trends in the prevalence of the co-use of cannabis and other cannabis-based products (CBP) with the misuse of tranquilizers, sedatives, and sleeping pills (TSSp) between 2009 and 2015; and (b) to identify the factors associated with the probability of the co-use of CBP with TSSp misuse during this period among Spanish younger adults (15–34 years old). We analyzed data collected from the Spanish National Surveys on Alcohol and Other Drugs (EDADES) in 2009, 2011, 2013, and 2015. CBP co-use with TSSp misuse were the dependent variables. We also analyzed sociodemographic features, self-perceived health status, lifestyle habits, perceived health risk of consumption, and perceived availability of substance using logistic regression models. The prevalence of CBP co-use with TSSp misuse has decreased in Spain. The factors associated with co-use were a lack of education (OR 2.34), alcohol (OR 7.2), tobacco (OR 6.3) and other illicit psychoactive drug (OR 6.5) consumption, perceived non-health risk for the consumption of CBP and TSSp (OR 3.27), and perceived availability of CBP (OR 2.96). Our study identified several factors that appear to affect CBP and TSSp co-use in younger adults, with potential implications for healthcare providers.
Myelin Disturbances Produced by Sub-Toxic Concentration of Heavy Metals: The Role of Oligodendrocyte Dysfunction
Authors: Maiuolo Jessica , Macrì Roberta , Bava Irene , Gliozzi Micaela , Musolino Vincenzo , Nucera Saverio , Carresi Cristina , Scicchitano Miriam , Bosco Francesca , Scarano Federica , Palma Ernesto , Gratteri Santo , Mollace Vincenzo
Published: September 2019

Evidence has been accumulated demonstrating that heavy metals may accumulate in various organs, leading to tissue damage and toxic effects in mammals. In particular, the Central Nervous System (CNS) seems to be particularly vulnerable to cumulative concentrations of heavy metals, though the pathophysiological mechanisms is still to be clarified. In particular, the potential role of oligodendrocyte dysfunction and myelin production after exposure to subtoxic concentration I confirmed. It is ok of heavy metals is to be better assessed. Here we investigated on the effect of sub-toxic concentration of several essential (Cu2 +, Cr3 +, Ni2 +, Co2+) and non-essential (Pb2 +, Cd2+, Al3+) heavy metals on human oligodendrocyte MO3.13 and human neuronal SHSY5Y cell lines (grown individually or in co-culture). MO3.13 cells are an immortal human–human hybrid cell line with the phenotypic characteristics of primary oligodendrocytes but following the differentiation assume the morphological and biochemical features of mature oligodendrocytes. For this reason, we decided to use differentiated MO3.13 cell line. In particular, exposure of both cell lines to heavy metals produced a reduced cell viability of co-cultured cell lines compared to cells grown separately. This effect was more pronounced in neurons that were more sensitive to metals than oligodendrocytes when the cells were grown in co-culture. On the other hand, a significant reduction of lipid component in cells occurred after their exposure to heavy metals, an effect accompanied by substantial reduction of the main protein that makes up myelin (MBP) in co-cultured cells. Finally, the effect of heavy metals in oligodendrocytes were associated to imbalanced intracellular calcium ion concentration as measured through the fluorescent Rhod-2 probe, thus confirming that heavy metals, even used at subtoxic concentrations, lead to dysfunctional oligodendrocytes. In conclusion, our data show, for the first time, that sub-toxic concentrations of several heavy metals lead to dysfunctional oligodendrocytes, an effect highlighted when these cells are co-cultured with neurons. The pathophysiological mechanism(s) underlying this effect is to be better clarified. However, imbalanced intracellular calcium ion regulation, altered lipid formation and, finally, imbalanced myelin formation seem to play a major role in early stages of heavy metal-related oligodendrocyte dysfunction.
Sesquiterpenes Are Agonists of the Pregnane X Receptor but Do Not Induce the Expression of Phase I Drug-Metabolizing Enzymes in the Human Liver
Authors: Šadibolová Michaela , Zárybnický Tomáš , Smutný Tomáš , Pávek Petr , Šubrt Zdeněk , Matoušková Petra , Skálová Lenka , Boušová Iva
Published: September 2019

