bluuebunny/crossref_metadata_2025 huggingface dataset:
Tool Wear Detection Using Lipschitz Exponent and Harmonic Wavelet
Authors: Wanqing Song , Qing Li , Yuming Wang
Published: November 2013

The paper researches a novel engineering application of Lipschitz exponent function and harmonic wavelet for detecting tool condition. Tool wear affects often the quality grade of products and is gradually formed during cutting process. Meanwhile, since cutting noise is very strong, we think tool wear belongs to detecting weak singularity signals in strong noise. It is difficult to obtain a reliable worn result by raw sampled data. We propose singularity analysis with harmonic wavelet for data processing and a new concept of Lipschitz exponent function. The method can be quantitative tool condition and make maintaining decision. Test result was validated with 27 kinds of cutting conditions with the sharp tool and the worn tool; 54 group data are sampled by acoustic emission (AE).
Flame‐Made Pt‐Loaded TiO2 Thin Films and Their Application as H2 Gas Sensors
Authors: Chomkitichai Weerasak , Ninsonthi Hathaithip , Liewhiran Chaikarn , Wisitsoraat Anurat , Sriwichai Saengrawee , Phanichphant Sukon
Published: November 2013

The hydrogen gas sensors were developed successfully using flame‐made platinum‐loaded titanium dioxide (Pt‐loaded TiO2) nanoparticles as the sensing materials. Pt‐loaded TiO2 thin films were prepared by spin‐coating technique onto Al2O3 substrates interdigitated with Au electrodes. Structural and gas‐sensing characteristics were examined by using scanning electron microscopy (SEM) and showed surface morphology of the deposited film. X‐ray diffraction (XRD) patterns can be confirmed to be the anatase and rutile phases of TiO2. High‐resolution transmission electron microscopy (HRTEM) showed that Pt nanoparticles deposited on larger TiO2 nanoparticles. TiO2 films loaded with Pt nanoparticles were used as conductometric sensors for the detection of H2. The gas sensing of H2 was studied at the operating temperatures of 300, 350, and 400°C in dry air. It was found that 2.00 mol% Pt‐loaded TiO2 sensing films showed higher response towards H2 gas than the unloaded film. In addition, the responses of Pt‐loaded TiO2 films at all operating temperatures were higher than that of unloaded TiO2 film. The response increased and the response time decreased with increasing of H2 concentrations.
Routing in Duty-Cycled Surveillance Sensor Networks
Authors: Shen Zhong , Zhang Peng
Published: November 2013

In many surveillance sensor networks, sensors are scheduled to work in a duty-cycled mode (i.e., periodically switching between active states and sleeping states) in order to prolong the network lifetime. The duty-cycled mode saves sensors' energy but brings other issues. In surveillance applications (e.g., forest fire alarm or intruder detection), it is desired to report detected events to the sink node as soon as possible. However, the duty-cycled mode may increase the data delivery latency. In this paper, we study minimum-delay routing in duty-cycled surveillance sensor networks. As the minimum-delay routes are time dependent (i.e., they change with time) in duty-cycled sensor networks, routing becomes a challenging task. We propose a distributed routing algorithm to find the minimum-delay routes at any time from all nodes to the sink node. Further, all minimum-delay routes can be found in one execution of our routing algorithm. We further provide a distributed route maintenance algorithm for finding the minimum-delay routes when the network dynamically changes. We theoretically prove the correctness of the proposed algorithm, and extensive simulation results show that the performance of our algorithm outperforms other existing algorithms.
Supervising Control for Unmanned Aerial Vehicles
Authors: Sarwar Saeed ur Rehman , Rehman Saeed ur
Published: November 2013

A small UAV is considered as a test UAV, and its already published aerodynamic data is used for its modeling. Proportional Integral Differential (PID) controller is designed for pitch attitude control. Atmospheric disturbances such as wind shear and turbulence significantly influence the attitude of UAVs. For this study rotary gust is considered as atmospheric disturbance. Pitch response in presence of atmospheric disturbance is presented. In order to improve the performance in presence of atmospheric disturbance, a supervisory mechanism is proposed. Supervisory mechanism is composed of two modules, “observer module” and “correction generator module.” The human thinking like logic is developed for observer module so that it keeps monitoring the status of flight through specified inputs and outputs from the system and instructs the correction generator module to augment main controller by adding compensation commands. Correction generator module works on fuzzy logic. Simulation results show significant reduction in pitch errors after augmenting the supervisory mechanism, hence proving the efficacy of proposed scheme.
Cichorium intybus: Traditional Uses, Phytochemistry, Pharmacology, and Toxicology
Authors: Street Renée A. , Sidana Jasmeen , Prinsloo Gerhard
Published: November 2013

The genusCichorium(Asteraceae) is made up of six species with major geographical presence in Europe and Asia.Cichorium intybus, commonly known as chicory, is well known as a coffee substitute but is also widely used medicinally to treat various ailments ranging from wounds to diabetes. Although this plant has a rich history of use in folklore, many of its constituents have not been explored for their pharmacological potential. Toxicological data onC. intybusis currently limited. This review focuses on the economic and culturally important medicinal uses ofC. intybus. Traditional uses, scientific validation, and phytochemical composition are discussed in detail.
Application of Stabilized Silver Nanoparticles as Thin Films as Corrosion Inhibitors for Carbon Steel Alloy in 1 M Hydrochloric Acid
Authors: Atta Ayman M. , Allohedan Hamad A. , El-Mahdy Gamal A. , Ezzat Abdel-Rahman O.
Published: November 2013

