bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustained Clinical Efficacy and Mucosal Healing of Thiopurine Maintenance Treatment in Ulcerative Colitis: A Real-Life Study
Authors: Pugliese Daniela , Aratari Annalisa , Festa Stefano , Ferraro Pietro Manuel , Monterubbianesi Rita , Guidi Luisa , Scribano Maria Lia , Papi Claudio , Armuzzi Alessandro
Published: October 2018

Background and Aims. Thiopurines are commonly used for treating ulcerative colitis (UC), despite the fact that controlled evidence supporting their efficacy is limited. The aim of this study was to evaluate the long-term outcome of thiopurines as maintenance therapy in a large cohort of UC patients. Methods. All UC patients receiving thiopurine monotherapy at three tertiary IBD centers from 1995 to 2015 were identified. The primary endpoint was steroid-free clinical remission. Secondary endpoints were mucosal healing (MH), defined as Mayo endoscopic subscore 0, long-term safety, and predictors of sustained clinical remission. Results. We identified 192 patients, contributing a total of 747 person-years of follow-up (median follow-up 36 months, range 1–210 months). Steroid dependency was the most common indication for thiopurine treatment (58%). Steroid-free remission occurred in 45.3% of patients; 36.3% stopped thiopurines because of treatment failure and 18.2% for adverse events or intolerance. The cumulative probability of maintaining steroid-free remission while on thiopurine treatment was 87%, 76%, 67.6%, and 53.4% at 12, 24, 36, and 60 months, respectively. MH occurred in 57.9% of patients after a median of 18 months (range 5–96). No independent predictors of sustained clinical remission could be identified. Conclusions. Thiopurines represent an effective and safe long-term maintenance therapy for UC patients.
Intuitionistic Unbalanced Linguistic Generalized Multiple Attribute Group Decision Making and Its Application to Green Products Selection
Authors: Han Bing , Tao Zhifu , Chen Huayou , Zhou Ligang
Published: October 2018

In many countries, green products play a critical role in energy recycling and environment protection. The selection of green products can be regarded as a multiple attribute decision making (MADM) problem. Due to the complexity and uncertainty of the problem, decision makers may give their personal preference values to different attributes of alternatives by intuitionistic unbalanced linguistic term sets. The main purpose of this paper is to put forward a new generalized multiple attribute group decision making (GMAGDM) approach based on the intuitionistic unbalanced linguistic dependent weighted generalized Heronian mean (IULDWGHM) operator and the intuitionistic unbalanced linguistic dependent weighted generalized geometric Heronian mean (IULDWGGHM) operator. The proposed method can not only relieve the influence of unfair assessments, but also consider the interaction effects of attributes. Furthermore, the appropriate parameter values and operators can be selected to meet the different risk preference of decision makers and actual requirements. Finally, a green products selection case is given to illustrate the effectiveness and universality of the developed approach.
Electrochemical Analysis of Ultrathin Polythiolsiloxane Films for Surface Biomodification
Authors: Chiang Hao-Chun , Levicky Rastislav
Published: October 2018

The ability of different crosslinkers to crosslink nanometer thick films of the polymer poly(mercaptopropyl)methylsiloxane (PMPMS), thus stabilizing these films on solid supports, was investigated. The four crosslinkers included 1,11-bismaleimidotriethyleneglycol (BM(PEG)3), tris-(2-maleimidoethyl)amine (TMEA), bismaleimidohexane (BMH), and 1,1′-(methylenedi-4,1-phenylene) bismaleimide (BMDPM). PMPMS films treated with the four crosslinkers were compared in the effectiveness of achieved crosslinking, continuity and stability of the films to rearrangement at elevated temperatures, and modification with single-stranded DNA. The results of electrochemical analyses show that more hydrophilic crosslinkers had difficulty reacting fully with PMPMS thiols, even in these nanometer thin layers. This observation highlights the critical importance of selecting crosslinkers that are chemically compatible. Optimal selection of crosslinker yielded films in which the polymer film was largely incapable of rearranging, even at elevated temperatures, yielding reproducible and stable layers. These results validate use of these supports for applications such as monitoring thermal denaturation of immobilized DNA duplexes.
Online Classification of Road Roughness Conditions with Vehicle Unsprung Mass Acceleration by Sliding Time Window
Authors: Li Zhongxing , Yu Wenhao , Cui Xiaoli
Published: October 2018

Suspension control systems are in need for more information of road roughness conditions to improve their performance under different roads. Existing methods of gauging road roughness are limited, and they usually involve visual inspections or special vehicles equipped with instruments that can gauge physical measurements of road irregularities. This paper proposes data collection for a period of a time from accelerometers fixed on unsprung mass and uses the mean square values of this datasets divided by vehicle speed to classify the roughness conditions of a section of a road. This approach is possible due to the existence of relationships between the power spectral densities of the road surface, unsprung mass accelerations via a transfer function, and vehicle speed. This paper gave the relationship between the resolution of road roughness classification and the length of time‐window and suggestions about choosing the appropriate time‐window length on the balance of road roughness resolution and classification delay. Moreover, to enhance the stability of classification, the influence of damping parameters of vehicle suspension on the classification output is studied, and a classification method of road roughness is proposed based on neural network and damping coefficient correction.
Seismic Vulnerability Assessment of Liquid Storage Tanks Isolated by Sliding‐Based Systems
Authors: Tsipianitis Alexandros , Tsompanakis Yiannis
Published: October 2018

