bluuebunny/crossref_metadata_2025 huggingface dataset:
Little-known pages of the history of the development of international legal thought: Ludwig Jacob (1759–1827)
Authors: Kostyantyn Savchuk
Published: June 2020

This article explores the contribution to the development of international law science by the outstanding German philosopher and economist Ludwig Kondratievich Jacob (Ludwig Heinrich von Jacob) (1759–1827), who for some time worked as a professor of diplomacy and political economy at Kharkiv University. L. Jacob's contribution to the development of the science of international law is not limited to reading lectures on positive international law, which was taught at the Department of Diplomacy and Political Economy in the first decades of Kharkiv University. L. K. Jacob prepared and published a series of textbooks on logic, grammar, psychology, aesthetics, rhetoric, political economy and law under the general title «Philosophy Course for High Schools of the Russian Empire», the seventh part of which was devoted to the problems of natural law, including international law. International Law Jacob interpreted it as part of natural law, which determines relations between independent states. Among the fundamental rights of the nation he distinguishes: 1) the right to independence, which includes the right to take possession of things that did not belong to anyone (it is clear that the author here justifies the right to take over the so-called res nullius, which was widely used in international law at the time, 2) the right to independence from any other nation; 3) the right to formal equality with any other nation. Considerable attention in his textbook L. K. Jakob attributes the right to international treaties, though he sees no distinction between treaties that nation conclude with other nations and with foreign individuals. Some emphasis is also placed on diplomatic law in the textbook. In the work of L. К. Jakob quite comprehensive doctrine of the right to war, which, again, is quite typical for proponents of natural law in the science of international law, is based on the identification of relations between independent nations (states) with relations between individuals in the natural state. His international legal doctrine is literally imbued with the ideas of the humanization of war – he strongly opposes treachery and the use of such means of war, which cause the enemy extreme pain, requires respect for the rights of prisoners of war.On the last pages of his textbook L. K. Jacob is installing an application in which he proposes the idea of uniting the independent states into a confederation, provided that each of them maintains complete independence in their internal affairs. In this project it is easy to see the impact of the ideas of the treatise «To Eternal Peace» by I. Kant, a consistent follower of the philosophical doctrine of which L. K. Jacob performed in his philosophical writings.
PEMANFAATAN POTENSI LIMBAH KULIT BAWANG MERAH (Allium Cepa. L) SEBAGAI SEDIAAN GEL HAND SANITIZER
Authors: Usman Yusnita
Published: June 2020

The increased health problems caused by microorganisms at the hands, hand sanitizer gel as the way out to maintained health and hand hygiene because it is more practical and easy to carry. The purpose of this study was to make formulations of gel with physically stable and had inhibitory activity against the Staphylococcus aureus bacteria. In this study three formulations were made with a ratio of Hydroxy ethyl selilulose 0.5% (F1), 1% (F2) and 2% (F3) then physical stability testing included organoleptic, homogeneity, pH and dispersion before and after accelerated storage, then antimicrobial activity by sump method. Organoleptic test showed there is no color, smell and texture changes. The results of the homogenety test, formula with concentration of Hydroxy ethyl cellulose 1% and 2% is homogeneous. The pH test results showed that the gel preparation did not change pH. Dispersing test showed concentration hydroxyethyl cellulose 1% has the highest dispersion value. but statistical paired T test results showed that the dispersion before and after storage was accelerated significantly different 0.043 (p <0.05), but still in accordance with the range of dispersion specifications for a good semisolid preparation.The MIC test results showed Formulation F1, F2 and F3 ethanol extract red onion skin gel are strong  inhibitory effect, ethanol extract of red onion skin gel F1 inhibitory zone is 16mm, F2 and F3 had the same inhibitory zone is 14.33. It can be concluded F2  has the best physical stability, but F1  is the most effective to inhibit Staphylococcus aureus.
EFEKTIFITAS PAPARAN SINAR UV DAN ALKOHOL 70% TERHADAP TOTAL BAKTERI PADA UANG KERTAS YANG BEREDAR DI MASA PANDEMI COVID-19
Authors: Elisanti Alinea Dwi , Ardianto Efri Tri , Ida Novita Cholifah , Hendriatno Eryk
Published: June 2020

Corona virus disease (COVID-19) has become a global pandemic in the world. Indonesia has declared this pandemic as a national disaster. Positive cases and deaths have increased every day. This was a long list of the effects of the COVID-19 pandemic on life. Several solutions have been designed to prevent the rapid transmission of this virus, one of them was by making sterilizer and hand sanitizer products. But there was still debate regarding the effectiveness of the use of UV rays and antiseptics as hygiene products offered.So we need a study to determine the effectiveness of UV exposure and the use of antiseptics to kill germs. This study used an experimental design, the sample used was in the form of folding money taken by the bacteria and grown on the media so that were classified into 3 groups, namely without treatment, 70% alcohol treatment and 10 seconds UV light treatment. The samples were analyzed using the dilution agar method and swab test with two repetitions. The results showed the average number of colony forming units (cfu) of bacteria using the dilution test method and swab test methode were 419 cfu on without treatment group; 4 cfu on alcohol 70% ; and 150 cfu on UV light (10 seconds). The alcohol 70% was more effective than 10 seconds UV light exposure to reduce the amount of bacterial cfu on folding money.
Countergradient Variation in Reptiles: Thermal Sensitivity of Developmental and Metabolic Rates Across Locally Adapted Populations
Authors: Pettersen Amanda K.
Published: June 2020

