bluuebunny/crossref_metadata_2025 huggingface dataset:
An Antenna Array Sidelobe Level Reduction Approach through Invasive Weed Optimization
Authors: Sun Geng , Liu Yanheng , Li Han , Liang Shuang , Wang Aimin , Li Boyu
Published: February 2018

The problems of synthesizing the beam patterns of the linear antenna array (LAA) and the circular antenna array (CAA) are addressed. First, an optimization problem is formulated for reducing the maximum sidelobe level (SLL) of the beam patterns. Then, the formulated problem is solved by using the invasive weed optimization (IWO) algorithm. Various simulations are performed to evaluate the effectiveness of the IWO algorithm for the synthesis of the beam patterns of the LAA and the CAA. The results show that IWO has a better performance in terms of the accuracy, the convergence rate, and the stability compared with other algorithms for the SLL reductions. Moreover, the electromagnetic simulation results also show that IWO achieves the best performance for the beam pattern synthesis of the antenna arrays in practical conditions.
Long‐Lived Termite Queens Exhibit High Cu/Zn‐Superoxide Dismutase Activity
Authors: Tasaki Eisuke , Kobayashi Kazuya , Matsuura Kenji , Iuchi Yoshihito
Published: February 2018

In most organisms, superoxide dismutases (SODs) are among the most effective antioxidant enzymes that regulate the reactive oxygen species (ROS) generated by oxidative energy metabolism. ROS are considered main proximate causes of aging. However, it remains unclear if SOD activities are associated with organismal longevity. The queens of eusocial insects, such as termites, ants, and honeybees, exhibit extraordinary longevity in comparison with the nonreproductive castes, such as workers. Therefore, the queens are promising candidates to study the underlying mechanisms of aging. Here, we found that queens have higher Cu/Zn‐SOD activity than nonreproductive individuals of the termite Reticulitermes speratus. We identified three Cu/Zn‐SOD sequences and one Mn‐SOD sequence by RNA sequencing in R. speratus. Although the queens showed higher Cu/Zn‐SOD activity than the nonreproductive individuals, there were no differences in their expression levels of the Cu/Zn‐SOD genes RsSOD1 and RsSOD3A. Copper (Cu2+ and Cu+) is an essential cofactor for Cu/Zn‐SOD enzyme activity, and the queens had higher concentrations of copper than the workers. These results suggest that the high Cu/Zn‐SOD activity of termite queens is related to their high levels of the cofactor rather than gene expression. This study highlights that Cu/Zn‐SOD activity contributes to extraordinary longevity in termites.
Antioxidative and Antimelanoma Effects of Various Tea Extracts via a Green Extraction Method
Authors: Chen Yihui , Huang Jyun-Yin , Lin Yichi , Lin I-Fan , Lu Yi-Ru , Liu Li-Heng , Wang Hui-Min David
Published: February 2018

Tea (Camellia sinensis) contains high level of antioxidant elements and is a well-known beverage consumed worldwide. The purpose of this study is to compare different concentrations of green tea, black tea, oolong tea 861, oolong tea 732, and jasmine green tea. These five types of tea extracts were known to have antioxidative properties, reducing power, and metal ion chelating activity. The current study compared these five extracts in terms of their inhibiting effects on human malignant melanoma: A2058 and A375. To determine the cell viability between normal cell and malignant melanoma cells, an MTT assay was applied to evaluate the cytotoxic potential on human melanoma cells, with all tea extracts showing decreased cell viability with increasing tea extract concentrations. Cytotoxicity on HaCat (normal skin cells) showed no effect on the cell viabilities at lower concentrations of the tea extracts. These results suggest the antioxidative effect of five tea extracts that protect against oxidation and melanoma production, with green tea and jasmine green tea showing the lowest cell viability when tested against malignant melanoma cells.
Questioning the Extreme Neurovirulence of Monkey B Virus(Macacine alphaherpesvirus 1)
Authors: Eberle R. , Jones-Engel L.
Published: February 2018

Monkey B virus (Macacine alphaherpesvirus1; BV) occurs naturally in macaques of the genusMacaca,which includes rhesus and long-tailed (cynomolgus) monkeys that are widely used in biomedical research. BV is closely related to the human herpes simplex viruses (HSV), and BV infections in its natural macaque host are quite similar to HSV infections in humans. Zoonotic BV is extremely rare, having been diagnosed in only a handful of North American facilities with the last documented case occurring in 1998. However, BV is notorious for its neurovirulence since zoonotic infections are serious, usually involving the central nervous system, and are frequently fatal. Little is known about factors underlying the extreme neurovirulence of BV in humans. Here we review what is actually known about the molecular biology of BV and viral factors affecting its neurovirulence. Based on what is known about related herpesviruses, areas for future research that may elucidate mechanisms underlying the neurovirulence of this intriguing virus are also reviewed.
Photobiomodulation Leads to Reduced Oxidative Stress in Rats Submitted to High‐Intensity Resistive Exercise
Authors: de Oliveira Helenita Antonia , Antonio Ednei Luiz , Arsa Gisela , Santana Eduardo Tadeu , Silva Flávio André , Júnior Daniel Arruda , dos Santos Simone , de Carvalho Paulo de Tarso Camillo , Leal-Junior Ernesto Cesar Pinto , Araujo Amanda , De Angelis Kátia , Bocalini Danilo Sales , Junior José Antonio Silva , Tucci Paulo José Ferreira , Serra Andrey Jorge
Published: February 2018

