bluuebunny/crossref_metadata_2025 huggingface dataset:
Metastatic Tumors of the Sinonasal Cavity: A 15-Year Review of 17 Cases
Authors: Chang Miao-Hsu , Kuo Ying-Ju , Ho Ching-Yin , Kuan Edward C. , Lan Ming-Ying
Published: April 2019

Extranasal cancers that metastasize to the sinonasal cavity are very rare. To date, there are only limited reports regarding this rare condition within the literature. Therefore, we retrospectively reviewed all patients diagnosed with metastatic cancer of the sinonasal tract from 2003 to 2018 at a tertiary academic medical center. Patient demographic data, clinical presentation, treatment modalities, and outcomes were investigated. There were a total of 17 patients (9 males and 8 females) included in the analysis. The mean age was 56.8 years (range 27–80). The most common primary malignancies were hepatocellular carcinoma (n = 3) and gastrointestinal tract adenocarcinoma (n = 3). The most common site of metastasis was the nasal cavity (n = 8). Five patients received radical tumor resection and the others underwent radiotherapy, chemotherapy, or combined chemoradiotherapy. The 2-year survival was 28%. In summary, metastasis to the sinonasal cavity remains extremely rare. A high degree of suspicion regarding the possibility of metastatic spread to the sinonasal region is necessary for patients with a previous history of malignancy who present with new sinonasal symptoms. The treatment strategy of sinonasal metastatic cancer is usually palliative therapy and the prognosis remains poor. However, early detection and diagnosis, coupled with aggressive treatment, may improve patient quality of life.
Implementing Adaptive Voltage Over-Scaling: Algorithmic Noise Tolerance vs. Approximate Error Detection
Authors: Rizzo Roberto Giorgio , Calimera Andrea
Published: April 2019

Adaptive Voltage Over-Scaling can be applied at run-time to reach the best tradeoff between quality of results and energy consumption. This strategy encompasses the concept of timing speculation through some level of approximation. How and on which part of the circuit to implement such approximation is an open issue. This work introduces a quantitative comparison between two complementary strategies: Algorithmic Noise Tolerance and Approximate Error Detection. The first implements a timing speculation by means approximate computing, while the latter exploits a more sophisticated approach that is based on the approximation of the error detection mechanism. The aim of this study was to provide both a qualitative and quantitative analysis on two real-life digital circuits mapped onto a state-of-the-art 28-nm CMOS technology.
A Potential Flow Theory and Boundary Layer Theory Based Hybrid Method for Waterjet Propulsion
Authors: Zhang Lei , Zhang Jia-Ning , Shang Yu-Chen
Published: April 2019

A hybrid method—coupled with the boundary element method (BEM) for wave-making resistance, the empirical method (EM) for viscous resistance, and the boundary layer theory (BLT) for capture of an area’s physical parameters—was proposed to predict waterjet propulsion performance. The waterjet propulsion iteration process was established from the force-balanced waterjet–hull system by applying the hybrid approach. Numerical validation of the present method was carried out using the 1/8.556 scale waterjet-propelled ITTC (International Towing Tank Conference) Athena ship model. Resistance, attitudes, wave cut profiles, waterjet thrust, and thrust deduction showed similar tendencies to the experimental curves and were in good agreement with the data. The application of the present hybrid method to the side-hull configuration research of a trimaran indicates that the side-hull arranged at the rear of the main hull contributed to energy-saving and high-efficiency propulsion. In addition, at high Froude numbers, the “fore-body trimaran” showed a local advantage in resistance and thrust deduction.
The Impact of Algorithmic Trading in a Simulated Asset Market
Authors: Mukerji Purba , Chung Christine , Walsh Timothy , Xiong Bo
Published: April 2019

In this work we simulate algorithmic trading (AT) in asset markets to clarify its impact. Our markets consist of human and algorithmic counterparts of traders that trade based on technical and fundamental analysis, and statistical arbitrage strategies. Our specific contributions are: (1) directly analyze AT behavior to connect AT trading strategies to specific outcomes in the market; (2) measure the impact of AT on market quality; and (3) test the sensitivity of our findings to variations in market conditions and possible future events of interest. Examples of such variations and future events are the level of market uncertainty and the degree of algorithmic versus human trading. Our results show that liquidity increases initially as AT rises to about 10% share of the market; beyond this point, liquidity increases only marginally. Statistical arbitrage appears to lead to significant deviation from fundamentals. Our results can facilitate market oversight and provide hypotheses for future empirical work charting the path for developing countries where AT is still at a nascent stage.
Maintaining Quality Online: Piloting an Online Language Course for Immigrants in Finland
Authors: Karttunen Miia , Juusola Sirpa
Published: April 2019

Finland’s educational system has aroused the interest of educational researchers worldwide. Teaching and learning with information and communication technologies (ICT) is one of the major methodologies in the present Finnish educational discourse. Feedback and assessment are questions of course design in online learning. This paper discusses and illustrates how to plan an online course for a higher education preparatory program in Finland by using digital methods with a focus on maintaining quality in the processes of feedback and evaluation. This paper also introduces and reflects recently published quality criteria that are recommended to be used in the design of online courses.
Design and Fabrication of Random Metal Foam Structures for Laser Powder Bed Fusion
Authors: Contuzzi Nicola , Campanelli Sabina Luisa , Caiazzo Fabrizia , Alfieri Vittorio
Published: April 2019