Environmental temperature is a key driver of variation in developmental physiological rates in reptiles. Cooler temperatures extend development time and can increase the amount of energy required to achieve hatching success, which can pose fitness consequences later in life. Yet, for locally-adapted populations, genetic variation can oppose environmental variation across ecological gradients, known as countergradient variation (CnGV). Biologists often seek to understand the presence of phenotypic variation, yet the absence of such variation across environmental gradients can also reveal insights into the mechanisms underlying local adaptation. While evidence for genetic variation opposing environmental variation in physiological rates has been summarized in other taxa, the generality of CnGV variation in reptiles is yet unknown. Here I present a summary of studies measuring development time and metabolic rates in locally-adapted populations across thermal clines for 15 species of reptiles across 8 families. CnGV in development time is found to be common, while no clear pattern emerges for the thermal sensitivity of metabolic rates across locally-adapted populations. CnGV in development time may be an adaptive response in order to decrease the costly development in cool climates, however, empirical work is needed to disentangle plastic from genetic responses, and to uncover potentially general mechanisms of local thermal adaptation in reptiles.
Phenotypic and Genotypic Characterization of Virulence Factors and Susceptibility to Antibiotics in Salmonella Infantis Strains Isolated from Chicken Meat: First Findings in Chile
Authors: Lapierre Lisette , Cornejo Javiera , Zavala Sebastián , Galarce Nicolás , Sánchez Fernando , Benavides María Belén , Guzmán Miguel , Sáenz Leonardo
Published: June 2020

Salmonella Infantis is a zoonotic pathogen that causes gastroenteritis in humans and animals, with poultry being its main reservoir. In Chile, there are no data to characterize S. Infantis strains in poultry production. In this study, 87 S. Infantis strains were isolated from chicken meat for sale in supermarkets in Santiago, Chile, and characterized according to their virulence genes, biofilm formation abilities, antibiotic susceptibility, and resistance genes. Through polymerase chain reaction or PCR, the strains were analyzed to detect the presence of 11 virulence genes, 12 antibiotic resistance genes, and integrase genes. Moreover, disc diffusion susceptibility to 18 antimicrobials and the ability to form biofilm in vitro were evaluated. Results demonstrated six different virulence gene profiles. Ninety-four percent of the strains were multi-resistant to antibiotics with weak biofilm formation abilities, 63.2% of the strains were broad spectrum β- lactam resistant, and the bla CTX-M-65 gene was amplified in 13 strains. Only 3.4% of the strains were fluoroquinolone resistant, and the qnrB gene was amplified in two strains. Colistin resistance was exhibited in 28.7% of the strains, but mrc genes were not amplified in any strain under study. The isolated S. Infantis strains are pathogenic and antibiotic multi-resistant, and thus, this Salmonella serotype should be under surveillance in the poultry food production chain with the aim of protecting public health.
Microbial Communities Associated with Farmed Genypterus chilensis: Detection in Water Prior to Bacterial Outbreaks Using Culturing and High-Throughput Sequencing
Authors: Levican Arturo , Fisher Jenny C. , McLellan Sandra L. , Avendaño-Herrera Ruben
Published: June 2020

The red conger eel (Genypterus chilensis, Guichenot) is a native species included in the Chilean Aquaculture Diversification Program due to high commercial demand. In the context of intensified farming, prior reports link two disease outbreaks with emerging pathogens in the Vibrio and Tenacibaculum genera. However, the roles remain unclear for the bacterial community and each specific bacterium is associated with the rearing environment for healthy specimens. The success of red conger eel farming therefore warrants research into the bacterial composition of aquaculture conditions and the antimicrobial susceptibilities thereof. This study used culturing methods and high-throughput sequencing to describe the bacterial community associated with water in which G. chilensis was farmed. With culturing methods, the predominant genera were Vibrio (21.6%), Pseudolteromonas (15.7%), Aliivibrio (13.7%), and Shewanella (7.8%). Only a few bacterial isolates showed amylase, gelatinase, or lipase activity, and almost all showed inhibition zones to commonly-used antibiotics in aquaculture. By contrast, high-throughput sequencing established Paraperlucidibaca, Colwellia, Polaribacter, Saprospiraceae, and Tenacibaculum as the predominant genera, with Vibrio ranking twenty-seventh in abundance. High-throughput sequencing also established a link between previous outbreaks with increased relative abundances of Vibrio and Tenacibaculum. Therefore, monitoring the presence and abundance of these potential pathogens could be useful in providing prophylactic measures to prevent future outbreaks.
Surface Optimization of Micro-Integrated Reflective Optical Elements by Thermoset Injection Molding
Authors: Guenther Thomas , Diegel Lars , Roeder Marcel , Drexler Marc , Haybat Mehmet , Wappler Peter , Soltani Mahdi , Zimmermann André
Published: June 2020