Nanometer scaled materials have attracted tremendous interest as corrosion protective films due to their high ability to form self‐assembled films on the metal surfaces. It is well known that the silver nanoparticles have higher reactivity towards aqueous acidic solution. The present work aims to prepare coated silver nanoparticles to protect carbon steel alloys from aqueous acidic corrosive media. In this respect, Ag nanoparticles colloid solutions were produced through reducing AgNO3 separately with trisodium citrate in an aqueous solution or in the presence of stabilizer such as poly(ethylene glycol) thiol and poly(vinyl pyrrolidone). The morphology of the modified silver nanoparticles was investigated by TEM and DLS. UV‐Vis absorption spectrum was used to study the effect of HCl on the stability of the dispersed silver nanoparticles. The corrosion inhibition efficiency of the poly (ethylene glycol)thiol, the self‐assembled monolayers of Ag nanoparticles, was determined by polarization method and electrochemical impedance spectroscopy (EIS). Polarization curves indicated that the coated silver poly (ethylene glycol)thiol acted as a mixed type inhibitor. The data of inhibition efficiencies obtained measured by polarization measurements are in good agreement with those obtained with electrochemical impedance.
Research on ISFLA-Based Optimal Control Strategy for the Coordinated Charging of EV Battery Swap Station
Authors: Huang Xueliang , Qiang Hao , Zhang Qidong , Li Haijuan
Published: November 2013

As an important component of the smart grid, electric vehicles (EVs) could be a good measure against energy shortages and environmental pollution. A main way of energy supply to EVs is to swap battery from the swap station. Based on the characteristics of EV battery swap station, the coordinated charging optimal control strategy is investigated to smooth the load fluctuation. Shuffled frog leaping algorithm (SFLA) is an optimization method inspired by the memetic evolution of a group of frogs when seeking food. An improved shuffled frog leaping algorithm (ISFLA) with the reflecting method to deal with the boundary constraint is proposed to obtain the solution of the optimal control strategy for coordinated charging. Based on the daily load of a certain area, the numerical simulations including the comparison of PSO and ISFLA are carried out and the results show that the presented ISFLA can effectively lower the peak-valley difference and smooth the load profile with the faster convergence rate and higher convergence precision.
Active Semisupervised Clustering Algorithm with Label Propagation for Imbalanced and Multidensity Datasets
Authors: Leng Mingwei , Cheng Jianjun , Wang Jinjin , Zhang Zhengquan , Zhou Hanhai , Chen Xiaoyun
Published: November 2013

The accuracy of most of the existing semisupervised clustering algorithms based on small size of labeled dataset is low when dealing with multidensity and imbalanced datasets, and labeling data is quite expensive and time consuming in many real-world applications. This paper focuses on active data selection and semisupervised clustering algorithm in multidensity and imbalanced datasets and proposes an active semisupervised clustering algorithm. The proposed algorithm uses an active mechanism for data selection to minimize the amount of labeled data, and it utilizes multithreshold to expand labeled datasets on multidensity and imbalanced datasets. Three standard datasets and one synthetic dataset are used to demonstrate the proposed algorithm, and the experimental results show that the proposed semisupervised clustering algorithm has a higher accuracy and a more stable performance in comparison to other clustering and semisupervised clustering algorithms, especially when the datasets are multidensity and imbalanced.
Bulky Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma Treated with Yttrium-90 Ibritumomab Tiuxetan
Authors: Tamura Shinobu , Ikeda Tokuji , Kurihara Toshio , Kakuno Yoshiteru , Nasu Hideki , Nakano Yoshio , Oshima Koichi , Fujimoto Tokuzo
Published: November 2013

An 84-year-old woman was admitted to our hospital with nonproductive cough and dyspnea on exertion. Computed tomography (CT) scan revealed extensive consolidation in the right lung. She was diagnosed with pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma using CT-guided lung biopsy. Her pulmonary images and respiratory symptoms did not improve two months after receiving 4 cycles of rituximab weekly; therefore, yttrium-90 ibritumomab tiuxetan was chosen as salvage therapy. The abnormal shadow on her pulmonary images was significantly reduced two months later, and she had no symptoms without nonhematological toxicities. She has had no progression for 18 months. Furthermore, radiation pneumonitis has not also been observed. We herein reported bulky pulmonary MALT lymphoma treated with yttrium-90 ibritumomab tiuxetan.
Effects of Lipophilic Extract ofViscum albumL. and Oleanolic Acid on Migratory Activity of NIH/3T3 Fibroblasts and on HaCat Keratinocytes
Authors: Kuonen R. , Weissenstein U. , Urech K. , Kunz M. , Hostanska K. , Estko M. , Heusser P. , Baumgartner S.
Published: November 2013

