bluuebunny/crossref_metadata_2025 huggingface dataset:
Розвиток доктрини прямої дії міжнародних угод у праві Європейського Союзу
Authors: БЕРЕЗОВСЬКА ІРИНА , СМИРНОВА КСЕНІЯ
Published: July 2019

Визнання Судом Європейського Союзу (Суд ЄС) прямої дії норм права Європейського Союзу (ЄС, Євросоюз) та його примату щодо внутрішнього права держав-членів стало основою для обґрунтування Судом ЄС концепції права Євросоюзу як нового (автономного) правопорядку та призвело до їх закріплення як фундаментальних принципів у системі права ЄС. Реалізація принципу прямої дії разом із принципом верховенства права Євросоюзу проявляється у можливості для фізичних і юридичних осіб посилатися на право ЄС і домагатися його реалізації через національні суди держав-членів. У своїй практиці Суд ЄС неодноразово звертався до питання прямої дії угод про асоціацію, укладених ЄС із третіми країнами, багатосторонніх угод та угод про партнерство і співробітництво. Істотною особли вістю принципу прямої дії в праві Євросоюзу є його диференційований характер: він має широке, але не всеохоплююче застосування. Визнання прямої дії за конкретною нормою права ЄС залежить, по-перше, від її змісту, а по-друге, від джерела, в якому вона закріплена. Започатковані у судовій практиці підходи в доктрині європейського права отримали назву “подвійного тесту”: спочатку аналізується положення угоди з метою перевірки, чи містить воно ясне, чітке та безумовне зобо в’язання, а потім перевіряється, чи такий висновок не буде скасовано внаслідок дослідження предмета й цілі угоди, в рамках якої має тлумачитися таке положення. Однак встановлені Судом ЄС підходи до прямої дії істотним чином змінювалися у разі, коли поставало питання щодо визнання прямої дії міжнародних багатосторонніх угод. Розвиток договірних відносин України з Євросоюзом вимагає врахування особливостей реалізації норм міжнародних угод у правопорядку ЄС. У широкому розумінні це питання охоплює принципи взаємодії між міжнародним правом і правом Євросоюзу (включаючи класичну дискусію щодо монізму та дуалізму в міжнародному праві). Натомість у більш вузькому розумінні йдеться про пряму дію положень міжнародних угод, укладених Євросоюзом, у правопорядках ЄС та його держав-членів. Саме на цьому зосереджена основна увага у дослідженні. Крім того, проаналізовано розвиток практики Суду ЄС щодо прямої дії міжнародних угод, що укладаються ЄС з іншими суб’єктами міжнародного права. Виокремлено проблему прямої дії в правопорядку ЄС положень Угоди про асоціацію з Україною.
Розвиток доктрини права Ради Європи та взаємодії міжнародних і національних правопорядків
Authors: ШПАКОВИЧ ОЛЬГА
Published: July 2019

Підвищення ролі міжнародного права в міжнародних відносинах вимагає нових підходів і до оцінки співвідношення з національним законодавством, а також шляхів вдосконалення механізмів імплементації міжнародних угод та актів міжнародних організацій у внутрішні правопорядки держав-членів. Акти органів Ради Європи (РЄ) та Європейського Союзу (ЄС), як і міжнародне право загалом, впливають на процес створення та застосування нормативних актів у національних правових системах. Акти органів міжнародних організацій, як і норми міжнародного права, можуть бути зразком для національного правового регулювання або ж державні органи, приймаючи відповідний нормативно-правовий акт, повинні враховувати його міжнародно-правові наслідки.
Метою статті є визначення особливостей правових систем РЄ та ЄС, співвідношення норм права ЄС із нормами конституцій держав-членів, а також місця актів органів РЄ та ЄС у національних правопорядках держав-членів.
Авторка доходить висновку, що, порівнюючи правові механізми взаємодії правових систем РЄ та ЄС із національними правовими системами, обидва механізми є об’єктивно необхідними, оскільки вони сприяють сумісності різних правових систем Європи та їхній здатності взаємодіяти між собою. Окрім цього, у процесі розробки кожного правового акта держави – члени РЄ та ЄС можуть передбачати спеціальний механізм або процедуру для втілення їх у життя. Відповідно, сам характер правових актів, а також намір держав повинен визначати процес імплементації. Незалежно від того, яке ставлення до норм міжнародного права проголошують держави, на практиці вони прагнуть розробити додаткові правові механізми національно-правового забезпечення ефективності реалізації актів органів РЄ та інститутів ЄС.
Scripture, Piety and the Practice of Peace in Nineteenth-Century New Zealand Missions
Authors: Troughton Geoffrey
Published: July 2019

Nineteenth-century missionary activity is more commonly associated in historiography with the violence of colonisation and imperialism than with peace. Nevertheless, in some places, rhetoric proclaiming Christianity as a peace-bringer became tied more decisively with the preaching of peace as an ethical imperative. This article explores the emergence and cultivation of a peace gospel in the mission to Māori in nineteenth-century New Zealand. It argues that formations of piety, especially bible reading, were central to the inculcation of an influential peace ethic.
Formative Worship ‘at the End of the World’: The Worship Practices of Methodists, Baptists and Plymouth Brethren in the Emergence of Protestantism in Argentina, 1867–1930
Authors: Cornou María Eugenia
Published: July 2019

