bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward Development of a Vocal Fold Contact Pressure Probe: Bench-Top Validation of a Dual-Sensor Probe Using Excised Human Larynx Models
Authors: Mehta Daryush D. , Kobler James B. , Zeitels Steven M. , Zañartu Matías , Erath Byron D. , Motie-Shirazi Mohsen , Peterson Sean D. , Petrillo Robert H. , Hillman Robert E.
Published: October 2019

A critical element in understanding voice production mechanisms is the characterization of vocal fold collision, which is widely considered a primary etiological factor in the development of common phonotraumatic lesions such as nodules and polyps. This paper describes the development of a transoral, dual-sensor intraglottal/subglottal pressure probe for the simultaneous measurement of vocal fold collision and subglottal pressures during phonation using two miniature sensors positioned 7.6 mm apart at the distal end of a rigid cannula. Proof-of-concept testing was performed using excised whole-mount and hemilarynx human tissue aerodynamically driven into self-sustained oscillation, with systematic variation of the superior–inferior positioning of the vocal fold collision sensor. In the hemilarynx experiment, signals from the pressure sensors were synchronized with an acoustic microphone, a tracheal-surface accelerometer, and two high-speed video cameras recording at 4000 frames per second for top–down and en face imaging of the superior and medial vocal fold surfaces, respectively. As expected, the intraglottal pressure signal exhibited an impulse-like peak when vocal fold contact occurred, followed by a broader peak associated with intraglottal pressure build-up during the de-contacting phase. As subglottal pressure was increased, the peak amplitude of the collision pressure increased and typically reached a value below that of the average subglottal pressure. Results provide important baseline vocal fold collision pressure data with which computational models of voice production can be developed and in vivo measurements can be referenced.
Extension of an FFT-Based Beam Propagation Method to Plasmonic and Dielectric Waveguide Discontinuities and Junctions
Authors: Shaaban Adel , Du Yi-Chun , Gomaa Lotfy Rabeh
Published: October 2019

We adapted a fast Fourier transform-based Beam Propagation Method (FFT-BPM) to investigate waveguide discontinuities in plasmonic waveguides. The adaptation of the FFT-BPM to treat transverse magnetic (TM) fields requires the circumvention of two major difficulties: the mixed derivatives of the magnetic field and waveguide refractive index profile in the TM wave equation and the step-like index change at the transverse metal-dielectric boundary of the plasmonic guide and the transverse boundaries of the dielectric waveguide as well. An equivalent-index method is adopted to transform TM fields to transverse electric (TE) ones, thus enabling the benefit of the full power and simplicity of the FFT-BPM. Moreover, an appropriate smoothing function is used to approximate the step-like refractive index profile in the transverse direction. At the junction plane, we used an accurate combined spatial-spectral reflection operator to calculate the reflected field. To validate our proposed scheme, we investigated the modal propagation in a silicon waveguide terminated by air (like a laser facet in two cases: with and without a coating layer). Then we considered a subwavelength plasmonic waveguide (metal-insulator-metal MIM) butt-coupled with a dielectric waveguide, where the power transmission efficiency has been calculated and compared with other numerical methods. The comparison reveals good agreement.
An Enhanced Feature Pyramid Object Detection Network for Autonomous Driving
Authors: Wu Yutian , Tang Shuming , Zhang Shuwei , Ogai Harutoshi
Published: October 2019

Feature Pyramid Network (FPN) builds a high-level semantic feature pyramid and detects objects of different scales in corresponding pyramid levels. Usually, features within the same pyramid levels have the same weight for subsequent object detection, which ignores the feature requirements of different scale objects. As we know, for most detection networks, it is hard to detect small objects and occluded objects because there is little information to exploit. To solve the above problems, we propose an Enhanced Feature Pyramid Object Detection Network (EFPN), which innovatively constructs an enhanced feature extraction subnet and adaptive parallel detection subnet. Enhanced feature extraction subnet introduces Feature Weight Module (FWM) to enhance pyramid features by weighting the fusion feature map. Adaptive parallel detection subnet introduces Adaptive Context Expansion (ACE) and Parallel Detection Branch (PDB). ACE aims to generate the features of adaptively enlarged object context region and original region. PDB predicts classification and regression results separately with the two features. Experiments showed that EFPN outperforms FPN in detection accuracy on Pascal VOC and KITTI datasets. Furthermore, the performance of EFPN meets the real-time requirements of autonomous driving systems.
Vibration Control of an Unbalanced Single-Side Cantilevered Rotor System with a Novel Integral Squeeze Film Bearing Damper
Authors: Zhang Yipeng , He Lidong , Yang Jianjiang , Wan Fangteng , Gao Jinji
Published: October 2019

In this paper, vibration control of an unbalanced single-side cantilevered rotor system using a novel integral squeeze film bearing damper in terms of stability, energy distribution, and vibration control is analyzed. A finite element model of such a system with an integral squeeze film bearing damper (ISFBD) is developed. The stability, energy distribution, and vibration control of the unbalanced single-side cantilevered rotor system are calculated and analyzed based on the finite element model. The stiffness of the integral squeeze film bearing damper is designed using theoretical calculation and finite element model (FEM) simulation. The influence of installation position and quantity of integral squeeze film bearing dampers on the vibration control of the unbalanced cantilevered rotor system is discussed. An experimental platform is developed to validate the vibration control effect. The results show that the installation position and quantity of the integral squeeze film bearing dampers have different effects on the stability, energy distribution, and vibration control of the unbalanced cantilevered rotor system. When ISFBDs are installed at both bearing housings, the vibration control is best, and the vibration components of the time and frequency domains have good vibration control effects in four working conditions.
A Sensor Fusion Framework for Indoor Localization Using Smartphone Sensors and Wi-Fi RSSI Measurements
Authors: Poulose Alwin , Kim Jihun , Han Dong Seog
Published: October 2019