Viscum albumL. lipophilic extract (VALE) contains pharmacologically active pentacyclic triterpenes that are known to exhibit immunomodulatory, antitumor, and wound healing activity. Preliminary clinical observations indicate that VALE was able to influence cutaneous wound healingin vivo. The objective of this study was to investigate wound closure related properties of VALEin vitro. As measured in a wound healing assay, VALE and its predominant triterpene oleanolic acid (OA) significantly and dose dependently promoted the migration of NIH/3T3 fibroblastsin vitro, thereby leading to an enhanced wound closure. Compared to the negative control, maximal stimulation by 26.1% and 26.2%, respectively, was attained with 10 μg/mL VALE and 1 μg/mL OA. Stimulation of proliferation in NIH/3T3 fibroblasts by VALE and OA could be excluded. At higher concentrations both substances affected proliferation and viability of NIH/3T3 fibroblasts and HaCat keratinocytes. In the toxic range of concentrations of VALE and OA, migration of NIH/3T3 fibroblasts was suppressed. The extent of the stimulatory effect on cell migration of VALE quite closely corresponded to the effect expected by the concentrations of OA contained in the crude extract VALE. These data support the casual observation thatViscum albumL. lipophilic extract might modulate wound healing related processesin vivo.
Variance-Constrained Multiobjective Control and Filtering for Nonlinear Stochastic Systems: A Survey
Authors: Ma Lifeng , Wang Zidong , Dong Hongli , Wei Guoliang
Published: November 2013

The multiobjective control and filtering problems for nonlinear stochastic systems with variance constraints are surveyed. First, the concepts of nonlinear stochastic systems are recalled along with the introduction of some recent advances. Then, the covariance control theory, which serves as a practical method for multi-objective control design as well as a foundation for linear system theory, is reviewed comprehensively. The multiple design requirements frequently applied in engineering practice for the use of evaluating system performances are introduced, including robustness, reliability, and dissipativity. Several design techniques suitable for the multi-objective variance-constrained control and filtering problems for nonlinear stochastic systems are discussed. In particular, as a special case for the multi-objective design problems, the mixedH2/H∞control and filtering problems are reviewed in great detail. Subsequently, some latest results on the variance-constrained multi-objective control and filtering problems for the nonlinear stochastic systems are summarized. Finally, conclusions are drawn, and several possible future research directions are pointed out.
Long-Term Vibration Monitoring of Cable-Stayed Bridge Using Wireless Sensor Network
Authors: Nguyen Khac-Duy , Kim Jeong-Tae , Park Young-Hwan
Published: November 2013

Wireless sensor networks provide a lot of advantages for vibration monitoring of bridges. The installation time and implementation cost of the monitoring system are greatly reduced by the adoption of this innovative technology. This paper presents a long-term vibration monitoring of the Hwamyung cable-stayed bridge in Korea using an Imote2-platformed wireless sensor network. First, the wireless vibration monitoring system of the bridge is briefly described by outlining the test history, the design of wireless sensor system, and the sensor deployment. Next, the vibration behaviors of the bridge are experimentally examined with respect to the variation of temperature, the wind loads induced by typhoons, and the change of bridge deck mass caused by pavement.
The Impact of Cost Uncertainty on Cournot Duopoly Game with Concave Demand Function
Authors: Askar S. S.
Published: November 2013

It is reported in the literature that the most fundamental idea to address uncertainty is to begin by condensing random variables. In this paper, we propose Cournot duopoly game where quantity-setting firms use nonlinear demand function that has no inflection points. A random cost function is introduced in this model. Each firm in the model wants to maximize its expected profit and also wants to minimize its uncertainty by minimizing the cost. To handle this multiobjective optimization problem, the expectation and worst-case approaches are used. A model of two rational firms that are in competition and produce homogenous commodities is introduced using an unknown demand function. The equilibrium points of this model are obtained and their dynamical characteristics such as stability, bifurcation, and chaos are investigated. Complete stability and bifurcation analysis are provided. The obtained theoretical results are verified by numerical simulation.
Exact Finite-Difference Schemes ford-Dimensional Linear Stochastic Systems with Constant Coefficients
Authors: Jiang Peng , Ju Xiaofeng , Liu Dan , Fan Shaoqun
Published: November 2013

The authors attempt to construct the exact finite-difference schemes for linear stochastic differential equations with constant coefficients. The explicit solutions to Itô and Stratonovich linear stochastic differential equations with constant coefficients are adopted with the view of providing exact finite-difference schemes to solve them. In particular, the authors utilize the exact finite-difference schemes of Stratonovich type linear stochastic differential equations to solve the Kubo oscillator that is widely used in physics. Further, the authors prove that the exact finite-difference schemes can preserve the symplectic structure and first integral of the Kubo oscillator. The authors also use numerical examples to prove the validity of the numerical methods proposed in this paper.
An Method for Vehicle-Flow Detection and Tracking in Real-Time Based on Gaussian Mixture Distribution
Authors: Zhang Ronghui , Ge Pingshu , Zhou Xi , Jiang Tonghai , Wang Rongben
Published: November 2013