Liquid‐filled tanks are effective storage infrastructure for water, oil, and liquefied natural gas (LNG). Many such large‐scale tanks are located in regions with high seismicity. Therefore, very frequently base isolation technology has to be adopted to reduce the dynamic distress of storage tanks, preventing the structure from typical modes of failure, such as elephant‐foot buckling, diamond‐shaped buckling, and roof damage caused by liquid sloshing. The cost‐effective seismic design of base‐isolated liquid storage tanks can be achieved by adopting performance‐based design (PBD) principles. In this work, the focus is given on sliding‐based systems, namely, single friction pendulum bearings (SFPBs), triple friction pendulum bearings (TFPBs), and mainly on the recently developed quintuple friction pendulum bearings (QFPBs). More specifically, the study is focused on the fragility analysis of tanks isolated by sliding‐bearings, emphasizing on isolators’ displacements due to near‐fault earthquakes. In addition, a surrogate model has been developed for simulating the dynamic response of the superstructure (tank and liquid content) to achieve an optimal balance between computational efficiency and accuracy.
Circular Polarization and Wavelength Selective Gratings Based on Holographic Cholesteric Liquid Crystal Templates
Authors: Chin Hsien-Kuo , Kuo Hui-Ying , Zheng Yang-Chen , Lin Jia-De , Lee Chia-Rong
Published: October 2018

Refilling cholesteric liquid crystal (CLC) template gratings with circular polarization, wavelength selectivity, and dual operation mode are first demonstrated. The gratings with template and nontemplate regions are obtained through the two-beam interfering photo-polymerization, washing-out, and refilling procedure. The refilling CLC has different chiral handedness (left or right) and reflection band (at green and red regions). When the wavelength of a probe beam is within the refilled CLC reflection band of the nontemplate region, the device works as an amplitude grating since the sample in the template and nontemplate regions reflects distinct colour region. In addition, the diffraction intensity of the grating can be electrically controlled. Therefore, this CLC-based device can be potentially used in controllable diffraction elements in optics.
Total Mandibular Subapical Alveolar Osteotomy to Correct Class II Division I Dentofacial Deformity
Authors: Cavalcante Rafael Correia , Bergamaschi Isabela Polesi , Sebastiani Aline Monise , Galina Fabiano , Fanderuff Marina , da Costa Delson João , Rebellato Nelson Luis Barbosa , Scariot Rafaela , Klüppel Leandro Eduardo
Published: October 2018

Introduction. Class II division I malocclusions are the most common dentofacial deformities seen in clinical practice. Severe cases or cases in which growth has ceased may require full correction combining orthodontic and surgical treatment. We report a case of a total mandibular subapical alveolar osteotomy, performed to correct a class II division I dentofacial deformity. Case Report. A 19-year-old female patient was referred to the oral and maxillofacial surgery department at the Federal University of Paraná with chin aesthetic complaints as well as class II malocclusion. The proposed treatment was total mandibular subapical alveolar osteotomy, retaining the chin position and eliminating the need for genioplasty, since, although the patient presented with a class II dentofacial deformity, the chin was well positioned. Under general anesthesia, a “V-shaped” incision was conducted from the right retromolar region to the left retromolar region. A ring of cortical bone was removed around the mental foramen, with the aim to create a space around the mental nerve. Fixation was conducted with plates and screws of the 2.0 system. The patient on six-year follow-up showed osteotomy stability, a better overall occlusion, and outcome satisfaction.
Evaluation ofBacillusStrains for Plant Growth Promotion and Predictability of Efficacy byIn VitroPhysiological Traits
Authors: Akinrinlola Rufus J. , Yuen Gary Y. , Drijber Rhae A. , Adesemoye Anthony O.
Published: October 2018

Bacilli are commonly used as plant growth-promoting agents but can be limited in effectiveness to certain crop and soil environments. The objectives of this study were to (1) identifyBacillusstrains that can be consistent in promoting the growth of corn, wheat, and soybean and (2) determine whether physiological traits expressedin vitrocan be predictive of growth promotion efficacy/consistency and be used for selecting effective strains. TwelveBacillusstrains isolated from wheat rhizospheres were evaluated in greenhouse pot tests with nonsterile soil for their effects on the growth of corn, soybean, and wheat. The strains also were assessedin vitrofor multiple physiological traits. All 12 strains increased corn growth significantly compared to the controls. The four most efficacious strains on corn—Bacillus megateriumR181,B. safensisR173,B. simplexR180, andPaenibacillus graminisR200—also increased the growth of soybean and wheat. No set of traits was a predictor of growth promotion efficacy. The number of traits expressed by a strain also was not an indicator of efficacy as strain R200 that was positive for only one trait showed high growth promotion efficacy. Effective strains can be identified through pot tests on multiple crop plants, butin vitrophysiological assays are unreliable for strain selection.
Plants Used as Anticancer Agents in the Ethiopian Traditional Medical Practices: A Systematic Review
Authors: Tuasha Nigatu , Petros Beyene , Asfaw Zemede
Published: October 2018

