bluuebunny/crossref_metadata_2025 huggingface dataset:
The New Synthetic Serum-Free Medium OptiPASS Promotes High Proliferation and Drug Efficacy Prediction on Spheroids from MDA-MB-231 and SUM1315 Triple-Negative Breast Cancer Cell Lines
Authors: Dubois Clémence , Daumar Pierre , Aubel Corinne , Gauthier Jean , Vidalinc Bernard , Mounetou Emmanuelle , Penault-Llorca Frédérique , Bamdad Mahchid
Published: March 2019

Triple-negative breast cancers are particularly aggressive. In vitro cultures are one of the major pathways for developing anticancer strategies. The effectiveness and reproducibility of the drug screenings depend largely on the homogeneity of culture media. In order to optimize the predictive responses of triple-negative breast cancer 3D cell culture models, these works were focused on the development of SUM1315 and MDA-MB-231 cell lines in OptiPASS medium, a new serum-free formulation (BIOPASS). In monolayer cell culture, OptiPASS medium was more suitable for MDA-MB-231 than SUM1315 cell line but maintained cell phenotype and allowed sufficient proliferation. For spheroids produced in OptiPASS, the size monitoring showed a 1.3 and 1.5-fold increase for MDA-MB-231 and SUM1315 cell lines, respectively and viability/mortality profiles were maintained. Spheroids drug sensitivity thresholds were also improved allowing quicker high throughput drug screenings. These results showed the suitability of OptiPASS for 2D and 3D cell cultures of these two triple-negative breast cancer cell lines, with reproducibility of spheroid formation superior to 98%. This opens the way to the common use of this synthetic medium in future preclinical breast cancer research studies.
Regulation of Actin Dynamics in the C. elegans Somatic Gonad
Authors: Kelley Charlotte A. , Cram Erin J
Published: March 2019

The reproductive system of the hermaphroditic nematode C. elegans consists of a series of contractile cell types—including the gonadal sheath cells, the spermathecal cells and the spermatheca–uterine valve—that contract in a coordinated manner to regulate oocyte entry and exit of the fertilized embryo into the uterus. Contraction is driven by acto-myosin contraction and relies on the development and maintenance of specialized acto-myosin networks in each cell type. Study of this system has revealed insights into the regulation of acto-myosin network assembly and contractility in vivo.
What Happened to the Participants of the Math Olympiad 1971? A Multiple-Case Study Concerning the Occupational Success of the Winning Team from Hungary, Math Olympiad–Occupational Success
Authors: Gasser Benedikt
Published: March 2019

The aim of this multiple-case study was to find out how the most successful team of the 1971 Mathematical Olympiad in Hungary developed professionally. It is impressive that in 1971, no fewer than four participants on the Hungarian team received gold medals and four participants received silver medals. Seven of the eight analyzed participants on the team came from a grammar school in Budapest. Three of the four gold medal winners achieved remarkable academic positions. On average, professional positions were achieved (as scored by the magnitude prestige scale) well above the average for a normal grammar school sample. Interestingly, the calculated average of the Hungarian team (156.5 ± 15.5) was slightly higher than that of the comparison team from Sweden (142.8 ± 30.5), but this difference was not significant (p = 0.351). In principle, excellence seems to result in excellence. For several former participants on the Hungarian team, it was shown that they continued to be extremely successful in the field of mathematics, with a thematic focus in the field of statistics and probability calculations.
Preliminary Study on the Contribution of External Forces to Ship Behavior
Authors: da Silva Augusto Silva , Oleinik Phelype Haron , de Paula Kirinus Eduardo , Costi Juliana , Guimarães Ricardo Cardoso , Pavlovic Ana , Marques Wiliam Correa
Published: March 2019

Computational modeling has become a prominent tool to simulate physical processes for research and development projects. The coastal region of southern Brazil is very susceptible to oil spill accidents. Currently, oil is intensively transported in the region due to the presence of the Rio Grande Harbor, the Transpetro Waterway Terminal (Petrobras) and the Riograndense S/A Oil Refinery. Therefore, simulations under ideal navigation conditions for ships with potentially polluting loads are important because their use can reduce oil spills and toxic compound accidents in the environment. Therefore, the main objective of this work is to present a preliminary study of the contribution of external forces to a ship’s behavior over a simulation period of 5 h. The methodology is based on the development of a numerical model using LaGrangian formalism and the calculus of variations, besides Maneuvering Modeling Group (MMG Model). The external forces considered were the wind acting directly on the ship, waves driven by wind, the rudder, the force acting on the hull, inertial forces, and seawater density. The results indicate that at the beginning of the simulation, the inertial forces were of primary importance for controlling the trajectory of the ship. After 5 h of simulations, the ship had completely changed its trajectory due to forces suffered by the ship, classified according to MMG Model.
Mapping the Loss of Ecosystem Services in a Region Under Intensive Land Use Along the Southern Coast of South Africa
Authors: Malherbe Hanlie , Pauleit Stephan , Lorz Carsten
Published: March 2019

Intensive land use activities worldwide have caused considerable loss to many ecosystem services. The dynamics of these threats must be quickly investigated to ensure timely update of management strategies and policies. Compared with complex models, mapping approaches that use scoring matrices to link land use/land cover and landscape properties with ecosystem services are relatively efficient and easier to apply. In this study, scoring matrices are developed and spatially explicit assessments of five ecosystem services, such as erosion control, water flow regulation, water quality maintenance, soil quality maintenance, and biodiversity maintenance, are conducted for a region under intense land use along the southern coast of South Africa. The complex interaction of land use/land cover and ecosystem services within a particular landscape is further elucidated by performing a spatial overview of the high-risk areas that contribute to the loss of ecosystem services. Results indicate that both agricultural activities and urban development contribute to the loss of ecosystem services. This study reveals that with sufficient knowledge from previous literature and inputs from experts, the use of scoring matrices can be adapted to different regional characteristics. This approach can be improved by adding additional landscape properties and/or adapting the matrix values as new data become available.
Means as Improper Integrals
Authors: Gray John E. , Vogt Andrew
Published: March 2019