With the development of additive manufacturing, the building of new categories of lightweight structures such as random foams have been offered. Nevertheless, given the complexity of the required parts, macroscopic defects may result or the process may even fail. Therefore, proper actions must be taken at the design stage. In this paper, a method of design for additive manufacturing (DfAM) to build metal random foam structures is proposed. Namely, a procedure is suggested to generate a structure that has interconnected porosity. This procedure is based on the aimed fractional density and several technical requirements, and then the geometry is optimized and meshed. To validate the algorithm, a test article consisting of a metal cylinder with spherical random pores ranging from 1 to 6 mm in diameter with a resulting fractional density of 40 ± 2% has been conceived and manufactured by means of laser powder bed fusion (LPBF). On the basis of the outcome of the manufacturing process, crucial information has been gathered to update the algorithm.
Effect of Microbiological Growth Components for Bacteria-Based Self-Healing on the Properties of Cement Mortar
Authors: Chen Xin , Yuan Jie , Alazhari Mohamed
Published: April 2019

Previous studies of bacteria-based self-healing concrete have shown that it is necessary to encapsulate and separate the self-healing ingredients (bacteria, nutrients, and precursors) in the concrete so that when a crack forms, capsules rupture, which allows the self-healing ingredients to come together and precipitate calcite into the crack. Because of the shearing action in the concrete mixer, there is a chance that these capsules, or other carriers, may rupture and release the self-healing ingredients. This would affect the efficiency of self-healing, but may detrimentally affect the concrete’s properties. This work investigated the effects of multi-component growth media, containing germination and sporulation aids for the bacterial aerobic oxidation pathway, on the basic properties of fresh and hardened concrete instead of the potential self-healing efficiency in a structural service. Tests were carried out to measure the effects of growth media on air content, fluidity, capillary absorption, strength development of cement mortar following corresponding standards, hydration kinetics, setting properties, and the microstructure of cement paste, according to certain specifications or using specific machines. The research has demonstrated that a multi-constituent growth media will not have a significant effect on the properties of concrete in the proportions likely to be released during mixing. This important conclusion will allow further development of these novel materials by removing one of the key technical barriers to increased adoption.
Use of Basalt Fiber-Reinforced Tailings for Improving the Stability of Tailings Dam
Authors: Zheng Binbin , Zhang Dongming , Liu Weisha , Yang Yonghao , Yang Han
Published: April 2019

As one of the largest artificial geotechnical structures on earth, the tailings dams are classified as one of the high-risk sources in China’s industry. How to improve the stability and safety of tailings dams remains a challenge for mine operators currently. In this paper, an innovative method is presented for improving the stability of tailings dams, in which the basalt fiber is used to reinforce tailings. The mechanical properties of tailings used for dam-construction have a great influence on the stability of tailings dam. In order to investigate the mechanical performance of basalt fiber-reinforced tailings (BFRT), a series of laboratory triaxial tests were conducted. The effects of five parameters (fiber length, fiber content, particle size, dry density and confining pressure) on the mechanical properties of BFRT were studied. The microstructure and the behavior of interfaces between basalt fibers and tailings particles were analyzed by using scanning electron microscopy (SEM). The triaxial experimental test results show that the mechanical properties of BFRT increase with the increases of fiber length and content, particle size, dry density and confining pressure. The SEM results indicate that the interfacial interaction between fibers and tailings particles is mainly affected by particle shape.
A Hybrid Framework Combining Genetic Algorithm with Iterated Local Search for the Dominating Tree Problem
Authors: Hu Shuli , Liu Huan , Wu Xiaoli , Li Ruizhi , Zhou Junping , Wang Jianan
Published: April 2019

Given an undirected, connected and edge-weighted graph, the dominating tree problem consists of finding a tree with minimum total edge weight such that for each vertex is either in the tree or adjacent to a vertex in the tree. In this paper, we propose a hybrid framework combining genetic algorithm with iterated local search (GAITLS) for solving the dominating tree problem. The main components of our framework are as follows: (1) the score functions D s c o r e and W s c o r e applied in the initialization and local search phase; (2) the initialization procedure with restricted candidate list (RCL) by controlling the parameter to balance the greediness and randomness; (3) the iterated local search with three phases, which is used to intensify the individuals; (4) the mutation with high diversity proposed to perturb the population. The experimental results on the classical instances show that our method performs much better than the-state-of-art algorithms.
A Regularization Method to Solve a Cauchy Problem for the Two-Dimensional Modified Helmholtz Equation
Authors: He Shangqin , Feng Xiufang
Published: April 2019

In this paper, the ill-posed problem of the two-dimensional modified Helmholtz equation is investigated in a strip domain. For obtaining a stable numerical approximation solution, a mollification regularization method with the de la Vallée Poussin kernel is proposed. An error estimate between the exact solution and approximation solution is given under suitable choices of the regularization parameter. Two numerical experiments show that our procedure is effective and stable with respect to perturbations in the data.
C-phycocyanin from Limnothrix Species KNUA002 Alleviates Cisplatin-Induced Ototoxicity by Blocking the Mitochondrial Apoptotic Pathway in Auditory Cells
Authors: Kim Ye-Ri , Do Jeong-Mi , Kim Kyung Hee , Stoica Alexandra R. , Jo Seung-Woo , Kim Un-Kyung , Yoon Ho-Sung
Published: April 2019