Background. This systematic review aimed at examining the use patterns of Ethiopian anticancer traditional medicinal plants (MPs) in view of recommending further validation studies. Methods. The information was retrieved from PubMed according to the PRISMA guideline. The electronic library of Addis Ababa University and relevant church‐based religious books were also inspected for additional data. Results. From 34 studies meeting specific inclusion/exclusion criteria, 119 anticancer MP species distributed in 98 genera and 57 families were recorded. Fabaceae (10.92 %) and Euphorbiaceae (10.08 %) were the most widely used families. Plumbago zeylanica (Plumbaginaceae) was the most frequently used anticancer MP species. Shrubs (42.02 %) and herbs (35.29 %) were dominant growth forms. About 89.08 % of the MPs were collected from wild habitats. Leaves (33.73 %) and roots (27.11 %) were the most frequently harvested parts. The most favored routes were dermal (33.33 %) and oral (29.25 %). About 87.07 % preparations were made from fresh plant materials. Breast cancer and skin cancer were treated with 14 % and 10.76 % of anticancer MPs, respectively. Conclusion. The review showed that anticancer MPs are widely used across the regions of Ethiopia. Most of the MPs are not scientifically experimented and yet are at a higher vulnerability to loss mainly by human activities. Calling for conservation measures, we recommend experimental validation of the frequently used anticancer MPs. This augments global anticancer drug researches.
Decoupling Optimization Design of Under‐Chassis Equipment Suspension System in High‐Speed Trains
Authors: Xia Zhanghui , Gong Dao , Zhou Jinsong , Sun Wenjing , Sun Yu
Published: October 2018

The vibrations of high‐speed trains may strongly affect the safety and ride comfort of passengers, which issue requires the damping optimization of under‐chassis equipment (UCE). In this study, the natural frequency of UCE is determined via the dynamic vibration absorber theory. The performed investigation of UCE‐car body system vibration behavior revealed that an eccentricity of UCE results in the coupling vibration in six degrees of freedom, which leads to significant changes in its vibration mode and frequency. Thus, the natural frequency of UCE deviates from the initially determined value, which implies that the vibration damping effect is weakened. In this study, two decoupling optimization design methods, namely, forward and inverse decoupling methods, are proposed to solve this problem. The analysis of results obtained proves the feasibility of the proposed methods, which yield favorable decoupling degrees for the UCE vibration modes and minimize the offset of the vibration mode frequency from the initial natural one. These methods are considered quite instrumental in the improvement of vibration damping effect for high‐speed trains.
Analysis of Static Narrowband On-Body Channel Polarization Distribution at 2.4 GHz
Authors: Liu Lingfeng , Zhang Peng , Wang Xiaonan , Zhang Xiaoyan , Jiang Nan
Published: October 2018

The polarization of on-body propagation channels has shown significant spatial selectivity and full-space distribution in numerous measurements due to the near-field characteristics and strong body scattering effect. To get a comprehensive image of such polarization distribution, in this work, we measured polarized on-body channels on static body at 2.4 GHz by monopole antennas, where standing and sitting postures are included. The polarization of the measured on-body antennas covers the full-space in Z-, H-, and V-direction relative to the skin of the body. Consequently, an extended cross-polarization discrimination (XPD) is also proposed to describe the depolarization and copolarization in the measurements. In the statistical characteristics of the channels, the V-polarization direction of the receiving antenna is more conducive for receiving signal and reducing the path losses. The results show that strong depolarization of on-body channels is more easily caused in sitting posture due to scattering effects from the legs. Simplified finite-difference-time-domain (FDTD) simulations are conducted to investigate the field polarization distribution of point sources on a static torso in cylindrical shape. The simulation results are in general consistent with the analysis of measured on-body channels.
3D Thermal Finite Element Analysis of the SLM 316L Parts with Microstructural Correlations
Authors: He Ketai , Zhao Xue
Published: October 2018

In this study, a multitrack and multilayer finite element model was developed to simulate the temperature field and molten pool contours during selective laser melting (SLM) of 316L stainless steel powder under different scanning strategies. The simulated temperature field and its evolution over time were compared with experimental measurement results. Furthermore, a correlation was established by the presented results between the predicted thermal behavior and the microstructure of SLM specimens. It was found that the maximum temperature of the molten pool rose slightly with the increase of scanning tracks, but when laser scanned multilayer, the maximum temperature rose first and then decreased. There are large columnar crystals in molten pools, growing in the direction of the maximum temperature gradient. The microstructure defects are more likely to occur at the bonding regions between adjacent layers and islands, where the heat and stress are concentrated. Moreover, the results also showed that the scanning strategy affects the microstructure and microhardness. Also, the SLM 316L parts under the S‐shaped strategy had finer grains and a higher Vicker hardness than that formed under the island strategy.
Couple‐Group Consensus: A Class of Delayed Heterogeneous Multiagent Systems in Competitive Networks
Authors: Ji Lianghao , Zhang Yue , Jiang Yiliu
Published: October 2018

This paper discusses the couple‐group consensus issues of a class of heterogeneous multiagent systems containing first‐order and second‐order dynamic agents under the influence of both input and communication delays. In distinction to the existing works, a novel distributed coordination control protocol is proposed which is not only on the foundation of the competitive interaction between the agents but also has no virtual velocity estimation in the first‐order dynamics. Furthermore, without the restrictive assumptions existing commonly in the related works, several sufficient algebraic criteria are established for the heterogeneous systems to realize couple‐group consensus asymptotically. The obtained conclusions show that the achievement of the systems’ couple‐group consensus intimately relates to the coupling weights between the agents, the systems control parameters, and the input time delays of the agents, while communication time delays between the agents are irrelevant to it. Finally, several simulations are illustrated to verify the effectiveness of the obtained theoretical results.
When Collective Knowledge Meets Crowd Knowledge in a Smart City: A Prediction Method Combining Open Data Keyword Analysis and Case-Based Reasoning
Authors: Kwon Ohbyung , Kim Yun Seon , Lee Namyeon , Jung Yuchul
Published: October 2018

