bluuebunny/crossref_metadata_2025 huggingface dataset:
Model of the songbird nucleus HVC as a network of central pattern generators
Authors: Armstrong Eve , Abarbanel Henry D. I.
Published: August 2016

We propose a functional architecture of the adult songbird nucleus HVC in which the core element is a “functional syllable unit” (FSU). In this model, HVC is organized into FSUs, each of which provides the basis for the production of one syllable in vocalization. Within each FSU, the inhibitory neuron population takes one of two operational states: 1) simultaneous firing wherein all inhibitory neurons fire simultaneously, and 2) competitive firing of the inhibitory neurons. Switching between these basic modes of activity is accomplished via changes in the synaptic strengths among the inhibitory neurons. The inhibitory neurons connect to excitatory projection neurons such that during state 1 the activity of projection neurons is suppressed, while during state 2 patterns of sequential firing of projection neurons can occur. The latter state is stabilized by feedback from the projection to the inhibitory neurons. Song composition for specific species is distinguished by the manner in which different FSUs are functionally connected to each other. Ours is a computational model built with biophysically based neurons. We illustrate that many observations of HVC activity are explained by the dynamics of the proposed population of FSUs, and we identify aspects of the model that are currently testable experimentally. In addition, and standing apart from the core features of an FSU, we propose that the transition between modes may be governed by the biophysical mechanism of neuromodulation.
Evacuation Network Optimization Model with Lane-Based Reversal and Routing
Authors: Zhao Xing , Feng Zhao-yan , Li Yan , Bernard Antoine
Published: August 2016

Sometimes, the evacuation measure may seem to be the best choice as an emergency response. To enable an efficiency evacuation, a network optimization model which integrates lane-based reversal design and routing with intersection crossing conflict elimination for evacuation is constructed. The proposed bilevel model minimizes the total evacuation time to leave the evacuation zone. A tabu search algorithm is applied to find an optimal lane reversal plan in the upper-level. The lower-level utilizes a simulated annealing algorithm to get two types of “a single arc for an intersection approach” and “multiple arcs for an intersection approach” lane-based route plans with intersection crossing conflict elimination. An experiment of a nine-intersection evacuation zone illustrates the validity of the model and the algorithm. A field case with network topology of Jianye District around the Nanjing Olympics Sports Center is studied to show the applicability of this algorithm.
The Design and Life Test of a Multifunction Power Amplifier for Space Application
Authors: Xu Xiuqin , Xu Hui , Shang Yongheng , Wang Zhiyu , Wang Yang , Wang Liping , Luo Hao , Huang Zhengliang , Yu Faxin
Published: August 2016

A new multifunction power amplifier (MFPA) is designed and fabricated for the application of point-to-point K-Band backhaul TR module. A DC temperature life test was performed to model the up-limit temperature effect of the designed MFPA under space application. After 240 hours of 100°C life test, the test results illustrate that the designed MFPA has only slight power degradation at the saturation region without change of the linear gain. The general performance of the designed MFPA satisfies the requirement of the application scenario.
A Generalized Class of Exponential Type Estimators for Population Mean under Systematic Sampling Using Two Auxiliary Variables
Authors: Khan Mursala
Published: August 2016

We have proposed a generalized class of exponential type estimators for population mean under the framework of systematic sampling using the knowledge of two auxiliary variables. The expressions for the mean square error of the proposed class of estimators have been corrected up to first order of approximation. Comparisons of the efficiency of the proposed class of estimators under the optimal conditions with the other existing estimators have been presented through a real secondary data. The statistical study provides strong evidence that the proposed class of estimators in survey estimation procedure results in substantial efficiency improvements over the other existing estimation approaches.
Study on the Accuracy Improvement of the Second-Kind Fredholm Integral Equations by Using the Buffa-Christiansen Functions with MLFMA
Authors: Wu Yue-Qian , Sheng Xin-Qing , Guo Xing-Yue , Zhou Hai-Jing
Published: August 2016

Former works show that the accuracy of the second-kind integral equations can be improved dramatically by using the rotated Buffa-Christiansen (BC) functions as the testing functions, and sometimes their accuracy can be even better than the first-kind integral equations. When the rotated BC functions are used as the testing functions, the discretization error of the identity operators involved in the second-kind integral equations can be suppressed significantly. However, the sizes of spherical objects which were analyzed are relatively small. Numerical capability of the method of moments (MoM) for solving integral equations with the rotated BC functions is severely limited. Hence, the performance of BC functions for accuracy improvement of electrically large objects is not studied. In this paper, the multilevel fast multipole algorithm (MLFMA) is employed to accelerate iterative solution of the magnetic-field integral equation (MFIE). Then a series of numerical experiments are performed to study accuracy improvement of MFIE in perfect electric conductor (PEC) cases with the rotated BC as testing functions. Numerical results show that the effect of accuracy improvement by using the rotated BC as the testing functions is greatly different with curvilinear or plane triangular elements but falls off when the size of the object is large.
Determination of Alcohol Content in Alcoholic Beverages Using 45 MHz Benchtop NMR Spectrometer
Authors: Isaac-Lam Meden F.
Published: August 2016