Thermoset materials offer a multitude of advantageous properties in terms of shrinkage and warpage as well as mechanical, thermal and chemical stability compared to thermoplastic materials. Thanks to these properties, thermosets are commonly used to encapsulate electronic components on a 2nd-level packaging prior to assembly by reflow soldering on printed circuits boards or other substrates. Based on the characteristics of thermosets to develop a distinct skin effect due to segregation during the molding process, the surface properties of injection molded thermoset components resemble optical characteristics. Within this study, molding parameters for thermoset components are analyzed in order to optimize the surface quality of injection molded thermoset components. Perspectively, in combination with a reflective coating by e.g., physical vapor deposition, such elements with micro-integrated reflective optical features can be used as optoelectronic components, which can be processed at medium-ranged temperatures up to 230 °C. The obtained results indicate the general feasibility since Ra values of 60 nm and below can be achieved. The main influencing parameters on surface quality were identified as the composition of filler materials and tool temperature.
Fire Risk Assessment Models Using Statistical Machine Learning and Optimized Risk Indexing
Authors: Choi Myoung-Young , Jun Sunghae
Published: June 2020

It is very difficult for us to accurately predict occurrence of a fire. But, this is very important to protect human life and property. So, we study fire hazard prediction and evaluation methods to cope with fire risks. In this paper, we propose three models based on statistical machine learning and optimized risk indexing for fire risk assessment. We build logistic regression, deep neural networks (DNN) and fire risk indexing models, and verify performances between proposed and traditional models using real investigated data related to fire occurrence in Korea. In general, fire prediction models currently in use do not provide satisfactory levels of accuracy. The reason for this result is that the factors affecting fire occurrence are very diverse and frequency of fire occurrence is very sparse. To improve accuracy of fire occurrence, we first build logistic regression and DNN models. In addition, we construct a fire risk indexing model for a more improved model of fire prediction. To illustrate comparison results between our research models and current fire prediction model, we use real fire data investigated in Korea between 2011 to 2017. From the experimental results of this paper, we can confirm that accuracy of prediction by the proposed method is superior to the existing fire occurrence prediction model. Therefore, we expect the proposed model to contribute to evaluating the possibility of fire risk in buildings and factories in the field of fire insurance and to calculate the fire insurance premium.
Atmospheric Pollutant Dispersion over Complex Terrain: Challenges and Needs for Improving Air Quality Measurements and Modeling
Authors: Giovannini Lorenzo , Ferrero Enrico , Karl Thomas , Rotach Mathias W. , Staquet Chantal , Trini Castelli Silvia , Zardi Dino
Published: June 2020

Pollutant dispersion processes over complex terrain are much more complicated than over flat areas, as they are affected by atmospheric interactions with the orography at different spatial scales. This paper reviews recent findings and progress in this field, focusing on both experimental and modeling perspectives. It highlights open questions and challenges to our capability for better understanding and representing atmospheric processes controlling the fate of pollutants over mountainous areas. In particular, attention is focused on new measurement techniques for the retrieval of spatially distributed turbulence information and air quality parameters, and on challenges for meteorological and dispersion models to reproduce fine-scale processes influenced by the orography. Finally, specific needs in this field are discussed, along with possible directions for future research efforts.
Simulation of Wind Speed Based on Different Driving Datasets and Parameterization Schemes Near Dunhuang Wind Farms in Northwest of China
Authors: Zhang Tiejun , Zhao Cailing , Gong Chongshui , Pu ZhaoXia
Published: June 2020

In this study, we evaluate the impacts of different datasets (e.g., NCEP global forecast system (GFS) and ERA5) that are used to derive the initial and boundary conditions, various planetary parameterization boundary layer (PBL) schemes and radiation parameterization schemes on wind speed simulations over wind farms near Dunhuang in Northwest of China. The mesoscale community Weather Research and Forecasting (WRF) model is employed to simulate the wind speeds in March of 2014. The sensitivity of numerical simulations to different PBL schemes, including the Yonsei University (YSU), the Asymmetric Convective Model (ACM2) and the Mellor–Yamada–Janjic (MYJ) scheme are examined. Besides, simulations with different radiation parameterization schemes, including the Rapid Radiative Transfer Model for general circulation model (GCM) applications (RRTMG) and the Fu–Liou–Gu radiative transfer scheme (FLG), are compared. Based on hourly observation data from three national basic meteorological observing stations and an anemometer tower in Dunhuang, the simulation results are evaluated. Results show that, using the GFS data as the initial data, the simulation error of 10-m wind speed is rather smaller under the combination of the YSU and FLG. When using the ERA5 data as the initial data, the error of the 2-m temperature simulation is smaller, and it is also less than that of the 10-m wind speed simulation. The simulation results show significant differences at different altitudes. The relative error of wind speed is larger at higher altitude. In the vertical direction, the wind speed is smaller at a lower height and so is the simulation error. In terms of wind speed from the anemometer tower, the error of the wind speed is related to the magnitude of the observed wind speed. Therefore, according to specific conditions of the simulated area, selecting an appropriate combination of initial data and parameterization schemes can effectively reduce the errors of simulated wind speed.
Tropical Atlantic Mixed Layer Buoyancy Seasonality: Atmospheric and Oceanic Physical Processes Contributions
Authors: Camara Ibrahima , Mignot Juliette , Kolodziejczyk Nicolas , Losada Teresa , Lazar Alban
Published: June 2020