Framed by formative worship theory, this paper examines the worship practices of the Methodists, the Baptists and the Plymouth (Free or Christian) Brethren in Argentina (1867–1930) and the beliefs and values these practices imprinted on a minority group striving to find its own identity at its inception in a predominantly Roman Catholic country. This essay not only aims to contribute to a better understanding of early evangelical Protestantism in Argentina, but also intends to foster a broader reflection on the formative power of Christian worship and the importance of its study, especially in missionary contexts. 1
PENGARUH PEMAKAIAN KERTAS LEM PERASAN SAMPAH IKAN TERHADAP JUMLAH LALAT TERPERANGKAP DI TPS TERMINAL BATURRADEN TAHUN 2018
Authors: . Desi Setianingsih , . Djamaluddin Ramlan , . Khomsatun
Published: July 2019

Fly is a transmitting vector of gastrointestinal disease. Indonesia is a fish-producing paradise. Garbage generated from fishery activities if not handled properly and properly can be a place to miss a fly that will cause many problems for humans. So there should be effort to control fly one of the way that is physically by using fly glue paper smeared with atraktan. The method used in this research is Pre Experiment with Static Group Comparison design. Data collection by observation and measurement. Data analysis using Rank Spearman test and Anova test. The results obtained from the measurements of the number of flies trapped for 7 days of research in 7 times the average replication on glue paper without the litter of fish waste (15 head), on glue paper with the waste of fish concentration 25% (11 fish), on paper glue with fresh fish garbage concentration 50% (9 tail), on glue paper with garbage concentration 75% (23 fish). The statistical calculation using Rank Spearman test showed significant value: 0.772> α: 0,05 and significant value: 0,081> α: 0,05. Data analysis using Anova test got result that is significant value> value α that is 0,209> 0,05. The conclusion of this research is that there is no effect of garbage volume by the number of trapped flies, no effect of flies density with number of trapped flies, and no effect of paper glue on the trash of fish trash on the number of trapped flies. Suggestions that can be given that is not to reduce the adhesiveness of the glue, the waste of fish waste is not smeared but only placed next to the glue paper.
Peran Sentralistik Kiai Dalam Mengembangkan Pola Manajerial dan Out Put Madrasah Diniyah di Era Milenial
Authors: Rois Fatqu , Munawaroh Himatul
Published: July 2019

Abstrak:Kata kunci: Kepemimpinan, Kiai dan Madrasah DiniyahKiai sebutan bagi seseorang yang mengajarkan tentang ilmu agama Islam di Indonesia yang mempunyai peranan penting bagi masyarakat. Seorang kiai mempunyai berbagai metode dalam mensyiarkan agama islam di masyarakat. Metode yang digunakan salah satunya adalah berbasis Madrasah diniyah. Saat ini madrasah diniyah mengalami masalah yang cukup kronis yang dapat membahayakan eksistensinya yaitu menurunnya jumlah santri yang belajar disana. Kiai sebagai penentu arah madrasah diniyah tentu mempunyai pengaruh yang sangat kuat, sehingga maju mundurnya suatu madrasah diniyah tergantung dari pola pikir dan tindak tanduk dari kiainya. Kiai harus mengetahui problematika yang ada dalam madrasah diniyah serta harus mampu membuat metode-metode praktis guna memperkuat lulusannnya. Kiai juga hendaknya memperluas wawasan dan koneksi supaya madrasah diniyah tetap eksis dan bisa memberikan lulusan yang bisa mandiri di masyarakat. Abstract:Keyword: Leader, Kiai and Diniyah SchoolKiai is the applellaton for man teaching Islamic knowledge in Indonesia he have urgent role for the society. Kiai have many methods for spread to doctrine of Islam in society. One of many methode from kiai with based diniyah school. Diniyah school now had heavy problem can bringing into annihilate this place is decrease amount of santri(applellation of students in diniyah school). Kiai as the leader from diniyah school have strong influence so succeed or broken it depend on from mindset and act kiai. Kiai must know a problem in diniyah school and making many methods to giving many skill out put. Kiai must expand insight and conections  for diniyah school still excist and can giving out put multy talent in society.
KEBERPIHAKAN PADA BAYANI ATAU IRFANI (Sebuah Pendekatan Baru dalam Memaknai Teks Al-Qur’an)
Authors: Supriadi Supriadi
Published: July 2019

Hermeneutika sebagai bagian dari filsafat bahasa telah menjadi instrument dalam menafsirkan sebuah teks termasuk didalamnya teks-teks wahyu dalam al-Qur’an, dengan kata lain yang menjadi kajian dalam hermeneutika  bukan hanya terbatas pada kenyataan untuk mencari makna pada suatu teks yang ada, tetapi juga menggali makna dengan tiga perangkat yaitu dunia teks, dunia si pembaca, dan dunia si pengarang. Hermeneutika bekerja dengan dua pendekatan wilayah yaitu bayani dan irfani, sehingga ada hermeneutika yang bekerja pada wilayah bayani yang disebut tafsir dan hermeneutika yang bekerja pada wilayah irfani yang disebut ta’wil yang terimplementasi pada tasawuf.Kemampuan para sufi dalam melakukan penta’wilan al-Qur’an didasarkan pada  asumsi bahwa al-Qur’an tidak memiliki makna tunggal, maka masih terbuka untuk mencapai makna yang terdalam, sehingga para sufi berusaha menggalinya dengan menganggap teks al-Qur’an sebagai isyarat atau symbol. Penggalian makna ini hanya ada satu jalan yaitu metode irfani dalam rangka mencari makna yang diinginkan si pengarang, yang diyakini kemungkinan itulah makna yang hakiki.
Soft Driving Epicyclical Mechanism for Robotic Finger
Authors: Ramirez Jose , Rubiano Astrid , Castiblanco Paola
Published: July 2019