The aim of this study was to determine whether oxidative stress markers are influenced by low‐intensity laser therapy (LLLT) in rats subjected to a high‐intensity resistive exercise session (RE). Female Wistar rats divided into three experimental groups (Ctr: control, 4J: LLLT, and RE) and subdivided based on the sampling times (instantly or 24 h postexercise) underwent irradiation with LLLT using three‐point transcutaneous method on the hind legs, which was applied to the gastrocnemius muscle at the distal, medial, and proximal points. Laser (4J) or placebo (device off) were carried out 60 sec prior to RE that consisted of four climbs bearing the maximum load with a 2 min time interval between each climb. Lipoperoxidation levels and antioxidant capacity were obtained in muscle. Lipoperoxidation levels were increased (4‐HNE and CL markers) instantly post‐RE. LLLT prior to RE avoided the increase of the lipid peroxidation levels. Similar results were also notified for oxidation protein assays. The GPx and FRAP activities did not reduce instantly or 24 h after RE. SOD increased 24 h after RE, while CAT activity did not change with RE or LLLT. In conclusion, LLLT prior to RE reduced the oxidative stress markers, as well as, avoided reduction, and still increased the antioxidant capacity.
Autoamputation of the Appendix in a Chronic Adnexal Abscess
Authors: Markey C. Michele , Vestal Lauren E.
Published: February 2018

Autoamputation of the appendix has rarely been described in the literature. We present a case of a pelvic mass, thought to be a dermoid cyst based on preoperative imaging. After surgical removal and pathological examination, the mass was found to be a chronic pelvic abscess containing the right adnexa as well as an autoamputated vermiform appendix. Differentiating between gynecologic and gastrointestinal disease preoperatively can be difficult and often a definitive diagnosis cannot be made until surgical exploration and pathological review. However, to our knowledge, this is the first described case of a chronic pelvic abscess containing an autoamputated vermiform appendix.
Endoscopic Treatment of Colonic Duplication Cyst: A Case Report and Review of the Literature
Authors: Garg Rajat , Saravolatz Louis D. , Barawi Mohammed
Published: February 2018

Colonic duplication cysts are a rare congenital abnormality commonly presenting before two years of age. In adults, it has been rarely reported, most often as an incidental finding. We report a case of 42-year-old female complaining of constipation and lower abdominal pain. Patient’s CT scan of the abdomen showed a cystic lesion at hepatic flexure and the diagnosis was confirmed endoscopically using endoscopic ultrasound (EUS). The cyst was treated employing hot snare to expose the cyst cavity. On our literature search, there have been no reported cases of colonic duplication cyst treated endoscopically. We here discuss incidence, diagnosis, characteristics, and treatment of duplication cysts with special emphasis on endoscopic therapy.
Calophyllum brasilienseModulates the Immune Response and PromotesLeishmania amazonensisIntracellular Death
Authors: Domeneghetti L. , Demarchi I. G. , Caitano J. Z. , Pedroso R. B. , Silveira T. G. V. , Lonardoni M. V. C.
Published: February 2018

Calophyllum brasilienseis a plant from the Brazilian rain forests and has been used in folk medicine for the treatment of various diseases, including leishmaniasis. This infectious disease depends on theLeishmaniasp. and the host immune response.C. brasilienseantileishmanial activity is well known, but the effects on immune response remain to be investigated. This study showed the leishmanicidal and immunomodulatory effects of a 30 μg/mL of hydroalcoholic extract ofC. brasiliensein murine macrophages before and afterLeishmania(Leishmania)amazonensisinfection. The semiquantitative cytokine RNA expression was determined by RT-PCR and the anti-Leishmaniaactivity was measured by infection index (IF). Hydroalcoholic extract ofC. brasiliensereduced more than 95% of IF when used before and afterLeishmaniainfection, with 3 and 24 h of treatment (p<0.05).C. brasilienseinhibited or reduced significantly (p<0.05) the TNF-α, IL-1β, IL-18, and IL-10 mRNA expression. The antileishmanial and anti-inflammatory effects showed the potential ofC. brasilienseas an alternative therapy for leishmaniasis and it must be investigated.
Improvement of Mechanical Properties in Polypropylene‐ and Glass‐Fibre‐Reinforced Peach Shell Lightweight Concrete
Authors: Wu Fan , Liu Changwu , Diao Zhaofeng , Feng Bo , Sun Wei , Li Xiaolong , Zhao Shuang
Published: February 2018

The use of the polypropylene fibre and glass fibre with different volume fractions to improve the mechanical properties of peach shell lightweight concrete was investigated in this study. The volume fractions of 0.25%, 0.50%, and 0.75% were used for each fibre. The results showed that, as the polypropylene fibre and glass fibre were added into peach shell concrete, the density was reduced by up to 6.1% and the compressive strength, splitting tensile strength, and flexural strength were increased by 19.1%, 54.3%, and 38.6%, respectively. The highest compressive strength, splitting tensile strength, and flexural strength of 29.3 MPa, 2.87 MPa, and 3.09 MPa, respectively, were produced by peach shell concrete with 0.75% glass fibre. The results indicated that the incorporation of fibres significantly enhanced the postfailure toughness of peach shell concrete. It was found that the glass fibre was more effective than the polypropylene fibre in improving the mechanical properties of peach shell concrete. Although the incorporation of fibres slightly increased the water absorption and porosity, the type and content of fibres had no significant effect on water absorption and porosity. Therefore, the mechanical properties of peach shell lightweight concrete can be improved by adding polypropylene fibres and glass fibres.
In Vitro Degradation Behaviors of Manganese-Calcium Phosphate Coatings on an Mg-Ca-Zn Alloy
Authors: Su Yichang , Su Yingchao , Zai Wei , Li Guangyu , Wen Cuie
Published: February 2018