The aim of this work is to study generalizations of the notion of the mean. Kolmogorov proposed a generalization based on an improper integral with a decay rate for the tail probabilities. This weak or Kolmogorov mean relates to the weak law of large numbers in the same way that the ordinary mean relates to the strong law. We propose a further generalization, also based on an improper integral, called the doubly-weak mean, applicable to heavy-tailed distributions such as the Cauchy distribution and the other symmetric stable distributions. We also consider generalizations arising from Abel–Feynman-type mollifiers that damp the behavior at infinity and alternative formulations of the mean in terms of the cumulative distribution and the characteristic function.
Asymptotic Profiles and Convergence Rates of the Linearized Compressible Navier–Stokes– Korteweg System
Authors: Wang Yinxia
Published: March 2019

In this paper, we consider the initial value problem for the linearized compressible Navier–Stokes–Korteweg system. Asymptotic profiles and convergence rates are established by Fourier splitting frequency technique. Moreover, some applications of asymptotic profile and convergence rates are exhibited.
An Improved Artificial Bee Colony Algorithm Based on Elite Strategy and Dimension Learning
Authors: Xiao Songyi , Wang Wenjun , Wang Hui , Tan Dekun , Wang Yun , Yu Xiang , Wu Runxiu
Published: March 2019

Artificial bee colony is a powerful optimization method, which has strong search abilities to solve many optimization problems. However, some studies proved that ABC has poor exploitation abilities in complex optimization problems. To overcome this issue, an improved ABC variant based on elite strategy and dimension learning (called ABC-ESDL) is proposed in this paper. The elite strategy selects better solutions to accelerate the search of ABC. The dimension learning uses the differences between two random dimensions to generate a large jump. In the experiments, a classical benchmark set and the 2013 IEEE Congress on Evolutionary (CEC 2013) benchmark set are tested. Computational results show the proposed ABC-ESDL achieves more accurate solutions than ABC and five other improved ABC variants.
Matrix Method for the Optimal Scale Selection of Multi-Scale Information Decision Systems
Authors: Chen Ying Sheng , Li Jin Jin , Huang Jian Xin
Published: March 2019

In multi-scale information systems, the information is often characterized at multi scales and multi levels. To facilitate the computational process of multi-scale information systems, we employ the matrix method to represent the multi-scale information systems and to select the optimal scale combination of multi-scale decision information systems in this study. To this end, we first describe some important concepts and properties of information systems using some relational matrices. The relational matrix is then introduced into multi-scale information systems, and used to describe some main concepts in systems, including the lower and upper approximate sets and the consistence of systems. Furthermore, from the view of the relation matrix, the scale significance is defined to describe the global optimal scale and the local optimal scale of multi-scale information systems. Finally, the relational matrix is used to compute the scale significance and to construct the optimal scale selection algorithms. The efficiency of these algorithms is examined by several practical examples and experiments.
First Integrals of the May–Leonard Asymmetric System
Authors: Antonov Valery , Fernandes Wilker , Romanovski Valery G. , Shcheglova Natalie L.
Published: March 2019

For the May–Leonard asymmetric system, which is a quadratic system of the Lotka–Volterra type depending on six parameters, we first look for subfamilies admitting invariant algebraic surfaces of degree two. Then for some such subfamilies we construct first integrals of the Darboux type, identifying the systems with one first integral or with two independent first integrals.
Expression, Purification and Characterization of Chondroitinase AC II from Marine Bacterium Arthrobacter sp. CS01
Authors: Fang Yangtao , Yang Suxiao , Fu Xiaodan , Xie Wancui , Li Li , Liu Zhemin , Mou Haijin , Zhu Changliang
Published: March 2019

Chondroitinase (ChSase), a type of glycosaminoglycan (GAG) lyase, can degrade chondroitin sulfate (CS) to unsaturate oligosaccharides, with various functional activities. In this study, ChSase AC II from a newly isolated marine bacterium Arthrobacter sp. CS01 was cloned, expressed in Pichia pastoris X33, purified, and characterized. ChSase AC II, with a molecular weight of approximately 100 kDa and a specific activity of 18.7 U/mg, showed the highest activity at 37 °C and pH 6.5 and maintained stability at a broad range of pH (5–7.5) and temperature (below 35 °C). The enzyme activity was increased in the presence of Mn2+ and was strongly inhibited by Hg2+. Moreover, the kinetic parameters of ChSase AC II against CS-A, CS-C, and HA were determined. TLC and ESI-MS analysis of the degradation products indicated that ChSase AC II displayed an exolytic action mode and completely hydrolyzed three substrates into oligosaccharides with low degrees of polymerization (DPs). All these features make ChSase AC II a promising candidate for the full use of GAG to produce oligosaccharides.
Assessing the Sensitizing and Allergenic Potential of the Albumin and Globulin Fractions from Amaranth (Amaranthus hypochondriacus) Grains before and after an Extrusion Process
Authors: Cárdenas-Torres Feliznando Isidro , Reyes-Moreno Cuauhtémoc , Vergara-Jiménez Marcela de Jesús , Cuevas-Rodríguez Edith Oliva , Milán-Carrillo Jorge , Gutiérrez-Dorado Roberto , Arámburo-Gálvez Jesús Gilberto , Ontiveros Noé , Cabrera-Chávez Francisco
Published: March 2019