This study investigates the physical processes controlling the mixed layer buoyancy using a regional configuration of an ocean general circulation model. Processes are quantified by using a linearized equation of state, a mixed-layer heat, and a salt budget. Model results correctly reproduce the observed seasonal near-surface density tendencies. The results indicate that the heat flux is located poleward of 10° of latitude, which is at least three times greater than the freshwater flux that mainly controls mixed layer buoyancy. During boreal spring-summer of each hemisphere, the freshwater flux partly compensates the heat flux in terms of buoyancy loss while, during the fall-winter, they act together. Under the seasonal march of the Inter-tropical Convergence Zone and in coastal areas affected by the river, the contribution of ocean processes on the upper density becomes important. Along the north Brazilian coast and the Gulf of Guinea, horizontal and vertical processes involving salinity are the main contributors to an upper water change with a contribution of at least twice as much the temperature. At the equator and along the Senegal-Mauritanian coast, vertical processes are the major oceanic contributors. This is mainly due to the vertical gradient of temperature at the mixed layer base in the equator while the salinity one dominates along the Senegal-Mauritania coast.
Investigation of Non-Methane Hydrocarbons at a Central Adriatic Marine Site Mali Lošinj, Croatia
Authors: Herjavić Glenda , Matasović Brunislav , Arh Gregor , Kovač-Andrić Elvira
Published: June 2020

For the first time, volatile hydrocarbons were measured in Croatia, at Mali Lošinj in the period from autumn 2004 to autumn 2005. Mali Lošinj site is conveniently located as a gateway to Croatia for any potential pollution from either Po valley in Italy, or other locations in southern Europe or even Africa. The sampling was performed on multisorbent tubes and then analyzed by thermal desorption gas chromatography with a flame ionization detector. The aim was to determine and estimate the non-methane hydrocarbons in Mali Lošinj, a location with Mediterranean vegetation and species which emit large quantities of volatile organic compounds. Ozone volume fraction and meteorological parameters were also continuously measured, from April to October 2005. Ethane, ethene, ethyne, propane, propene, n-pentane, n-hexane, benzene and toluene were identified in all air samples. Benzene and toluene have been found in ambient air and significant positive correlations between ethyne and ethane, propane and propene indicate emissions from transport.
Design Optimization and Sizing for Fly-Gen Airborne Wind Energy Systems
Authors: Aull Mark , Stough Andy , Cohen Kelly
Published: June 2020

Traditional on-shore horizontal-axis wind turbines need to be large for both performance reasons (e.g., clearing ground turbulence and reaching higher wind speeds) and for economic reasons (e.g., more efficient land use, lower maintenance costs, and fewer controllers and grid attachments) while their efficiency is scale and mass independent. Airborne wind energy (AWE) system efficiency is a function of system size and AWE system operating altitude is less directly coupled to system power rating. This paper derives fly-gen AWE system parameters from small number of design parameters, which are used to optimize a design for energy cost. This paper then scales AWE systems and optimizes them at each scale to determine the relationships between size, efficiency, power output, and cost. The results indicate that physics and economics favor a larger number of small units, at least offshore or where land cost is small.
ORP5 and ORP8: Sterol Sensors and Phospholipid Transfer Proteins at Membrane Contact Sites?
Authors: Santos Nina Criado , Girik Vladimir , Nunes-Hasler Paula
Published: June 2020

Oxysterol binding related proteins 5 and 8 (ORP5 and ORP8) are two close homologs of the larger oxysterol binding protein (OSBP) family of sterol sensors and lipid transfer proteins (LTP). Early studies indicated these transmembrane proteins, anchored to the endoplasmic reticulum (ER), bound and sensed cholesterol and oxysterols. They were identified as important for diverse cellular functions including sterol homeostasis, vesicular trafficking, proliferation and migration. In addition, they were implicated in lipid-related diseases such as atherosclerosis and diabetes, but also cancer, although their mechanisms of action remained poorly understood. Then, alongside the increasing recognition that membrane contact sites (MCS) serve as hubs for non-vesicular lipid transfer, added to their structural similarity to other LTPs, came discoveries showing that ORP5 and 8 were in fact phospholipid transfer proteins that rather sense and exchange phosphatidylserine (PS) for phosphoinositides, including phosphatidylinositol-4-phosphate (PI(4)P) and potentially phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2). Evidence now points to their action at MCS between the ER and various organelles including the plasma membrane, lysosomes, mitochondria, and lipid droplets. Dissecting exactly how this unexpected phospholipid transfer function connects with sterol regulation in health or disease remains a challenge for future studies.
Genome-Wide Identification of RNA Silencing-Related Genes and Their Expressional Analysis in Response to Heat Stress in Barley (Hordeum vulgare L.)
Authors: Hamar Éva , Szaker Henrik Mihály , Kis András , Dalmadi Ágnes , Miloro Fabio , Szittya György , Taller János , Gyula Péter , Csorba Tibor , Havelda Zoltán
Published: June 2020