Nowadays, the development or improvement of soft actuation mechanisms is a crucial topic for the achievement of dexterous manipulation using. Then, a primary target of research is the design of actuation and driving devices. Consequently, in this paper, we introduce a soft driving epicyclical mechanism that mimics human muscle behavior and fulfills motion requirements to achieve grasping gestures using a robotic finger. The prototype is experimentally assessed, and results show that our approach has enough performance for the implementation in grasping tasks. Furthermore, we introduce the basis for a new soft epicyclical mechanism merger with shape memory alloys to allow active stiffness control of the mechanism.
Isolation of Strong Antioxidants from Paeonia Officinalis Roots and Leaves and Evaluation of Their Bioactivities
Authors: Dienaitė Lijana , Pukalskienė Milda , Pukalskas Audrius , Pereira Carolina V. , Matias Ana A. , Venskutonis Petras Rimantas
Published: July 2019

Paeonia officinalis extracts from leaves and roots were tested for their antioxidant potential using in vitro chemical (Folin-Ciocalteu, 2,2-diphenyl-1-picrylhydrazyl radical (DPPH), 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), oxygen radical absorbance capacity (ORAC), hydroxyl radical antioxidant capacity (HORAC), hydroxyl radical scavenging capacity HOSC)) and cellular antioxidant activity (CAA) assays. Leaf extracts were stronger antioxidants than root extracts, while methanol was a more effective solvent than water in chemical assays. However, the selected water extract of leaves was a stronger antioxidant in CAA than the methanol extract (0.106 vs. 0.046 µmol quercetin equivalents/mg). Twenty compounds were identified by ultra performance liquid chromatography-quadrupole-time-of-flight (UPLC-Q-TOF) mass spectrometer, while on-line screening of their antioxidant capacity by high performance liquid chromatography (HPLC) with a DPPH•-scavenging detector revealed that gallic acid derivatives are the major peony antioxidants. Root water and leaf methanol extracts inhibited α-amylase in a dose dependent manner. The IC50 value for the strongest inhibitor, the methanol extract of leaves, was 1.67 mg/mL. In addition, the cytotoxicity assessment of extracts using human Caco-2 cells demonstrated that none of them possessed cytotoxic effects.
Effect of Manitoba-Grown Red-Osier Dogwood Extracts on Recovering Caco-2 Cells from H2O2-Induced Oxidative Damage
Authors: Yang Runqiang , Hui Qianru , Jiang Qian , Liu Shangxi , Zhang Hua , Wu Jiandong , Lin Francis , O Karmin , Yang Chengbo
Published: July 2019

Red-osier dogwood, a native species of flowering plant in North America, has been reported to have anti-oxidative properties because of abundant phenolic compounds; this could be promising as a functional food or a feed additive. In the present study, an oxidative damage model using 1.0 mM hydrogen peroxide (H2O2) in Caco-2 cells was established to evaluate the antioxidative effects of red-osier dogwood extracts (RDE). The results showed that 1.0 mM H2O2 pre-exposure for 3 h significantly decreased cell viability, and increased interleukin 8 (IL-8) secretion and the intracellular reactive oxygen species (ROS) level. Caco-2 cells were treated with 100 µg/mL RDE for 24 h after pre-exposure to H2O2. It was found that the decreased cell viability caused by H2O2 was significantly restored by a subsequent 100 µg/mL RDE treatment. Furthermore, the IL-8 secretion and ROS level were significantly blocked by RDE, accompanied by the enhanced gene expression of hemeoxygenase-1 (HO-1), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px), and the enhanced protein expression of the nuclear factor (erythroid-derived 2)-like 2 (Nrf-2). Moreover, RDE improved barrier functions in Caco-2 cells. Using RDE reduced the diffusion of fluorescein isothiocyanate (FITC)-dextran and increased the transepithelial resistance (TEER) value. The relative mRNA level of tight junction claudin-1, claudin-3, and occludin was elevated by RDE. These extracts also repaired the integrity of zonula occludens-1 (ZO-1) damaged by H2O2 and increased the protein expressions of ZO-1 and claudin-3 in the H2O2-pretreated cells. These results illustrated that RDE reduced the ROS level and enhanced the barrier function in oxidative-damaged epithelial cells.
Small-Scale Bioreactor for Sterile Hydroponics and Hairy Roots: Metabolic Diversity and Salicylic Acid Exudation by Hairy Roots of Hyoscyamus niger
Authors: Kareem Zana Jamal , Su Ling , Rathgeb Anna , Sirrenberg Anke , Hadacek Franz , Rashid Ahmad Hama Ameen H. , Karlovsky Petr
Published: July 2019

The volume and complexity of commercial bioreactors for sterile hydroponics and hairy roots are too large for comparative analysis of many cultures. Here a small-scale bioreactor fabricated from standard glass materials and suitable for both airlift and bubble aeration mode is described. The performance of the bioreactor was tested by growing oilseed rape (Brassica napus L.) and rose plants (Rosa canina L.) in sterile hydroponics and by cultivating hairy roots of henbane (Hyoscyamus niger L.) and sesame (Hyoscyamus niger L.). Plants grown in hydroponics for up to six weeks did not show chloroses or necroses. Hairy roots grew faster or comparably fast in bioreactors as compared to shaking flasks. Root exudates of roses and exudates of hairy roots of henbane were subjected to targeted and nontargeted analysis by HPLC coupled with optical and mass spectrometric detectors. The diversity and concentration of hairy root exudates were higher in bioreactors than in shaking flasks. The composition of hairy root exudates of three accessions of H. niger did not match the genetic relatedness among the accessions. Hairy roots of Hyoscyamus niger exuded salicylic acid in amounts varying among plant accessions and between bioreactors and shaking flask cultures.
Special Issue on Liquid Crystal on Silicon Devices: Modeling and Advanced Spatial Light Modulation Applications
Authors: Márquez Andrés , Lizana Ángel
Published: July 2019