Sesquiterpenes, the main components of plant essential oils, are bioactive compounds with numerous health-beneficial activities. Sesquiterpenes can interact with concomitantly administered drugs due to the modulation of drug-metabolizing enzymes (DMEs). The aim of this study was to evaluate the modulatory effects of six sesquiterpenes (farnesol, cis-nerolidol, trans-nerolidol, α-humulene, β-caryophyllene, and caryophyllene oxide) on the expression of four phase I DMEs (cytochrome P450 3A4 and 2C, carbonyl reductase 1, and aldo-keto reductase 1C) at both the mRNA and protein levels. For this purpose, human precision-cut liver slices (PCLS) prepared from 10 patients and transfected HepG2 cells were used. Western blotting, quantitative real-time PCR and reporter gene assays were employed in the analyses. In the reporter gene assays, all sesquiterpenes significantly induced cytochrome P450 3A4 expression via pregnane X receptor interaction. However in PCLS, their effects on the expression of all the tested DMEs at the mRNA and protein levels were mild or none. High inter-individual variabilities in the basal levels as well as in modulatory efficacy of the tested sesquiterpenes were observed, indicating a high probability of marked differences in the effects of these compounds among the general population. Nevertheless, it seems unlikely that the studied sesquiterpenes would remarkably influence the bioavailability and efficacy of concomitantly administered drugs.
Invariant Natural Killer T-Cells and Total CD1d Restricted Cells Differentially Influence Lipid Metabolism and Atherosclerosis in Low Density Receptor Deficient Mice
Authors: VanderLaan Paul A. , Reardon Catherine A. , Cabana Veneracion G. , Wang Chyung-Ru , Getz Godfrey S.
Published: September 2019

Natural killer T (NKT) cells are a distinct subset of lymphocytes that bridge the innate and adaptive immune response and can be divided into type I invariant NKT cells (iNKT) and type II NKT cells. The objective of this study is to examine the effects of NKT cell on lipid metabolism and the initiation and progression of atherosclerosis in LDL receptor deficient (LDLR−/−) mice. Mice were fed an atherogenic diet for 4 or 8 weeks and plasma lipids, lipoproteins, and atherosclerosis were measured. The selective absence of iNKT cells in Jα18−/−LDLR−/− mice led to an increase in plasma cholesterol levels in female mice. Transgenic Vα14tg/LDLR−/− mice with elevated numbers of iNKT cells had increased late atherosclerosis of the innominate artery, though absence of either iNKT cells or all NKT cells and other CD1d expressing cells had varying effects on atherosclerotic lesion burden in the ascending aortic arch and aortic root. These studies not only highlight the potential modulatory role played by NKT cells in atherosclerosis and lipid metabolism, but also raise the possibility that divergent roles may be played by iNKT and CD1d restricted cells such as type II NKT cells or other CD1d expressing cells.
Liraglutide Inhibits Hepatitis C Virus Replication Through an AMP Activated Protein Kinase Dependent Mechanism
Authors: Lee Mei-Yueh , Chen Wei-Chun , Hsu Wei-Hao , Chen Szu-Chia , Lee Jin-Ching
Published: September 2019