In order to decrease the degradation rate of magnesium (Mg) alloys for the potential orthopedic applications, manganese-calcium phosphate coatings were prepared on an Mg-Ca-Zn alloy in calcium phosphating solutions with different addition of Mn2+. Influence of Mn content on degradation behaviors of phosphate coatings in the simulated body fluid was investigated to obtain the optimum coating. With the increasing Mn addition, the corrosion resistance of the manganese-calcium phosphate coatings was gradually improved. The optimum coating prepared in solution containing 0.05 mol/L Mn2+ had a uniform and compact microstructure and was composed of MnHPO4·3H2O, CaHPO4·2H2O, and Ca3(PO4)2. The electrochemical corrosion test in simulated body fluid revealed that polarization resistance of the optimum coating is 36273 Ωcm2, which is about 11 times higher than that of phosphate coating without Mn addition. The optimum coating also showed the most stable surface structure and lowest hydrogen release in the immersion test in simulated body fluid.
An Updated Review of the Molecular Mechanisms in Drug Hypersensitivity
Authors: Chen Chun-Bing , Abe Riichiro , Pan Ren-You , Wang Chuang-Wei , Hung Shuen-Iu , Tsai Yi-Giien , Chung Wen-Hung
Published: February 2018

Drug hypersensitivity may manifest ranging from milder skin reactions (e.g., maculopapular exanthema and urticaria) to severe systemic reactions, such as anaphylaxis, drug reactions with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS), or Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Current pharmacogenomic studies have made important strides in the prevention of some drug hypersensitivity through the identification of relevant genetic variants, particularly for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs). The associations identified by these studies are usually drug, phenotype, and ethnic specific. The drug presentation models that explain how small drug antigens might interact with HLA and T cell receptor (TCR) molecules in drug hypersensitivity include the hapten theory, the p-i concept, the altered peptide repertoire model, and the altered TCR repertoire model. The broad spectrum of clinical manifestations of drug hypersensitivity involving different drugs, as well as the various pathomechanisms involved, makes the diagnosis and management of it more challenging. This review highlights recent advances in our understanding of the predisposing factors, immune mechanisms, pathogenesis, diagnostic tools, and therapeutic approaches for drug hypersensitivity.
Accuracy and Precision of a Veterinary Neuronavigation System for Radiation Oncology Positioning
Authors: Vanhaezebrouck Isabelle F. , Ballegeer Elizabeth A. , Frey Stephen , Sieffert Rob
Published: February 2018

Conformal radiation treatment plans such as IMRT and other radiosurgery techniques require very precise patient positioning, typically within a millimeter of error for best results. CT cone beam, real-time navigation, and infrared position sensors are potential options for success but rarely present in veterinary radiation centers. A neuronavigation system (Brainsight Vet, Rogue Research) was tested 22 times on a skull for positioning accuracy and precision analysis. The first 6 manipulations allowed the authors to become familiar with the system but were still included in the analyses. Overall, the targeting mean error in 3D was 1.437 mm with SD 1.242 mm. This system could be used for positioning for radiation therapy or radiosurgery.
Tactile Sensor Array with Fiber Bragg Gratings in Quasi-Distributed Sensing
Authors: Pedroso Marcelo A. , Negri Lucas H. , Kamizi Marcos A. , Fabris José L. , Muller Marcia
Published: February 2018

This work describes the development of a quasi-distributed real-time tactile sensing system with a reduced number of fiber Bragg grating-based sensors and reports its use with a reconstruction method based on differential evolution. The sensing system is comprised of six fiber Bragg gratings encapsulated in silicone elastomer to form a tactile sensor array with total dimensions of 60 × 80 mm, divided into eight sensing cells with dimensions of 20 × 30 mm. Forces applied at the central position of the sensor array resulted in linear response curves for the gratings, highlighting their coupled responses and allowing the application of compressive sensing. The reduced number of sensors regarding the number of sensing cells results in an undetermined inverse problem, solved with a compressive sensing algorithm with the aid of differential evolution method. The system is capable of identifying and quantifying up to four different loads at four different cells with relative errors lower than 10.5% and signal-to-noise ratio better than 12 dB.
Research on the Vibration Insulation of High‐Speed Train Bogies in Mid and High Frequency
Authors: Liu Jia , Jin Xuesong
Published: February 2018

According to a large amount of the test data, the mid and high frequency vibrations of high‐speed bogies are very notable, especially in the 565~616 Hz range, which are just the passing frequencies corresponding to the 22nd to 24th polygonal wear of the wheel. In order to investigate the main cause of wheel higher‐order polygon formation, a 3D flexible model of a Chinese high‐speed train bogie is developed using the explicit finite element method. The results show that the couple vibration of bogie and wheelset may lead to the high‐order wears of wheel. In order to reduce the coupled resonance of the wheelset and the bogie frame, the effects of the stiffness and damping of the primary suspensions, wheelset axle radius, and bogie frame strength on the vibration transmissibility are discussed carefully. The numerical results show that the resonance peaks in high frequency range can be reduced by reducing the stiffness of axle box rotary arm joint, reducing the wheelset axle radius or strengthening the bogie frame location. The related results may provide a reference for structure improvement of the existing bogies and structure design of the new high‐speed bogies.
Water Absorption Properties of Cement Pastes: Experimental and Modelling Inspections
Authors: Casnedi Ludovica , Cocco Ombretta , Meloni Paola , Pia Giorgio
Published: February 2018