Background: The first cases of food allergy to amaranth grain have recently been published. This pseudocereal is considered hypoallergenic, and there is scarce information about the allergenic potential of amaranth proteins, either before or after food processing. Objective: To evaluate, in a mouse model of food allergy, the sensitizing and allergenic potential of extruded and non-extruded albumin and globulin fractions from amaranth grains. Materials and Methods: Amaranth (Amaranthus hypochondriacus) flour was obtained and the albumin and globulin fractions isolated. These protein fractions were also obtained after flour extrusion. An intraperitoneal 28-day protocol was carried out to evaluate the sensitizing and allergenic potential of the proteins. The common and rarely allergenic proteins ovalbumin and potato acidic phosphatase were utilized as reference. Specific IgE and IgG antibodies were evaluated for all the proteins tested. Mast cell protease-1 (mMCP-1) responses were evaluated in serum samples collected after intragastric challenges with the proteins of interest. All serological evaluations were carried out using ELISA. Results: Mice were sensitized to the non-extruded albumin fraction from amaranth grains and to ovalbumin (p = 0.0045). The extrusion process of amaranth proteins abrogated the IgE responses triggered under non-extruded conditions (p = 0.0147). mMCP-1 responses were significantly detected in the group of mice sensitized to ovalbumin (p = 0.0138), but not in others. Conclusions: The non-extruded albumin fraction from amaranth has the potential to sensitize BALB/c mice, but this sensitizing potential fails to induce detectable serum levels of the mast cell degranulation marker mMCP-1 after intragastric challenges. Furthermore, the extrusion process abolished the sensitization potential of the amaranth albumins.
Epidemiological Survey and Retrospective Analysis of Salmonella Infections between 2000 and 2017 in Warmia and Masuria Voivodship in Poland
Authors: Dmochowska Paula , Spyczak von Brzezinski Maria , Żelazowski Jacek , Wojtkiewicz Joanna , Jung Susanne , Harazny Joanna M.
Published: March 2019

Background and Objectives: Salmonellosis is a major foodborne bacterial infection throughout the world. Epidemiological surveillance is one of the key factors to reduce the number of infections caused by this pathogen in both humans and animals. The first outcome measure was the prevalence of non-typhoid Salmonella (NTS) infections between 2000 and 2017 among the population of the predominantly agricultural and touristic Polish region of Warmia and Masuria (WaM). The second outcome measure was the comparison of the NTS hospitalization rate of all registered NTS cases, an investigation of the monthly reports of infections, and the exploration of the annual minimal and maximal NTS infection number in WaM in the above-mentioned time period. The last outcome was a comparison of the prevalence of NTS infections in the region and in its administrative districts by considering both rural and urban municipalities three years before and three years after the accession of Poland into the European Union (EU) in 2004. Materials and Methods: The total number of infections and hospitalizations in the 19 districts of the WaM voivodship in Poland was registered monthly between 2000–2017 by the Provincial Sanitary-Epidemiological Station in Olsztyn, Poland. Results: Between 2000 and 2017, the number of diagnosed salmonellosis cases decreased significantly in WaM; the decrease was higher in urban districts than in rural ones, and the ratio of hospitalizations and the total number of NTS cases increased significantly across all districts. The lowest number of cases was reported in the winter months and was stable from 2007, whereas the highest number was reported in the summer months with a higher tendency of outbreaks. Conclusion: The falling number of salmonellosis cases in 2000–2017 in WaM reflects the general trend in Poland and Europe. The decrease of NTS infections in WaM is related to the accession of Poland into the EU.
Numerical and Experimental Investigation of the Heat Input Effect on the Mechanical Properties and Microstructure of Dissimilar Weld Joints of 690-MPa QT and TMCP Steel
Authors: Njock Bayock Francois , Kah Paul , Layus Pavel , Karkhin Victor
Published: March 2019

The study evaluates numerically and experimentally the effect of welding heat input parameters on the microstructure and hardness of the heat-affected zone (HAZ) of quenched and tempered (QT) and thermo-mechanically controlled process (TMCP) 690-MPa high-strength steel. Numerical analyses and experimental comparisons were applied using three heat input values (10, 14, and 17 kJ/cm) in order to predict the thermal fields during welding. Experimental analysis was carried out of the microstructure and microhardness behavior in different HAZ areas. The numerical values indicate that the maximum respective values of temperature measured in QT steel and TMCP steel were about 1300 and 1200 °C for a heat input of 10 kJ/cm, 1400 and 1300 °C for a heat input of 14 kJ/cm, and 1600 and 1450 °C for a heat input of 17 kJ/cm. The cooling times resulted, for a heat input of 10 kJ/cm, in numerical t8/5 (14.5 s) and experimental (18.84 s) increases in hardness in the coarse-grain heat-affected zone (CGHAZ) of the QT steel (317 HV0.1), due to the formation of bainite and lath martensite structures with grain growth. Decreased hardness in the CGHAZ of TMCP steel (240 HV0.1) was caused by primary recrystallization of the microstructure and the formation of more equilibrium products of austenite decomposition. Increasing the heat input (14 to 17 kJ/cm) led to numerical t8/5 (29 s) and experimental (36 s) decreases in hardness in the CGHAZ of QT steel (270 HV0.1) due to the full austenite (thermal weld cycle), and maintained the relative value of TMCP steel (235 HV0.1).
High-Temperature Friction and Wear Properties of NiCr/hBN Self-Lubricating Composites
Authors: Zhu Xuewei , Wei Xiaofeng , Huang Yuxiang , Wang Fu , Yan Pengpeng
Published: March 2019