Barley (Hordeum vulgare L.) is an economically important crop cultivated in temperate climates all over the world. Adverse environmental factors negatively affect its survival and productivity. RNA silencing is a conserved pathway involved in the regulation of growth, development and stress responses. The key components of RNA silencing are the Dicer-like proteins (DCLs), Argonautes (AGOs) and RNA-dependent RNA polymerases (RDRs). Despite its economic importance, there is no available comprehensive report on barley RNA silencing machinery and its regulation. In this study, we in silico identified five DCL (HvDCL), eleven AGO (HvAGO) and seven RDR (HvRDR) genes in the barley genome. Genomic localization, phylogenetic analysis, domain organization and functional/catalytic motif identification were also performed. To understand the regulation of RNA silencing, we experimentally analysed the transcriptional changes in response to moderate, persistent or gradient heat stress treatments: transcriptional accumulation of siRNA- but not miRNA-based silencing factor was consistently detected. These results suggest that RNA silencing is dynamically regulated and may be involved in the coordination of development and environmental adaptation in barley. In summary, our work provides information about barley RNA silencing components and will be a ground for the selection of candidate factors and in-depth functional/mechanistic analyses.
A Novel Efficient FEM Thin Shell Model for Bio-Impedance Analysis
Authors: Tang Jiawei , Lu Mingyang , Xie Yuedong , Yin Wuliang
Published: June 2020

In this paper, a novel method for accelerating eddy currents calculation on a cell model using the finite element method (FEM) is presented. Due to the tiny thickness of cell membrane, a full-mesh cell model requires a large number of mesh elements and hence intensive computation resources and long time. In this paper, an acceleration method is proposed to reduce the number of mesh elements and therefore reduce the computing time. It is based on the principle of replacing the thin cell membrane with an equivalent thicker structure. The method can reduce the number of mesh elements to 23% and the computational time to 17%, with an error of less than 1%. The method was verified using 2D and 3D finite element methods and can potentially be extended to other thin shell structures. The simulation results were validated by measurement and analytical results.
Whole Exome Sequencing of Multi-Regional Biopsies from Metastatic Lesions to Evaluate Actionable Truncal Mutations Using a Single-Pass Percutaneous Technique
Authors: Heong Valerie , Tay Darwin , Goh Shane Ee , Wee Bernard , Tan Tuan Zea , Soo Ross , Pang Brendan , Lim Diana , Gopinathan Anil , Ow Samuel , Chee Cheng Ean , Goh Boon Cher , Lee Soo Chin , Yong Wei Peng , Wong Andrea , Omar Mohamed Feroz Mohd , Soong Richie , Tan David SP
Published: June 2020

We investigate the feasibility of obtaining multiple spatially-separated biopsies from a single lesion to explore intratumor heterogeneity and identify actionable truncal mutations using whole exome sequencing (WES). A single-pass radiologically-guided percutaneous technique was used to obtain four spatially-separated biopsies from a single metastatic lesion. WES was performed to identify putative truncal variants (PTVs), defined as a non-synonymous somatic (NSS) variant present in all four spatially separated biopsies. Actionable truncal mutations—filtered using the FoundationOne panel—were defined as clinically relevant PTVs. Mutational landscapes of each biopsy and their association with patient outcomes were assessed. WES on 50 biopsied samples from 13 patients across six cancer types were analyzed. Actionable truncal mutations were identified in 9/13 patients; 31.1 ± 5.12 more unique NSS variants were detected with every additional multi- region tumor biopsy (MRTB) analyzed. The number of PTVs dropped by 16.1 ± 17.9 with every additional MRTB, with the decrease most pronounced (36.8 ± 19.7) when two MRTB were analyzed compared to one. MRTB most reliably predicted PTV compared to in silico analysis of allele frequencies and cancer cell fraction based on one biopsy sample. Three patients treated with actionable truncal mutation-directed therapy derived clinical benefit. Multi-regional sampling for genomics analysis is feasible and informative to help prioritize precision-therapy strategies.
Cisplatin Resistance in Testicular Germ Cell Tumors: Current Challenges from Various Perspectives
Authors: Lobo João , Jerónimo Carmen , Henrique Rui
Published: June 2020

Testicular germ cell tumors share a marked sensitivity to cisplatin, contributing to their overall good prognosis. However, a subset of patients develop resistance to platinum-based treatments, by still-elusive mechanisms, experiencing poor quality of life due to multiple (often ineffective) interventions and, eventually, dying from disease. Currently, there is a lack of defined treatment opportunities for these patients that tackle the mechanism(s) underlying the emergence of resistance. Herein, we aim to provide a multifaceted overview of cisplatin resistance in testicular germ cell tumors, from the clinical perspective, to the pathobiology (including mechanisms contributing to induction of the resistant phenotype), to experimental models available for studying this occurrence. We provide a systematic summary of pre-target, on-target, post-target, and off-target mechanisms putatively involved in cisplatin resistance, providing data from preclinical studies and from those attempting validation in clinical samples, including those exploring specific alterations as therapeutic targets, some of them included in ongoing clinical trials. We briefly discuss the specificities of resistance related to teratoma (differentiated) phenotype, including the phenomena of growing teratoma syndrome and development of somatic-type malignancy. Cisplatin resistance is most likely multifactorial, and a combination of therapeutic strategies will most likely produce the best clinical benefit.
Positive Feedback Loop of SNAIL-IL-6 Mediates Myofibroblastic Differentiation Activity in Precancerous Oral Submucous Fibrosis
Authors: Peng Chih-Yu , Liao Yi-Wen , Lu Ming-Yi , Yang Chieh-Mei , Hsieh Pei-Ling , Yu Cheng-Chia
Published: June 2020