An intermingled fractal units’ model is shown in order to simulate pore microstructures as pore fraction and pore size distribution. This model is aimed at predicting capillary water absorption coefficient and sorptivity values in cement pastes. The results obtained are in good agreement with the experimental ones. For validating this model, a comparison with other procedures has been shown. It is possible to establish that the newly proposed method matches better with the experimental results. That is probably due to the fact that pore size distribution has been considered as a whole. Moreover, even though the proposed model is based on fractal base units, it is able to simulate and predict different properties as well as nonfractal porous microstructure.
Expression of miRNAs in Serum Exosomes versus Hippocampus in Methamphetamine‐Induced Rats and Intervention of Rhynchophylline
Authors: Li Han-cheng , Lin Ying-bo , Li Chan , Luo Chao-hua , Zhou Yu-ting , Ou Jing-ying , Li Jing , Mo Zhi-xian
Published: February 2018

Objective. To compare the expressions of miRNAs (microRNAs) in serum exosomes and in hippocampus and to provide insights into the miRNA‐mediated relationship between peripheral and central nervous systems in the presence of methamphetamine. Methods. Published results on conditioned place preference (CPP) in rats conditioned by methamphetamine were replicated. The expressions of miRNAs in serum exosomes and hippocampus were determined by gene‐chip sequencing. We then predicted the potential target genes of selected, differentially expressed (DE) miRNAs and then carried out functional analysis of these target genes. We also verified our results by RT‐qPCR. Results. Methamphetamine reward could greatly increase the activity time and distance in the intrinsically nonpreferred side of the behavioral apparatus compared with control rats (P < 0.01). Rhynchophylline treatment significantly counteracted these changes (P < 0.01). Methamphetamine‐induced CPP upregulated 23 miRNAs (log2 fold change [FC] > 1, P < 0.01) in serum exosomes, whereas rhynchophylline treatment could downregulate these miRNAs (log2 FC < −1, P < 0.01). Analysis of hippocampal miRNAs profiles found 22 DE miRNAs (log2 FC > 1 or <−1, P < 0.01). When methamphetamine induced CPP, 11 of those miRNAs were upregulated, whereas rhynchophylline treatment could downregulate these miRNAs. The other 11 miRNAs behaved in the opposite way. We selected six DE miRNAs from each of serum exosomes and hippocampus for target gene prediction and functional analysis. We found that, in both, the DE miRNAs and their target genes may be related to neuronal information transmission and synaptic transmission. Conclusions. Rhynchophylline blocked the alteration of behavior and the expression of some DE miRNAs induced by methamphetamine. The biological functions of these DE miRNAs target genes are correlated between serum exosomes and hippocampus. As to these biological processes and pathways which are involved in the development of addiction at multiple stages, we speculate that these DE miRNAs in serum exosomes and hippocampus are closely related to methamphetamine addiction.
Acoustic Emission and Damage Characteristics of Granite Subjected to High Temperature
Authors: Xu X. L. , Zhang Z.-Z.
Published: February 2018

Acoustic emission (AE) signals can be detected from rocks under the effect of temperature and loading, which can be used to reflect rock damage evolution process and predict rock fracture. In this paper, uniaxial compression tests of granite at high temperatures from 25°C to 1000°C were carried out, and AE signals were monitored simultaneously. The results indicated that AE ring count rate shows the law of “interval burst” and “relatively calm,” which can be explained from the energy point of view. From 25°C to 1000°C, the rock failure mode changes from single splitting failure to multisplitting failure, and then to incomplete shear failure, ideal shear failure, and double shear failure, until complete integral failure. Thermal damage (DT) defined by the elastic modulus shows logistic increase with the rise of temperature. Mechanical damage (DM) derived by the AE ring count rate can be divided into initial stage, stable stage, accelerated stage, and destructive stage. Total damage (D) increases with the rise of strain, which is corresponding to the stress‐strain curve at various temperatures. Using AE data, we can further analyze the mechanism of deformation and fracture of rock, which helps to gather useful data for predicting rock stability at high temperatures.
Analysis of Drug Effects on Primary Human Coronary Artery Endothelial Cells Activated by Serum Amyloid A
Authors: Lakota K. , Hrušovar D. , Ogrič M. , Mrak-Poljšak K. , Čučnik S. , Tomšič M. , Božič B. , Žigon P. , Sodin-Semrl S.
Published: February 2018

Background. RA patients have a higher incidence of cardiovascular diseases compared to the general population. Serum amyloid A (SAA) is an acute-phase protein, upregulated in sera of RA patients. Aim. To determine the effects of medications on SAA-stimulated human coronary artery endothelial cells (HCAEC). Methods. HCAEC were preincubated for 2 h with medications from sterile ampules (dexamethasone, methotrexate, certolizumab pegol, and etanercept), dissolved in medium (captopril) or DMSO (etoricoxib, rosiglitazone, meloxicam, fluvastatin, and diclofenac). Human recombinant apo-SAA was used to stimulate HCAEC at a final 1000 nM concentration for 24 hours. IL-6, IL-8, sVCAM-1, and PAI-1 were measured by ELISA. The number of viable cells was determined colorimetrically. Results. SAA-stimulated levels of released IL-6, IL-8, and sVCAM-1 from HCAEC were significantly attenuated by methotrexate, fluvastatin, and etoricoxib. Both certolizumab pegol and etanercept significantly decreased PAI-1 by an average of 43%. Rosiglitazone significantly inhibited sVCAM-1 by 58%. Conclusion. We observed marked influence of fluvastatin on lowering cytokine production in SAA-activated HCAEC. Methotrexate showed strong beneficial effects for lowering released Il-6, IL-8, and sVCAM-1. Interesting duality was observed for NSAIDs, with meloxicam exhibiting opposite-trend effects from diclofenac and etoricoxib. This represents unique insight into specific responsiveness of inflammatory-driven HCAEC relevant to atherosclerosis.
Adaptive Constrained Control for Uncertain Nonlinear Time-Delay System with Application to Unmanned Helicopter
Authors: Li Rong , Wu Qingxian , Yang Qingyun , Ye Hui
Published: February 2018