Vehicle-flow detection and tracking by digital image are one of the most important technologies in the traffic monitoring system. Gaussian mixture distribution method is used to eliminate the influence of moving vehicle firstly in this text, and then we built the background images for vehicle flow. Combining the advantages of background difference algorithm with inter frame difference operator, the real-time background is segmented integrally and dynamically updated accurately by matching the reconstructed image with current background. In order to ensure the robustness of vehicle detection, three by three window templates are adopted to remove the isolated noise spot in the image of vehicle contour. The template structural element is used to do some graphical morphological filtering. So, the corrosion and expansion sets are obtained. To narrow the target search scope and improve the calculation speed and precision of the algorithm, Kalman filtering model is used to realize the tracking of fast moving vehicles. Experimental results show that the method has good real-time and reliable performance.
Radioimmunotherapy Combined with Maintenance Anti-CD20 Antibody May Trigger Long-Term Protective T Cell Immunity in Follicular Lymphoma Patients
Authors: Buchegger Franz , Larson Steven M. , Mach Jean-Pierre , Chalandon Yves , Dietrich Pierre-Yves , Cairoli Anne , Prior John O. , Romero Pedro , Speiser Daniel E.
Published: November 2013

Growing evidence suggests that the patient’s immune response may play a major role in the long-term efficacy of antibody therapies of follicular lymphoma (FL). Particular long-lasting recurrence free survivals have been observed after first line, single agent rituximab or after radioimmunotherapy (RIT). Rituximab maintenance, furthermore, has a major efficacy in prolonging recurrence free survival after chemotherapy. On the other hand, RIT as a single step treatment showed a remarkable capacity to induce complete and partial remissions when applied in recurrence and as initial treatment of FL or given for consolidation. These clinical results strongly suggest that RIT combined with rituximab maintenance could stabilize the high percentages of patients with CR and PR induced by RIT. While the precise mechanisms of the long-term efficacy of these 2 treatments are not elucidated, different observations suggest that the patient’s T cell immune response could be decisive. With this review, we discuss the potential role of the patient’s immune system under rituximab and RIT and argue that the T cell immunity might be particularly promoted when combining the 2 antibody treatments in the early therapy of FL.
Using Participatory Crowdsourcing in South Africa to Create a Safer Living Environment
Authors: Bhana Bhaveer , Flowerday Stephen , Satt Aharon
Published: November 2013

The increase in urbanisation is making the management of city resources a difficult task. Data collected through observations (utilising humans as sensors) of the city surroundings can be used to improve decision making in terms of managing these resources. However, the data collected must be of a certain quality in order to ensure that effective and efficient decisions are made. This study is focused on the improvement of emergency and nonemergency services (city resources) through the use of participatory crowdsourcing (humans as sensors) as a data collection method (collect public safety data), utilising voice technology in the form of an interactive voice response (IVR) system. This study proposes public safety data quality criteria which were developed to assess and identify the problems affecting data quality. This study is guided by design science methodology and applies three driving theories: the data information knowledge action result (DIKAR) model, the characteristics of a smart city, and a credible data quality framework. Four critical success factors were developed to ensure that high quality public safety data is collected through participatory crowdsourcing utilising voice technologies.
Positive Solutions for a Mixed-Order Three-Point Boundary Value Problem forp-Laplacian
Authors: Torres Francisco J.
Published: November 2013

The author investigates the existence and multiplicity of positive solutions for boundary value problem of fractional differential equation withp-Laplacian operator. The main tool is fixed point index theory and Leggett-Williams fixed point theorem.
Performance Analysis of High-Speed Deep/Shallow Recessed Hybrid Bearing
Authors: Wang Lei , Jiang Shuyun
Published: November 2013

The present paper proposes a theoretical analysis of the performance of deep/shallow recessed hybrid bearing. It is intended that, on the basis of the numerical results drawn from this study, appropriate shallow recess depth and width can be determined for use in the bearing design process. By adopting bulk flow theory, the turbulent Reynolds equation and energy equation are modified and solved numerically including concentrated inertia effects at the recess edge with different depth and width of shallow recess. The results indicate that the load capacity, drag torque increases as the depth of shallow recess is shallower and the width ratio (half angle of deep recess versus half angle of shallow recess) is smaller. In contrast, the flow rate decreases as the depth of shallow recess is shallower and the width ratio is smaller. Nevertheless, the appropriate design of the depth and width of shallow recess might well induce the performance of high-speed deep/shallow recessed hybrid bearing.
Application of Harmony Search to Design Storm Estimation from Probability Distribution Models
Authors: Yoon Sukmin , Jeong Changsam , Lee Taesam
Published: November 2013

The precision of design storm estimation depends on the selection of an appropriate probability distribution model (PDM) and parameter estimation techniques. Generally, estimated parameters for PDMs are provided based on the method of moments, probability weighted moments, and maximum likelihood (ML). The results using ML are more reliable than the other methods. However, the ML is more laborious than the other methods because an iterative numerical solution must be used. In the meantime, metaheuristic approaches have been developed to solve various engineering problems. A number of studies focus on using metaheuristic approaches for estimation of hydrometeorological variables. Applied metaheuristic approaches offer reliable solutions but use more computation time than derivative-based methods. Therefore, the purpose of the current study is to enhance parameter estimation of PDMs for design storms using a recently developed metaheuristic approach known as a harmony search (HS). The HS is compared to the genetic algorithm (GA) and ML via simulation and case study. The results of this study suggested that the performance of the GA and HS was similar and showed more accurate results than that of the ML. Furthermore, the HS required less computation time than the GA.
Empirical Analysis of Server Consolidation and Desktop Virtualization in Cloud Computing
Authors: Chang Bao Rong , Tsai Hsiu-Fen , Chen Chi-Ming
Published: November 2013