NiCr/hBN self-lubricating composites with hBN solid-lubricant contents of 8%, 9%, 10%, 11%, and 12% (mass fractions) were prepared by powder-metallurgy method. Their tribological properties at room temperature and 600, 700, and 800 °C were studied. SEM and XRD were performed to analyze their wear-surface morphology and abrasive-dust composition. Results indicate that the NiCr/hBN self-lubricating composites have favorable tribological properties at room temperature and 600 °C. The optimum comprehensive friction and wear performance are achieved at 10% hBN, and the main wear mechanism is abrasive wear. At 700 and 800 °C, the friction and wear properties of NiCr/hBN self-lubricating composites obviously decline. The wear surface experiences oxidation and the spinel oxides Cr2O3, NiCr2O4, and CrBO3 are formed. The main wear mechanism becomes combined scratching and glue form of adhesive wear, leading to greatly increased wear rate for the NiCr/hBN sel-lubricating composites.
The Effect of Different Annealing Temperatures on Recrystallization Microstructure and Texture of Clock-Rolled Tantalum Plates with Strong Texture Gradient
Authors: Zhu Jialin , Liu Shifeng , Yang Shuai , Zhang Yu , Zhang Jing , Zhang Chenghang , Deng Chao
Published: March 2019

The texture and the bulk stored energy along the thickness direction were extremely inhomogeneous in the clock-rolled tantalum sheets with 70% reduction. Therefore, the effects of different annealing temperatures on the microstructure and texture distribution of tantalum plates through the thickness were investigated by X-ray diffraction (XRD) and electron backscatter diffraction (EBSD). The results showed that the occurrence of strong {111} recrystallization texture in the center layer can be attributed to the subgrains nucleation mechanism when annealed at the low temperature. Many subgrains with {111} orientation appeared in the center layer, due to its high stored energy and preferential nucleation sites of the {111} deformed matrix, and rapidly grew into the effective nucleus, resulting in the large {111} grain size and strong {111} texture after complete recrystallization. Contrarily, at the high temperature, high-angle grain boundaries had sufficient driving force to generate migration, due to the lack of recovery, and the growth time of recrystallized nucleus was much shorter, contributing to relatively uniform recrystallization microstructure and texture distribution along the thickness.
Influences of the Heating and Cooling Rates on the Dissolution and Precipitation Behavior of a Nickel-Based Single-Crystal Superalloy
Authors: Wang Xiao-Yan , Wen Zhi-Xun , Cheng Hao , Gu Shu-Ning , Lu Guang-Xian
Published: March 2019

The effects of the heating rate before solution treatment, and the cooling rate after solution treatment on the morphological distribution and evolution of the precipitation phase of nickel-based single crystal superalloy were studied. The dissolution, precipitation, and growth of the precipitation phase and the matrix phase during heat treatment were analyzed by the means of high-power scanning electron microscopy. The results show that the morphology of the precipitated phase has nothing to do with the distribution of the precipitated phase and the heating rate in the heating process, but the cooling rate in the cooling process affects the shape, size, and distribution of the precipitated phase. The faster the cooling rate, the smaller the precipitated phase is, the more irregular the shape is, the smaller the equivalent edge length is, and the smaller the channel width of the matrix phase is.
Characterization of Double Leached Waelz Oxide for Identification of Fluoride Mineral
Authors: Sar Suchandra , Sundqvist Öqvist Lena , Sparrman Tobias , Engström Fredrik , Samuelsson Caisa
Published: March 2019

Double leached Waelz oxide (DLWO), with 76% zinc, is a secondary zinc containing raw materials obtained by the treatment of electric arc furnace dust. The content of fluoride in DLWO is still too high for direct leaching, as fluoride has a detrimental effect on electrowinning for zinc production. Knowledge of the characteristics of DLWO, and especially on how a fluoride mineral might exist, can contribute to further improvement of the selective leaching for the removal of fluoride. In this study, DLWO was characterized using analytical techniques, such as inductively coupled plasma-optical emission spectroscopy (ICP-OES), 19F liquid-state nuclear magnetic resonance (19F LS NMR), X-ray powder diffraction analysis (XRD), scanning electron microscopy coupled with energy dispersive spectroscopy (SEM-EDS) and 19F solid-state nuclear magnetic resonance (19F SS NMR). This study showed that DLWO mainly consisted of zincite (ZnO), cerussite (PbCO3) and a spinel containing zinc, iron and manganese. The fluoride mineral identified was calcium fluoride (CaF2). In SEM analysis, fluorine was found in larger grains together with calcium and oxygen, which was possibly calcium carbonate.
High-Pressure Oxidative Leaching and Iodide Leaching Followed by Selective Precipitation for Recovery of Base and Precious Metals from Waste Printed Circuit Boards Ash
Authors: Batnasan Altansukh , Haga Kazutoshi , Huang Hsin-Hsiung , Shibayama Atsushi
Published: March 2019