Oral submucosal fibrosis (OSF) is a premalignant disorder of the oral cavity, and areca nut chewing is known to be a major etiological factor that could induce epithelial to mesenchymal transition (EMT) and activate buccal mucosal fibroblasts (BMFs). However, this detailed mechanism is not fully understood. In this study, we showed that the upregulation of Snail in OSF samples and fibrotic BMFs (fBMFs) may result from constant irritation by arecoline, a major alkaloid of the areca nut. The elevation of Snail triggered myofibroblast transdifferentiation and was crucial to the persistent activation of fBMFs. Meanwhile, Snail increased the expression of numerous fibrosis factors (e.g., α-SMA and collagen I) as well as IL-6. Results from bioinformatics software and a luciferase-based reporter assay revealed that IL-6 was a direct target of Snail. Moreover, IL-6 in BMFs was found to further increase the expression of Snail and mediate Snail-induced myofibroblast activation. These findings suggested that there was a positive loop between Snail and IL-6 to regulate the areca nut-associated myofibroblast transdifferentiation, which implied that the blockage of Snail may serve as a favorable therapeutic strategy for OSF treatment.
Phase I Radiation Dose-Escalation Study to Investigate the Dose-Limiting Toxicity of Concurrent Intra-Arterial Chemotherapy for Unresectable Hepatocellular Carcinoma
Authors: Cho Yeona , Kim Jun Won , Kim Ja Kyung , Lee Kwan Sik , Lee Jung Il , Lee Hyun Woong , Lee Kwang-Hun , Joo Seung-Moon , Lim Jin Hong , Lee Ik Jae
Published: June 2020

Concurrent intra-arterial chemotherapy and radiotherapy (iA-CCRT) can increase the response rate in hepatocellular carcinoma (HCC), but may cause a higher toxicity. We conducted this Phase I study to investigate the dose-limiting toxicity of iA-CCRT for HCC. In total, 52.5 Gy in 25 fractions was prescribed as planning target volume (PTV) 1 at dose level 1. The dose escalation was 0.2 Gy per fraction and up to 2.5 Gy, with 62.5 Gy at level 3. Concurrent intra-arterial 5-fluorouracil was administered during the first and fifth weeks of radiotherapy (RT). Toxicities were graded using the Common Toxicity Criteria for Adverse Events, version 4.0. Results: Seventeen patients with HCC were analyzed: four at dose level 1, 6 at level 2, and 7 at level 3. The mean irradiated dose administered to the uninvolved liver at each dose level was 21.3, 21.6, and 18.2 Gy, respectively. There was no grade ≥3 gastrointestinal toxicity; two patients experienced grade 3 hyperbilirubinemia. All patients had Child-Pugh class A disease, but 3 patients developed class B disease after iA-CCRT. During a median follow-up of 13 months, the median progression-free survival (PFS) and overall survival (OS) were 10 and 22 months, respectively. Patients treated at dose level 3 showed improved PFS and OS. Conclusions: Radiation dose escalation of iA-CCRT did not cause any significant toxicities in patients with advanced HCC. Further large-scale studies with long-term follow-up are needed to determine the efficacy and feasibility of higher doses of iA-CCRT.
RIG-I Plays a Dominant Role in the Induction of Transcriptional Changes in Zika Virus-Infected Cells, which Protect from Virus-Induced Cell Death
Authors: Schilling Mirjam , Bridgeman Anne , Gray Nicki , Hertzog Jonny , Hublitz Philip , Kohl Alain , Rehwinkel Jan
Published: June 2020

The Zika virus (ZIKV) has received much attention due to an alarming increase in cases of neurological disorders including congenital Zika syndrome associated with infection. To date, there is no effective treatment available. An immediate response by the innate immune system is crucial for effective control of the virus. Using CRISPR/Cas9-mediated knockouts in A549 cells, we investigated the individual contributions of the RIG-I-like receptors MDA5 and RIG-I to ZIKV sensing and control of this virus by using a Brazilian ZIKV strain. We show that RIG-I is the main sensor for ZIKV in A549 cells. Surprisingly, we observed that loss of RIG-I and consecutive type I interferon (IFN) production led to virus-induced apoptosis. ZIKV non-structural protein NS5 was reported to interfere with type I IFN receptor signaling. Additionally, we show that ZIKV NS5 inhibits type I IFN induction. Overall, our study highlights the importance of RIG-I-dependent ZIKV sensing for the prevention of virus-induced cell death and shows that NS5 inhibits the production of type I IFN.
Beneficial Effect of IL-4 and SDF-1 on Myogenic Potential of Mouse and Human Adipose Tissue-Derived Stromal Cells
Authors: Archacka Karolina , Bem Joanna , Brzoska Edyta , Czerwinska Areta M. , Grabowska Iwona , Kasprzycka Paulina , Hoinkis Dzesika , Siennicka Katarzyna , Pojda Zygmunt , Bernas Patrycja , Binkowski Robert , Jastrzebska Kinga , Kupiec Aleksandra , Malesza Malgorzata , Michalczewska Emilia , Soszynska Marta , Ilach Katarzyna , Streminska Wladyslawa , Ciemerych Maria A.
Published: June 2020