Insulin resistance and diabetes are both associated with chronic hepatitis C virus (HCV) infection, and the glucagon-like peptide-1(GLP-1) receptor agonist, liraglutide, is a common therapy for diabetes. Our aim was to investigate whether liraglutide treatment can inhibit HCV replication. A cell culture-produced HCV infectious system was generated by transfection of in vitro-transcribed genomic JFH-1 ribonucleic acid (RNA) into Huh-7.5 cells. Total RNA samples were extracted to determine the efficiency of HCV replication. The Ava5 cells were treated with liraglutide and cell viability was calculated. A Western blot analysis of the protein expression was performed. The immunoreactive blot signals were also detected. Liraglutide activated GLP-1 receptors in the HCV infectious system, and inhibited subgenomic HCV RNA replication in the HuH-7.5 cells. The Western blot analysis revealed both HCV protein and replicon RNA were reduced after treatment with liraglutide in a dose-dependent manner. Liraglutide decreased the cell viability of HCV RNA at an optimum concentration of 120 μg/mL, activated the 5′ adenosine monophosphate-activated protein kinase (AMPK) and the phosphorylated- transducer of regulated cyclic adenosine monophosphate (CAMP) response element-binding protein 2 (TORC2), thereby decreasing the cell viability of phosphoenolpyruvate carboxykinase (PEPCK) and G6pase RNA Therefore, we conclude that liraglutide can inhibit HCV replication via an AMPK/TORC2-dependent pathway.
Transcriptome Analysis of Sogatella furcifera (Homoptera: Delphacidae) in Response to Sulfoxaflor and Functional Verification of Resistance-Related P450 Genes
Authors: Wang Xue-Gui , Ruan Yan-Wei , Gong Chang-Wei , Xiang Xin , Xu Xiang , Zhang Yu-Ming , Shen Li-Tao
Published: September 2019

The white-back planthopper (WBPH), Sogatella furcifera, is a major rice pest in China and in some other rice-growing countries of Asia. The extensive use of pesticides has resulted in severe resistance of S. furcifera to variety of chemical insecticides. Sulfoxaflor is a new diamide insecticide that acts on nicotinic acetylcholine receptors (nAChRs) in insects. The aim of this study was to explore the key genes related to the development of resistance to sulfoxaflor in S. furcifera and to verify their functions. Transcriptomes were compared between white-back planthoppers from a susceptible laboratory strain (Sus-Lab) and Sus-Lab screened with the sublethal LC25 dose of sulfoxaflor for six generations (SF-Sel). Two P450 genes (CYP6FD1 and CYP4FD2) and three transcription factors (NlE78sf, C2H2ZF1 and C2H2ZF3) with upregulated expression verified by qRT-PCR were detected in the Sus-Lab and SF-Sel strains. The functions of CYP6FD1 and CYP4FD2 were analyzed by RNA interference, and the relative normalized expressions of CYP6FD1 and CYP4FD2 in the SF-Sel population were lower than under dsGFP treatment after dsRNA injection. Moreover, the mortality rates of SF-Sel population treated with the LC50 concentration of sulfoxaflor after the injecting of dsRNA targeting CYP6FD1 and CYP4FD2 were significantly higher than in the dsGFP group from 72 h to 96 h (p < 0.05), and mortality in the CYP6FD1 knockdown group was clearly higher than that of the CYP4FD2 knockdown group. The interaction between the tertiary structures of CYP6FD1 and CYP4FD2 and sulfoxaflor was also predicted, and CYP6FD1 showed a stronger metabolic ability to process sulfoxaflor. Therefore, overexpression of CYP6FD1 and CYP4FD2 may be one of the primary factors in the development of sulfoxaflor resistance in S. furcifera.
Ophthalmological Findings in Mucopolysaccharidoses
Authors: Tomatsu Shizuka , Pitz Susanne , Hampel Ulrike
Published: September 2019

The mucopolysaccharidoses (MPS) are a heterogenous group of lysosomal storage disorders caused by the accumulation of glycosaminoglycans (GAGs). The accrual of these compounds results in phenotypically varied syndromes that produce multi-organ impairment with widespread systemic effects. The low incidence of MPS (approximately 1/25,000 live births) in conjunction with the high childhood mortality rate had limited the availability of research into certain clinical features, especially ocular manifestations. As the recent successes of hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) have greatly increased life expectancy in these patients, they have served as a focal point for the transition of research towards improvement of quality of life. Ophthalmological findings in MPS include corneal clouding, glaucoma, optic neuropathies, and retinopathies. While corneal clouding is the most common ocular feature of MPS (especially type I, IVA, and VI), its response to HSCT and ERT is minimal. This review discusses known eye issues in the MPS subtypes, diagnosis of these ocular diseases, current clinical and surgical management, noteworthy research progress, and ultimately presents a direction for future studies.
Experiments on the Ultrasonic Bonding Additive Manufacturing of Metallic Glass and Crystalline Metal Composite
Authors: Li Guiwei , Zhao Ji , Fuh Jerry Ying Hsi , Wu Wenzheng , Jiang Jili , Wang Tianqi , Chang Shuai
Published: September 2019