Alcohol or ethanol is considered the most widely used recreational drug worldwide, and its production, consumption, and sale are strictly regulated by laws. Alcohol content of alcoholic beverages (wine, beers, and spirits) is about 3–50% v/v. Analytical methods to determine the alcohol content must be reliable, precise, and accurate. In this study, the amount of ethanol in several alcoholic beverages was determined using a 45 MHz low-field benchtop NMR (nuclear magnetic resonance) spectrometer. Internal standard and standard addition analytical methods were utilized to quantify ethanol. For both methods, acetic acid or acetonitrile was used as internal standard to quantify alcohol content by using the peak area corresponding to the methyl peaks of ethanol, acetic acid, or acetonitrile. Results showed that internal standard method gave values of percent alcohol that are in close agreement with the indicated label as confirmed by running the samples in a 400 MHz high-field NMR spectrometer using acetic acid as internal standard. This study demonstrates the utility of a benchtop NMR spectrometer that can provide an alternative technique to analyze percent alcohol in alcoholic products.
Measurement of Circumferential Liquid Film Based on LIF and Virtual Stereo Vision Sensor
Authors: Xue Ting , Lin Xiaokang , Yang Liuxiangzi
Published: August 2016

Gas-liquid annular flow is widely used in many industrial applications such as petroleum, chemical, and nuclear engineering. The feature parameters of liquid film in the annular flow are of great significance to understand the flow characteristics and measure the flow precisely. For the annular flow, the circumferential features of liquid film are more important than the axial features to acquire abundant flow structures and reveal the flow mechanism. In the paper, a measurement platform based on the laser-induced fluorescence (LIF) and virtual stereo vision sensor is presented. The virtual stereo vision sensor comprises a high-speed camera and two optical reflection sets, which can acquire the liquid film from two views simultaneously and reconstruct the features of liquid film. Image processing techniques are proceeded with to extract the feature parameters of liquid film; then the circumferential flow characteristic can be reconstructed by views transformation and fusion. The flow characteristic based on the thickness distribution is analysed. The experimental results show that the method is valid and effective, which can give a more detailed and accurate description for the liquid film in annular flows.
Diet-Intestinal Microbiota Axis in Osteoarthritis: A Possible Role
Authors: Li Yusheng , Luo Wei , Deng Zhenhan , Lei Guanghua
Published: August 2016

Intestinal microbiota is highly involved in host physiology and pathology through activity of the microbiome and its metabolic products. Osteoarthritis (OA) is a common form of arthritis characterized by articular cartilage destruction and osteophyte formation. Although various person-level risk factors, such as age, sex, and obesity, have been proposed for the pathogenesis of OA, the underlying links between these person-level factors and OA are still enigmatic. Based on the current understanding in the crosstalk between intestinal microbiota and these risk factors, intestinal microbiota could be considered as a major hidden risk factor that provides a unifying mechanism to explain the involvement of these person-level risk factors in OA.
In Vivo Tracking of Systemically Administered Allogeneic Bone Marrow Mesenchymal Stem Cells in Normal Rats through Bioluminescence Imaging
Authors: Cao Juan , Hou Shike , Ding Hui , Liu Ziquan , Song Meijuan , Qin Xiaojing , Wang Xue , Yu Mengyang , Sun Zhiguang , Liu Jinyang , Sun Shuli , Xiao Peixin , Lv Qi , Fan Haojun
Published: August 2016

Recently, mesenchymal stem cells (MSCs) are increasingly used as a panacea for multiple types of disease short of effective treatment. Dozens of clinical trials published demonstrated strikingly positive therapeutic effects of MSCs. However, as a specific agent, little research has focused on the dynamic distribution of MSCs after in vivo administration. In this study, we track systemically transplanted allogeneic bone marrow mesenchymal stem cells (BMSCs) in normal rats through bioluminescence imaging (BLI) in real time. Ex vivo organ imaging, immunohistochemistry (IHC), and RT‐PCR were conducted to verify the histological distribution of BMSCs. Our results showed that BMSCs home to the dorsal skin apart from the lungs and kidneys after tail vein injection and could not be detected 14 days later. Allogeneic BMSCs mainly appeared not at the parenchymatous organs but at the subepidermal connective tissue and adipose tissue in healthy rats. There were no significant MSCs‐related adverse effects except for transient decrease in neutrophils. These findings will provide experimental evidences for a better understanding of the biocharacteristics of BMSCs.
An Improved L-Shaped Method for Solving Process Flexibility Design Problems
Authors: Yang Huasheng , Gupta Jatinder N. D. , Yu Lina , Zheng Li
Published: August 2016