Sensor fusion frameworks for indoor localization are developed with the specific goal of reducing positioning errors. Although many conventional localization frameworks without fusion have been improved to reduce positioning error, sensor fusion frameworks generally provide a further improvement in positioning accuracy. In this paper, we propose a sensor fusion framework for indoor localization using the smartphone inertial measurement unit (IMU) sensor data and Wi-Fi received signal strength indication (RSSI) measurements. The proposed sensor fusion framework uses location fingerprinting and trilateration for Wi-Fi positioning. Additionally, a pedestrian dead reckoning (PDR) algorithm is used for position estimation in indoor scenarios. The proposed framework achieves a maximum of 1.17 m localization error for the rectangular motion of a pedestrian and a maximum of 0.44 m localization error for linear motion.
Chatter Mitigation in Milling Process Using Discrete Time Sliding Mode Control with Type 2-Fuzzy Logic System
Authors: Paul Satyam , Morales-Menendez Ruben
Published: October 2019

In order to achieve a high-quality machining process with superior productivity, it is very important to tackle the phenomenon of chatter in an effective manner. The problems like tool wear and improper surface finish affect the milling process and are caused by self-induced vibration termed as chatter. A strategy to control chatter vibration actively in the milling process is presented. The mathematical modeling of the process is carried out initially. In this paper, an innovative technique of discrete time sliding mode control (DSMC) is blended with the type-2 fuzzy logic system. The proposed active controller results in a significantly high mitigation of vibration. The DSMC is linked to the time-varying gain which is an innovative approach to mitigate chattering. The theorem is laid down which validates that the system states are bounded in the case of DSMC-type-2 fuzzy. Stability analysis is carried out using Lyapunov candidate. The nonlinearities linked with the cutting forces and damper friction are handled effectively by using the type-2 fuzzy logic system. The performance of the DSMC-type-2 fuzzy concept is compared with the discrete time PID (D-PID) and discrete time sliding mode control for validating the effectiveness of the controller. The better performance of DSMC-type-2 fuzzy over D-PID and DSMC-T1 fuzzy in the minimization of milling chatter are validated by a numerical analysis approach.
Trajectory Tracking of Flexible-Joint Robots Actuated by PMSM via a Novel Smooth Switching Control Strategy
Authors: Wang Yue , Yu Haisheng , Yu Jinpeng , Wu Herong , Liu Xudong
Published: October 2019

This paper presents the trajectory tracking control of a flexible-joint manipulator driven by permanent magnet synchronous motor (PMSM). Combining the PMSM electrical equation and mechanical equation of robotic manipulators, a novel smooth switching control scheme is proposed. Firstly, the position loop controller of the system is designed, with an improved hierarchical sliding mode control (IHSMC) algorithm proposed to further the response speed of the system, additionally, a robust interconnection and damping assignment passivity-based controller (IDA-PBC) is designed to improve the steady state performance of the system. Then, the IDA-PBC control strategy is leveraged to design the current loop controller of the system, on which basis a hybrid controller with smooth switching is designed. Furthermore, Gaussian function is applied as the smooth switching function of the hybrid controller to promote the switching performance. As a result, the hybrid controller has both good dynamic and steady performance. The simulation results verify the effectiveness of the algorithms.
A New Period-Sequential Index Forecasting Algorithm for Time Series Data
Authors: Jiang Hongyan , Fang Dianjun , Spicher Klaus , Cheng Feng , Li Boxing
Published: October 2019

A period-sequential index algorithm with sigma-pi neural network technology, which is called the (SPNN-PSI) method, is proposed for the prediction of time series datasets. Using the SPNN-PSI method, the cumulative electricity output (CEO) dataset, Volkswagen sales (VS) dataset, and electric motors exports (EME) dataset are tested. The results show that, in contrast to the moving average (MA), exponential smoothing (ES), and autoregressive integrated moving average (ARIMA) methods, the proposed SPNN-PSI method shows satisfactory forecasting quality due to lower error, and is more suitable for the prediction of time series datasets. It is also concluded that: There is a trend that the higher the correlation coefficient value of the reference historical datasets, the higher the prediction quality of SPNN-PSI method, and a higher value (>0.4) of correlation coefficient for SPNN-PSI method can help to improve occurrence probability of higher forecasting accuracy, and produce more accurate forecasts for the big datasets.
Experimental Study on Dynamics of Wooden House Wall Panels with Different Thermal Isolation
Authors: Szczepański Marcin , Migda Wojciech , Jankowski Robert
Published: October 2019

Wood frame buildings are very popular in regions that are exposed to different dynamic excitations including earthquakes. Therefore, their seismic resistance is really important in order to prevent structural damages and human losses. The aim of the present paper is to show the results of experimental tests focused on the dynamic response of wall panels of a wooden frame building with thermal isolation made of mineral wool and polyurethane foam. Firstly, the static and the dynamic mechanical analysis (DMA) tests were conducted so as to determine the basic thermomechanical properties of the analyzed isolation materials. Then, the elements of the exterior walls with two types of thermal insulation were tested under harmonic excitation for different amplitudes of displacement. The results of the static material tests indicate that the polyurethane foam behaves in a highly nonlinear way both during compression and tension. Moreover, the results of the DMA tests show that the storage and loss modulus of the polyurethane foam are significantly larger in relation to the values obtained for the mineral wool. The results of the dynamic tests on wall panels show that the use of polyurethane foam as thermal isolation leads to a substantial increase in stiffness and damping properties, as compared to the case when the mineral wood is used.
An Ultra-High-SMSR External-Cavity Diode Laser with a Wide Tunable Range around 1550 nm
Authors: Wang Yan , Wu Hao , Chen Chao , Zhou Yinli , Wang Yubing , Liang Lei , Tian Zhenhua , Qin Li , Wang Lijun
Published: October 2019