This paper deals with the recovery of gold from waste printed circuit boards (WPCBs) ash by high-pressure oxidative leaching (HPOL) pre-treatment and iodide leaching followed by reduction precipitation. Base metals present in WPCB ash were removed via HPOL using a diluted sulfuric acid solution at elevated temperatures. Effects of potassium iodide concentration, hydrogen peroxide concentration, sulfuric acid concentration, leaching temperature, and leaching time on gold extraction from pure gold chips with KI–H2O2–H2SO4 were investigated. The applicability of the optimized iodide leaching process for the extraction of gold from the leach residue obtained after HPOL were examined at different pulp densities ranging from 50 g/t to 200 g/t. Results show that the removal efficiency was 99% for Cu, 95.7% for Zn, 91% for Ni, 87.3% for Al, 82% for Co, and 70% for Fe under defined conditions. Under the optimal conditions, the percentage of gold extraction from the gold chips and the residue of WPCBs was 99% and 95%, respectively. About 99% of the gold was selectively precipitated from the pregnant leach solution by sequential precipitation with sodium hydroxide and L-ascorbic acid. Finally, more than 93% of gold recovery was achieved from WPCB ash by overall combined processes.
Optimizing the Conditions of Metal Solidification with Vibration
Authors: Kudryashova Olga , Khmeleva Marina , Danilov Pavel , Dammer Vladislav , Vorozhtsov Alexander , Eskin Dmitry
Published: March 2019

Vibration treatment of solidifying metals results in improvement in the ingot structure. There is a need to study this process not only because of the practical potential of vibration treatment but also due to the lack of understanding the process. An important practical challenge is to find optimal conditions for liquid metal processing. In this paper, the authors consider a solidification process in the particular case of a cylindrical chill mold with vibration as a solution of the Stefan problem. An integral value of mechanical stresses in the melt during solidification is considered as an efficiency criterion of vibration treatment. A dependence of this value on the vibration frequency and amplitude is obtained through solving the Stefan problem numerically. The solution allows one to find the optimal vibration frequency and amplitude. We verified the numerical solution with experimental data obtained upon vibration treatment of aluminum melt under different conditions. The experimentally found optimal conditions for metal processing were similar to those proposed in theory, i.e., a vibration frequency of about 60 Hz and an amplitude of about 0.5 mm.
Deformation of a Red Blood Cell in a Narrow Rectangular Microchannel
Authors: Takeishi Naoki , Ito Hiroaki , Kaneko Makoto , Wada Shigeo
Published: March 2019

The deformability of a red blood cell (RBC) is one of the most important biological parameters affecting blood flow, both in large arteries and in the microcirculation, and hence it can be used to quantify the cell state. Despite numerous studies on the mechanical properties of RBCs, including cell rigidity, much is still unknown about the relationship between deformability and the configuration of flowing cells, especially in a confined rectangular channel. Recent computer simulation techniques have successfully been used to investigate the detailed behavior of RBCs in a channel, but the dynamics of a translating RBC in a narrow rectangular microchannel have not yet been fully understood. In this study, we numerically investigated the behavior of RBCs flowing at different velocities in a narrow rectangular microchannel that mimicked a microfluidic device. The problem is characterized by the capillary number C a , which is the ratio between the fluid viscous force and the membrane elastic force. We found that confined RBCs in a narrow rectangular microchannel maintained a nearly unchanged biconcave shape at low C a , then assumed an asymmetrical slipper shape at moderate C a , and finally attained a symmetrical parachute shape at high C a . Once a RBC deformed into one of these shapes, it was maintained as the final stable configurations. Since the slipper shape was only found at moderate C a , measuring configurations of flowing cells will be helpful to quantify the cell state.
Biological Evaluation and Molecular Dynamics Simulation of Chalcone Derivatives as Epidermal Growth Factor-Tyrosine Kinase Inhibitors
Authors: Sangpheak Kanyani , Tabtimmai Lueacha , Seetaha Supaphorn , Rungnim Chompoonut , Chavasiri Warinthorn , Wolschann Peter , Choowongkomon Kiattawee , Rungrotmongkol Thanyada
Published: March 2019

Targeted cancer therapy has become a high potential cancer treatment. Epidermal growth factor receptor (EGFR), which plays an important role in cell signaling, enhanced cell survival and proliferation, has been suggested as molecular target for the development of novel cancer therapeutics. In this study, a series of chalcone derivatives was screened by in vitro cytotoxicity against the wild type (A431 and A549) and mutant EGFR (H1975 and H1650) cancer cell lines, and, subsequently, tested for EGFR-tyrosine kinase (TK) inhibition. From the experimental screening, all chalcones seemed to be more active against the A431 than the A549 cell line, with chalcones 1c, 2a, 3e, 4e, and 4t showing a more than 50% inhibitory activity against the EGFR-TK activity and a high cytotoxicity with IC50 values of < 10 µM against A431 cells. Moreover, these five chalcones showed more potent on H1975 (T790M/L858R mutation) than H1650 (exon 19 deletion E746-A750) cell lines. Only three chalcones (1c, 2a and 3e) had an inhibitory activity against EGFR-TK with a relative inhibition percentage that was close to the approved drug, erlotinib. Molecular dynamics studies on their complexes with EGFR-TK domain in aqueous solution affirmed that they were well-occupied within the ATP binding site and strongly interacted with seven hydrophobic residues, including the important hinge region residue M793. From the above information, as well as ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties, all three chalcones could serve as lead compounds for the development of EGFR-TK inhibitors.
Computational Drug Design Applied to the Study of Metabotropic Glutamate Receptors
Authors: Llinas del Torrent Claudia , Pérez-Benito Laura , Tresadern Gary
Published: March 2019