Physical server transited to virtual server infrastructure (VSI) and desktop device to virtual desktop infrastructure (VDI) have the crucial problems of server consolidation, virtualization performance, virtual machine density, total cost of ownership (TCO), and return on investments (ROI). Besides, how to appropriately choose hypervisor for the desired server/desktop virtualization is really challenging, because a trade-off between virtualization performance and cost is a hard decision to make in the cloud. This paper introduces five hypervisors to establish the virtual environment and then gives a careful assessment based on C/P ratio that is derived from composite index, consolidation ratio, virtual machine density, TCO, and ROI. As a result, even though ESX server obtains the highest ROI and lowest TCO in server virtualization and Hyper-V R2 gains the best performance of virtual machine management; both of them however cost too much. Instead the best choice is Proxmox Virtual Environment (Proxmox VE) because it not only saves the initial investment a lot to own a virtual server/desktop infrastructure, but also obtains the lowest C/P ratio.
Thermodynamics in Modified Gravity with Curvature Matter Coupling
Authors: Sharif M. , Zubair M.
Published: November 2013

The first and generalized second laws of thermodynamics are studied inf(R,Lm)gravity, a more general modified theory with curvature matter coupling. It is found that one can translate the Friedmann equations to the form of first law accompanied with entropy production term. This behavior is due to the nonequilibrium thermodynamics in this theory. We establish the generalized second law of thermodynamics and develop the constraints on coupling parameters for two specific models. It is concluded that laws of thermodynamics in this modified theory are more general and can reproduce the corresponding results in Einstein,f(R)gravity, andf(R)gravity with arbitrary as well as nonminimal curvature matter coupling.
Examination of the Quantitative Relationship between Vegetation Canopy Height and LAI
Authors: Yuan Yongwei , Wang Xinsheng , Yin Fang , Zhan Jinyan
Published: November 2013

Accurate estimation of vegetation biophysical variables such as the vegetation canopy height (H) is of great importance to the applications of the land surface models. It is difficult to obtain the data ofHat the regional scale or larger scale, but the remote sensing provides the most useful and most effective method. The leaf area index (LAI) is closely related to theH, and we analyzed its relationship with the correlation analysis based on the dataset at 86 site-years of field measurements from sites worldwide in this study. The result indicates that there is significant positive exponent correlation between these two parameters and the change of LAI would exert great impacts onH. The higher the LAI is, the higher theHis, and vice versa. Besides, the coefficients of different land cover types are very heterogeneous, and LAI of the needleleaf forest shows strong correlation withH, while that of the cropland shows weak correlation withH. The results may provide certain reference information for the extraction of the data ofHat the regional scale with the remote sensing data.
Effects of the Boron-Doped p+Emitter on the Efficiency of the n-Type Silicon Solar Cell
Authors: Kim Eun-Young , Kim Jeong
Published: November 2013

The optimum structure of the p+emitter for the n-type silicon solar cell was determined with the simulation of the boron doping concentration. The boron concentration (NB) in the p+emitter was varied in the range of1×1017and2×1022 atoms/cm3while maintaining the base doping concentration at2×1016 atoms/cm3. With the increase of the boron concentration, the open circuit voltage (VOC) of the cell increased up to 0.525 V and then was nearly saturated atNB>5×1018 atoms/cm3. On the other hand, the short circuit current density (JSC) began to decrease atNB>1×1019 atoms/cm3due to the increase of the surface recombination loss, and without considering the variation of the contact resistance along the emitter doping level, the maximum efficiency of the cell was obtained at aroundNB=5×1018 atoms/cm3. While the contact resistance of the electrode decreases with the increase of the doping concentration in the p+emitter, and with consideration of the variation of the contact resistance, the optimum value ofNBfor maximum efficiency shifted to the higher doping level.
Investigation of 1D Siliver Nanoparticle Arrays for Use as Molecule Concentration‐Specific SERS Substrates
Authors: Gao Jun , Qian Huan , Xu Shang , Han Min
Published: November 2013

One‐dimensional arrays of silver nanoparticles with a particle size of 10.5 nm and interparticle spacing of 8.5 nm were fabricated by depositing nanoparticles in gas phase on block copolymer self‐assembled templates. The substrate showed a surface‐enhanced Raman scattering (SERS) enhancement factor as high as 1 × 107 with good reproducibility and stability. The dependence of the average enhancement factor and the SERS intensity on the packing density of the analyte molecules were investigated. For a tiny amount of analytes in the range of 1 × 10−14  to 3 × 10−13  mol/mm2, the SERS signal showed a linear dependence on the molecule packing density on a logarithmic scale, with a slope of about 1.25. The substrates are promising for quantitative detection of trace level molecules.
Dual Targeting of EWS-FLI1 Activity and the Associated DNA Damage Response with Trabectedin and SN38 Synergistically Inhibits Ewing Sarcoma Cell Growth
Authors: Grohar Patrick J. , Segars Laure E. , Yeung Choh , Pommier Yves , D'Incalci Maurizio , Mendoza Arnulfo , Helman Lee J.
Published: November 2013

Purpose: The goal of this study is to optimize the activity of trabectedin for Ewing sarcoma by developing a molecularly targeted combination therapy.