In this paper, a widely tunable external cavity diode laser (ECDL) with an ultra-high side mode suppression ratio (SMSR) was fabricated. Three configurations were constructed to investigate the relationship between the grating features and the SMSR. When a 1200 grooves/mm grating with a first order diffraction efficiency of 91% is utilized in the external-cavity laser system, a maximum SMSR of 65 dB can be achieved. In addition, the tunable range reaches 209.9 nm. The results show that the laser performance can be improved by proper high grating groove number and first-order diffraction efficiency.
A Review on Improving the Quality of Perovskite Films in Perovskite Solar Cells via the Weak Forces Induced by Additives
Authors: Yang Jien , Chen Songhua , Xu Jinjin , Zhang Qiong , Liu Hairui , Liu Zhiyong , Yuan Mingjian
Published: October 2019

Perovskite solar cells (PSCs) employing organic-inorganic halide perovskite as active layers have attracted the interesting of many scientists since 2009. The power conversion efficiency (PCE) have pushed certified 25.2% in 2019 from initial 3.81% in 2009, which is much faster than that of any type of solar cell. In the process of optimization, many innovative approaches to improve the morphology of perovskite films were developed, aiming at elevate the power conversion efficiency of perovskite solar cells (PSCs) as well as long-term stability. In the context of PSCs research, the perovskite precursor solutions modified with different additives have been extensively studied, with remarkable progress in improving the whole performance. In this comprehensive review, we focus on the forces induced by additives between the cations and anions of perovskite precursor, such as hydrogen bonds, coordination or some by-product (e.g., mesophase), which will lead to form intermediate adduct phases and then can be converted into high quality films. A compact uniform perovskite films can not only upgrade the power conversion efficiency (PCE) of devices but also improve the stability of PSCs under ambient conditions. Therefore, strategies for the implementation of additives engineering in perovskites precursor solution will be critical for the future development of PSCs. How to manipulate the weak forces in the fabrication of perovskite film could help to further develop high-efficiency solar cells with long-term stability and enable the potential of future practical applications.
A Blind Nonlinearity Compensator Using DBSCAN Clustering for Coherent Optical Transmission Systems
Authors: Giacoumidis Elias , Lin Yi , Jarajreh Mutsam , O’Duill Sean , McGuinness Kevin , Whelan Paul F. , Barry Liam P.
Published: October 2019

Coherent fiber-optic communication systems are limited by the Kerr-induced nonlinearity. Benchmark optical and digital nonlinearity compensation techniques are typically complex and tackle deterministic-induced nonlinearities. However, these techniques ignore the impact of stochastic nonlinear distortions in the network, such as the interaction of fiber nonlinearity with amplified spontaneous emission from optical amplification. Unsupervised machine learning clustering (e.g., K-means) has recently been proposed as a practical approach to the blind compensation of stochastic and deterministic nonlinear distortions. In this work, the Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm is employed, for the first time, for blind nonlinearity compensation. DBSCAN is tested experimentally in a 40 Gb/s 16 quadrature amplitude-modulated system at 50 km of standard single-mode fiber transmission. It is shown that at high launched optical powers, DBSCAN can offer up to 0.83 and 8.84 dB enhancement in Q-factor when compared to conventional K-means clustering and linear equalisation, respectively.
The Anodic Behaviour of Bulk Copper in Ethaline and 1-Butyl-3-Methylimidazolium Chloride
Authors: Karim Wrya O. , Aziz Shujahadeen B. , Brza Mohamed. A. , Abdullah Ranjdar M. , Kadir Mohd. F. Z.
Published: October 2019

The anodic dissolution of bulk metallic copper was conducted in ionic liquids (ILs)—a deep eutectic solvent (DES) ((CH3)3NC2H4OH) comprised of a 1:2 molar ratio mixture of choline chloride Cl (ChCl), and ethylene glycol (EG)—and imidazolium-based ILs, such as C4mimCl, using electrochemical techniques, such as cyclic voltammetry, anodic linear sweep voltammetry, and chronopotentiometry.To investigate the electrochemical dissolution mechanism, electrochemical impedance spectroscopy (EIS) was used. In addition to spectroscopic techniques, for instance, UV-visible spectroscopy, microscopic techniques, such as atomic force microscopy (AFM), were used. The significant industrial importance of metallic copper has motivated several research groups to deal with such an invaluable metal. It was confirmed that the speciation of dissolved copper from the bulk phase at the interface region is [CuCl3]− and [CuCl4]2− in such chloride-rich media, and the EG determine the structure of the interfacial region in the electrochemical dissolution process. A super-saturated solution was produced at the electrode/solution interface and CuCl2 was deposited on the metal surface.
A Method for Estimating Annual Cumulative Soil/Ecosystem Respiration and CH4 Flux from Sporadic Data Collected Using the Chamber Method
Authors: Yang Meng , Yu Guirui , He Nianpeng , Grace John , Wang Qiufeng , Zhou Yan
Published: October 2019