Since the first liquid crystal displays (LCDs) at the beginning of the seventies—based on the twisted-nematic cell configuration [...]
Optimization Study on a Novel High-Speed Oil-Free Centrifugal Water Pump with Hydrodynamic Bearings
Authors: Xue Rong , Cai Yijie , Fang Xufeng , Chen Liang , Zhang Xingqun , Hou Yu
Published: July 2019

In aerospace fields and industrial sectors, high-speed centrifugal pumps are prevalent and in increasingly strict demand regarding characteristics such as the long life, small volume, light weight, and low noise. In this study, we present a novel high-speed centrifugal water pump with hydrodynamic bearings used to employ work fluid as lubricant. A three-dimensional numerical study of the turbulent fluid flow was carried out to predict the performance of the pump. The computational model was validated against experimental results during hydraulic tests. Additionally, the effect of the blade number on the head and efficiency of the pump was researched. The blade number of the impeller was changed from 4 to 8 and that of the stay vane was from 3 to 14. The results indicate that the blade number and the matching characteristic of the impeller and the stay vane significantly influenced the performance of the pump. The structure based on the seven-blade impeller and the six-blade stay vane had the highest efficiency (30.8%). Numerical investigations of this study may help reduce the significant cost and time of experimental work for a particular design.
Preparation of Amphiphilic Chitosan–Graphene Oxide–Cellulose Nanocrystalline Composite Hydrogels and Their Biocompatibility and Antibacterial Properties
Authors: Yang Ming-Chien , Tseng Yi-Qun , Liu Kun-Ho , Cheng Yu-Wei , Chen Wan-Tzu , Chen Wei-Ting , Hsiao Chia-Wei , Yung Ming-Chi , Hsu Chuan-Chih , Liu Ting-Yu
Published: July 2019

Environmental-friendly nanocomposite hydrogels of carboxymethyl-hexanoyl chitosan (CHC), graphene oxide (GO) and cellulose nanocrystals (CNCs) were combined to produce a bio-hydrogel with great biocompatibility and antibacterial ability. The size of the GO nanosheets was about 200–500 nm, and the CNCs had a length of 100–200 nm and a width of 10–20 nm, as shown by transmission electron microscopy (TEM). X-ray photoelectron spectroscopy (XPS) was utilized for the analysis of the oxygen functional groups of GO. The homogeneous dispersion of the CHC/GO/CNC nanocomposite hydrogel showed significantly higher water absorption capacity and water retention capability. In addition, inhibition of a variety of microorganisms (gram-negative and gram-positive bacteria and fungi) by the introduction of the CHC/GO/CNC nanocomposite hydrogel demonstrated that there is a great opportunity to use it in the bio-medical field, such as for plastic masks and wound dressings.
Rebar Shape Time-Evolution During a Reinforced Concrete Corrosion Test: An Electrochemical Model
Authors: de Vera Guillem , Miró Marina , Segovia Enrique Gonzalo , Poveda Pedro , Climent Miguel Ángel
Published: July 2019

An electrochemical model is presented to calculate the rebar shape time-evolution in reinforced mortar specimens during forced corrosion tests. This provides a more realistic description than the usually used geometric models. The current distribution along the rebar perimeter is calculated by using Finite Element Method (FEM) to solve Laplace equation. Then, Faraday’s law is used to relate current distribution to rebar volume increase due to corrosion products creation. The shape of the rebar section is obtained as a function of corrosion time.
Multi-Channel Regression Inversion Method for Passive Remote Sensing of Ice Water Path in the Terahertz Band
Authors: Weng Chensi , Liu Lei , Gao Taichang , Hu Shuai , Li Shulei , Dou Fangli , Shang Jian
Published: July 2019

Retrieval of ice cloud properties using passive terahertz wave radiometer from space has gained increasing attention currently. A multi-channel regression inversion method for passive remote sensing of ice water path (IWP) in the terahertz band is presented. The characteristics of the upward terahertz radiation in the clear-sky and cloudy-sky are first analyzed using the Atmospheric Radiative Transfer Simulator (ARTS). Nine representative center frequencies with different offsets are selected to study the changes of terahertz radiation caused by microphysical parameters of ice clouds. Then, multiple linear regression method is applied to the inversion of IWP. Combinations of different channels are selected for regression to eliminate the influence of other factors (i.e., particle size and cloud height). The optimal fitting equation are obtained by the stepwise regression method using two oxygen absorption channels (118.75 ± 1.1 GHz, 118.75 ± 3.0 GHz), two water vapor absorption channels (183.31 ± 1.0 GHz, 183.31 ± 7.0 GHz), and two window channels (243.20 ± 2.5 GHz, 874.4 ± 6.0 GHz). Finally, the errors of the proposed inversion method are evaluated. The simulation results show that the absolute errors of this method for the low IWP cases are below 7 g/m2, and the relative errors for the high IWP cases are generally ranging from 10 to 30%, indicating that the multi-channel regression inversion method can achieve satisfactory accuracy.
Commuter Exposure to Black Carbon, Fine Particulate Matter and Particle Number Concentration in Ferry and at the Pier in Istanbul
Authors: Onat Burcu , Alver Şahin Ülkü , Uzun Burcu , Akın Özcan , Özkaya Fazilet , Ayvaz Coşkun
Published: July 2019