One of the significant issues in a smart city is maintaining a healthy environment. To improve the environment, huge amounts of data are gathered, manipulated, analyzed, and utilized, and these data might include noise, uncertainty, or unexpected mistreatment of the data. In some datasets, the class imbalance problem skews the learning performance of the classification algorithms. In this paper, we propose a case-based reasoning method that combines the use of crowd knowledge from open source data and collective knowledge. This method mitigates the class imbalance issues resulting from datasets, which diagnose wellness levels in patients suffering from stress or depression. We investigate effective ways to mitigate class imbalance issues in which the datasets have a higher proportion of one class over another. The results of this proposed hybrid reasoning method, using a combination of crowd knowledge extracted from open source data (i.e., a Google search, or other publicly accessible source) and collective knowledge (i.e., case-based reasoning), were that it performs better than other traditional methods (e.g., SMO, BayesNet, IBk, Logistic, C4.5, and crowd reasoning). We also demonstrate that the use of open source and big data improves the classification performance when used in addition to conventional classification algorithms.
A Fluid-Solid-Magnetic Coupling Algorithm of Internal Crack Growth in the Weld of Oil and Gas Pipelines
Authors: Cui Wei , Song Rixuan , Xia Fafeng , Zhang Qiang , Wang Peter
Published: October 2018

In order to characterize the dynamic process of the crack growth in the weld of oil and gas pipelines, a mathematical model of fluid-solid-magnetic multifield coupling was constructed in this paper. Based on this model, the bidirectional fluid-solid coupling and unidirectional magnetic structure coupling caused by the weld deformation were achieved by dynamic application of the fluid permeation pressure, calculating the internal crack growth in the pipe weld, reconstructing the computational grid near the internal crack, and discussing the characteristics of the magnetic leakage field in the process of the internal crack growth in pipe weld. Thus, a fluid-solid-magnetic coupling algorithm for the internal crack growth in pipe welds considering fluid permeation pressure is established. According to the characteristics of the internal crack opening distance, internal crack growth length, crack tip energy release rate, peak values of magnetic induction intensity level, and vertical component, the process of the internal crack growth is measured. The results show that the fluid osmotic pressure accelerates the process of the internal crack growth and this algorithm can solve the problem of the characterization and evaluation of crack growth in pipe welds under fluid-solid-magnetic coupling action.
A Multiobjective Optimization for Train Routing at the High-Speed Railway Station Based on Tabu Search Algorithm
Authors: Feng Ziyan , Cao Chengxuan , Liu Yutong , Zhou Yaling
Published: October 2018

This paper focuses on the train routing problem at a high-speed railway station to improve the railway station capacity and operational efficiency. We first describe a node-based railway network by defining the turnout node and the arrival-departure line node for the mathematical formulation. Both considering potential collisions of trains and convenience for passengers’ transfer in the station, the train routing problem at a high-speed railway station is formulated as a multiobjective mixed integer nonlinear programming model, which aims to minimize trains’ departure time deviations and total occupation time of all tracks and keep the most balanced utilization of arrival-departure lines. Since massive decision variables for the large-scale real-life train routing problem exist, a fast heuristic algorithm is proposed based on the tabu search to solve it. Two sets of numerical experiments are implemented to demonstrate the rationality and effectiveness of proposed method: the small-scale case confirms the accuracy of the algorithm; the resulting heuristic proved able to obtain excellent solution quality within 254 seconds of computing time on a standard personal computer for the large-scale station involving up to 17 arrival-departure lines and 46 trains.
Impaired GABA Neural Circuits Are Critical for Fragile X Syndrome
Authors: Gao Fei , Qi Lijun , Yang Zhongzhen , Yang Tao , Zhang Yan , Xu Hui , Zhao Huan
Published: October 2018

Fragile X syndrome (FXS) is an inheritable neuropsychological disease caused by silence of the fmr1 gene and the deficiency of Fragile X mental retardation protein (FMRP). Patients present neuronal alterations that lead to severe intellectual disability and altered sleep rhythms. However, the neural circuit mechanisms underlying FXS remain unclear. Previous studies have suggested that metabolic glutamate and gamma-aminobutyric acid (GABA) receptors/circuits are two counter-balanced factors involved in FXS pathophysiology. More and more studies demonstrated that attenuated GABAergic circuits in the absence of FMRP are critical for abnormal progression of FXS. Here, we reviewed the changes of GABA neural circuits that were attributed to intellectual-deficient FXS, from several aspects including deregulated GABA metabolism, decreased expressions of GABA receptor subunits, and impaired GABAergic neural circuits. Furthermore, the activities of GABA neural circuits are modulated by circadian rhythm of FMRP metabolism and reviewed the abnormal condition of FXS mice or patients.
Thermodynamics of Modified Cosmic Chaplygin Gas
Authors: Sharif M. , Ashraf Sara
Published: October 2018