Under physiological conditions skeletal muscle regeneration depends on the satellite cells. After injury these cells become activated, proliferate, and differentiate into myofibers reconstructing damaged tissue. Under pathological conditions satellite cells are not sufficient to support regeneration. For this reason, other cells are sought to be used in cell therapies, and different factors are tested as a tool to improve the regenerative potential of such cells. Many studies are conducted using animal cells, omitting the necessity to learn about human cells and compare them to animal ones. Here, we analyze and compare the impact of IL-4 and SDF-1, factors chosen by us on the basis of their ability to support myogenic differentiation and cell migration, at mouse and human adipose tissue-derived stromal cells (ADSCs). Importantly, we documented that mouse and human ADSCs differ in certain reactions to IL-4 and SDF-1. In general, the selected factors impacted transcriptome of ADSCs and improved migration and fusion ability of cells in vitro. In vivo, after transplantation into injured muscles, mouse ADSCs more eagerly participated in new myofiber formation than the human ones. However, regardless of the origin, ADSCs alleviated immune response and supported muscle reconstruction, and cytokine treatment enhanced these effects. Thus, we documented that the presence of ADSCs improves skeletal muscle regeneration and this influence could be increased by cell pretreatment with IL-4 and SDF-1.
A Cellular Automaton Model as a First Model-Based Assessment of Interacting Mechanisms for Insulin Granule Transport in Beta Cells
Authors: Müller Michael , Glombek Mathias , Powitz Jeldrick , Brüning Dennis , Rustenbeck Ingo
Published: June 2020

In this paper a first model is derived and applied which describes the transport of insulin granules through the cell interior and at the membrane of a beta cell. A special role is assigned to the actin network, which significantly influences the transport. For this purpose, microscopically measured actin networks are characterized and then further ones are artificially generated. In a Cellular Automaton model, phenomenological laws for granule movement are formulated and implemented. Simulation results are compared with experiments, primarily using TIRF images and secretion rates. In this respect, good similarities are already apparent. The model is a first useful approach to describe complex granule transport processes in beta cells, and offers great potential for future extensions. Furthermore, the model can be used as a tool to validate hypotheses and associated mechanisms regarding their effect on exocytosis or other processes. For this purpose, the source code for the model is provided online.
Investigation of Interfacial Free Energy of Three-Phase Contact on a Glass Sphere in Case of Cationic-Anionic Surfactant Aqueous Mixtures
Authors: Alexandrova Lidia A. , Grigorov Ljudmil S. , Grozev Nikolay A. , Karakashev Stoyan I.
Published: June 2020

The wetting of adsorbed surfactants solids is important for various technological applications in particular for the process of foam flotation. The present work aims at calculating the surface tensions of the three phase interfaces at different surfactant concentrations using the Girifalco and Good method. For this purpose, the surface tension and contact angle vs. surfactant concentration of the test substances amines and sulfonates and their mixture were measured for liquid–air interface. Calculated surface tension of solid–air interface vs. concentration for C10 amine and mixed systems are close to those for the liquid–air surface, but are slightly lower. In the case of mixed systems, the graph has a specific structure similar to that of liquid–air surface dependence. In contrast to the solid–air interface results, the solid–liquid surface tension values are significantly lower. In case of the mixed surfactant systems, C10amine/C10 sulfonate, a synergetic effect on the surface tension is observed. The specific behavior of the mixed systems is interpreted with the emergence of aggregates consisting of the anionic and cationic surfactants. It is shown that in the whole area of concentrations complete wetting does not occur.
Comparison between Statistical Models and Machine Learning Methods on Classification for Highly Imbalanced Multiclass Kidney Data
Authors: Jeong Bomi , Cho Hyunjeong , Kim Jieun , Kwon Soon Kil , Hong SeungWoo , Lee ChangSik , Kim TaeYeon , Park Man Sik , Hong Seoksu , Heo Tae-Young
Published: June 2020