This paper investigates a class of nonlinear time-delayed systems with output prescribed performance constraint. The neural network and DOB (disturbance observer) are designed to tackle the uncertainties and external disturbance, and prescribed performance function is constructed for the output prescribed performance constrained problem. Then the robust controller is designed by using adaptive backstepping method, and the stability analysis is considered by using Lyapunov-Krasovskii. Furthermore, the proposed method is employed into the unmanned helicopter system with time-delay aerodynamic uncertainty. Finally, the simulation results illustrate that the proposed robust prescribed performance control system achieved a good control performance.
Modified Backtracking Search Optimization Algorithm Inspired by Simulated Annealing for Constrained Engineering Optimization Problems
Authors: Wang Hailong , Hu Zhongbo , Sun Yuqiu , Su Qinghua , Xia Xuewen
Published: February 2018

The backtracking search optimization algorithm (BSA) is a population-based evolutionary algorithm for numerical optimization problems. BSA has a powerful global exploration capacity while its local exploitation capability is relatively poor. This affects the convergence speed of the algorithm. In this paper, we propose a modified BSA inspired by simulated annealing (BSAISA) to overcome the deficiency of BSA. In the BSAISA, the amplitude control factor (F) is modified based on the Metropolis criterion in simulated annealing. The redesigned F could be adaptively decreased as the number of iterations increases and it does not introduce extra parameters. A self-adaptive ε-constrained method is used to handle the strict constraints. We compared the performance of the proposed BSAISA with BSA and other well-known algorithms when solving thirteen constrained benchmarks and five engineering design problems. The simulation results demonstrated that BSAISA is more effective than BSA and more competitive with other well-known algorithms in terms of convergence speed.
Multiframe Ultrasonic TOFD Weld Inspection Imaging Based on Wavelet Transform and Image Registration
Authors: Duan Jiaxu , Luo Lin , Gao Xiaorong , Peng Jianping , Li Jinlong
Published: February 2018

TOFD (time of flight diffraction) is a kind of weld defect detection technology by using ultrasonic diffraction wave signal. Because the diffraction intensity is far less than ultrasonic echo wave intensity, thus, the noise contained in TOFD signal is fairly large, and the formed image is not clear enough. Therefore, it is difficult to determine the size of defects accurately. In this paper, a method of noise reduction of TOFD signal and improving the resolution of the image are discussed based on the combination of wavelet thresholding and image registration. Wavelet multiresolution analysis method is adopted and the A-scan signal is decomposed into different frequency components. We propose a new threshold function to process the wavelet coefficients, which guarantees to denoise while preserving the useful information as much as possible. Setting up the ultrasonic TOFD inspection system and the image data with randomly distributed noise can be obtained via fine shake of the probes during testing. Then, image registration based on maximum correlation and blending is adopted to eliminate the noise in further step. The result shows that the proposed method can achieve denoising, together with resolution enhancement.
Factors Predicting Self-Care Behaviors among Low Health Literacy Hypertensive Patients Based on Health Belief Model in Bushehr District, South of Iran
Authors: Larki Azam , Tahmasebi Rahim , Reisi Mahnoush
Published: February 2018

The aim of this study was to determine the factors influencing adherence to self-care behaviors among low health literacy hypertensive patients based on health belief model. A cross-sectional study was conducted among 152 hypertensive patients with low health literacy. Patients with limited health literacy were identified by S-TOFHLA. The data were collected using H-scale for assessing self-care behaviors and, HK-LS for assessing knowledge of hypertension. A researcher-made questionnaire was applied for collecting data of health belief model constructs. Data were analyzed by SPSS version 22 with using multiple logistic regression analyses. Perceived self-efficacy was associated with all self-care behaviors except medication regimens. There was a significant association between perceived susceptibility and adherence to both low-salt diet (OR = 3.47) and nonsmoking behavior (OR = 1.10). Individuals who had more perceived severity (OR = 1.82) had significantly greater adherence to their medication regimens. Perceived benefits and barriers were not significantly associated with either type of hypertension self-care behaviors. It seems that designing and implementation of educational programs to increase self-efficacy of patients and promote their beliefs about perceived susceptibility and severity of complications may improve self-care behaviors among low health literacy hypertensive patients.
Stochasticity, Selection, and the Evolution of Cooperation in a Two‐Level Moran Model of the Snowdrift Game
Authors: McLoone Brian , Fan Wai-Tong Louis , Pham Adam , Smead Rory , Loewe Laurence
Published: February 2018

The Snowdrift Game, also known as the Hawk‐Dove Game, is a social dilemma in which an individual can participate (cooperate) or not (defect) in producing a public good. It is relevant to a number of collective action problems in biology. In a population of individuals playing this game, traditional evolutionary models, in which the dynamics are continuous and deterministic, predict a stable, interior equilibrium frequency of cooperators. Here, we examine how finite population size and multilevel selection affect the evolution of cooperation in this game using a two‐level Moran process, which involves discrete, stochastic dynamics. Our analysis has two main results. First, we find that multilevel selection in this model can yield significantly higher levels of cooperation than one finds in traditional models. Second, we identify a threshold effect for the payoff matrix in the Snowdrift Game, such that below (above) a determinate cost‐to‐benefit ratio, cooperation will almost surely fix (go extinct) in the population. This second result calls into question the explanatory reach of traditional continuous models and suggests a possible alternative explanation for high levels of cooperative behavior in nature.
Cross-talk Signaling between HER3 and HPV16 E6 and E7 Mediates Resistance to PI3K Inhibitors in Head and Neck Cancer
Authors: Brand Toni M. , Hartmann Stefan , Bhola Neil E. , Li Hua , Zeng Yan , O'Keefe Rachel A. , Ranall Max V. , Bandyopadhyay Sourav , Soucheray Margaret , Krogan Nevan J. , Kemp Carolyn , Duvvuri Umamaheswar , LaVallee Theresa , Johnson Daniel E. , Ozbun Michelle A. , Bauman Julie E. , Grandis Jennifer R.
Published: February 2018