Ototoxicity, or adverse pharmacological effects on the inner ear or auditory nerve, is a common side effect of cisplatin, a platinum-based drug widely used in anticancer chemotherapy. Although the incidence of ototoxicity is high among patients that receive cisplatin therapy, there is currently no effective treatment for it. The generation of excessive reactive oxygen species (ROS) is considered to be the major cause of cisplatin-induced ototoxicity. C-phycocyanin (C-PC), a blue phycobiliprotein found in cyanobacteria and red algae, has antioxidant and anticancer activities in different experimental models in vitro and in vivo. Thus, we tested the ability of C-PC from Limnothrix sp. KNUA002 to protect auditory cells from cisplatin-induced ototoxicity in vitro. Pretreatment with C-PC from Limnothrix sp. KNUA002 inhibited apoptosis and protected mitochondrial function by preventing ROS accumulation in cisplatin-treated House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, a mouse auditory cell line. Cisplatin increased the expression of Bax and reduced the expression of Bcl-2, which activate and inhibit, respectively, the mitochondrial apoptotic pathway in response to oxidative stress. Pretreatment with C-PC prior to cisplatin treatment caused the Bax and Bcl-2 levels to stay close to the levels in untreated control cells. Our results suggest that C-PC from Limnothrix sp. KNUA002 protects cells against cisplatin-induced cytotoxicity by inhibiting the mitochondrial apoptotic pathway.
Antifungal and Antioxidant Properties of Chitosan Polymers Obtained from Nontraditional Polybius henslowii Sources
Authors: Avelelas Francisco , Horta André , Pinto Luís F.V. , Cotrim Marques Sónia , Marques Nunes Paulo , Pedrosa Rui , Leandro Sérgio Miguel
Published: April 2019

Chitin was extracted from Polybius henslowii, a swimming crab, captured in large quantities throughout the Portuguese coast by purse seine vessels as bycatch. After standard chitin extraction procedures, water-soluble chitosan products were obtained via two different methods: (1) N-acetylation with the addition of acetic anhydride and (2) a reaction with hydrogen peroxide. The chemical structure and molecular weight of chitosan derivatives, water-soluble chitosan (WSC) and chitooligosaccharides (COS), were confirmed by Fourier Transform Infrared Spectroscopy (FT-IR) and gel permeation chromatography (GPC). Antioxidant and metal chelation activities were evaluated, and the growth inhibition capacity was tested on four phytopatogens. The chitooligosaccharides from pereopods (pCOS) and shell body parts (sCOS) inhibited all fungal species tested, particularly Cryphonectria parasitica with 84.7% and 85.5%, respectively. Both radical scavenging and antifungal activities proved to be dose-dependent. Chitooligosaccharides with a low molecular weight (2.7, 7.4, and 10.4 Kg·mol−1) showed the highest activity among all properties tested. These results suggested that chitosan derivatives from P. henslowii raw material could potentially be used against phytopathogens or as ingredient in cosmetics and other products related to oxidative stress.
Effects of Quercetin-Loaded Nanoparticles on MCF-7 Human Breast Cancer Cells
Authors: Niazvand Firoozeh , Orazizadeh Mahmoud , Khorsandi Layasadat , Abbaspour Mohammadreza , Mansouri Esrafil , Khodadadi Ali
Published: April 2019

Background and objectives: Previous studies have shown anti-tumor activity of quercetin (QT). However, the low bioavailability of QT has restricted its use. This study aimed to assess the toxic effect of QT encapsulated in solid lipid nanoparticles (QT-SLNs) on the growth of MCF-7 human breast cancer cells. Materials and Methods: MCF-7 and MCF-10A (non-tumorigenic cell line) cell lines treated with 25 µmol/mL of QT or QT-SLNs for 48 h. Cell viability, colony formation, oxidative stress, and apoptosis were evaluated to determine the toxic effects of the QT-SLNs. Results: The QT-SLNs with appropriate characteristics (particle size of 85.5 nm, a zeta potential of −22.5 and encapsulation efficiency of 97.6%) were prepared. The QT-SLNs showed sustained QT release until 48 h. Cytotoxicity assessments indicated that QT-SLNs inhibited MCF-7 cells growth with a low IC50 (50% inhibitory concentration) value, compared to the free QT. QT-SLNs induced a significant decrease in the viability and proliferation of MCF-7 cells, compared to the free QT. QT-SLN significantly increased reactive oxygen species (ROS) level and MDA contents and significantly decreased antioxidant enzyme activity in the MCF-7 cells. Following QT-SLNs treatment, the expression of the Bcl-2 protein significantly decreased, whereas Bx expression showed a significant increase in comparison with free QT-treated cells. Furthermore, The QT-SLNs significantly increased apoptotic and necrotic indexes in MCF-7 cells. Viability, proliferation, oxidative stress and apoptosis of MCF-10A cells were not affected by QT or QT-SLNs. Conclusions: According to the results of this study, SLN significantly enhanced the toxic effect of QT against human breast cancer cells.
Improved Reliability and Mechanical Performance of Ag Microalloyed Sn58Bi Solder Alloys
Authors: Ren Guang , Collins Maurice N.
Published: April 2019