Ultrasonic vibrations were applied to weld Ni-based metallic glass ribbons with Al and Cu ribbons to manufacture high-performance metallic glass and crystalline metal composites with accumulating formation characteristics. The effects of ultrasonic vibration energy on the interfaces of the composite samples were studied. The ultrasonic vibrations enabled solid-state bonding of metallic glass and crystalline metals. No intermetallic compound formed at the interfaces, and the metallic glass did not crystallize. The hardness and modulus of the composites were between the respective values of the metallic glass and the crystalline metals. The ultrasonic bonding additive manufacturing can combine the properties of metallic glass and crystalline metals and broaden the application fields of metallic materials.
Flexible Polycaprolactone and Polycaprolactone/Graphene Scaffolds for Tissue Engineering
Authors: Evlashin Stanislav , Dyakonov Pavel , Tarkhov Mikhail , Dagesyan Sarkis , Rodionov Sergey , Shpichka Anastasia , Kostenko Mikhail , Konev Stepan , Sergeichev Ivan , Timashev Petr , Akhatov Iskander
Published: September 2019

Developing bone scaffolds can greatly improve the patient’s quality of life by accelerating the rehabilitation process. In this paper, we studied the process of composite polycaprolactone supercritical foaming for tissue engineering. The influence of graphene oxide and reduced graphene oxide on the foaming parameters was studied. The structural and mechanical properties were studied. The scaffolds demonstrated mechanical flexibility and endurance. The co-culturing and live/dead tests demonstrated that the obtained scaffolds are biocompatible. Different composite scaffolds induced various surface cell behaviors. The experimental data demonstrate that composite foams are promising candidates for in vivo medical trials.
Analytical Solution of Urysohn Integral Equations by Fixed Point Technique in Complex Valued Metric Spaces
Authors: Hammad Hasanen A. , De la Sen Manuel
Published: September 2019

The purpose of this article is to introduce a fixed point result for a general contractive condition in the context of complex valued metric spaces. Also, some important corollaries under this contractive condition are obtained. As an application, we find a unique solution for Urysohn integral equations, and some illustrative examples are given to support our obtaining results. Our results extend and generalize the results of Azam et al. Previous known related results in the literarure and some other known results in the literature.
Effects of Harvest Time on Phytochemical Constituents and Biological Activities of Panax ginseng Berry Extracts
Authors: Song Seung-Yeap , Park Dae-Hun , Seo Seong-Wook , Park Kyung-Mok , Bae Chun-Sik , Son Hong-Seok , Kim Hyung-Gyun , Lee Jung-Hee , Yoon Goo , Shim Jung-Hyun , Im Eunok , Rhee Sang Hoon , Yoon In-Soo , Cho Seung-Sik
Published: September 2019

Ginseng (Panax ginseng) has long been used as a traditional medicine for the prevention and treatment of various diseases. Generally, the harvest time and age of ginseng have been regarded as important factors determining the efficacy of ginseng. However, most studies have mainly focused on the root of ginseng, while studies on other parts of ginseng such as its berry have been relatively limited. Thus, the aim of this study iss to determine effects of harvest time on yields, phenolics/ginsenosides contents, and the antioxidant/anti-elastase activities of ethanol extracts of three- and four-year-old ginseng berry. In both three- and fourfour-year-old ginseng berry extracts, antioxidant and anti-elastase activities tended to increase as berries ripen from the first week to the last week of July. Liquid chromatography-tandem mass spectrometry analysis has revealed that contents of ginsenosides except Rg1 tend to be the highest in fourfour-year-old ginseng berries harvested in early July. These results indicate that biological activities and ginsenoside profiles of ginseng berry extracts depend on their age and harvest time in July, suggesting the importance of harvest time in the development of functional foods and medicinal products containing ginseng berry extracts. To the best of our knowledge, this is the first report on the influence of harvest time on the biological activity and ginsenoside contents of ginseng berry extracts.
Mechanochemical Synthesis and Isomerization of N-Substituted Indole-3-carboxaldehyde Oximes †
Authors: Baláž Matej , Kudličková Zuzana , Vilková Mária , Imrich Ján , Balážová Ľudmila , Daneu Nina
Published: September 2019