Experimental Design: We have recently shown that trabectedin interferes with the activity of EWS-FLI1 in Ewing sarcoma cells. In this report, we build on this work to develop a trabectedin-based combination therapy with improved EWS-FLI1 suppression that also targets the drug-associated DNA damage to Ewing sarcoma cells.

Results: We demonstrate by siRNA experiments that EWS-FLI1 drives the expression of the Werner syndrome protein (WRN) in Ewing sarcoma cells. Because WRN-deficient cells are known to be hypersensitive to camptothecins, we utilize trabectedin to block EWS-FLI1 activity, suppress WRN expression, and selectively sensitize Ewing sarcoma cells to the DNA-damaging effects of SN38. We show that trabectedin and SN38 are synergistic, demonstrate an increase in DNA double-strand breaks, an accumulation of cells in S-phase and a low picomolar IC50. In addition, SN38 cooperates with trabectedin to augment the suppression of EWS-FLI1 downstream targets, leading to an improved therapeutic index in vivo. These effects translate into the marked regression of two Ewing sarcoma xenografts at a fraction of the dose of camptothecin used in other xenograft studies.

Conclusions: These results provide the basis and rationale for translating this drug combination to the clinic. In addition, the study highlights an approach that utilizes a targeted agent to interfere with an oncogenic transcription factor and then exploits the resulting changes in gene expression to develop a molecularly targeted combination therapy. Clin Cancer Res; 20(5); 1190–203. ©2013 AACR.
Importance of 5α-Reductase Gene Polymorphisms on Circulating and Intraprostatic Androgens in Prostate Cancer
Authors: Lévesque Éric , Laverdière Isabelle , Lacombe Louis , Caron Patrick , Rouleau Mélanie , Turcotte Véronique , Têtu Bernard , Fradet Yves , Guillemette Chantal
Published: November 2013

Purpose: Polymorphisms in the genes SRD5A1 and SRD5A2 encoding androgen biosynthetic 5α-reductase enzymes have been associated with an altered risk of biochemical recurrence after radical prostatectomy in localized prostate cancer.

Experimental Design: To gain potential insights into SRD5A biologic effects, we examined the relationship between SRD5A prognostic markers and endogenous sex-steroid levels measured by mass spectrometry in plasma samples and corresponding prostatic tissues of patients with prostate cancer.

Results: We report that five of the seven SRD5A markers differentially affect sex-steroid profiles of dihydrotestosterone and its metabolites in both the circulation and prostatic tissues of patients with prostate cancer. Remarkably, a 32% increase in intraprostatic testosterone levels was observed in the presence of the high-risk SRD5A rs2208532 polymorphism. Moreover, SRD5A2 markers were associated predominantly with circulating levels of inactive glucuronides. Indeed, the rs12470143 SRD5A2 protective allele was associated with high circulating androstane-3α, 17β-diol-17-glucuronide (3α-diol-17G) levels as opposed to lower levels of both 3α-diol-17G and androsterone-glucuronide observed with the rs2208532 SRD5A2 risk allele. Moreover, SRD5A2 rs676033 and rs523349 (V89L) risk variants, in strong linkage disequilibrium, were associated with higher circulating levels of 3α-diol-3G. The SRD5A2 rs676033 variant further correlated with enhanced intraprostatic exposure to 5α-reduced steroids (dihydrotestosterone and its metabolite 3β-diol). Similarly, the SRD5A1 rs166050C risk variant was associated with greater prostatic exposure to androsterone, whereas no association was noted with circulating steroids.

Conclusions: Our data support the association of 5α-reductase germline polymorphisms with the hormonal milieu in patients with prostate cancer. Further studies are needed to evaluate if these variants influence 5α-reductase inhibitor efficacy. Clin Cancer Res; 20(3); 576–84. ©2013 AACR.
Cladribine with Immediate Rituximab for the Treatment of Patients with Variant Hairy Cell Leukemia
Authors: Kreitman Robert J. , Wilson Wyndham , Calvo Katherine R. , Arons Evgeny , Roth Laura , Sapolsky Jeffrey , Zhou Hong , Raffeld Mark , Stetler-Stevenson Maryalice
Published: November 2013

Purpose: In contrast with the classic form, variant hairy cell leukemia (HCLv) responds poorly to single-agent purine analogs, expresses unmutated BRAF, has shorter overall survival, and lacks effective standard therapy. No treatment has achieved a high complete remission (CR) rate even in small series, and of 39 reported cases from six studies, overall response rate after cladribine was 44% with 8% CRs. Rituximab has been found to increase the sensitivity of malignant cells to cladribine, suggesting that combination with cladribine might improve response in HCLv. To test this hypothesis, patients with HCLv were treated with simultaneous cladribine and rituximab.

Experimental Design: Patients with HCLv with 0 to 1 prior courses of cladribine received cladribine 0.15 mg/kg for days 1 to 5, with eight weekly doses of rituximab 375 mg/m2 beginning day 1. Restaging was performed, and minimal residual disease (MRD) in blood and marrow was quantified using PCR, immunohistochemistry, and flow cytometry.

Results: By 6 months, 9 (90%) of 10 patients achieved CR, compared with 3 (8%) of 39 reported cases treated with cladribine alone (P < 0.0001). Of the 9 CRs, 8 remain free of MRD at 12 to 48 (median 27) months of follow-up. No dose-limiting toxicities were observed when beginning cladribine and rituximab on the same day, although most patients required short-term steroids to prevent and treat rituximab infusion reactions. Cytopenias in CRs resolved in 7 to 211 (median 34) days without major infections.