This paper presents measurements and analyses of the concentrations of black carbon (BC), particle number concentration (PNC), and PM2.5 (≤2.5 μm) while commuting by ferries in Istanbul. In this context, exposures to the mentioned pollutants were estimated for car ferry, fast ferry, and at the piers, and for two travel routes, for a total of 89 trips. BC, PNC, and PM2.5 measurements were simultaneously performed in a ferry and at the piers, and the correlation between pollutant concentrations, meteorological parameters, and environmental factors were analyzed. The mean concentrations for all pollutants in car ferry were lower than the average concentrations in fast ferry. The concentration ratios of fast ferry to car ferry for BC, PNC, and PM2.5 were 6.4, 1.2, and 1.3, respectively. High variability in the concentrations was observed at the piers and in ferry during berthing. The highest mean concentrations (±standard deviation) of BC (14.3 ± 10.1 µg m−3) and PNC (42,005 ± 30,899 pt cm−3) were measured at Yalova pier. The highest mean concentration (±standard deviation) of PM2.5 (26.1 ± 11.5) was measured at Bostancı pier. It was observed that the main external sources of BC, PNC, and PM2.5 at the piers were road transport, residential heating, and shipping activity. There were no significant correlations between BC, PNC, and PM2.5 in fast ferry, while BC was positively correlated with PNC (r = 0.61, p < 0.01) and PM2.5 (r = 0.76, p < 0.01) in car ferry. At the piers, significant relations between pollutants and meteorological variables were observed. It was noticed that there was no significant difference between summer and winter in ferry and at the pier concentrations of BC, PNC, and PM2.5 except for Yenikapı pier and Bakırköy pier. The highest total exposure to PNC and PM2.5 was in car ferry mode, while the highest total exposure to BC was in fast ferry mode.
Ellagitannins and Flavano-Ellagitannins: Red Wines Tendency in Different Areas, Barrel Origin and Ageing Time in Barrel and Bottle
Authors: Rasines-Perea Zuriñe , Jacquet Rémi , Jourdes Michael , Quideau Stéphane , Teissedre Pierre-Louis
Published: July 2019

During maturation and ageing in oak barrels polyphenolic compounds from oak wood, and particularly C-glucosidic ellagitannins, can be released from wood to the wine. These ellagitannins can be involved in oxidation reactions, affecting the wine’s organoleptic properties such as astringency. In this study C-glucosidic ellagitannins and flavano-ellagitannins, acutissimins A and B and epiacutissimins A and B, as well as mongolicain A, which is the result compound of acutissimin A oxidation, were identified and quantified. The quantification was carried out by HPLC-UV-MS in 185 commercial samples from different cultivar areas (Bordeaux and Rioja), different barrel oak wood (French oak barrels and American oak barrels) and different ageing periods. The results show differences between the two zones in terms of compound concentrations. Moreover, the ageing process in bottle for Bordeaux wines are unlike Rioja wines behavior in bottle.
Accuracy of Tumour-Associated Circulating Endothelial Cells as a Screening Biomarker for Clinically Significant Prostate Cancer
Authors: Bhakdi Sebastian , Suriyaphol Prapat , Thaicharoen Ponpan , Grote Sebastian , Komoltri Chulaluk , Chaiyaprasithi Bansithi , Charnkaew Komgrid
Published: July 2019

Even though more than 350,000 men die from prostate cancer every year, broad-based screening for the disease remains a controversial topic. Guidelines demand that the only commonly accepted screening tool, prostate-specific antigen (PSA) testing, must be followed by prostate biopsy if results are elevated. Due to the procedure’s low positive predictive value (PPV), however, over 80% of biopsies are performed on healthy men or men with clinically insignificant cancer—prompting calls for new ways of vetting equivocal PSA readings prior to the procedure. Responding to the challenge, the present study investigated the diagnostic potential of tumour-associated circulating endothelial cells (tCECs), which have previously been described as a novel, blood-based biomarker for clinically significant cancers. Specifically, the objective was to determine the diagnostic accuracy of a tCEC-based blood test to detect clinically significant prostate cancer (defined as Gleason score ≥ 3 + 4) in high-risk patients. Performed in a blinded, prospective, single-centre set-up, it compared a novel tCEC index test with transrectal ultrasound-guided biopsy as a reference on a total of 170 patients and found that a tCEC add-on test will almost double the PPV of a standalone PSA test (32% vs. 17%; p = 0.0012), while retaining a negative predictive value above 90%.
Nomogram for Predicting Survival in Patients Treated with Liposomal Irinotecan Plus Fluorouracil and Leucovorin in Metastatic Pancreatic Cancer
Authors: Chen Li-Tzong , Macarulla Teresa , Blanc Jean-Frédéric , Mirakhur Beloo , de Jong Floris A. , Belanger Bruce , Bekaii-Saab Tanios , Siveke Jens T.
Published: July 2019