This study aims to compare the classification performance of statistical models on highly imbalanced kidney data. The health examination cohort database provided by the National Health Insurance Service in Korea is utilized to build models with various machine learning methods. The glomerular filtration rate (GFR) is used to diagnose chronic kidney disease (CKD). It is calculated using the Modification of Diet in Renal Disease method and classified into five stages (1, 2, 3A and 3B, 4, and 5). Different CKD stages based on the estimated GFR are considered as six classes of the response variable. This study utilizes two representative generalized linear models for classification, namely, multinomial logistic regression (multinomial LR) and ordinal logistic regression (ordinal LR), as well as two machine learning models, namely, random forest (RF) and autoencoder (AE). The classification performance of the four models is compared in terms of accuracy, sensitivity, specificity, precision, and F1-Measure. To find the best model that classifies CKD stages correctly, the data are divided into a 10-fold dataset with the same rate for each CKD stage. Results indicate that RF and AE show better performance in accuracy than the multinomial and ordinal LR models when classifying the response variable. However, when a highly imbalanced dataset is modeled, the accuracy of the model performance can distort the actual performance. This occurs because accuracy is high even if a statistical model classifies a minority class into a majority class. To solve this problem in performance interpretation, we not only consider accuracy from the confusion matrix but also sensitivity, specificity, precision, and F-1 measure for each class. To present classification performance with a single value for each model, we calculate the macro-average and micro-weighted values for each model. We conclude that AE is the best model classifying CKD stages correctly for all performance indices.
Stealthy Secret Key Generation
Authors: Lin Pin-Hsun , Janda Carsten R. , Jorswieck Eduard A. , Schaefer Rafael F.
Published: June 2020

In order to make a warden, Willie, unaware of the existence of meaningful communications, there have been different schemes proposed including covert and stealth communications. When legitimate users have no channel advantage over Willie, the legitimate users may need additional secret keys to confuse Willie, if the stealth or covert communication is still possible. However, secret key generation (SKG) may raise Willie’s attention since it has a public discussion, which is observable by Willie. To prevent Willie’s attention, we consider the source model for SKG under a strong secrecy constraint, which has further to fulfill a stealth constraint. Our first contribution is that, if the stochastic dependence between the observations at Alice and Bob fulfills the strict more capable criterion with respect to the stochastic dependence between the observations at Alice and Willie or between Bob and Willie, then a positive stealthy secret key rate is identical to the one without the stealth constraint. Our second contribution is that, if the random variables observed at Alice, Bob, and Willie induced by the common random source form a Markov chain, then the key capacity of the source model SKG with the strong secrecy constraint and the stealth constraint is equal to the key capacity with the strong secrecy constraint, but without the stealth constraint. For the case of fast fading models, a sufficient condition for the existence of an equivalent model, which is degraded, is provided, based on stochastic orders. Furthermore, we present an example to illustrate our results.
Research on Extraction of Compound Fault Characteristics for Rolling Bearings in Wind Turbines
Authors: Xiang Ling , Su Hao , Li Ying
Published: June 2020

Wind turbines work in strong background noise, and multiple faults often occur where features are mixed together and are easily misjudged. To extract composite fault of rolling bearings from wind turbines, a new hybrid approach was proposed based on multi-point optimal minimum entropy deconvolution adjusted (MOMEDA) and the 1.5-dimensional Teager kurtosis spectrum. The composite fault signal was deconvoluted using the MOMEDA method. The deconvoluted signal was analyzed by applying the 1.5-dimensional Teager kurtosis spectrum. Finally, the frequency characteristics were extracted for the bearing fault. A bearing composite fault signal with strong background noise was utilized to prove the validity of the method. Two actual cases on bearing fault detection were analyzed with wind turbines. The results show that the method is suitable for the diagnosis of wind turbine compound faults and can be applied to research on the health behavior of wind turbines.
Decentralized Plug-and-Play Protection Scheme for Low Voltage DC Grids
Authors: van der Blij Nils H. , Purgat Pavel , Soeiro Thiago B. , Ramirez-Elizondo Laura M. , Spaan Matthijs T. J. , Bauer Pavol
Published: June 2020

Since the voltages and currents in dc grids do not have a natural zero-crossing, the protection of these grids is more challenging than the protection of conventional ac grids. Literature presents several unit and non-unit protection schemes that rely on communication, or knowledge about the system’s topology and parameters in order to achieve selective protection in these grids. However, communication complicates fast fault detection and interruption, and a system’s parameters are subject to uncertainty and change. This paper demonstrates that, in low voltage dc grids, faults propagate fast through the grid and interrupted inductive currents commutate to non-faulted sections of the grid, which both can cause circuit breakers in non-faulted sections to trip. A decentralized plug-and-play protection scheme is proposed that ensures selectivity via an augmented solid-state circuit breaker topology and by utilizing the proposed time-current characteristic. It is experimentally shown that the proposed scheme provides secure and selective fault interruption for radial and meshed low voltage dc grids under various conditions.
Derivation of OCC Modulator for Grid-Tied Single-Stage Buck-Boost Inverter Operating in the Discontinuous Conduction Mode
Authors: Zhao Ben , Huangfu Yigeng , Abramovitz Alexander
Published: June 2020

This paper is concerned with the derivation of a one-cycle controller for driving a single-stage buck-boost DC-AC micro-inverter in grid-tied applications. The topology under study is based on a full-bridge switch arrangement with no unfolder circuit. The proposed micro-inverter attains a high gain by applying a multi-winding tapped inductor and, therefore, can operate at grid-level voltage without using a DC-DC step-up stage. To minimize the switching loss, the proposed inverter is operated in the discontinuous conduction mode. The operation principles of the proposed topology in the discontinuous conduction mode are discussed and analyzed. Based on the analysis, the one-cycle control law and modulator circuitry needed to control the proposed micro-inverter are developed. The feasibility of the proposed modulation scheme is verified by simulation.