Conclusion: Although cladribine alone lacks effectiveness for early or relapsed HCLv, cladribine with immediate rituximab achieves CRs without MRD and is feasible to administer. Clin Cancer Res; 19(24); 6873–81. ©2013 AACR.
Activity of the Monocarboxylate Transporter 1 Inhibitor AZD3965 in Small Cell Lung Cancer
Authors: Polański Radosław , Hodgkinson Cassandra L. , Fusi Alberto , Nonaka Daisuke , Priest Lynsey , Kelly Paul , Trapani Francesca , Bishop Paul W. , White Anne , Critchlow Susan E. , Smith Paul D. , Blackhall Fiona , Dive Caroline , Morrow Christopher J.
Published: November 2013

Purpose: The monocarboxylate transporter 1 (MCT1) inhibitor, AZD3965, is undergoing phase I evaluation in the United Kingdom. AZD3965 is proposed, via lactate transport modulation, to kill tumor cells reliant on glycolysis. We investigated the therapeutic potential of AZD3965 in small cell lung cancer (SCLC) seeking rationale for clinical testing in this disease and putative predictive biomarkers for trial use.

Experimental Design: AZD3965 sensitivity was determined for seven SCLC cell lines, in normoxia and hypoxia, and for a tumor xenograft model. Proof of mechanism was sought via changes in intracellular/tumor lactate. Expression of MCT1 and related transporter MCT4 was assessed by Western blot analysis. Drug resistance was investigated via MCT4 siRNAi and overexpression. The expression and clinical significance of MCT1 and MCT4 were explored in a tissue microarray (TMA) from 78 patients with SCLC.

Results: AZD3965 sensitivity varied in vitro and was highest in hypoxia. Resistance in hypoxia was associated with increased MCT4 expression. In vivo, AZD3965 reduced tumor growth and increased intratumor lactate. In the TMA, high MCT1 expression was associated with worse prognosis (P = 0.014). MCT1 and hypoxia marker CA IX expression in the absence of MCT4 was observed in 21% of SCLC tumors.

Conclusions: This study provides a rationale to test AZD3965 in patients with SCLC. Our results suggest that patients with tumors expressing MCT1 and lacking in MCT4 are most likely to respond. Clin Cancer Res; 20(4); 926–37. ©2013 AACR.
Immediate Effectiveness of Humming on the Supraglottic Compression in Subjects with Muscle Tension Dysphonia
Authors: Ogawa Makoto , Hosokawa Kiyohito , Yoshida Misao , Yoshii Tadashi , Shiromoto Osamu , Inohara Hidenori
Published: November 2013

Aims: To verify whether humming corrects supraglottic compression in muscle tension dysphonia (MTD) patients. Methods: We enrolled 23 MTD participants (13 male, 10 female) showing supraglottic compression. Each individual was instructed to perform 3 types of phonation under transnasal laryngofiberscopy: natural phonation, humming phonation without pitch change and subsequent um-hum phonation, i.e. humming with pitch glide up as if agreeing with someone. The degree of supraglottic compression was estimated with 2 parameters. The false vocal fold and anterior-posterior indices (the FVF and AP indices) were calculated by normalizing the lateral width and AP length of the visible vocal cords at phonation normalized to the mean vocal cord length at inspiration, respectively. These indices were compared among the tasks. Results: All the MTD participants but 5 females accomplished decreases in the vocal roughness scores upon the phonatory tasks. The whole MTD group showed significant increases in the FVF and AP indices even after humming without pitch change with a dominance of the AP index. The humming-responsive MTD subgroup showed greater increases in both indices than the humming-resistant subgroup. Conclusion: These data demonstrate that humming corrects both the lateral and AP components of supraglottic compression in most MTD patients.
Positive Correlation between Baseline PET or PET/CT Findings and Clinical Parameters in Multiple Myeloma Patients
Authors: Park Silvia , Lee Su Jin , Chang Won Jin , Maeng Chi Hoon , Hong Jung Yong , Choi Moon Ki , Kim Young Saing , Jung Chul Won , Jang Jun Ho , Kim Seok Jin , Kim Won Seog , Choi Joon Young , Kim Kihyun
Published: November 2013

Recently, positron emission tomography (PET) has been incorporated into a series of prospective studies as a predictor of outcomes in multiple myeloma (MM), and the number of 18F-fluorodeoxuglucose (FDG)-avid focal lesions (FLs) and the intensity of tumor metabolism have been designated as important surrogate markers for predicting prognosis. Here, we compared initial clinical characteristics of MM patients with baseline PET parameters: the number of FLs and the maximum standardized uptake value (SUVmax). A total of 59 patients diagnosed with MM between August 2004 and February 2012 were reviewed. At diagnosis, 23 patients (40.0%) had ≤3 FLs, 11 patients (18.6%) 4-9 FLs, and 25 patients (42.4%) ≥10 FLs. The median SUVmax was 5.3 (range 0-24.3), and 40 patients (67.8%) showed a SUVmax >4. No clinical characteristics were significantly different between groups with a SUVmax ≤4 and a SUVmax >4. However, there were significant differences in several clinical indices between the FLs ≤3 and FLs >3 groups; elevated β2-microglobulin, elevated lactate dehydrogenase, anemia and more advanced disease by the Durie-Salmon stage corresponded to FLs >3 at baseline PET. Adverse baseline PET findings are positively correlated with prognostically relevant clinical parameters. Regarding PET parameters, FLs are more likely to be well correlated with disease aggressiveness and pathophysiology compared to SUVmax.
MicroRNA Function in Human Diseases
Authors: Natarajan Sathish Kumar , Smith Mary Anne , Wehrkamp Cody J. , Mohr Ashley M. , Mott Justin L.
Published: November 2013