Metabotropic glutamate (mGlu) receptors are a family of eight GPCRs that are attractive drug discovery targets to modulate glutamate action and response. Here we review the application of computational methods to the study of this family of receptors. X-ray structures of the extracellular and 7-transmembrane domains have played an important role to enable structure-based modeling approaches, whilst we also discuss the successful application of ligand-based methods. We summarize the literature and highlight the areas where modeling and experiment have delivered important understanding for mGlu receptor drug discovery. Finally, we offer suggestions of future areas of opportunity for computational work.
The Antidepressant-like Effect of Flavonoids from Trigonella Foenum-Graecum Seeds in Chronic Restraint Stress Mice via Modulation of Monoamine Regulatory Pathways
Authors: Wang Jiancheng , Cheng Cuilin , Xin Chao , Wang Zhenyu
Published: March 2019

Fenugreek (Trigonella Foenum-Graecum) seeds flavonoids (FSF) have diverse biological activities, while the antidepressant-like effect of FSF has been seldom explored. The aim of this study was to evaluate the antidepressant-like effect of FSF and to identify the potential molecular mechanisms. LC-MS/MS was used for the determination of FSF. Chronic restraint stress (CRS) was used to establish the animal model of depression. Observation of exploratory behavior in the forced swimming test (FST), tail suspension test (TST) and sucrose preference test (SPT) indicated the stress level. The serum corticosterone (CORT) level was measured. The monoamine neurotransmitters (5-HT, NE and DA) and their metabolites, as well as monoamine oxidase A (MAO-A) enzyme activity in the prefrontal cortex, hippocampus and striatum, were evaluated. The protein expression levels of KLF11, SIRT1, MAO-A were also determined by western blot analysis. The results showed that FSF treatment significantly reversed the CRS-induced behavioral abnormalities, including reduced sucrose preference and increased immobility time. FSF administration markedly restored CRS induced changes in concentrations of serum corticosterone, prefrontal cortex neurotransmitters (NE, 5-HT and DA), hippocampus neurotransmitters (NE, 5-HT and DA) and striatum neurotransmitters (NE). FSF treatment exhibited significant inhibition of MAO-A activity in the prefrontal cortex and hippocampus. FSF also significantly down-regulated the KLF11, SIRT1 and MAO-A protein expression levels in the prefrontal cortex and hippocampus. These findings indicate that FSF could exhibit an antidepressant-like effect by down-regulating the KLF11/SIRT1-MAO-A pathways, inhibiting MAO-A expression and activity, as well as up-regulating monoamine neurotransmitters levels.
Study on a Fermented Whole Wheat: Phenolic Content, Activity on PTP1B Enzyme and In Vitro Prebiotic Properties
Authors: Balli Diletta , Bellumori Maria , Paoli Paolo , Pieraccini Giuseppe , Di Paola Monica , De Filippo Carlotta , Di Gioia Diana , Mulinacci Nadia , Innocenti Marzia
Published: March 2019

Fermented cereals, staple foods in Asia and Africa, are recently receiving a growing interest in Western countries. The object of this work is the characterization of a fermented wheat used as a food ingredient and dietary supplement. To this aim, the phenolic composition, the activity on protein tyrosine phosphatase 1B (PTP1B), an enzyme overexpressed in type-II diabetes, the in vitro prebiotic properties on Lactobacillus reuteri and the microbial composition were investigated. Basic and acidic hydrolysis were tested for an exhaustive recovery of bound phenols: the acidic hydrolysis gave best yields. Methyl ferulate and neocarlinoside were identified for the first time in wheat. The inhibitory power of the extracts of several batches were investigated on PTP1B enzyme. The product was not able to inhibit the enzyme, otherwise, for the first time, a complete inhibition was observed for schaftoside, a major C-flavonoid of wheat. The microbial composition was assessed identifying Lactobacillus, Enterococcus, and Pediococcus as the main bacterial species. The fermented wheat was a suitable substrate for the grown of L. reuteri, recognized for its health properties in the human gut. The proposed method for phenols is easier compared to those based on strong basic hydrolysis; our results assessed the bound phenols as the major fraction, differently from that suggested by the literature for fermented cereals.
Structure–Activity Study, Characterization, and Mechanism of Action of an Antimicrobial Peptoid D2 and Its d- and l-Peptide Analogues
Authors: Greco Ines , Hansen Johannes E. , Jana Bimal , Molchanova Natalia , Oddo Alberto , Thulstrup Peter W. , Damborg Peter , Guardabassi Luca , Hansen Paul R.
Published: March 2019

Methicillin-resistant Staphylococcus pseudintermedius (MRSP) constitutes an emerging health problem for companion animals in veterinary medicine. Therefore, discovery of novel antimicrobial agents for treatment of Staphylococcus-associated canine infections is urgently needed to reduce use of human antibiotics in veterinary medicine. In the present work, we characterized the antimicrobial activity of the peptoid D2 against S. pseudintermedius and Pseudomonas aeruginosa, which is another common integumentary pathogen in dogs. Furthermore, we performed a structure–activity relationship study of D2, which included 19 peptide/peptoid analogs. Our best compound D2D, an all d-peptide analogue, showed potent minimum inhibitory concentrations (MICs) against canine S. pseudintermedius (2–4 µg/mL) and P. aeruginosa (4 µg/mL) isolates as well as other selected dog pathogens (2–16 µg/mL). Time–kill assays demonstrated that D2D was able to inhibit MRSP in 30 min at 1× MIC, significantly faster than D2. Our results suggest that at high concentrations D2D is rapidly lysing the bacterial membrane while D2 is inhibiting macromolecular synthesis. We probed the mechanism of action at sub-MIC concentrations of D2, D2D, the l-peptide analog and its retro analog by a macromolecular biosynthesis assay and fluorescence spectroscopy. Our data suggest that at sub-MIC concentrations D2D is membrane inactive and primarily works by cell wall inhibition, while the other compounds mainly act on the bacterial membrane.
The Polymorphisms of Oligonucleotide Probes in Wheat Cultivars Determined by ND-FISH
Authors: Ren Tianheng , He Maojie , Sun Zixin , Tan Feiquan , Luo Peigao , Tang Zongxiang , Fu Shulan , Yan Benju , Ren Zhenglong , Li Zhi
Published: March 2019