Measurements of greenhouse gas fluxes over many ecosystems have been made as part of the attempt to quantify global carbon and nitrogen cycles. In particular, annual flux observations are of great value for regional flux assessments, as well as model development and optimization. The chamber method is a popular approach for soil/ecosystem respiration and CH4 flux observations of terrestrial ecosystems. However, in situ flux chamber measurements are usually made with non-continuous sampling. To date, efficient methods for the application of such sporadic data to upscale temporally and obtain annual cumulative fluxes have not yet been determined. To address this issue, we tested the adequacy of non-continuous sampling using multi-source data aggregation. We collected 330 site-years monthly soil/ecosystem respiration and 154 site-years monthly CH4 flux data in China, all obtained using the chamber method. The data were randomly divided into a training group and verification group. Fluxes of all possible sampling months of a year, i.e., 4094 different month combinations were used to obtain the annual cumulative flux. The results showed a good linear relationship between the monthly flux and the annual cumulative flux. The flux obtained during the warm season from May to October generally played a more important role in annual flux estimations, as compared to other months. An independent verification analysis showed that the monthly flux of 1 to 4 months explained up to 67%, 89%, 94%, and 97% of the variability of the annual cumulative soil/ecosystem respiration and 92%, 99%, 99%, and 99% of the variability of the annual cumulative CH4 flux. This study supports the use of chamber-observed sporadic flux data, which remains the most commonly-used method for annual flux estimating. The flux estimation method used in this study can be used as a guide for designing sampling programs with the intention of estimating the annual cumulative flux.
YAP Inhibition by Nuciferine via AMPK-Mediated Downregulation of HMGCR Sensitizes Pancreatic Cancer Cells to Gemcitabine
Authors: Zhou Ling , Wang Qiaoyun , Zhang Han , Li Youjie , Xie Shuyang , Xu Maolei
Published: October 2019

Nuciferine, a major aporphine alkaloid constituent of lotus leaves, is a raw material for obesity treatment. Extensive studies have revealed that obesity is associated with pancreatic cancer (PC). However, it has not been clarified whether nuciferine could be used in PC treatment or prevention. Here, we show that nuciferine could enhance the sensitivity of PC cells to gemcitabine in both cultured cells and the xenograft mouse model. The mechanism study demonstrated that nuciferine induced YAP Ser127 phosphorylation [pYAP(Ser127)] through AMPK-mediated 3-hydroxy-3-methyl-glutaryl-coA reductase (HMGCR) downregulation. Remarkably, wild-type YAP overexpression or YAP Ser127 mutant could resist to nuciferine and no longer sensitize PC cells to gemcitabine. Knockdown of AMPK attenuated pYAP(Ser127) induced by nuciferine. Moreover, knockdown of AMPK reversed nuciferine-mediated HMGCR downregulation. Notably, HMGCR inhibiting could restrain YAP by phosphorylation Ser 127, and therefore enhance the efficiency of gemcitabine in PC cells. In line with this consistent, overexpression of HMGCR reduced growth inhibition caused by nuciferine and/or gemcitabine treatment in PC cells. In summary, these results provide an effective supplementary agent and suggest a therapeutic strategy to reduce gemcitabine resistance in PC.
Detection of Superoxide Alterations Induced by 5-Fluorouracil on HeLa Cells with a Cell-Based Biosensor
Authors: Mavrikou Sophia , Tsekouras Vasileios , Karageorgou Maria-Argyro , Moschopoulou Georgia , Kintzios Spyridon
Published: October 2019

Background: In vitro cell culture monitoring can be used as an indicator of cellular oxidative stress for the assessment of different chemotherapy agents. Methods: A cell-based bioelectric biosensor was used to detect alterations in superoxide levels in the culture medium of HeLa cervical cancer cells after treatment with the chemotherapeutic agent 5-fluorouracil (5-FU). The cytotoxic effects of 5-fluorouracil on HeLa cells were assessed by the MTT proliferation assay, whereas oxidative damage and induction of apoptosis were measured fluorometrically by the mitochondria-targeted MitoSOX™ Red and caspase-3 activation assays, respectively. Results: The results of this study indicate that 5-FU differentially affects superoxide production and caspase-3 activation when applied in cytotoxic concentrations against HeLa cells, while superoxide accumulation is in accordance with mitochondrial superoxide levels. Our findings suggest that changes in superoxide concentration could be detected with the biosensor in a non-invasive and rapid manner, thus allowing a reliable estimation of oxidative damage due to cell apoptosis. Conclusions: These findings may be useful for facilitating future high throughput screening of different chemotherapeutic drugs with a cytotoxic principle based on free radical production.
Diagnostic Issues of Asymptomatic Neurosyphilis in HIV-Positive Patients: A Retrospective Study
Authors: Ceccarelli Giancarlo , Borrazzo Cristian , Lazzaro Alessandro , Innocenti Giuseppe Pietro , Celani Luigi , Cavallari Eugenio Nelson , Pinacchio Claudia , Santinelli Letizia , Mastroianni Claudio Maria , d’Ettorre Gabriella
Published: October 2019