NAPOLI-1 (NCT01494506) was a phase III study of liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. This post hoc analysis of NAPOLI-1 aimed to develop a predictive nomogram for overall survival (OS) at 6 and 12 months. Analyses were derived from all patients in NAPOLI-1 randomized to receive nal-IRI+5-FU/LV, nal-IRI monotherapy, or 5-FU/LV combination therapy. OS was associated with baseline factors using univariate and multivariable Cox analyses. A predictive nomogram was derived and validated using a concordance index and calibration plots. The univariate analyses identified 21 independent factors that contributed to OS, with eight factors significantly associated with OS. The Karnofsky Performance Score contributed the largest number of points (100), followed by presence of liver metastasis (98) and randomization to nal-IRI+5-FU/LV (96). The other baseline factors showing effects were albumin (g/dL), neutrophil/lymphocyte ratio, carbohydrate antigen 19-9 (U/mL), disease stage at diagnosis, and body mass index (kg/m2). The nomogram was used to predict the 6- and 12-month survival probability. The mean absolute errors between the observed and predicted probabilities for OS at 3, 6, and 9 months were 0.07, 0.08, and 0.07, respectively. This nomogram, based on NAPOLI-1, provides additional insight to aid decision-making for patients with mPDAC after previous gemcitabine-based therapy.
Extent of Resection, MGMT Promoter Methylation Status and Tumor Location Independently Predict Progression-Free Survival in Adult Sporadic Pilocytic Astrocytoma
Authors: Jungk Christine , Reinhardt Annekathrin , Warta Rolf , Capper David , von Deimling Andreas , Herold-Mende Christel , Unterberg Andreas
Published: July 2019

In adults, pilocytic astrocytomas (PA) account for less than 2% of gliomas, resulting in uncertainty regarding the clinical course and optimal treatment, particularly in cases where gross total resection (GTR) could not be achieved. Moreover, information on molecular markers and their prognostic impact is sparse. In order to improve risk stratification, we analyzed our institutional series of 58 patients aged 17 years and older with histology-proven intracranial PA World Health Organization grade I for clinical and molecular prognosticators. Anaplastic and NF1-associated tumors were excluded. O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was determined by pyrosequencing or 450k/850k DNA methylation array. A univariate log-rank test and multivariate StepAIC were applied to identify prognostic factors. The median age was 30 years (range 17–66). Tumors were located in the cerebral/cerebellar hemispheres, midline structures and cerebello-pontine angle in 53%, 38% and 9%. MGMT promoter methylation was present in eight patients (14%). GTR (39/58 patients) significantly reduced the likelihood of tumor recurrence (p = 0.0001). Tumor relapse occurred in 16 patients (28%) after a median progression-free survival (PFS) of 135 months (range 6–153 months); there was one tumor-related death. PFS at 5 and 10 years was 67% and 53%. In multivariate analysis, PFS was significantly prolonged in patients with GTR (HR 0.1; CI 0.03–0.37; p < 0.001), unmethylated MGMT promoter (HR 0.18; CI 0.05–0.64; p = 0.009) and midline tumors (HR 0.21; CI 0.06–0.78; p = 0.02). In conclusion, MGMT promoter methylation status and tumor location were identified as novel prognostic factors in adult PAs, pointing at distinct molecular subtypes and detecting patients in need of close observance and intensified treatment.
GSK3-β Stimulates Claspin Degradation via β-TrCP Ubiquitin Ligase and Alters Cancer Cell Survival
Authors: Cabrera Elisa , Raninga Prahlad , Khanna Kum Kum , Freire Raimundo
Published: July 2019

Claspin is essential for activating the DNA damage checkpoint effector kinase Chk1, a target in oncotherapy. Claspin functions are tightly correlated to Claspin protein stability, regulated by ubiquitin-dependent proteasomal degradation. Here we identify Glycogen Synthase Kinase 3-β (GSK3-β) as a new regulator of Claspin stability. Interestingly, as Chk1, GSK3-β is a therapeutic target in cancer. GSK3-β inhibition or knockdown stabilizes Claspin, whereas a GSK3-β constitutively active form reduces Claspin protein levels by ubiquitination and proteasome-mediated degradation. Our results also suggest that GSK3-β modulates the interaction of Claspin with β-TrCP, a critical E3 ubiquitin ligase that regulates Claspin stability. Importantly, GSK3-β knock down increases Chk1 activation in response to DNA damage in a Claspin-dependent manner. Therefore, Chk1 activation could be a pro-survival mechanism that becomes activated upon GSK3-β inhibition. Importantly, treating triple negative breast cancer cell lines with Chk1 or GSK3-β inhibitors alone or in combination, demonstrates that Chk1/GSK3-β double inhibition restrains cell growth and triggers more apoptosis compared to individual treatments, thereby revealing novel possibilities for a combination therapy for cancer.
Surface-Doped Graphitic Carbon Nitride Catalyzed Photooxidation of Olefins and Dienes: Chemical Evidence for Electron Transfer and Singlet Oxygen Mechanisms
Authors: Chatzoudis Apostolos , Giannopoulos Vasileios , Hollmann Frank , Smonou Ioulia
Published: July 2019

A new photocatalytic reactivity of carbon-nanodot-doped graphitic carbon nitride (CD-C3N4) with alkenes and dienes, has been disclosed. We have shown that CD-C3N4 photosensitizes the oxidation of unsaturated substrates in a variety of solvents according to two competing mechanisms: the energy transfer via singlet oxygen (1O2) and/or the electron transfer via superoxide (O·−2). The singlet oxygen, derived by the CD-C3N4 photosensitized process, reacts with alkenes to form allylic hydroperoxides (ene products) whereas with dienes, endoperoxides. When the electron transfer mechanism operates, cleavage products are formed, derived from the corresponding dioxetanes. Which of the two mechanisms will prevail depends on solvent polarity and the particular substrate. The photocatalyst remains stable under the photooxidation conditions, unlike the most conventional photosensitizers, while the heterogeneous nature of CD-C3N4 overcomes usual solubility problems.
Pleurotus ostreatus as a Biocatalyst to Obtain Bicyclic Hydroxylactones with Three or Four Methyl Groups
Authors: Grabarczyk Małgorzata , Mączka Wanda , Wińska Katarzyna , Kondas Adrianna , Żarowska Barbara , Maciejewska Gabriela , Gębarowska Elżbieta , Pietr Stanisław Jerzy
Published: July 2019