Non-denaturing fluorescence in situ hybridization (ND-FISH) has been used to distinguish wheat chromosomes and to detect alien chromosomes in the wheat genome. In this study, five different oligonucleotide probes were used with ND-FISH to examine 21 wheat cultivars and lines. These oligonucleotide probes distinguished 42 wheat chromosomes and also detected rye chromatin in the wheat genome. Moreover, the signal patterns of the oligonucleotide probes Oligo-pTa535-1 and Oligo-pSc119.2-1 showed high polymorphism in the wheat chromosomes. A total of 17.6% of the A group chromosomes, 25.9% of the B group chromosomes and 8.9% of the D group chromosomes showed obvious mutations when they were compared to the standard ND-FISH signal patterns, and most of them were Oligo-pSc119.2-1 mutants. The results suggested that these polymorphisms could be induced by the crossing of wheat cultivars. The results provided more information for the further application of oligonucleotide probes and ND-FISH.
Genotype-Related Differences in the Phenolic Compound Profile and Antioxidant Activity of Extracts from Olive (Olea europaea L.) Leaves
Authors: Orak Hakime Hülya , Karamać Magdalena , Amarowicz Ryszard , Orak Adnan , Penkacik Kamila
Published: March 2019

The phenolic compound contents and antioxidant activities of the leaf extracts of nine olive genotypes were determined, and the obtained data were analysed using chemometric techniques. In the crude extracts, 12 compounds belonging to the secoiridoids, phenylethanoids, and flavonoids were identified. Oleuropein was the primary component for all genotypes, exhibiting a content of 21.0 to 98.0 mg/g extract. Hydroxytyrosol, verbascoside, luteolin 7-O-glucoside, and luteolin 4′-O-glucoside were also present in noticeable quantities. Genotypes differed to the greatest extent in the content of verbascoside (0.45–21.07 mg/g extract). The content of hydroxytyrosol ranged from 1.33 to 4.03 mg/g extract, and the aforementioned luteolin glucosides were present at 1.58–8.67 mg/g extract. The total phenolic content (TPC), DPPH• and ABTS•+ scavenging activities, ferric reducing antioxidant power (FRAP), and ability to inhibit the oxidation of β-carotene-linoleic acid emulsion also varied significantly among genotypes. A hierarchical cluster analysis enabled the division of genotypes into three clusters with similarity above 60% in each group. GGE biplot analysis showed olive genotypes variability with respect to phenolic compound contents and antioxidant activities. Significant correlations among TPC, FRAP, the values of both radical scavenging assays, and the content of oleuropein were found. The contents of 7-O-glucoside and 4′-O-glucoside correlated with TPC, TEAC, FRAP, and the results of the emulsion oxidation assay.
Special Issue: Mass Spectrometric Proteomics
Authors: Iadarola Paolo
Published: March 2019

The term “Proteomics” refers to the characterization of the proteome, that is, all proteins present in a biological system [...]
A DFT Study of Hydrogen Storage in High-Entropy Alloy TiZrHfScMo
Authors: Hu Jutao , Shen Huahai , Jiang Ming , Gong Hengfeng , Xiao Haiyan , Liu Zijiang , Sun Guangai , Zu Xiaotao
Published: March 2019

In recent years, high-entropy alloys have been proposed as potential hydrogen storage materials. Despite a number of experimental efforts, there is a lack of theoretical understanding regarding the hydrogen absorption behavior of high-entropy alloys. In this work, the hydrogen storage properties of a new TiZrHfScMo high-entropy alloy are investigated. This material is synthesized successfully, and its structure is characterized as body-centered cubic. Based on density functional theory, the lattice constant, formation enthalpy, binding energy, and electronic properties of hydrogenated TiZrHfScMo are all calculated. The calculations reveal that the process of hydrogenation is an exothermic process, and the bonding between the hydrogen and metal elements are of covalent character. In the hydrogenated TiZrHfScMo, the Ti and Sc atoms lose electrons and Mo atoms gain electrons. As the H content increases, the  bonding is weakened, and the  and  bonding are strengthened. Our calculations demonstrate that the TiZrHfScMo high-entropy alloy is a promising hydrogen storage material, and different alloy elements play different roles in the hydrogen absorption process.
Poly-ε-Caprolactone/Gelatin Hybrid Electrospun Composite Nanofibrous Mats Containing Ultrasound Assisted Herbal Extract: Antimicrobial and Cell Proliferation Study
Authors: Ramalingam Raghavendra , Dhand Chetna , Leung Chak Ming , Ezhilarasu Hariharan , Prasannan Praseetha , Ong Seow Theng , Subramanian Sundarapandian , Kamruddin Mohammed , Lakshminarayanan Rajamani , Ramakrishna Seeram , Verma Navin Kumar , Arunachalam Kantha Deivi
Published: March 2019