Introduction: Asymptomatic neurosyphilis (ANS) is a disease that is difficult to diagnose in people living with HIV (PLWH). The European Guidelines on the management of syphilis suggest that ANS should be suspected and thus the lumbar puncture (LP) should be performed in cases of (1) late syphilis (acquired >2 years previously), (2) CD4+ cells ≤ 350/mm3 and/or a serum Venereal Disease Research Laboratory/Rapid Plasma Reagin (VDRL/RPR) title > 1:32, (3) “serological failure” after syphilis therapy, and (4) the use of alternative treatment for syphilis. In the present study, we aimed to verify the accuracy of the guideline’s criteria for the indication of LP in the suspicion of ANS in a cohort of PLWH. Methods: This retrospective study was carried out in a cohort of PLWH referred at a single medical center of a large academic hospital in Italy. Clinical and laboratory data of patients diagnosed with late syphilis were extracted from the cohort and analyzed. The European Guidelines of syphilis were adopted for patient management. Results: Out of a cohort of 713 PLWH, only 51 (7%) had a diagnosis of late syphilis and were therefore included in the study. Thirty-one subjects (61%) met one or more diagnostic criteria to perform LP: 39% (12/31) of patients undergoing LP had a diagnosis of ANS. The accuracy of predictive criteria for ANS, suggested by the guidelines, was 62% for RPR > 1:32 and 74% for CD4+ ≤ 350 cc/µL. The simultaneous occurrence of both criteria (RPR > 1:32 plus CD4+ ≤ 350 cc/µL) achieved a diagnostic accuracy of 59%. Interestingly, only 17% of patients who underwent LP for serological failure were eventually diagnosed positive for ANS. Conclusion: Asymptomatic neurosyphilis represents a challenging, but not uncommon, diagnosis. Therefore, it requires a careful investigation. Low CD4+ cell count and RPR > 1:32 remain excellent predictors of neurosyphilis, but have become the only acceptable predictors of ANS in PLWH. “Serologic failure” should be regarded with caution as a criterion to perform LP in order to investigate possible ANS in HIV-syphilis coinfected patients asymptomatic for neurological disorders. The retrospective nature of this single-site study may represent a limit to the interpretation of the data. Thus, larger clinical studies on the topic are warranted.
A Qualitative Study Examining the Illness Narrative Master Plots of People with Head and Neck Cancer
Authors: Reid Kate , Soundy Andrew
Published: October 2019

Background: There is a need to understand the common plots (master plots) of illness narratives for people who are treated for cancer. Improved insight would enhance therapeutic relationships and help reduce stress for health care professionals (HCPs). Aim: Identify and refine the most supported narrative master plots, which convey meaning for the tellers’ lived experience from diagnosis to a year post-treatment for a group of Head and Neck Cancer (H&NC) patients. Method: A purposive sample of individuals with H&NC using a single qualitative interview was undertaken. A narrative analysis was used. Results: Eighteen people (57.8 years, six female and 12 male) with H&NC participated. The average time since treatment began was 10 months. Five master plots were identified: (1) The responsive and reflective narrative, (2) The frail narrative, (3) The recovery narrative, (4) The survive or die narrative and (5) The personal project narrative. Discussion: The identification of narrative master plots of people with H&NC enables HCPs to understand and prepare for the different stories and reactions presented to them. This is important to prevent people’s reactions being labelled in restrictive ways. The implications of recognising the different experiences are discussed further within the manuscript. Research is needed to build on these findings to promote better patient-centred care in practice.
The Structural Binding Mode of the Four Autotaxin Inhibitor Types that Differentially Affect Catalytic and Non-Catalytic Functions
Authors: Salgado-Polo Fernando , Perrakis Anastassis
Published: October 2019

Autotaxin (ATX) is a secreted lysophospholipase D, catalysing the conversion of lysophosphatidylcholine (LPC) to bioactive lysophosphatidic acid (LPA). LPA acts through two families of G protein-coupled receptors (GPCRs) controlling key cellular responses, and it is implicated in many physiological processes and pathologies. ATX, therefore, has been established as an important drug target in the pharmaceutical industry. Structural and biochemical studies of ATX have shown that it has a bimetallic nucleophilic catalytic site, a substrate-binding (orthosteric) hydrophobic pocket that accommodates the lipid alkyl chain, and an allosteric tunnel that can accommodate various steroids and LPA. In this review, first, we revisit what is known about ATX-mediated catalysis, crucially in light of allosteric regulation. Then, we present the known ATX catalysis-independent functions, including binding to cell surface integrins and proteoglycans. Next, we analyse all crystal structures of ATX bound to inhibitors and present them based on the four inhibitor types that are established based on the binding to the orthosteric and/or the allosteric site. Finally, in light of these data we discuss how mechanistic differences might differentially modulate the activity of the ATX-LPA signalling axis, and clinical applications including cancer.
Synergistic Anti-Tumor Effect of mTOR Inhibitors with Irinotecan on Colon Cancer Cells
Authors: Reita Damien , Bour Cyril , Benbrika Radhia , Groh Audrey , Pencreach Erwan , Guérin Eric , Guenot Dominique
Published: October 2019