Ag microalloyed Sn58Bi has been investigated in this study as a Pb-free solder candidate to be used in modern electronics industry in order to cope with the increasing demands for low temperature soldering. Microstructural and mechanical properties of the eutectic Sn58Bi and microalloyed Sn57.6Bi0.4Ag solder alloys were compared. With the addition of Ag microalloy, the tensile strength was improved, and this was attributed to a combination of microstructure refinement and an Ag3Sn precipitation hardening mechanism. However, ductility was slightly deteriorated due to the brittle nature of the Ag3Sn intermetallic compounds (IMCs). Additionally, a board level reliability study of Ag microalloyed Sn58Bi solder joints produced utilizing a surface-mount technology (SMT) process, were assessed under accelerated temperature cycling (ATC) conditions. Results revealed that microalloyed Sn57.6Bi0.4Ag had a higher characteristic lifetime with a narrower failure distribution. This enhanced reliability corresponds with improved bulk mechanical properties. It is postulated that Ag3Sn IMCs are located at the Sn–Bi phase boundaries and suppress the solder microstructure from coarsening during the temperature cycling, hereby extending the time to failure.
Microstructure Formation of Low-Carbon Ferritic Stainless Steel during High Temperature Plastic Deformation
Authors: Shao Yi , Li Xiaohua , Ma Junjie , Liu Chenxi , Yan Zesheng
Published: April 2019

In this paper, the effects of the deformation temperature, the deformation reduction and the deformation rate on the microstructural formation, ferritic and martensitic phase transformation, stress–strain behaviors and micro-hardness in low-carbon ferritic stainless steel were investigated. The increase in deformation temperature promotes the formation of the fine equiaxed dynamic strain-induced transformation ferrite and suppresses the martensitic transformation. The higher deformation temperature results in a lower starting temperature for martensitic transformation. The increase in deformation can effectively promote the transformation of DSIT ferrite, and decrease the martensitic transformation rate, which is caused by the work hardening effect on the metastable austenite. The increase in the deformation rate leads to an increase in the ferrite fraction, because a high density of dislocation remains that can provide sufficient nucleation sites for ferrite transformation. The slow deformation rate results in dynamic recovery according to the stress–strain curve.
Leaching Kinetics of Sulfides from Refractory Gold Concentrates by Nitric Acid
Authors: Rogozhnikov Denis A. , Shoppert Andrei A. , Dizer Oleg A. , Karimov Kirill A. , Rusalev Rostislav E.
Published: April 2019

The processing of refractory gold-containing concentrates by hydrometallurgical methods is becoming increasingly important due to the depletion of rich and easily extracted mineral resources, as well as due to the need to reduce harmful emissions from metallurgy, especially given the high content of arsenic in the ores. This paper describes the investigation of the kinetics of HNO3 leaching of sulfide gold-containing concentrates of the Yenisei ridge (Yakutia, Russia). The effect of temperature (70–85 °C), the initial concentration of HNO3 (10–40%) and the content of sulfur in the concentrate (8.22–22.44%) on the iron recovery into the solution was studied. It has been shown that increasing the content of S in the concentrate from 8.22 to 22.44% leads to an average of 45% increase in the iron recovery across the entire range temperatures and concentrations of HNO3 per one hour of leaching. The leaching kinetics of the studied types of concentrates correlates well with the new shrinking core model, which indicates that the reaction is regulated by interfacial diffusion and diffusion through the product layer. Elemental S is found on the surface of the solid leach residue, as confirmed by XRD and SEM/EDS analysis. The apparent activation energy is 60.276 kJ/mol. The semi-empirical expression describing the reaction rate under the studied conditions can be written as follows: 1/3ln(1 − X) + [(1 − X)−1/3 − 1] = 87.811(HNO3)0.837(S)2.948e−60276/RT·t.
Estimation of Air Damping in Out-of-Plane Comb-Drive Actuators
Authors: Mirzazadeh Ramin , Mariani Stefano
Published: April 2019

The development of new compliant resonant microsystems and the trend towards further miniaturization have recently raised the issue of the accuracy and reliability of computational tools for the estimation of fluid damping. Focusing on electrostatically actuated torsional micro-mirrors, a major dissipation contribution is linked to the constrained flow of air at comb fingers. In the case of large tilting angles of the mirror plate, within a period of oscillation the geometry of the air domain at comb-drives gets largely distorted, and the dissipation mechanism is thereby affected. In this communication, we provide an appraisal of simple analytical solutions to estimate the dissipation in the ideal case of air flow between infinite plates, at atmospheric pressure. The results of numerical simulations are also reported to assess the effect on damping of the finite size of actual geometries.
Research on the Disc Sensitive Structure of a Micro Optoelectromechanical System (MOEMS) Resonator Gyroscope
Authors: Shen Xiang , Zhao Liye , Xia Dunzhu
Published: April 2019