The purpose of the study was to explore microbial transformations in cultures of basidiomycetes Pleurotus ostreatus, two bicyclic unsaturated lactones occurring in the form of two diastereoisomers. Some of these strains were able to transform unsaturated lactones into four known and three new derivatives. The structures of all lactones were established on the basis of spectroscopic data. Both substrates and products caused a complete inhibition of growth of A. alternata and F. linii strains.
Recent Developments in Carriers and Non-Aqueous Solvents for Enzyme Immobilization
Authors: Zhao Zongpei , Zhou Meng-Cheng , Liu Run-Lin
Published: July 2019

Immobilization techniques are generally based on reusing enzymes in industrial applications to reduce costs and improve enzyme properties. These techniques have been developing for decades, and many methods for immobilizing enzymes have been designed. To find a better immobilization method, it is necessary to review the recently developed methods and have a clear overview of the advantages and limitations of each method. This review introduces the recently reported immobilization methods and discusses the improvements in enzyme properties by different methods. Among the techniques to improve enzyme properties, metal–organic frameworks, which have diverse structures, abundant organic ligands and metal nodes, offer a promising platform.
Ex-Situ Synthesis and Study of Nanosized Mo-Containing Catalyst for Petroleum Residue Hydro-Conversion
Authors: Kadieva Malkan Kh. , Maximov Anton L. , Kadiev Khusain M.
Published: July 2019

This study represents the results of ex-situ synthesis and research of the properties of concentrated suspensions with new catalysts for petroleum residue hydro-conversion. Suspensions were prepared and stabilized in a petroleum residue medium through reverse emulsions containing water-soluble Mo-precursor and S-containing agents (elemental sulfur, thiocarbamide) in the absence of a solid carrier. The resulting ex-situ catalyst dispersions had Mo content of 6–10 wt % and contained nanosized and submicron catalyst particles stabilized in a petroleum residue medium. The effects of S-containing agents on the properties of catalytic particles (sulfidation level, dispersity, structural and morphological features) were studied. The synthesis conditions for the optimal ex-situ catalyst providing the lowest coke yield (0.2 wt %) and the highest conversion (55.5 wt %) during petroleum residue hydro-conversion in a single pass mode have been determined.
An Omics Approach to Extracellular Vesicles from HIV-1 Infected Cells
Authors: Barclay Robert A. , Khatkar Pooja , Mensah Gifty , DeMarino Catherine , Chu Jeffery S. C. , Lepene Benjamin , Zhou Weidong , Gillevet Patrick , Torkzaban Bahareh , Khalili Kamel , Liotta Lance , Kashanchi Fatah
Published: July 2019

Human Immunodeficiency Virus-1 (HIV-1) is the causative agent of Acquired Immunodeficiency Syndrome (AIDS), infecting nearly 37 million people worldwide. Currently, there is no definitive cure, mainly due to HIV-1′s ability to enact latency. Our previous work has shown that exosomes, a small extracellular vesicle, from uninfected cells can activate HIV-1 in latent cells, leading to increased mostly short and some long HIV-1 RNA transcripts. This is consistent with the notion that none of the FDA-approved antiretroviral drugs used today in the clinic are transcription inhibitors. Furthermore, these HIV-1 transcripts can be packaged into exosomes and released from the infected cell. Here, we examined the differences in protein and nucleic acid content between exosomes from uninfected and HIV-1-infected cells. We found increased cyclin-dependent kinases, among other kinases, in exosomes from infected T-cells while other kinases were present in exosomes from infected monocytes. Additionally, we found a series of short antisense HIV-1 RNA from the 3′ LTR that appears heavily mutated in exosomes from HIV-1-infected cells along with the presence of cellular noncoding RNAs and cellular miRNAs. Both physical and functional validations were performed on some of the key findings. Collectively, our data indicate distinct differences in protein and RNA content between exosomes from uninfected and HIV-1-infected cells, which can lead to different functional outcomes in recipient cells.
The Dynamic 3D Genome in Gametogenesis and Early Embryonic Development
Authors: Li Feifei , An Ziyang , Zhang Zhihua
Published: July 2019

During gametogenesis and early embryonic development, the chromatin architecture changes dramatically, and both the transcriptomic and epigenomic landscape are comprehensively reprogrammed. Understanding these processes is the holy grail in developmental biology and a key step towards evolution. The 3D conformation of chromatin plays a central role in the organization and function of nuclei. Recently, the dynamics of chromatin structures have been profiled in many model and non-model systems, from insects to mammals, resulting in an interesting comparison. In this review, we first introduce the research methods of 3D chromatin structure with low-input material suitable for embryonic study. Then, the dynamics of 3D chromatin architectures during gametogenesis and early embryonic development is summarized and compared between species. Finally, we discuss the possible mechanisms for triggering the formation of genome 3D conformation in early development.
Electrical Vehicles: Current State of the Art, Future Challenges, and Perspectives
Authors: Skouras Theodoros , Gkonis Panagiotis , Ilias Charalampos , Trakadas Panagiotis , Tsampasis Eleftherios , Zahariadis Theodore
Published: July 2019