Electrospun fibers have emerged as promising materials in the field of biomedicine, due to their superior physical and cell supportive properties. In particular, electrospun mats are being developed for advanced wound dressing applications. Such applications require the firers to possess excellent antimicrobial properties in order to inhibit potential microbial colonization from resident and non-resident bacteria. In this study, we have developed Poly-ε-Caprolactone /gelatin hybrid composite mats loaded with natural herbal extract (Gymnema sylvestre) to prevent bacterial colonization. As-spun scaffolds exhibited good wettability and desirable mechanical properties retaining their fibrous structure after immersing them in phosphate buffered saline (pH 7.2) for up to 30 days. The initial burst release of Gymnema sylvestre prevented the colonization of bacteria as confirmed by the radial disc diffusion assay. Furthermore, the electrospun mats promoted cellular attachment, spreading and proliferation of human primary dermal fibroblasts and cultured keratinocytes, which are crucial parenchymal cell-types involved in the skin recovery process. Overall these results demonstrated the utility of Gymnema sylvestre impregnated electrospun PCL/Gelatin nanofibrous mats as an effective antimicrobial wound dressing.
KMnF3:Yb3+,Er3+ Core-Active-Shell Nanoparticles with Broadband Down-Shifting Luminescence at 1.5 μm for Polymer-Based Waveguide Amplifiers
Authors: Zhang Yongling , Lv Peng , Wang Dongxia , Qin Zhengkun , Wang Fei , Zhang Daming , Zhao Dan , Qin Guanshi , Qin Weiping
Published: March 2019

In this study, we prepared cubic-phase oleic-acid-coated KMnF3: Yb3+,Er3+ nanoparticles (NPs) and NaYF4:Yb3+,Er3+ NPs, which were about 23 nm. From the down-shifting emissions spectra of the two NPs obtained by 980 nm excitation, we observed the fact that the KMnF3: 18%Yb3+,1%Er3+ NPs were a luminescent material with a broadband near-infrared emission of 1.5 μm, and full-width at half-maximum (FWHM) of 55 cm−1, which was wider than that of the NaYF4: 18%Yb3+,1% NPs. Therefore, we believe that the oleic-acid-coated KMnF3:Yb3+,Er3+ NPs have great potential in fabricating broadband waveguide amplifiers. Through epitaxial growth of a KMnF3: Yb3+ active-shell on the core NPs, we compounded KMnF3:Yb3+,Er3+@KMnF3:Yb3+ core-active-shell NPs whose 1.5-μm infrared emissions intensity was 3.4 times as strong as that of the core NPs. In addition, we manufactured waveguide amplifiers using KMnF3:18%Yb3+,1%Er3+@KMnF3:2%Yb3+ NPs as the core materials of the waveguide amplifiers. When the input signal power was 0.2 mW and the pump power was 200 mW, we achieved a relative gain of 0.6 dB at 1534 nm in a 10-mm long waveguide.
Nanoparticles for Bioapplications: Study of the Cytotoxicity of Water Dispersible CdSe(S) and CdSe(S)/ZnO Quantum Dots
Authors: Mirnajafizadeh Fatemeh , Ramsey Deborah , McAlpine Shelli , Wang Fan , Stride John
Published: March 2019

Semiconductor nanocrystals or quantum dots (QDs) have unique optical and physical properties that make them potential imaging tools in biological and medical applications. However, concerns over the aqueous dispersivity, toxicity to cells, and stability in biological environments may limit the use of QDs in such applications. Here, we report an investigation into the cytotoxicity of aqueously dispersed CdSe(S) and CdSe(S)/ZnO core/shell QDs in the presence of human colorectal carcinoma cells (HCT-116) and a human skin fibroblast cell line (WS1). The cytotoxicity of the precursor solutions used in the synthesis of the CdSe(S) QDs was also determined in the presence of HCT-116 cells. CdSe(S) QDs were found to have a low toxicity at concentrations up to 100 µg/mL, with a decreased cell viability at higher concentrations, indicating a highly dose-dependent response. Meanwhile, CdSe(S)/ZnO core/shell QDs exhibited lower toxicity than uncoated QDs at higher concentrations. Confocal microscopy images of HCT-116 cells after incubation with CdSe(S) and CdSe(S)/ZnO QDs showed that the cells were stable in aqueous concentrations of 100 µg of QDs per mL, with no sign of cell necrosis, confirming the cytotoxicity data.
Computational Screening of Metal–Organic Framework Membranes for the Separation of 15 Gas Mixtures
Authors: Yang Wenyuan , Liang Hong , Peng Feng , Liu Zili , Liu Jie , Qiao Zhiwei
Published: March 2019

The Monte Carlo and molecular dynamics simulations are employed to screen the separation performance of 6013 computation-ready, experimental metal–organic framework membranes (CoRE-MOFMs) for 15 binary gas mixtures. After the univariate analysis, principal component analysis is used to reduce 44 performance metrics of 15 mixtures to a 10-dimension set. Then, four machine learning algorithms (decision tree, random forest, support vector machine, and back propagation neural network) are combined with k times repeated k-fold cross-validation to predict and analyze the relationships between six structural feature descriptors and 10 principal components. Based on the linear correlation value R and the root mean square error predicted by the machine learning algorithm, the random forest algorithm is the most suitable for the prediction of the separation performance of CoRE-MOFMs. One descriptor, pore limiting diameter, possesses the highest weight importance for each principal component index. Finally, the 30 best CoRE-MOFMs for each binary gas mixture are screened out. The high-throughput computational screening and the microanalysis of high-dimensional performance metrics can provide guidance for experimental research through the relationships between the multi-structure variables and multi-performance variables.