MicroRNAs are emerging as a hot topic in research, and rightfully so. They show great promise as targets of treatment and as markers for common human diseases, such as cancer and metabolic diseases. In this review, we address some of the basic questions regarding microRNA function in human disease and the clinical significance of microRNAs. Specifically, microRNAs in epigenetics, cancer, and metabolic diseases are discussed, with examples taken from cholangiocarcinoma and nonalcoholic fatty liver disease.
Is Flow-Mediated Dilation Nitric Oxide Mediated?
Authors: Green Daniel J. , Dawson Ellen A. , Groenewoud Hans M.M. , Jones Helen , Thijssen Dick H.J.
Published: November 2013

Flow-mediated dilation (FMD) is a noninvasive index of endothelial function and vascular health in humans. Studies examining the role of nitric oxide (NO) are not conclusive. In this article, we quantified the contribution of NO in FMD of conduit arteries and explored the effect of the protocol (ie, distal cuff, ≈5-minute ischemia) and method of analysis (ie, automated and continuous edge detection) on the NO dependency of this test. A systematic review and 3-stage meta-analysis of published crossover studies that measured FMD under local infusion of saline or the NO synthase blocker
N
G
monomethyl-L-arginine (L-NMMA) was undertaken. Twenty studies met the inclusion criteria for stage 1 (374 individual comparisons). The meta-analyzed outcome was the difference in FMD between infusion of saline (ie, FMD
saline
) and NO synthase blocker (ie, FMD
L-NMMA
). Overall, FMD
saline
was 8.2% (95% confidence interval [CI], 6.8%–9.6%) compared with FMD
L-NMMA
of 3.7% (95% CI, 3.1%–4.3%;
P
<0.001). Stage 2 analysis focused on studies that used the most commonly adopted approach in healthy volunteers (ie, distal cuff placement, ≈5-minute occlusion), which similarly revealed a significant NO contribution to FMD (FMD
saline
, 6.5% [95% CI, 5.7%–7.3%]; FMD
L-NMMA
, 0.9% [95% CI, 0.5%–1.3%];
P
<0.001). Stage 3 meta-analyzed the studies that adopted the commonly adopted approach and automated, continuous method of analysis, which also revealed a significant contribution of NO to the FMD (FMD
saline
, 6.9% [95% CI, 6.0%–7.8%]; FMD
L-NMMA
, 2.4% [95% CI, 1.1%–3.7%];
P
<0.001). This comprehensive analysis demonstrates that FMD of conduit arteries in humans is, at least in part, mediated by NO.
Pulmonary Embolism in Ischemic Stroke: Clinical Presentation, Risk Factors, and Outcome
Authors: Pongmoragot Jitphapa , Rabinstein Alejandro A. , Nilanont Yongchai , Swartz Richard H. , Zhou Limei , Saposnik Gustavo ,   The Investigators of the Registry of the Canadian Stroke Network (RCSN) and University of Toronto Stroke Program for the Stroke Outcomes Research Canada (SORCan [www.sorcan.ca]) Working Group
Published: November 2013

Background

Limited information is available on the frequency of pulmonary embolism (
PE
) in patients with an acute ischemic stroke (
AIS
). We evaluated clinical characteristics, predisposing factors, and outcomes in
AIS
patients with
PE
.

Methods and Results

We included all
AIS
patients admitted to participating institutions in the
R
egistry of the
C
anadian
S
troke
N
etwork. Clinically
PE
was documented by a physician and confirmed by computed tomography pulmonary angiography within 30 days of the stroke case index. The primary outcome was death or disability at discharge. Secondary outcomes included disposition, length of hospital stay, mortality at 3 months and 1 year. Among 11 287 patients with
AIS
,
PE
was found in 89 (0.78%) patients. History of cancer, deep vein thrombosis (
DVT
)/
PE
, and
DVT
during the hospitalization were associated with
PE
.
PE
was associated with higher risk of death at 30 days (25.8% versus 13.6%;
P
<0.001), at 1 year (47.2% versus 24.6%;
P
<0.001), and disability at discharge (85.4% versus 63.6%;
P
<0.001). Mean length of stay was longer in stroke patients with
PE
(36 versus 16 days;
P
=0.001). After adjusting for age, sex, and stroke severity,
PE
remained associated with lower survival at 30 days and 1 year, and death or disability at discharge (
OR
3.02; 95%
CI
1.56 to 5.83).

Conclusions

In this large cohort study,
PE
occurred in nearly 1% of
AIS
patients.
PE
was more common in patients with severe stroke, history of cancer, previous
DVT
/
PE
or acute
DVT
and associated with lower short‐ and long‐term survival, greater disability, and longer length of stay.