Human papillomavirus (HPV) type 16 is implicated in approximately 75% of head and neck squamous cell carcinomas (HNSCC) that arise in the oropharynx, where viral expression of the E6 and E7 oncoproteins promote cellular transformation, tumor growth, and maintenance. An important oncogenic signaling pathway activated by E6 and E7 is the PI3K pathway, a key driver of carcinogenesis. The PI3K pathway is also activated by mutation or amplification of PIK3CA in over half of HPV(+) HNSCC. In this study, we investigated the efficacy of PI3K-targeted therapies in HPV(+) HNSCC preclinical models and report that HPV(+) cell line- and patient-derived xenografts are resistant to PI3K inhibitors due to feedback signaling emanating from E6 and E7. Receptor tyrosine kinase profiling indicated that PI3K inhibition led to elevated expression of the HER3 receptor, which in turn increased the abundance of E6 and E7 to promote PI3K inhibitor resistance. Targeting HER3 with siRNA or the mAb CDX-3379 reduced E6 and E7 abundance and enhanced the efficacy of PI3K-targeted therapies. Together, these findings suggest that cross-talk between HER3 and HPV oncoproteins promotes resistance to PI3K inhibitors and that cotargeting HER3 and PI3K may be an effective therapeutic strategy in HPV(+) tumors.

Significance: These findings suggest a new therapeutic combination that may improve outcomes in HPV(+) head and neck cancer patients. Cancer Res; 78(9); 2383–95. ©2018 AACR.
The FACT inhibitor CBL0137 Synergizes with Cisplatin in Small-Cell Lung Cancer by Increasing NOTCH1 Expression and Targeting Tumor-Initiating Cells
Authors: De Sarmishtha , Lindner Daniel J. , Coleman Claire J. , Wildey Gary , Dowlati Afshin , Stark George R.
Published: February 2018

Traditional treatments of small-cell lung cancer (SCLC) with cisplatin, a standard-of-care therapy, spare the tumor-initiating cells (TIC) that mediate drug resistance. Here we report a novel therapeutic strategy that preferentially targets TICs in SCLC, in which cisplatin is combined with CBL0137, an inhibitor of the histone chaperone facilitates chromatin transcription (FACT), which is highly expressed in TICs. Combination of cisplatin and CBL0137 killed patient-derived and murine SCLC cell lines synergistically. In response to CBL0137 alone, TICs were more sensitive than non-TICs, in part, because CBL0137 increased expression of the tumor suppressor NOTCH1 by abrogating the binding of negative regulator SP3 to the NOTCH1 promoter, and in part because treatment decreased the high expression of stem cell transcription factors. The combination of cisplatin and CBL0137 greatly reduced the growth of a patient-derived xenograft in mice and also the growth of a syngeneic mouse SCLC tumor. Thus, CBL0137 can be a highly effective drug against SCLC, especially in combination with cisplatin.

Significance: These findings reveal a novel therapeutic regimen for SCLC, combining cisplatin with an inhibitor that preferentially targets tumor-initiating cells. Cancer Res; 78(9); 2396–406. ©2018 AACR.
RSK Regulates PFK-2 Activity to Promote Metabolic Rewiring in Melanoma
Authors: Houles Thibault , Gravel Simon-Pierre , Lavoie Geneviève , Shin Sejeong , Savall Mathilde , Méant Antoine , Grondin Benoit , Gaboury Louis , Yoon Sang-Oh , St-Pierre Julie , Roux Philippe P.
Published: February 2018

Metabolic reprogramming is a hallmark of cancer that includes increased glucose uptake and accelerated aerobic glycolysis. This phenotype is required to fulfill anabolic demands associated with aberrant cell proliferation and is often mediated by oncogenic drivers such as activated BRAF. In this study, we show that the MAPK-activated p90 ribosomal S6 kinase (RSK) is necessary to maintain glycolytic metabolism in BRAF-mutated melanoma cells. RSK directly phosphorylated the regulatory domain of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2), an enzyme that catalyzes the synthesis of fructose-2,6-bisphosphate during glycolysis. Inhibition of RSK reduced PFKFB2 activity and glycolytic flux in melanoma cells, suggesting an important role for RSK in BRAF-mediated metabolic rewiring. Consistent with this, expression of a phosphorylation-deficient mutant of PFKFB2 decreased aerobic glycolysis and reduced the growth of melanoma in mice. Together, these results indicate that RSK-mediated phosphorylation of PFKFB2 plays a key role in the metabolism and growth of BRAF-mutated melanomas.