We examine the thermodynamic features of an exotic fluid known as modified cosmic Chaplygin gas in the context of homogeneous isotropic universe model. For this purpose, the behavior of physical parameters is discussed that help to analyze nature of the universe. Using specific heat formalism, the validity of third law of thermodynamics is checked. Furthermore, with the help of thermodynamic entities, the thermal equation of state is also discussed. The thermodynamic stability is explored by means of adiabatic, specific heat and isothermal conditions from classical thermodynamics. It is concluded that the considered fluid configuration is thermodynamically stable and expands adiabatically for an appropriate choice of parameters.
Analytical Solution for One-Dimensional Consolidation of Soil with Exponentially Time-Growing Drainage Boundary under a Ramp Load
Authors: Sun Ming , Zong Meng-fan , Ma Shao-jun , Wu Wen-bing , Liang Rong-zhu
Published: October 2018

By introducing the exponentially time-growing drainage boundary, this paper investigated the one-dimensional consolidation problem of soil under a ramp load. Firstly, the one-dimensional consolidation equations of soil are established when there is a ramp load acting on the soil surface. Then, the analytical solution of excess pore water pressure and consolidation degree is derived by means of the method of separation of variables and the integral transform technique. The rationality of this solution is also verified by comparing it with other existing analytical solutions. Finally, the consolidation behavior of soil is studied in detail for different interface parameters or loading scheme. The results show that the exponentially time-growing drainage boundary can reflect the phenomenon that the excess pore water pressure at the drainage boundaries dissipates smoothly rather than abruptly from its initial value to the value of zero. By adjusting the values of interface parametersbandc, the presented solution can be degraded to Schiffman’s solution, which can compensate for the shortcoming that Terzaghi’s drainage boundary can only consider the two extreme cases of fully pervious and impervious boundaries. The significant advantage of the exponentially time-growing drainage boundary is that it can be applied to describe the asymmetric drainage characteristics of the top and bottom drainage surfaces of the actual soil layer by choosing the appropriate interface parametersbandc.
Cytotoxicity Evaluation of Ammonia-Modified Graphene Oxide Particles in Lung Cancer Cells and Embryonic Stem Cells
Authors: Keremidarska-Markova Milena , Hristova-Panusheva Kamelia , Andreeva Tonya , Speranza Giorgio , Wang Dayong , Krasteva Natalia
Published: October 2018

Potential toxicity of graphene oxide (GO) is a subject of increasing research interest in the recent years. Here, we have evaluated the cytotoxicity of ammonia-modified GO (GO-NH2) and pristine GO particles in human lung cancer cells, A549 and embryonic stem cells, Lep3 exposed to different particles concentrations (0.1, 1, 10, 20, and 50 μg/ml) for different times (24 and 48h). Compared with GO, GO-NH2 particles possessed smaller size, positive surface charge and higher thickness. An increased propensity to aggregation in cell cultures was also found for GO-NH2 particles. Cytotoxicity evaluation revealed that GO-NH2 particles are more toxic than pristine GO. Applied at concentrations of 10, 20 and 50 μg/ml for 24h they affect significantly cell morphology of viable embryonic stem cells whereas human lung cancer A549 cells seem to be relatively more resistant to short-time exposure. After 48h exposure however cell proliferation of A549 cells was strongly suppressed in a dose-dependent manner while the proliferation ability of embryonic stem cells was not affected. These results suggested that both GO particles exert different degree of cytotoxicity which is time, dose and cell dependent. In general, ammonia-modified GO particles are more toxic than the pristine GO which should be taken into account for future biomedical applications.
Haar Wavelet Method for Nonlinear Vibration of Functionally Graded CNT‐Reinforced Composite Beams Resting on Nonlinear Elastic Foundations in Thermal Environment
Authors: Fan Jianyu , Huang Jin
Published: October 2018

This paper presents a simple and effective approach based on the Haar wavelet discretization method (HWDM) for the nonlinear vibration analysis of carbon nanotube‐reinforced composite (CNTRC) beams resting on a nonlinear elastic foundation in a thermal environment. Material properties are assumed to be functionally graded (FG) in the thickness direction and temperature‐dependent and are evaluated through the extended rule of mixture. Based on the first‐order shear deformation beam theory in conjunction with the von Kármán nonlinearity, the nonlinear governing equations of CNTRC beams on nonlinear elastic foundations are derived as well as the related boundary conditions. Moreover, the initial thermal stress due to uniform temperature rise is considered in this study. To evaluate the nonlinear natural frequencies, the obtained equations are discretized into a set of nonlinear algebraic equations through HWDM and then the direct iteration technique is employed to solve the resulting algebraic equations. The convergence and comparison studies are carried out, and the results indicate that the numerical rate of convergence of the proposed method is in agreement with the convergence theorem, and good accuracy of the present results is observed. Studies on the effects of different parameters such as CNT volume fraction, distribution type of CNTs, foundation stiffness coefficients, boundary condition, slenderness ratio, temperature rise, and initial thermal stress on the linear frequencies and the nonlinear frequency ratios are also reported. This study offers an insight into the vibration behaviors of CNTRC beams resting on nonlinear elastic foundation subjected to the uniform temperature rise.
mTORC1/2 and Protein Translation Regulate Levels of CHK1 and the Sensitivity to CHK1 Inhibitors in Ewing Sarcoma Cells
Authors: Koppenhafer Stacia L. , Goss Kelli L. , Terry William W. , Gordon David J.
Published: October 2018