A micro optoelectromechanical system (MOEMS) resonator gyroscope based on a waveguide micro-ring resonator was proposed. This sensor was operated by measuring the shift of the transmission spectrum. Modal analysis was carried out for the disc sensitive structure of the MOEMS resonator gyroscope (MOEMS-RG). We deduced the equations between the equivalent stiffness and voltage of each tuning electrode and the modal parameters. A comprehensive investigation of the influences of the structure parameters on the sensitivity noise of the MOEMS-RG is presented in this paper. The mechanical sensitivity and transducer sensitivities of the MOEMS-RG, with varying structural parameters, are calculated based on the finite-element method. Frequency response test and the fiber optic spectrometer displacement test were implemented to verify the reliability of the model. Research results indicate that the resonant frequencies of the operating modes are tested to be 5768.407 Hz and 5771.116 Hz and the resonant wavelength change ΔX was 0.08 nm for 45° rotation angle. The resonant wavelength, which has a good linear response in working range, changes from −0.071 nm to 0.080 μm. The MOEMS-RG, with an optimized disc sensitive structure, can detect the deformation of the sensitive membrane effectively, and has a high sensitivity. This resonator shows very large meff, low f 0 , and very high Q. Therefore, this resonator can provide a small A R W B ( 0.09 ° / h ), which makes it a promising candidate for a low-cost, batch-fabricated, small size inertial-grade MOEMS gyroscope. The multi-objective optimization method could be expanded to include other objectives, constraints, or variables relevant to all kinds of gyroscopes or other microelectromechanical systems devices.
Gelatin-Coated Microfluidic Channels for 3D Microtissue Formation: On-Chip Production and Characterization
Authors: Pitingolo Gabriele , Riaud Antoine , Nastruzzi Claudio , Taly Valerie
Published: April 2019

Traditional two-dimensional (2D) cell culture models are limited in their ability to reproduce human structures and functions. On the contrary, three-dimensional (3D) microtissues have the potential to permit the development of new cell-based assays as advanced in vitro models to test new drugs. Here, we report the use of a dehydrated gelatin film to promote tumor cells aggregation and 3D microtissue formation. The simple and stable gelatin coating represents an alternative to conventional and expensive materials like type I collagen, hyaluronic acid, or matrigel. The gelatin coating is biocompatible with several culture formats including microfluidic chips, as well as standard micro-well plates. It also enables long-term 3D cell culture and in situ monitoring of live/dead assays.
Fractal Characteristics and Heterogeneity of the Nanopore Structure of Marine Shale in Southern North China
Authors: Yu Kun , Ju Yiwen , Qi Yu , Qiao Peng , Huang Cheng , Zhu Hongjian , Feng Hongye
Published: April 2019

The characteristics of the nanopore structure in shale play a crucial role in methane adsorption and in determining the occurrence and migration of shale gas. In this study, using an integrated approach of X-ray diffraction (XRD), N2 adsorption, and field emission scanning electron microscopy (FE-SEM), we systematically focused on eight drilling samples of marine Taiyuan shale from well ZK1 in southern North China to study the characteristics and heterogeneity of their nanopore structure. The results indicated that different sedimentary environments may control the precipitation of clay and quartz between transitional shale and marine shale, leading to different organic matter (OM)–clay relationships and different correlations between total organic carbon (TOC) and mineral content. The shale with high TOC content tended to have more heterogeneous micropores, leading to a higher fractal dimension and a more complex nanopore structure. With the increase of TOC content and thermal evolution of OM, the heterogeneity of the pore structure became more significant. Quartz from marine shale possessed abundant macropores, resulting in a decrease of the Brunauere–Emmette–Teller (BET) surface area (SA) and an increase of the average pore size (APS), while clay minerals developed a large number of micropores which worked together with OM to influence the nanopore structure of shale, leading to the increase of the SA and the decrease of the APS. The spatial order of interlayer pores increased with the increase of mixed-layer illite–smectite (MLIS) content, which naturally reduced the fractal dimensions. In contrast, kaolinite, chlorite, and illite have a small number of nanopores, which might enhance the complexity and reduce the connectivity of the nanopore system by mean of pore-blocking. Taiyuan shale with higher heterogeneity is highly fractal, and its fractal dimensions are principally related to the micropores. The fractal dimensions correlate positively with the SA and total pore volume, suggesting that marine shale with higher heterogeneity may possess a larger SA and a higher total pore volume.
Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf.) Hull Extract and Active Compounds Inhibit Proliferation of Primary Human Leiomyoma Cells and Protect against Sexual Hormone-Induced Mice Smooth Muscle Hyperproliferation
Authors: Lin Po-Han , Shih Chun-Kuang , Yen Yu-Ting , Chiang Wenchang , Hsia Shih-Min
Published: April 2019

Uterine leiomyomas, also known as fibroids, are benign neoplasms of the uterus and have a high incidence rate in women of reproductive age. Hysterectomy or myomectomy is the initial treatment, but fibroids will recur if the patient is still exposed to similar risk factors. Therefore, developing new therapeutic strategies are urgently necessary. In this study, the anti-proliferation effects of each fraction of adlay seeds were evaluated in uterine leiomyomas, and we identified the potential phytochemical compounds. We found that the ethyl acetate fraction of adlay hull (AHE-ea) appeared to be highly efficient in the anti-proliferation of rat uterine leiomyoma ELT3 cells and primary human uterine leiomyoma (hUL) cells. The proliferation of primary human normal uterine smooth muscle (UtSMC) and normal uterine myometrial (hUM) cells were also suppressed by AHE-ea. Two phytosterols, stigmasterol and β-sitosterol, were identified from AHE-ea fraction. Mice treated with AHE-ea and stigmasterol alone demonstrated reduced diethylstilbestrol/medroxyprogesterone 17-acetate (DES/MPA)-induced uterine myometrial hyperplasia, which is the critical step for the development of leiomyoma. Taken together, our results suggest that the AHE-ea fraction could be considered as a natural plant-based medicine in the prevention or treatment of uterine leiomyoma growth.
The Effects of Mono-(2-Ethylhexyl) Phthalate (MEHP) on Human Estrogen Receptor (hER) and Androgen Receptor (hAR) by YES/YAS In Vitro Assay
Authors: Kim Da-Hye , Park Chang Gyun , Kim Sang Hun , Kim Young Jun
Published: April 2019