Performing solution-phase oximation reactions with hydroxylamine hydrochloride (NH2OH·HCl) carries significant risk, especially in aqueous solutions. In the present study, four N-substituted indole-3-carboxaldehyde oximes were prepared from the corresponding aldehydes by solvent-free reaction with NH2OH·HCl and a base (NaOH or Na2CO3) using a mechanochemical approach, thus minimizing the possible risk. In all cases, the conversion to oximes was almost complete. The focus of this work is on 1-methoxyindole-3-carboxaldehyde oxime, a key intermediate in the production of indole phytoalexins with useful antimicrobial properties. Under optimized conditions, it was possible to reach almost 95% yield after 20 min of milling. Moreover, for the products containing electron-donating substituents (-CH3, -OCH3), the isomerization from the oxime anti to syn isomer under acidic conditions was discovered. For the 1-methoxy analog, the acidic isomerization of pure isomers in solution resulted in the formation of anti isomer, whereas the prevalence of syn isomer was observed in solid state. From NMR data the syn and anti structures of produced oximes were elucidated. This work shows an interesting and possibly scalable alternative to classical synthesis and underlines environmentally friendly and sustainable character of mechanochemistry.
Impact of Temperature, Ethanol and Cell Wall Material Composition on Cell Wall-Anthocyanin Interactions
Authors: Medina-Plaza Cristina , Beaver Jordan W. , Lerno Larry , Dokoozlian Nick , Ponangi Ravi , Blair Tom , Block David E. , Oberholster Anita
Published: September 2019

The effects of temperature and ethanol concentration on the kinetics of anthocyanin adsorption and desorption interactions with five cell wall materials (CWM) of different composition were investigated. Using temperatures of 15 °C and 30 °C and model wine with ethanol concentrations of 0% and 15% (v/v) over 120 min, the adsorption and desorption rates of five anthocyanin-glucosides were recorded in triplicate. Small-scale experiments were conducted using a benchtop incubator to mimic a single berry fermentation. Results indicate that more than 90% of the adsorption occurs within the first 60 min of the addition of anthocyanins to CWM. However, desorption appears to occur much faster, with maximum desorption being reached after 30 min. The extent of both adsorption and desorption was clearly dependent not only on temperature and ethanol concentration but also on the CWM composition.
Polyamines Disrupt the KaiABC Oscillator by Inducing Protein Denaturation
Authors: Li Jinkui , Zhang Lingya , Xiong Junwen , Cheng Xiyao , Huang Yongqi , Su Zhengding , Yi Ming , Liu Sen
Published: September 2019

Polyamines are positively charged small molecules ubiquitously existing in all living organisms, and they are considered as one kind of the most ancient cellular components. The most common polyamines are spermidine, spermine, and their precursor putrescine generated from ornithine. Polyamines play critical roles in cells by stabilizing chromatin structure, regulating DNA replication, modulating gene expression, etc., and they also affect the structure and function of proteins. A few studies have investigated the impact of polyamines on protein structure and function previously, but no reports have focused on a protein-based biological module with a dedicated function. In this report, we investigated the impact of polyamines (putrescine, spermidine, and spermine) on the cyanobacterial KaiABC circadian oscillator. Using an established in vitro reconstitution system, we noticed that polyamines could disrupt the robustness of the KaiABC oscillator by inducing the denaturation of the Kai proteins (KaiA, KaiB, and KaiC). Further experiments showed that the denaturation was likely due to the induced change of the thermal stability of the clock proteins. Our study revealed an intriguing role of polyamines as a component in complex cellular environments and would be of great importance for elucidating the biological function of polyamines in future.