The treatment of Ewing sarcoma has changed very little in the past two decades and novel treatment approaches are needed. We recently identified that Ewing sarcoma cells are uniquely vulnerable to inhibitors of ribonucleotide reductase (RNR), the rate-limiting enzyme in the synthesis of deoxyribonucleotides. We subsequently found that the inhibition of checkpoint kinase 1 (CHK1) increases the sensitivity of Ewing sarcoma cells to inhibitors of RNR, such as gemcitabine. However, Ewing sarcoma cells exhibit high levels of the CHK1 protein, which may represent an adaptive response to elevated levels of endogenous DNA replication stress. Consequently, we began this work with the aim of determining the impact of CHK1 levels on drug sensitivity, as well as identifying the mechanisms and pathways that regulate CHK1 levels in Ewing sarcoma cells. In this report, we show that the high levels of the CHK1 protein in Ewing sarcoma cells limit the efficacy of CHK1 inhibitors. However, inhibition of mTORC1/2 activates the translational repressor 4E-BP1, reduces protein synthesis, and decreases levels of the CHK1 protein in Ewing sarcoma cells. Similarly, we identified that the CHK1 inhibitor prexasertib also activates 4E-BP1, inhibits protein synthesis, and reduces CHK1 protein levels in Ewing sarcoma cells. Moreover, the combination of prexasertib and gemcitabine was synergistic in vitro, caused tumor regression in vivo, and significantly prolonged mouse survival in a Ewing sarcoma xenograft experiment. Overall, our results provide insight into Ewing sarcoma biology and support further investigation of the CHK1 pathway as a therapeutic target in Ewing sarcoma tumors.
Association of Imatinib Plasma Concentration and Single-nucleotide Polymorphisms with Adverse Drug Reactions in Patients with Gastrointestinal Stromal Tumors
Authors: Zhang Qiang , Xu Jianghao , Qian Yi , Chen Liang , Li Qingya , Xu Kangjing , Chen Ming , Sun Luning , He Zhongyuan , Yang Li , Zhang Diancai , Wang Linjun , Sun Xiaofeng , Wang Yongqing , Xu Hao , Xu Zekuan
Published: October 2018

Gastrointestinal stromal tumors (GIST) are the most prevalent mesenchymal tumors of the digestive tract. To investigate the association of imatinib mesylate plasma concentration with adverse drug reactions (ADRs) and influences of genetic polymorphisms on ADRs in GIST patients taking imatinib, a cohort of GIST patients consecutively treated with imatinib were included in the observational study. Clinical, pathologic and genotype information was recorded at enrollment and blood samples were collected at time as design. The plasma concentration of the imatinib was detected by LC-MS/MS. A questionnaire was used to evaluate the ADRs at each visit. SNPs in 13 genes were analyzed for a possible association with ADRs. The mean plasma trough concentration of 129 patients taking imatinib was 1.45 ± 0.79 μg/ml, average peak concentration was 2.63 ± 1.07 μg/ml. The imatinib concentration in patients treated with 600 mg/day was significantly higher than other dosage groups (P < 0.05). The ADRs were mostly mild. Edema, vomiting, and fatigue were significantly correlated with imatinib concentration (P < 0.05). Mutations of IL13 rs1800925 and CXCL14 rs7716492 were related with the incidence of leukopenia and rash in our research, separately (P < 0.05). We confirmed that with the increase of imatinib concentration, the incidence of edema, vomiting, and fatigue rises as well. Mutations of IL13 rs1800925 and CXCL14 rs7716492 may be the promising biomarkers to predict the ADRs of imatinib. The results of the study are of guiding significance for the use of imatinib in patients with GIST.
A Human Ribonuclease Variant and ERK-Pathway Inhibitors Exhibit Highly Synergistic Toxicity for Cancer Cells
Authors: Hoang Trish T. , Tanrikulu I. Caglar , Vatland Quinn A. , Hoang Trieu M. , Raines Ronald T.
Published: October 2018

Pancreatic-type ribonucleases (ptRNases) are prevalent secretory enzymes that catalyze the cleavage of RNA. Ribonuclease inhibitor (RI) is a cytosolic protein that has femtomolar affinity for ptRNases, affording protection from the toxic catalytic activity of ptRNases, which can invade human cells. A human ptRNase variant that is resistant to inhibition by RI is a cytotoxin that is undergoing a clinical trial as a cancer chemotherapeutic agent. We find that the ptRNase and protein kinases in the ERK pathway exhibit strongly synergistic toxicity toward lung cancer cells (including a KRASG12C variant) and melanoma cells (including BRAFV600E variants). The synergism arises from inhibiting the phosphorylation of RI and thereby diminishing its affinity for the ptRNase. These findings link seemingly unrelated cellular processes, and suggest that the use of a kinase inhibitor to unleash a cytotoxic enzyme could lead to beneficial manifestations in the clinic.
Zone Formation of Lymphocyte Infiltration at Invasive Front as a Biomarker of Prognosis in Endometrial Carcinomas
Authors: Miyamoto Morikazu , Takano Masashi , Tsuda Hitoshi , Matuura Hiroko , Aoyama Tadashi , Soyama Hiroaki , Kato Kento , Iwahashi Hideki , Ishibashi Hiroki , Yoshikawa Tomoyuki , Suzuki Ayako , Hirata Junko , Furuya Kenichi
Published: October 2018