Endocrine active compounds with structural similarities to natural hormones such as 17β-estradiol (E2) and androgen are suspected to affect the human endocrine system by inducing hormone-dependent effects. This study aimed to detect the (anti-)estrogenic and (anti-)androgenic activities of mono-(2-ethylhexyl) phthalate (MEHP) by yeast estrogen/androgen bioassay (YES/YAS). In addition, the mechanism and uptake of MEHP to receptors during agonistic and antagonistic activities were investigated through the activation signal recovery test and chromatographic analysis using liquid chromatography and tandem mass spectrometry (LC-MS/MS). Estrogenic and androgenic activities of MEHP were not observed. However, MEHP exhibited anti-estrogenic (IC50 = 125 μM) and anti-androgenic effects (IC50 = 736 μM). It was confirmed that these inhibitory effects of MEHP were caused by receptor-mediated activity of the estrogen receptor and non-receptor-mediated activity of the androgen receptor in an activation signal recovery test. When IC50 concentrations of anti-estrogenic and androgenic activity of MEHP were exposed to yeast cells, the uptake concentration observed was 0.0562 ± 0.0252 μM and 0.143 ± 0.0486 μM by LC-MS/MS analysis.
Magnetically Assisted Control of Stem Cells Applied in 2D, 3D and In Situ Models of Cell Migration
Authors: Harrison Richard , Luckett Jeni , Marsh Sarah , Lugo Leija Hilda Anaid , Salih Shelanah , Alkharji Reem , Sottile Virginie
Published: April 2019

The success of cell therapy approaches is greatly dependent on the ability to precisely deliver and monitor transplanted stem cell grafts at treated sites. Iron oxide particles, traditionally used in vivo for magnetic resonance imaging (MRI), have been shown to also represent a safe and efficient in vitro labelling agent for mesenchymal stem cells (MSCs). Here, stem cells were labelled with magnetic particles, and their resulting response to magnetic forces was studied using 2D and 3D models. Labelled cells exhibited magnetic responsiveness, which promoted localised retention and patterned cell seeding when exposed to magnet arrangements in vitro. Directed migration was observed in 2D culture when adherent cells were exposed to a magnetic field, and also when cells were seeded into a 3D gel. Finally, a model of cell injection into the rodent leg was used to test the enhanced localised retention of labelled stem cells when applying magnetic forces, using whole body imaging to confirm the potential use of magnetic particles in strategies seeking to better control cell distribution for in vivo cell delivery.
Effect of Protein Conformation and AMP Protonation State on Fireflies’ Bioluminescent Emission
Authors: Garcia-Iriepa Cristina , Navizet Isabelle
Published: April 2019

The emitted color in fireflies’ bioluminescent systems depends on the beetle species the system is extracted from and on different external factors (pH, temperature…) among others. Controlling the energy of the emitted light (i.e., color) is of crucial interest for the use of such bioluminescent systems. For instance, in the biomedical field, red emitted light is desirable because of its larger tissue penetration and lower energies. In order to investigate the influence of the protein environment and the AMP protonation state on the emitted color, the emission spectra of the phenolate-keto and phenolate-enol oxyluciferin forms have been simulated by means of MD simulations and QM/MM calculations, considering: two different protein conformations (with an open or closed C-terminal domain with respect to the N-terminal) and two protonation states of AMP. The results show that the emission spectra when considering the protein characterized by a closed conformation are blue-shifted compared to the open conformation. Moreover, the complete deprotonation of AMP phosphate group (AMP2−) can also lead to a blue-shift of the emission spectra but only when considering the closed protein conformation (open form is not sensitive to changes of AMP protonation state). These findings can be reasoned by the different interactions (hydrogen-bonds) found between oxyluciferin and the surrounding (protein, AMP and water molecules). This study gets partial insight into the possible origin of the emitted color modulation by changes of the pH or luciferase conformations.
Probing the Effect of Bulky Lesion-Induced Replication Fork Conformational Heterogeneity Using 4-Aminobiphenyl-Modified DNA
Authors: Cai Ang , Bian Ke , Chen Fangyi , Tang Qi , Carley Rachel , Li Deyu , Cho Bongsup P.
Published: April 2019

Bulky organic carcinogens are activated in vivo and subsequently react with nucleobases of cellular DNA to produce adducts. Some of these DNA adducts exist in multiple conformations that are slowly interconverted to one another. Different conformations have been implicated in different mutagenic and repair outcomes. However, studies on the conformation-specific inhibition of replication, which is more relevant to cell survival, are scarce, presumably due to the structural dynamics of DNA lesions at the replication fork. It is difficult to capture the exact nature of replication inhibition by existing end-point assays, which usually detect either the ensemble of consequences of all the conformers or the culmination of all cellular behaviors, such as mutagenicity or survival rate. We previously reported very unusual sequence-dependent conformational heterogeneities involving FABP-modified DNA under different sequence contexts (TG1*G2T [67%B:33%S] and TG1G2*T [100%B], G*, N-(2′-deoxyguanosin-8-yl)-4′-fluoro-4-aminobiphenyl) (Cai et al. Nucleic Acids Research, 46, 6356–6370 (2018)). In the present study, we attempted to correlate the in vitro inhibition of polymerase activity to different conformations from a single FABP-modified DNA lesion. We utilized a combination of surface plasmon resonance (SPR) and HPLC-based steady-state kinetics to reveal the differences in terms of binding affinity and inhibition with polymerase between these two conformers (67%B:33%S and 100%B).
Antibacterial Activity of Different Blossom Honeys: New Findings
Authors: Bucekova Marcela , Jardekova Lucia , Juricova Valeria , Bugarova Veronika , Di Marco Gabriele , Gismondi Angelo , Leonardi Donatella , Farkasovska Jarmila , Godocikova Jana , Laho Maros , Klaudiny Jaroslav , Majtan Viktor , Canini Antonella , Majtan Juraj
Published: April 2019