Advanced colorectal cancer has a poor prognosis because of metastasis formation and resistance to combined therapies. Downstream of PI3K/Akt and Ras/MAPK pathways, the mTOR kinase plays a decisive role in treatment failure. We previously established that irinotecan has antiangiogenic properties and it is known that new mammalian target of rapamycin (mTOR) catalytic AZD inhibitors, unlike rapamycin, target both mTORC1 and mTORC2. Thus, we hypothesized that the complete inhibition of the PI3K/AKT/mTOR/HIF-1α axis with mTOR catalytic inhibitors and low doses of irinotecan may have antitumor effects. We showed that the AZD8055 and AZD2014 inhibitors were much more potent than rapamycin to reduce cell viability of four colon cell lines. On the other hand, whereas AZD2014 alone inhibits migration by 40%, the drug combination led to 70% inhibition. Similarly, neither irinotecan nor AZD2014 significantly reduced cell invasion, whereas a combination of the two inhibits invasion by 70%. In vivo, irinotecan and AZD2014 combination drastically reduced ectopic patient-derived colon tumor growth and this combination was more potent than Folfox or Folfiri. Finally, the combination totally inhibited liver and lung metastases developed from orthotopic implantation of SW480 cells. Thus, the use of mTOR catalytic inhibitors, in association with other chemotherapeutic agents like irinotecan at low doses, is potentially a hope for colon cancer treatment.
The Histone Demethylase LSD1/ΚDM1A Mediates Chemoresistance in Breast Cancer via Regulation of a Stem Cell Program
Authors: Verigos John , Karakaidos Panagiotis , Kordias Dimitris , Papoudou-Bai Alexandra , Evangelou Zoi , Harissis Haralampos V. , Klinakis Apostolos , Magklara Angeliki
Published: October 2019

Breast cancer is the leading cause of cancer death in the female population, despite advances in diagnosis and treatment. The highly heterogeneous nature of the disease represents a major obstacle to successful therapy and results in a significant number of patients developing drug resistance and, eventually, suffering from tumor relapse. Cancer stem cells (CSCs) are a small subset of tumor cells characterized by self-renewal, increased tumor-initiation capacity, and resistance to conventional therapies. As such, they have been implicated in the etiology of tumor recurrence and have emerged as promising targets for the development of novel therapies. Here, we show that the histone demethylase lysine-specific demethylase 1 (LSD1) plays an important role in the chemoresistance of breast cancer cells. Our data, from a series of in vitro and in vivo assays, advocate for LSD1 being critical in maintaining a pool of tumor-initiating cells that may contribute to the development of drug resistance. Combinatory administration of LSD1 inhibitors and anti-cancer drugs is more efficacious than monotherapy alone in eliminating all tumor cells in a 3D spheroid system. In conclusion, we provide compelling evidence that LSD1 is a key regulator of breast cancer stemness and a potential target for the design of future combination therapies.
Galvanic Exchange as a Novel Method for Carbon Nitride Supported CoAg Catalyst Synthesis for Oxygen Reduction and Carbon Dioxide Conversion
Authors: Nazir Roshan , Kumar Anand , Ali Sardar , Saad Mohammed Ali Saleh , Al-Marri Mohammed J.
Published: October 2019

A bimetallic alloy of CoAg nanoparticles (NPs) on a carbon nitride (CN) surface was synthesized using a galvanic exchange process for the oxygen reduction reaction (ORR) and carbon dioxide electrocatalytic conversion. The reduction potential of cobalt is ([Co2+(aq) + 2e− → Co(s)], −0.28 eV) is smaller than that of Ag ([Ag+(aq) + e− → Ag(s)], 0.80 eV), which makes Co(0) to be easily replaceable by Ag+ ions. Initially, Co NPs (nanoparticles) were synthesized on a CN surface via adsorbing the Co2+ precursor on the surface of CN and subsequently reducing them with NaBH4 to obtain Co/CN NP. The Co NPs on the surface of CN were then subjected to galvanic exchange, where the sacrificial Co atoms were replaced by Ag atoms. As the process takes place on a solid surface, only the partial replacement of Co by Ag was possible generating CoAg/CN NPs. Synthesized CoAg/CN bimetallic alloy were characterized using different techniques such as powder x-ray diffraction (PXRD), x-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and electron diffraction spectroscopy (EDS) to confirm the product. Both the catalysts, Co/CN and CoAg/CN, were evaluated for oxygen reduction reaction in 1M KOH solution and carbon dioxide conversion in 0.5 M KHCO3. In the case of ORR, the CoAg/CN was found to be an efficient electrocatalyst with the onset potential of 0.93 V, which is comparable to commercially available Pt/C having Eonset at 0.91 V. In the electrocatalytic conversion of CO2, the CoAg/CN showed better performance than Co/CN. The cathodic current decreased dramatically below −0.9V versus Ag/AgCl indicating the high conversion of CO2.
Simultaneous Optimal Production of Flavonol Aglycones and Degalloylated Catechins from Green Tea Using a Multi-Function Food-Grade Enzyme
Authors: Rha Chan-Su , Kim Shin-Woo , Byoun Kyoung Hee , Hong Yong Deog , Kim Dae-Ok
Published: October 2019

(1) Background: Green tea (GT) contains well-known phytochemical compounds; namely, it is rich in flavan-3-ols (catechins) and flavonols comprising all glycoside forms. These compounds in GT might show better biological activities after a feasible enzymatic process, and the process on an industrial scale should consider enzyme specificity and cost-effectiveness. (2) Methods: In this study, we evaluated the most effective method for the enzymatic conversion of flavonoids from GT extract. One enzyme derived from Aspergillus niger (molecular weight 80–90 kDa) was ultimately selected, showing two distinct but simultaneous activities: intense glycoside hydrolase activity via deglycosylation and weak tannin acyl hydrolase activity via degalloylation. (3) Results: The optimum conditions for producing flavonol aglycones were pH 4.0 and 50 °C. Myricetin glycosides were cleaved 3.7–7.0 times faster than kaempferol glycosides. Flavonol aglycones were produced effectively by both enzymatic and hydrochloride treatment in a time-course reaction. Enzymatic treatment retained 80% (w/w) catechins, whereas 70% (w/w) of catechins disappeared by hydrochloride treatment. (4) Conclusions: This enzymatic process offers an effective method of conditionally producing flavonol aglycones and de-galloylated catechins from conversion of food-grade enzyme.
Biodiesel Production from Castor oil by Two-Step Catalytic Transesterification: Optimization of the Process and Economic Assessment
Authors: Sánchez Nuria , Encinar José María , Nogales Sergio , González Juan Félix
Published: October 2019