Objective: The clinical significance of lymphocyte infiltration (LI) at the invasive front in endometrial carcinomas (EC) has not been determined. The aim of the current study was to evaluate the association between zone formation of LI at the invasive front of the tumor margin and prognoses of the patients with EC. Methods: All available pathological slides of the enrolled cases were reviewed, and the degree of LI at the invasive front was categorized into 2 groups: strong LI and weak LI. Clinical significance of LI was evaluated retrospectively. Results: A total of 333 cases with EC were enrolled in the study: 225 cases with weak LI and 108 cases with strong LI. Weak LI was more frequently observed in the patients with grade1/2 endometrioid EC. Multivariate analyses for progression-free survival (PFS) and overall survival (OS) revealed that weak LI was identified as an independent worse prognostic factor for OS (p = 0.004) in addition to PFS (p = 0.022). Conclusion: Weak LI at the invasive front of the tumor margin was associated with worse prognoses in EC. Although further studies are needed, it is suggested that LI could be a biomarker of prognoses in EC.
Risky Alcohol Use: The Impact on Health Service Use
Authors: Miquel Laia , Manthey Jakob , Rehm Jürgen , Vela Emili , Bustins Montserrat , Segura Lidia , Vieta Eduard , Colom Joan , Anderson Peter , Gual Antoni
Published: October 2018

Objective: To examine health services use on the basis of alcohol consumption. Material and Methods: A cross-sectional study was carried out on patients visiting the Primary Health Care (PHC) settings in Catalonia during 2011 and 2012; these patients had a history of alcohol consumption. Information about outpatient visits in the PHC setting, hospitalizations, specialists’ visits and emergency room visits for the year 2013 was obtained from 2 databases (the Information System for the Development of Research in PHC and the Catalan Health Surveillance System). Risky drinkers were defined as those who consumed more than 280 g per week for men or more than 170 g per week for women, or any amount of alcohol while being involved in a high risk work activity, or taking medication that significantly interferes with alcohol or when being pregnant. Binge drinkers (> 60 g in men or > 50 g in women in a short amount of time more than once a month) were also considered risky drinkers. Results: A total of 606,948 patients reported consuming alcohol (of which 10.5% were risky drinkers). Risky drinkers were more likely to be admitted to hospitals or emergency departments (range of ORs 1.08–1.18) compared to light drinkers. Male risky drinkers used fewer PHC services than male light drinkers (OR 0.89, 95% CI 0.87–0.92). In general, risky alcohol users used services more and had longer hospital stays. When stratifying by socioeconomic level of the residential area, we found that risky drinking failed significance, while current or past cigarette smoking was associated with higher healthcare use. Conclusions: Risky drinkers use more expensive services, such as hospitals and emergency rooms, but not PHC services, which may suggest that prevention strategies and alcohol interventions should also be implemented in those settings.
Upregulation of P21-Activated Kinase 1 (PAK1)/CREB Axis in Squamous Non-Small Cell Lung Carcinoma
Authors: Chung Jae Heun , Kim Dae Hyun , Kim Yun Seong , Son Bong Soo , Kim Dohyung , Hwang Chungsu , Shin Donghoon , Noh Sang Gyun , Han Jun Hee , Kim Dae Kyung , Kim Jae Ho , Koo Ja Seok , Chung Hae Young , Yoon Seong Hoon
Published: October 2018

Background/Aims: p21-activated Ser/Thr kinase 1 (PAK1) is essential for the genesis and development of many cancers. The purpose of this study was to investigate the role of the PAK1–cyclic AMP response element-binding (CREB) axis in non-small cell lung cancer (NSCLC) tumorigenesis and its related mechanisms. Methods: Western blot assay and immunohistochemical staining were employed to investigate the PAK1 and CREB expression in the tissue microarray of human squamous NSCLC. Co-immunoprecipitation and immunofluorescence confocal assays were performed to determine the link between PAK1 and CREB. NSCLC xenograft models were used to study oncogenic function of PAK1 in vivo. Results: We observed that PAK1 and CREB expression levels were significantly elevated in human squamous NSCLC-tissue specimens, compared with those in adjacent normal bronchial or bronchiolar epithelial-tissue specimens, as well as their phosphorylated forms, based on western blotting. We showed in vitro that PAK1 knockdown by small-interfering RNA (siRNA) blocked CREB phosphorylation, whereas plasmid-based PAK1 overexpression resulted in CREB phosphorylation at Ser133, based on western blotting. In addition, PAK1 interacted with CREB in co-immunoprecipitation assays. Additionally, our in vitro findings detected by flow cytometry revealed that PAK1 silencing attenuated cell cycle progression, inducing apoptosis. Inhibition of PAK1 expression reduced tumor sizes and masses by modulating CREB expression and activation in xenograft models. Conclusion: These results suggest a novel mechanism whereby the PAK1–CREB axis drives carcinogenesis of squamous-cell carcinomas, and have important implications in the development of targeted therapeutics for squamous-cell lung cancer.
Proteasome Biology Is Compromised in White Matter After Asphyxic Cardiac Arrest in Neonatal Piglets
Authors: Santos Polan T. , O'Brien Caitlin E. , Chen May W. , Hopkins C. Danielle , Adams Shawn , Kulikowicz Ewa , Singh Rashmi , Koehler Raymond C. , Martin Lee J. , Lee Jennifer K.
Published: October 2018

Background

Neurological deficits in hypoxic‐ischemic encephalopathy, even with therapeutic hypothermia, are partially attributed to white matter injury. We theorized that proteasome insufficiency contributes to white matter injury.