Significance: RSK promotes glycolytic metabolism and the growth of BRAF-mutated melanoma by driving phosphorylation of an important glycolytic enzyme. Cancer Res; 78(9); 2191–204. ©2018 AACR.
The Balance Players of the Adaptive Immune System
Authors: Andersen Mads Hald
Published: February 2018

Equilibrium between immune activation and suppression may be necessary to maintain immune homeostasis, because proinflammatory effector T cells (defined as antiregulatory T cells) counteract the functions of regulatory immune cells. These self-reactive T cells recognize human leukocyte antigen (HLA)–restricted epitopes derived from proteins expressed by regulatory immune cells such as IDO, PD-L1, PD-L2, or arginase. The activation of such proinflammatory effector T cells offers a novel way to directly target the tumor microenvironment, potentially giving them considerable clinical value, especially in patients with cancer. Vaccination against genetically stable cells with regular HLA expression is an attractive way to directly target immunosuppressive cells in addition to attracting proinflammatory cells into the tumor microenvironment. Importantly, vaccination toward IDO or PD-L1 to potentiate such T cells have proven safe, with minimal toxicity in the clinical phase I trials conducted thus far.Cancer Res; 78(6); 1379–82. ©2018 AACR.
T-Cell Exhaustion Signatures Vary with Tumor Type and Are Severe in Glioblastoma
Authors: Woroniecka Karolina , Chongsathidkiet Pakawat , Rhodin Kristen , Kemeny Hanna , Dechant Cosette , Farber S. Harrison , Elsamadicy Aladine A. , Cui Xiuyu , Koyama Shohei , Jackson Christina , Hansen Landon J. , Johanns Tanner M. , Sanchez-Perez Luis , Chandramohan Vidyalakshmi , Yu Yen-Rei Andrea , Bigner Darell D. , Giles Amber , Healy Patrick , Dranoff Glenn , Weinhold Kent J. , Dunn Gavin P. , Fecci Peter E.
Published: February 2018

Purpose: T-cell dysfunction is a hallmark of glioblastoma (GBM). Although anergy and tolerance have been well characterized, T-cell exhaustion remains relatively unexplored. Exhaustion, characterized in part by the upregulation of multiple immune checkpoints, is a known contributor to failures amid immune checkpoint blockade, a strategy that has lacked success thus far in GBM. This study is among the first to examine, and credential as bona fide, exhaustion among T cells infiltrating human and murine GBM.

Experimental Design: Tumor-infiltrating and peripheral blood lymphocytes (TILs and PBLs) were isolated from patients with GBM. Levels of exhaustion-associated inhibitory receptors and poststimulation levels of the cytokines IFNγ, TNFα, and IL2 were assessed by flow cytometry. T-cell receptor Vβ chain expansion was also assessed in TILs and PBLs. Similar analysis was extended to TILs isolated from intracranial and subcutaneous immunocompetent murine models of glioma, breast, lung, and melanoma cancers.

Results: Our data reveal that GBM elicits a particularly severe T-cell exhaustion signature among infiltrating T cells characterized by: (1) prominent upregulation of multiple immune checkpoints; (2) stereotyped T-cell transcriptional programs matching classical virus-induced exhaustion; and (3) notable T-cell hyporesponsiveness in tumor-specific T cells. Exhaustion signatures differ predictably with tumor identity, but remain stable across manipulated tumor locations.

Conclusions: Distinct cancers possess similarly distinct mechanisms for exhausting T cells. The poor TIL function and severe exhaustion observed in GBM highlight the need to better understand this tumor-imposed mode of T-cell dysfunction in order to formulate effective immunotherapeutic strategies targeting GBM. Clin Cancer Res; 24(17); 4175–86. ©2018 AACR.

See related commentary by Jackson and Lim, p. 4059
Mechanistic Exploration of Cancer Stem Cell Marker Voltage-Dependent Calcium Channel α2δ1 Subunit-mediated Chemotherapy Resistance in Small-Cell Lung Cancer
Authors: Yu Jiangyong , Wang Shuhang , Zhao Wei , Duan Jianchun , Wang Zhijie , Chen Hanxiao , Tian Yanhua , Wang Di , Zhao Jun , An Tongtong , Bai Hua , Wu Meina , Wang Jie
Published: February 2018

Purpose: Chemoresistance in small-cell lung cancer (SCLC) is reportedly attributed to the existence of resistant cancer stem cells (CSC). Studies involving CSC-specific markers and related mechanisms in SCLC remain limited. This study explored the role of the voltage-dependent calcium channel α2δ1 subunit as a CSC marker in chemoresistance of SCLC, and explored the potential mechanisms of α2δ1-mediated chemoresistance and strategies of overcoming the resistance.

Experimental Design: α2δ1-positive cells were identified and isolated from SCLC cell lines and patient-derived xenograft (PDX) models, and CSC-like properties were subsequently verified. Transcriptome sequencing and Western blotting were carried out to identify pathways involved in α2δ1-mediated chemoresistance in SCLC. In addition, possible interventions to overcome α2δ1-mediated chemoresistance were examined.

Results: Different proportions of α2δ1+ cells were identified in SCLC cell lines and PDX models. α2δ1+ cells exhibited CSC-like properties (self-renewal, tumorigenic, differentiation potential, and high expression of genes related to CSCs and drug resistance). Chemotherapy induced the enrichment of α2δ1+ cells instead of CD133+ cells in PDXs, and an increased proportion of α2δ1+ cells corresponded to increased chemoresistance. Activation and overexpression of ERK in the α2δ1-positive H1048 cell line was identified at the protein level. mAb 1B50-1 was observed to improve the efficacy of chemotherapy and delay relapse as maintenance therapy in PDX models.

Conclusions: SCLC cells expressing α2δ1 demonstrated CSC-like properties, and may contribute to chemoresistance. ERK may play a key role in α2δ1-mediated chemoresistance. mAb 1B50-1 may serve as a potential anti-SCLC drug. Clin Cancer Res; 24(9); 2148–58. ©2018 AACR.
Human Papillomavirus DNA Methylation as a Biomarker for Cervical Precancer: Consistency across 12 Genotypes and Potential Impact on Management of HPV-Positive Women
Authors: Clarke Megan A. , Gradissimo Ana , Schiffman Mark , Lam Jessica , Sollecito Christopher C. , Fetterman Barbara , Lorey Thomas , Poitras Nancy , Raine-Bennett Tina R. , Castle Philip E. , Wentzensen Nicolas , Burk Robert D.
Published: February 2018

Purpose: Human papillomavirus (HPV) DNA methylation testing is a promising triage option for women testing HPV positive during cervical cancer screening. However, the extent to which methylation indicates precancer for all 12 carcinogenic HPV types has not been evaluated.