The use of biodiesel and the requirement of improving its production in a more efficient and sustainable way are becoming more and more important. In this research work, castor oil was demonstrated to be an alternative feedstock for obtaining biodiesel. The production of biodiesel was optimized by the use of a two-step process. In this process, methanol and KOH (as a catalyst) were added in each step, and the glycerol produced during the first stage was removed before the second reaction. The reaction conditions were optimized, considering catalyst concentration and methanol/oil molar ratio for both steps. A mathematical model was obtained to predict the final ester content of the biodiesel. Optimal conditions (0.08 mol·L−1 and 0.01 mol·L−1 as catalyst concentration, 5.25:1 and 3:1 as methanol/oil molar ratio for first and second step, respectively) were established, taking into account the biodiesel quality and an economic analysis. This type of process allowed cost saving, since the amounts of methanol and catalyst were significantly reduced. An estimation of the final manufacturing cost of biodiesel production was carried out.
The S100A4 Transcriptional Inhibitor Niclosamide Reduces Pro-Inflammatory and Migratory Phenotypes of Microglia: Implications for Amyotrophic Lateral Sclerosis
Authors: Serrano Alessia , Apolloni Savina , Rossi Simona , Lattante Serena , Sabatelli Mario , Peric Mina , Andjus Pavle , Michetti Fabrizio , Carrì Maria Teresa , Cozzolino Mauro , D’Ambrosi Nadia
Published: October 2019

S100A4, belonging to a large multifunctional S100 protein family, is a Ca2+-binding protein with a significant role in stimulating the motility of cancer and immune cells, as well as in promoting pro-inflammatory properties in different cell types. In the CNS, there is limited information concerning S100A4 presence and function. In this study, we analyzed the expression of S100A4 and the effect of the S100A4 transcriptional inhibitor niclosamide in murine activated primary microglia. We found that S100A4 was strongly up-regulated in reactive microglia and that niclosamide prevented NADPH oxidase 2, mTOR (mammalian target of rapamycin), and NF-κB (nuclear factor-kappa B) increase, cytoskeletal rearrangements, migration, and phagocytosis. Furthermore, we found that S100A4 was significantly up-regulated in astrocytes and microglia in the spinal cord of a transgenic rat SOD1-G93A model of amyotrophic lateral sclerosis. Finally, we demonstrated the increased expression of S100A4 also in fibroblasts derived from amyotrophic lateral sclerosis (ALS) patients carrying SOD1 pathogenic variants. These results ascribe S100A4 as a marker of microglial reactivity, suggesting the contribution of S100A4-regulated pathways to neuroinflammation, and identify niclosamide as a possible drug in the control and attenuation of reactive phenotypes of microglia, thus opening the way to further investigation for a new application in neurodegenerative conditions.
Inhibition of Rho-Kinase Downregulates Th17 Cells and Ameliorates Hepatic Fibrosis by Schistosoma japonicum Infection
Authors: Zhou Wei , Yang Yingying , Mei Congjin , Dong Panpan , Mu Shasha , Wu Hongchu , Zhou Yonghua , Zheng Yi , Guo Fukun , Yang Jun-Qi
Published: October 2019

Background: Schistosomiasis is an immunopathogenic disease in which Th17 cells play vital roles. Hepatic granuloma formation and subsequent fibrosis are its main pathologic manifestations and the leading causes of hepatic cirrhosis, and effective therapeutic interventions are lacking. In this study, we explored the effects of fasudil, a selective RhoA–Rho-associated kinase (ROCK) inhibitor, on Th17 cells and the pathogenesis of schistosomiasis. Methods: Mice were infected with Schistosoma japonicum and treated with fasudil. The worm burden, hepatic granuloma formation, and fibrosis were evaluated. The roles of fasudil on Th17, Treg, and hepatic stellate cells were analyzed. Results: Fasudil therapy markedly reduced the granuloma size and collagen deposit in livers from mice infected with S. japonicum. However, fasudil therapy did not affect the worm burden in infected mice. The underlying cellular and molecular mechanisms were investigated. Fasudil suppressed the activation and induced the apoptosis of CD4+ T cells. Fasudil inhibited the differentiation and effector cytokine secretion of Th17 cells, whereas it upregulated Treg cells in vitro. It also restrained the in vivo interleukin (IL)-4 and IL-17 levels in infected mice. Fasudil directly induced the apoptosis of hepatic stellate cells and downregulated the expressions of hepatic fibrogenic genes, such as collagen type I (Col-I), Col-III, and transforming growth factor-1 (TGF-β1). These effects may contribute to its anti-pathogenic roles in schistosomiasis. Conclusions: Fasudil inhibits hepatic granuloma formation and fibrosis with downregulation of Th17 cells. Fasudil might serve as a novel therapeutic agent for hepatic fibrosis due to schistosome infections and perhaps other disorders.
A Mathematical Model of Lysosomal Ion Homeostasis Points to Differential Effects of Cl− Transport in Ca2+ Dynamics
Authors: Astaburuaga Rosario , Quintanar Haro Orlando Daniel , Stauber Tobias , Relógio Angela
Published: October 2019