Methods and Results

Neonatal piglets received hypoxia‐ischemia (
HI
) or sham procedure with normothermia, hypothermia, or hypothermia+rewarming. Some received a proteasome activator drug (oleuropein) or white matter–targeted, virus‐mediated proteasome knockdown. We measured myelin oligodendrocyte glycoprotein, proteasome subunit 20S (P20S), proteasome activity, and carbonylated and ubiquitinated protein levels in white matter and cerebral cortex.
HI
reduced myelin oligodendrocyte glycoprotein levels regardless of temperature, and myelin oligodendrocyte glycoprotein loss was associated with increased ubiquitinated and carbonylated protein levels. Ubiquitinated and carbonyl‐damaged proteins increased in white matter 29 hours after
HI
during hypothermia to exceed levels at 6 to 20 hours. In cortex, ubiquitinated proteins decreased. Ubiquitinated and carbonylated protein accumulation coincided with lower P20S levels in white matter; P20S levels also decreased in cerebral cortex. However, proteasome activity in white matter lagged behind that in cortex 29 hours after
HI
during hypothermia. Systemic oleuropein enhanced white matter P20S and protected the myelin, whereas proteasome knockdown exacerbated myelin oligodendrocyte glycoprotein loss and ubiquitinated protein accumulation after
HI
. At the cellular level, temperature and
HI
interactively affected macroglial P20S enrichment in subcortical white matter. Rewarming alone increased macroglial P20S immunoreactivity, but this increase was blocked by
HI
.

Conclusions

Oxidized and ubiquitinated proteins accumulate with
HI
‐induced white matter injury. Proteasome insufficiency may drive this injury. Hypothermia did not prevent myelin damage, protect the proteasome, or preserve oxidized and ubiquitinated protein clearance after
HI
.
Underutilization of Evidence‐Based Smoking Cessation Support Strategies Despite High Smoking Addiction Burden in Peripheral Artery Disease Specialty Care: Insights from the International PORTRAIT Registry
Authors: Patel Krishna K. , Jones Philip G. , Ellerbeck Edward F. , Buchanan Donna M. , Chan Paul S. , Pacheco Christina M. , Moneta Gregory , Spertus John A. , Smolderen Kim G.
Published: October 2018

Background

Smoking is the most important risk factor for peripheral artery disease (
PAD
). Smoking cessation is key in
PAD
management. We aimed to examine smoking rates and smoking cessation interventions offered to patients with
PAD
consulting a vascular specialty clinic; and assess changes in smoking behavior over the year following initial visit.

Methods and Results

A total of 1272 patients with
PAD
and new or worsening claudication were enrolled at 16 vascular specialty clinics (2011–2015, PORTRAIT (Patient‐Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) registry). Interviews collected smoking status and cessation interventions at baseline, 3, 6, and 12 months. Among smokers, transition state models analyzed smoking transitions at each time point and identified factors associated with quitting and relapse. On presentation, 474 (37.3%) patients were active, 660 (51.9%) former, and 138 (10.8%) never smokers. Among active smokers, only 16% were referred to cessation counseling and 11% were prescribed pharmacologic treatment. At 3 months, the probability of quitting smoking was 21%; among those continuing to smoke at 3 months, the probability of quitting during the next 9 months varied between 11% and 12% (
P
<0.001). The probability of relapse among initial quitters was 36%. At 12 months, 72% of all smokers continued to smoke.

Conclusions

More than one third of patients with claudication consulting a
PAD
provider are active smokers and few received evidence‐based cessation interventions. Patients appear to be most likely to quit early in their treatment course, but many quickly relapse and 72% of all patients smoking at baseline are still smoking at 12 months. Better strategies are needed to provide continuous cessation support.

Clinical Trial Registration

URL
:
https://www.clinicaltrials.gov
. Unique identifier:
NCT
01419080.
Secular Rule and Islamic Ethics: Engaging with Muslim-Only Marriages in the Netherlands
Authors: Moors Annelies , de Koning Martijn , Vroon-Najem Vanessa
Published: October 2018

From the mid-2000s, Dutch policy makers, the media, and others have started to define Muslim-only marriages as a problem. This contribution unpacks a recent hype, when a Dutch TV station broadcasted the conclusion of a polygamous marriage at a mosque, while simultaneously the largest right-wing political party presented an initiative to further criminalize Muslim-only marriages. In both the TV program and the policy initiative, the same feminist organization, Femmes for Freedom, was involved. Using liberal arguments such as freedom of partner choice to limit the freedom of a religious minority, interestingly, the dividing lines were neither between Muslims and non-Muslims, nor between more ‘mainstream’ and more ‘Salafi-oriented’ mosques. Arguing for the need to protect women, many supported the current Dutch law demanding that couples conclude a civil marriage prior to a religious marriage, as the former would protect women better, while others called for better educating Muslims about women’s rights in Islam. Whereas the voices of women in Muslim-only marriages were not heard, our research with converts entering into polygamous marriages indicates that they may opt for these marriages themselves with their main concerns centering on the equal treatment of wives and men’s openness about polygamy.