Antibacterial activity is the most investigated biological property of honey. The goal of this study was to evaluate the antibacterial activity of 57 Slovak blossom honeys against Staphylococcus aureus and Pseudomonas aeruginosa and investigate the role of several bioactive substances in antibacterial action of honeys. Inhibitory and bactericidal activities of honeys were studied to determine the minimum inhibitory and bactericidal concentrations. The contents of glucose oxidase (GOX) enzyme, hydrogen peroxide (H2O2), and total polyphenols (TP) were determined in honeys. We found that honey samples showed different antibacterial efficacy against the tested bacteria as follows: wildflower honeys > acacia honeys > rapeseed honeys. Overall antibacterial activity of the honeys was statistically-significantly correlated with the contents of H2O2 and TP in honeys. A strong correlation was found between the H2O2 and TP content. On the other hand, no correlation was found between the content of GOX and level of H2O2. Antibacterial activity of 12 selected honeys was markedly reduced by treatment with catalase, but it remained relatively stable after inactivation of GOX with proteinase-K digestion. Obtained results suggest that the antibacterial activity of blossom honeys is mainly mediated by H2O2 levels present in honeys which are affected mainly by polyphenolic substances and not directly by GOX content.
Molecular Recognition of the Hybrid-Type G-Quadruplexes in Human Telomeres
Authors: Wu Guanhui , Chen Luying , Liu Wenting , Yang Danzhou
Published: April 2019

G-quadruplex (G4) DNA secondary structures formed in human telomeres have been shown to inhibit cancer-specific telomerase and alternative lengthening of telomere (ALT) pathways. Thus, human telomeric G-quadruplexes are considered attractive targets for anticancer drugs. Human telomeric G-quadruplexes are structurally polymorphic and predominantly form two hybrid-type G-quadruplexes, namely hybrid-1 and hybrid-2, under physiologically relevant solution conditions. To date, only a handful solution structures are available for drug complexes of human telomeric G-quadruplexes. In this review, we will describe two recent solution structural studies from our labs. We use NMR spectroscopy to elucidate the solution structure of a 1:1 complex between a small molecule epiberberine and the hybrid-2 telomeric G-quadruplex, and the structures of 1:1 and 4:2 complexes between a small molecule Pt-tripod and the hybrid-1 telomeric G-quadruplex. Structural information of small molecule complexes can provide important information for understanding small molecule recognition of human telomeric G-quadruplexes and for structure-based rational drug design targeting human telomeric G-quadruplexes.
Anticandidal Potential of Stem Bark Extract from Schima superba and the Identification of Its Major Anticandidal Compound
Authors: Wu Chun , Wu Hong-Tan , Wang Qing , Wang Guey-Horng , Yi Xue , Chen Yu-Pei , Zhou Guang-Xiong
Published: April 2019

Plant-derived extracts are a promising source of new drugs. Schima superba is traditionally used in China for heat clearing, detoxification, and treatment of furuncles. In this study, the anticandidal properties and mechanism of action of S. superba (SSE) were explored using a stem bark extract. SSE possessed high polyphenol and saponin contents of 256.6 ± 5.1 and 357.8 ± 31.5 µg/mg, respectively. A clear inhibition zone was observed for C. albicans growth through the disc diffusion method and the 50% inhibition of C. albicans by SSE was 415.2 µg/mL. Transcriptomic analysis in C. albicans treated with different doses of SSE was conducted through RNA-seq. Average values of 6068 genes and 20,842,500 clean reads were identified from each sample. Among these samples, 1680 and 1956 genes were differentially expressed genes (DEGs) from the SSE treatments of 0.2 and 0.4 mg/mL, respectively. C. albicans growth was inhibited by the changes in gene expression associated with the cell wall and membrane composition including the regulation of chitin degradation and ergosterol biosynthesis. This result could be reflected in the irregularly wrinkled morphology of the ruptured cell as revealed through SEM analysis. ESI-MS and NMR analyses revealed that the major compound purified from SSE was sasanquasaponin III and the 50% inhibition of C. albicans was 93.1 µg/mL. In summary, the traditional Chinese medicine S. superba can be applied as an anticandidal agent in complementary and alternative medicine.
A Virtual Reality System for Practicing Conversation Skills for Children with Autism
Authors: Stewart Rosenfield Natalia , Lamkin Kathleen , Re Jennifer , Day Kendra , Boyd LouAnne , Linstead Erik
Published: April 2019