The establishment and maintenance of ion gradients between the interior of lysosomes and the cytosol are crucial for numerous cellular and organismal functions. Numerous ion transport proteins ensure the required variation in luminal concentrations of the different ions along the endocytic pathway to fit the needs of the organelles. Failures in keeping proper ion homeostasis have pathological consequences. Accordingly, several human diseases are caused by the dysfunction of ion transporters. These include osteopetrosis, caused by the dysfunction of Cl−/H+ exchange by the lysosomal transporter ClC-7. To better understand how chloride transport affects lysosomal ion homeostasis and how its disruption impinges on lysosomal function, we developed a mathematical model of lysosomal ion homeostasis including Ca2+ dynamics. The model recapitulates known biophysical properties of ClC-7 and enables the investigation of its differential activation kinetics on lysosomal ion homeostasis. We show that normal functioning of ClC-7 supports the acidification process, is associated with increased luminal concentrations of sodium, potassium, and chloride, and leads to a higher Ca2+ uptake and release. Our model highlights the role of ClC-7 in lysosomal acidification and shows the existence of differential Ca2+ dynamics upon perturbations of Cl−/H+ exchange and its activation kinetics, with possible pathological consequences.
The Effect of the Indium(III) Phthalocyanine Chloride Films on the Behavior of Flexible Devices of Flat and Disperse Heterojunction
Authors: Sánchez-Vergara María Elena , Carrera-Téllez Raquel , Smith-Ruiz Paulina , Rios Citlalli , Salcedo Roberto
Published: October 2019

By means of flat-heterojunction structures based on small semiconductor molecules (MSCs), an analysis of the indium(III) phthalocyanine chloride (In(III)PcCl) film as a constituent of optoelectronic devices was performed. The study included the behavior of In(III)PcCl playing three different roles: a donor species, an electronic acceptor, and a hole layer carrier. The flat-heterojunction structures were prepared by vacuum deposition method that permits a controlled layer-by-layer growth of high purity films. The investigated structures were characterized by scanning electron microscopy (SEM), Energy-dispersive X-ray spectroscopy (EDS), UV-vis spectroscopy and optical bandgaps were obtained by Tauc’s and Cody’s methods. As the structures exhibit a large spectral absorption in the visible range, they were incorporated into flat-heterojunction devices based on flexible and rigid substrates. However, during the synthesis of those structures, the disperse heterojunction arrangement was found and indeed it showed to be more efficient than the initial flat-heterojunction. In order to complement these results, disperse heterojunction arrangement structure as well as its bandgap value were obtained by DFT calculations. Finally, the electronic behavior of both fabricated devices, disperse heterojunction and flat-heterojunction were compared.
Analysis of Paint Flow Pulsations during High-Speed Rotary Bell Atomization
Authors: Oswald Walter , Lauk Jan , Gödeke Lutz , Ehrhard Peter , Willenbacher Norbert
Published: October 2019

High-speed rotary bell atomization is the preeminent coating technique in the automotive industry. It is widely accepted that a narrow droplet size distribution and constant spray are necessary in order to guarantee uniform film thickness and high-quality appearance. This may be deteriorated by paint flow pulsations. So far, however, no studies exist regarding such fluctuations quantitatively for this type of atomizers. We fill this gap using image analysis of high-speed recordings close to the bell edge. We could show that the fundamental pulsation frequency increases linearly with rotational speed. A ratio of pulsation frequency and true rotational speed of about 3 was found, indicating that pulsations were initiated mainly by the three struts of the distributor disc. The coefficient of variation, i.e., the amplitude of fluctuation increased with decreasing liquid volume rate and rotational speed. Beyond that, we could show that the formation of droplets larger than 100 μm, which are assumed to cause paint defects, is promoted by the degree of fluctuation. These findings may stimulate development of bell cups showing less paint flow pulsations.
New, Amino Acid Based Zwitterionic Polymers as Promising Corrosion Inhibitors of Mild Steel in 1 M HCl
Authors: Jafar Mazumder Mohammad A.
Published: October 2019

The zwitterionic monomers, N,N’-diallylamino propanephosphonate and amino acid residual N,N’-diallyl-l-methionine hydrochloride were synthesized, with excellent yields. These monomers were utilized in the preparation of zwitterionic homo and co-cyclopolymers 5–7 in aqueous solution using 2,2′-azobis (2-methylpropionamidine) dihydrochloride as an initiator. The polymers were characterized by FT-IR, NMR, and TGA. The performance of these synthesized polymers on mild steel in acidic solution was investigated by gravimetric method, Tafel extrapolation, linear polarization resistance, and electrochemical impedance spectroscopy. At 313 K, the maximum inhibition efficiencies of corrosion inhibitors 5–7 at 4.50 × 10−4 mol L−1 were found to be 85.2%, 83.3%, and 99.5%, respectively. The inhibition efficiencies obtained from gravimetric weight loss, potentiodynamic polarization, and electrochemical impedance spectroscopy measurements were in good agreement. Different adsorption isotherms were also explored to find the best fit, and found to obey Langmuir adsorption isotherm. The thermodynamic parameters, such as activation energy (Ea), standard enthalpy of activation (ΔH*), standard entropy of activation (ΔS*), adsorption–desorption equilibrium constant (Kads), and standard free energy of adsorption (ΔGoads), were determined. Electrochemical data indicated that the zwitterionic copolymer 7 acts as a mixed type inhibitor under the influence of anodic control. The surface morphology of mild steel corrosion was evaluated without and with corrosion inhibitors by AFM, SEM-EDX, and XPS, which confirmed the adsorption of inhibitor molecules on the metal surface.