Experimental Design: In this nested case–control study, we tested up to 30 cases of precancer [cervical intraepithelial neoplasia grade 3 (CIN3)/adenocarcinoma in situ (AIS)] and 30 normal controls for each carcinogenic type (single infections with 16/18/31/33/35/39/45/51/52/56/58/59). Next-generation bisulfite sequencing was performed on CpG sites within the L1 and L2 genes. We calculated differences in methylation, ORs, and AUC. Using a fixed sensitivity of 80%, we evaluated the specificity and the risk of CIN3/AIS for best performing CpG sites, and compared the performance of an explorative multi-type methylation assay with current triage strategies.

Results: Methylation was positively associated with CIN3/AIS across all 12 types. AUCs for the top sites ranged from 0.71 (HPV51 and HPV56) to 0.86 (HPV18). A combined 12-type methylation assay had the highest Youden index (0.46), compared with cytology (0.31) and a 5-type methylation assay, including only previously described types (0.26). The 12-type methylation assay had higher sensitivity (80% vs. 76.6%) and lower test positivity compared with cytology (38.5% vs. 48.7%). The risk of CIN3/AIS was highest for methylation positives and lowest for cytology or HPV16/18 positives.

Conclusions: HPV DNA methylation is a general phenomenon marking the transition from HPV infection to precancer for all 12 carcinogenic types. Development of a combined multitype methylation assay may serve as a triage test for HPV-positive women. Clin Cancer Res; 24(9); 2194–202. ©2018 AACR.
Harnessing the Power of Patient-Reported Outcomes in Oncology
Authors: Nipp Ryan D. , Temel Jennifer S.
Published: February 2018

Patient-reported outcomes (PRO) represent an increasingly important mechanism for incorporating patients' experiences and perspectives into their care to enhance cancer care delivery and outcomes. In this article, we discuss the importance of integrating PROs into both the clinical and research settings in oncology and highlight potential challenges. Clin Cancer Res; 24(8); 1777–9. ©2018 AACR.

See related article by Kim et al., p. 1780
Impact of the Anticancer Drug NT157 on Tyrosine Kinase Signaling Networks
Authors: Su Shih-Ping , Flashner-Abramson Efrat , Klein Shoshana , Gal Mor , Lee Rachel S. , Wu Jianmin , Levitzki Alexander , Daly Roger J.
Published: February 2018

The small-molecule drug NT157 has demonstrated promising efficacy in preclinical models of a number of different cancer types, reflecting activity against both cancer cells and the tumor microenvironment. Two known mechanisms of action are degradation of insulin receptor substrates (IRS)-1/2 and reduced Stat3 activation, although it is possible that others exist. To interrogate the effects of this drug on cell signaling pathways in an unbiased manner, we have undertaken mass spectrometry–based global tyrosine phosphorylation profiling of NT157-treated A375 melanoma cells. Bioinformatic analysis of the resulting dataset resolved 5 different clusters of tyrosine-phosphorylated peptides that differed in the directionality and timing of response to drug treatment over time. The receptor tyrosine kinase AXL exhibited a rapid decrease in phosphorylation in response to drug treatment, followed by proteasome-dependent degradation, identifying an additional potential target for NT157 action. However, NT157 treatment also resulted in increased activation of p38 MAPK α and γ, as well as the JNKs and specific Src family kinases. Importantly, cotreatment with the p38 MAPK inhibitor SB203580 attenuated the antiproliferative effect of NT157, while synergistic inhibition of cell proliferation was observed when NT157 was combined with a Src inhibitor. These findings provide novel insights into NT157 action on cancer cells and highlight how globally profiling the impact of a specific drug on cellular signaling networks can identify effective combination treatments. Mol Cancer Ther; 17(5); 931–42. ©2018 AACR.
RHD-Positive Alleles among D- C/E+ Individuals from India
Authors: Kulkarni Swati S. , Gogri Harita , Parchure Disha , Mishra Garima , Ghosh Kanjaksha , Rajadhyaksha Sunil , Madkaikar Manisha , Férec Claude , Fichou Yann
Published: February 2018

Background: Molecular bases of blood group systems, including Rh blood group, have been poorly studied in the Indian population so far, while specificities of Europeans, East Asians and Africans have been well known for years. In order to gain insights into the molecular bases of this population, we sought to characterize the RHD allele in D- Indian donors expressing C and/or E antigen(s). Methods:RHD gene was analyzed in 171 serologically D-, C/E+ samples by standard molecular methods such as quantitative, multiplex PCR of short fluorescent fragments (QMPSF) and direct sequencing when necessary. Results:RHD whole gene deletion at the homozygous state was found to be the most common genotype associated with D- phenotype (118/171, 69.0%). Nonfunctional, negative hybrid genes with reported molecular backgrounds were observed in approximately one-third of the samples, while only four samples carry single-nucleotide variations, including one novel nonsense (RHD(Y243X)), one novel frameshift (RHD(c.701delG)), and two missense (RHD(T148R) and RHD(T148R, T195M)) alleles. Conclusion: Overall we report for the first time the molecular bases of D antigen negativity in the D-, C/E+ Indian population, which appears to be qualitatively similar to other populations, but with a population-specific, quantitative distribution of D-- alleles.