We describe a virtual reality environment, Bob’s Fish Shop, which provides a system where users diagnosed with Autism Spectrum Disorder (ASD) can practice social interactions in a safe and controlled environment. A case study is presented which suggests such an environment can provide the opportunity for users to build the skills necessary to carry out a conversation without the fear of negative social consequences present in the physical world. Through the repetition and analysis of these virtual interactions, users can improve social and conversational understanding.
Investigation of the Impact of Cross-Polymerization on the Structural and Frictional Properties of Alkylsilane Monolayers Using Molecular Simulation
Authors: Black Jana E. , Summers Andrew Z. , Iacovella Christopher R. , Cummings Peter T. , McCabe Clare
Published: April 2019

Cross-linked chemisorbed n-alkylsilane (CH3(CH2)n−1Si(OH)3) monolayers on amorphous silica surfaces have been studied and their structural properties and frictional performance were compared to those of equivalent monolayers without cross-linkages. The simulations isolated for the first time the effects of both siloxane cross-linkages and the fraction of chains chemisorbed to the surface, providing insight into a longstanding fundamental question in the literature regarding molecular-level structure. The results demonstrate that both cross-linkages and the fraction of chemisorbed chains affect monolayer structure in small but measurable ways, particularly for monolayers constructed from short chains; however, these changes do not appear to have a significant impact on frictional performance.
Highly Optimized Nitrogen-Doped MWCNTs through In-Depth Parametric Study Using Design of Experiments
Authors: Plunkett Alexander , Kröning Katharina , Fiedler Bodo
Published: April 2019

The in-situ nitrogen doping of multiwalled carbon nanotubes via chemical vapor deposition is investigated employing design of experiments (DoE). The establishment of empirical DoE models allowed for the prediction of product features as a function of process conditions in order to systematically synthesize tailor-made nitrogen-doped carbon nanotubes. The high informative content of this approach revealed effects of individual parameters and their interaction with each other. Hence, new valuable insights into the effect of temperature, injection rate, and carrier gas flow on the doping level were obtained which give motivation to approach further theoretical studies on the doping mechanism. Ultimately, competitive nitrogen-doped carbon nanotube features were optimized and yielded promising combinations of achieved doping level, graphitization, and aspect ratios in comparison to present literature values.
The Good, the Bad, and the Ugly of Pregnancy Nutrients and Developmental Programming of Adult Disease
Authors: Hsu Chien-Ning , Tain You-Lin
Published: April 2019

Maternal nutrition plays a decisive role in developmental programming of many non-communicable diseases (NCDs). A variety of nutritional insults during gestation can cause programming and contribute to the development of adult-onset diseases. Nutritional interventions during pregnancy may serve as reprogramming strategies to reverse programming processes and prevent NCDs. In this review, firstly we summarize epidemiological evidence for nutritional programming of human disease. It will also discuss evidence from animal models, for the common mechanisms underlying nutritional programming, and potential nutritional interventions used as reprogramming strategies.
Number of Eating Occasions and Source of Foods and Drinks Among Young Children in the United States: NHANES, 2009–2014
Authors: Barrera Chloe M. , Moore Latetia V. , Perrine Cria G. , Hamner Heather C.
Published: April 2019

An understanding of the source of children’s foods and drinks is needed to identify the best intervention points for programs and policies aimed at improving children’s diets. The mean number and type of eating occasions and the relative proportions of foods and drinks consumed from different sources were calculated among children aged 1–4 years (n = 2640) using data from the 2009–2014 National Health and Nutrition Examination Surveys. Children consumed 2.9 meals and 2.4 snacks each day. Among children who received anything from childcare, childcare provided 36.2% of their foods and drinks. The majority of foods and drinks came from stores for all children (53.2% among those receiving anything from childcare and 84.9% among those not). Among children receiving food from childcare, childcare is an important source of foods and drinks. Because most foods and drinks consumed by children come from stores, parents and caregivers may benefit from nutrition education to promote healthful choices when buying foods.
Associations of Lipophilic Micronutrients with Physical and Cognitive Fitness in Persons with Mild Cognitive Impairment
Authors: Gerger Perihan , Pai Roopa Kalsank , Stuckenschneider Tim , Falkenreck Julia , Weigert Hannah , Stahl Wilhelm , Weber Bernd , Nelles Gereon , Spazzafumo Liana , Schneider Stefan , Polidori M. Cristina
Published: April 2019

Age-associated cognitive impairment in general and dementia in particular are a global concern. Preventive lifestyle strategies are highly used but there is a lack of information on the reciprocal relationships between nutrition biomarkers and measures of both cognitive and physical performance. To fill this gap of knowledge, the relationship between plasma levels of the robust nutrition- and antioxidant defense-related biomarkers carotenoid and tocopherols and both indicators of cognitive and physical performance was investigated in a group of persons with mild cognitive impairment participating in the NeuroExercise Study at the German Sport University in Cologne, Germany. In 56 participants with full dataset, significant correlations independently of fruit and vegetable intake were found between plasma levels of β-cryptoxanthin and Timed Up&Go test (p < 0.05), γ-tocopherol and number of daily steps (p < 0.01), as well as between four out of six measured carotenoids—lutein; zeaxanthin; β-cryptoxanthin and β-carotene—and the computerized CogState International Shopping List subtest (p < 0.01). In light of the increasing attention towards the nutritional cognitive neuroscience of carotenoids, computerized measures of cognitive performance might be further implemented in future studies investigating the effects of lifestyle interventions against cognitive and physical impairment.