The goal of the study presented in this article is to provide a general overview of the various aspects related to electric vehicles (EVs), along with all associated emerging challenges and perspectives. In this context, the basic types of EVs and the corresponding charging technologies are analyzed. Since EVs are expected to be a key component of future smart electrical grids (SEG), connection to the grid issues, along with advanced charging techniques (i.e., wireless power transfer), are analyzed as well. To this end, the main features, the requirements of vehicle to grid (V2G) communications, as well as future developments and scenarios of electrification, are also presented and analyzed. Moreover, integration issues with currently deployed fifth generation (5G) mobile wireless networks are also outlined, in order to ensure optimum transmission and reception quality in V2G communications and improved user experience. This integration is also expanded in autonomous vehicles (AVs) technology (self-driving objects), since optimized information processing from various diverse sources is required in order to ensure advanced traffic management aspects.
Willow Short-Rotation Coppice as Model System for Exploring Ecological Theory on Biodiversity–Ecosystem Function
Authors: Weih Martin , Glynn Carolyn , Baum Christel
Published: July 2019

Plantations of willow (Salix spp.) are today grown as short-rotation coppice (SRC) for the sustainable production of biomass. While developing these production systems in the past, much ecological knowledge on plant–plant, plant–environment and trophic interactions has been generated. This knowledge can contribute to the further development of biodiversity–ecosystem function (BEF) theory, which frequently lacks a sound understanding of the complex mechanisms behind the observed patterns of diversity-productivity relationships. Thus, willow SRC systems are suitable models to explore BEF theory; they are simple enough to allow the study of the complex ecological mechanisms involved and they have many similarities to grassland systems in which much of recent BEF theory development has been achieved. This paper briefly reviews the current observational and mechanistic knowledge on diversity–productivity relationships in willow SRC, as well as the most important above- and below-ground trophic interactions that are likely to affect them. If the available knowledge is integrated and combined with further experimental work targeting mechanisms behind patterns, research on willow SRC as a model offers a great opportunity for filling the gaps in the understanding what presently hampers the development of predictive BEF theory.
Long-Lasting Remission in De Novo Breast Myeloid Sarcoma Treated with Decitabine and Radiotherapy
Authors: Minoia Carla , de Fazio Vincenza , Scognamillo Giovanni , Scattone Anna , Maggialetti Nicola , Ferrari Cristina , Guarini Attilio
Published: July 2019

Myeloid sarcoma (MS) represents a rare disease with an adverse clinical outcome for patients not candidate to acute myeloid leukemia (AML)-like chemotherapies. Here we present the case of an elderly patient affected by a bilateral breast localization of MS treated with the hypomethylating agent decitabine associated to radiotherapy. The association of the two treatment modalities has allowed an optimal and long-lasting disease control.
Left Ventricular Dysfunction and Plasmatic NT-proBNP Are Associated with Adverse Evolution in Respiratory Syncytial Virus Bronchiolitis
Authors: Rodriguez-Gonzalez Moises , Perez-Reviriego Alvaro Antonio , Castellano-Martinez Ana , Lubian-Lopez Simon , Benavente-Fernandez Isabel
Published: July 2019

Aim: To investigate whether the presence of left ventricular myocardial dysfunction (LVMD) assessed by Tei index (LVTX) impacts the outcomes of healthy infants with Respiratory Syncytial Virus Bronchiolitis (RSVB). To explore whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) increases the accuracy of traditional clinical markers in predicting the outcomes. Methods: A single-centre, prospective, cohort study including healthy infants aged 1–12 months old admitted for RSVB between 1 October 2016 and 1 April 2017. All patients underwent clinical, laboratory and echocardiographic evaluation within 24 h of admission. Paediatric intensive care unit (PICU) admission was defined as severe disease. Results: We enrolled 50 cases of RSVB (median age of 2 (1–6.5) months; 40% female) and 50 age-matched controls. We observed higher values of LVTX in infants with RSVB than in controls (0.42 vs. 0.36; p = 0.008). Up to nine (18%) children presented with LVMD (LVTX > 0.5), with a higher incidence of PICU admission (89% vs. 5%; p < 0.001). The diagnostic performance of NT-proBNP in predicting LVMD was high (area under the receiver operator characteristic curve (AUC) 0.95, CI 95% 0.90–1). The diagnostic yield of the predictive model for PICU admission that included NT-proBNP was excellent (AUC 0.945, CI 95% 0.880–1), and significantly higher than the model without NT-proBNP (p = 0.026). Conclusions: LVMD could be present in healthy infants with RSVB who develop severe disease. NT-proBNP seems to improve traditional clinical markers for outcomes.
Artificial Intelligence Applications in Reservoir Engineering: A Status Check
Authors: Ertekin Turgay , Sun Qian
Published: July 2019

This article provides a comprehensive review of the state-of-art in the area of artificial intelligence applications to solve reservoir engineering problems. Research works including proxy model development, artificial-intelligence-assisted history-matching, project design, and optimization, etc. are presented to demonstrate the robustness of the intelligence systems. The successes of the developments prove the advantages of the AI approaches in terms of high computational efficacy and strong learning capabilities. Thus, the implementation of intelligence models enables reservoir engineers to accomplish many challenging and time-intensive works more effectively. However, it is not yet astute to completely replace the conventional reservoir engineering models with intelligent systems, since the defects of the technology cannot be ignored. The trend of research and industrial practices of reservoir engineering area would be establishing a hand-shaking protocol between the conventional modeling and the intelligent systems. Taking advantages of both methods, more robust solutions could be obtained with significantly less computational overheads.