Process flexibility, where a plant is able to produce different types of products, is introduced to mitigate mismatch risk caused by demand uncertainties. Thelong chain designproposed by Jordan and Graves in 1995 has been shown to be able to reap most benefits of full-flexibility structure (where each plant is able to produce all products) in balanced systems (where the numbers of products and plants are equal). However, when systems are not balanced or asymmetric or when response dimension is taken into consideration, long chain design may not be the best configuration. Therefore, this paper models the process flexibility design problem in more general settings. The paper considers both balanced and unbalanced systems with asymmetric plants considering response dimension. The problem is formulated as a two-stage stochastic program which is solved by an adapted L-shaped method, combining it with several enhancements. To the best of our knowledge, this is the first time L-shaped method is used to solve the process flexibility design problem. The effectiveness and efficiency of the proposed method and enhancements are evaluated. Finally, the comparison between design methods proposed in this paper and in existing literature shows the superiority of the former.
EEG-Based BCI System Using Adaptive Features Extraction and Classification Procedures
Authors: Mondini Valeria , Mangia Anna Lisa , Cappello Angelo
Published: August 2016

Motor imagery is a common control strategy in EEG-based brain-computer interfaces (BCIs). However, voluntary control of sensorimotor (SMR) rhythms by imagining a movement can be skilful and unintuitive and usually requires a varying amount of user training. To boost the training process, a whole class of BCI systems have been proposed, providing feedback as early as possible while continuously adapting the underlying classifier model. The present work describes a cue-paced, EEG-based BCI system using motor imagery that falls within the category of the previously mentioned ones. Specifically, our adaptive strategy includes a simple scheme based on a common spatial pattern (CSP) method and support vector machine (SVM) classification. The system’s efficacy was proved by online testing on 10 healthy participants. In addition, we suggest some features we implemented to improve a system’s “flexibility” and “customizability,” namely, (i) a flexible training session, (ii) an unbalancing in the training conditions, and (iii) the use of adaptive thresholds when giving feedback.
Adjoining a Constant Function ton-Dimensional Chebyshev Space
Authors: Alyazidi-Asiry Mansour
Published: August 2016

This paper is concerned with extending a Chebyshev system ofncontinuous nonconstant functions into a set ofn+1functions including a constant function. Necessary and sufficient conditions for the new set to be a Chebyshev system are discussed and some results are obtained.
Intrastromal Injection of Bevacizumab in the Management of Corneal Neovascularization: About 25 Eyes
Authors: Sarah Belghmaidi , Ibtissam Hajji , Mohammed Baali , Hasna Soummane , Abdeljalil Moutaouakil
Published: August 2016

Introduction. Corneal neovessels are a major risk factor for corneal graft rejection, due to the loss of the immune privilege. The purpose of this study is to evaluate the effectiveness of intrastromal injection of bevacizumab in the treatment of corneal neovascularization.Material and Methods. This is a prospective study that included 25 eyes of 22 patients with deep corneal neovessels, treated with intrastromal injections of bevacizumab.Results. The average age of patients was 31 years ranging from 16 to 44 years. The causes of neovascularization were dominated by herpetic keratitis (10 cases). The evolution was marked by complete regress of neovessels in 16 patients, partial regress in 6 cases, and reduced opacity and improved visual acuity in 5 patients. No side effects were noted.Discussion. Short-term results demonstrated the effectiveness of intrastromal injection of bevacizumab in the treatment of corneal neovessels. It may be an option or a complement to other useful treatments in stabilizing or improving vision.Conclusion. Bevacizumab is an effective additional treatment for the improvement of corneal transplants prognosis with preoperative corneal neovascularization.
Colon Adenoma Implicating Myasthenia Gravis: A Case Report of a Patient with Postcolectomy Complications
Authors: Papachatzakis Y. , Tseliou E. , Tatouli I. , Dialoupi I. , Michas F. , Papadopoulou E. , Kousouris D. , Kontogiannis S. , Dimopoulos M. A.
Published: August 2016

We report the case of a 63-year-old patient with myasthenia gravis (MG) due to acetylcholine receptor antibodies (AChR) who underwent colectomy due to colon adenoma and developed myasthenic crisis and anastomosis leakage after surgery. The patient underwent two plasma exchanges, 4 and 6 days preoperatively, and received intravenous prednisolone and immunoglobulin infusion due to the crisis, which included primarily bulbar symptoms. The patient developed on the 10th postoperative day bowel obstruction symptoms and anastomosis leakage which required surgical repair and ileostomy. Bowel obstruction occurred in a patient with AChR related myasthenia after plasma exchange and during immunosuppression although it is more commonly reported in patients with thymoma related myasthenia.
The Diagnostic Accuracy of Linear Endoscopic Ultrasound for Evaluating Symptoms Suggestive of Common Bile Duct Stones
Authors: Wang Min , He Xu , Tian Chuan , Li Jian , Min Feng , Li Hong-yan
Published: August 2016

Background. In order to assess the diagnostic accuracy of linear EUS for evaluating clinically suggestive CBD stones in high-risk groups.Methods. 202 patients with clinically suggestive CBD stones in high-risk groups who underwent linear EUS examination between January 2012 and January 2015 were retrospectively reviewed. Endoscopic retrograde cholangiopancreatography (ERCP) with stone extraction or surgical choledochoscopy was only performed when a CBD stone was detected by linear EUS. Cases that were negative for CBD stones were followed up for at least 6 months.Results. Of 202 enrolled patients, 126 were positive for CBD stones according to linear EUS findings. 124 patients successfully underwent ERCP, and ERCP failed in 2 who were later successfully treated by surgical intervention. There were 2 false-positive cases with positive findings for CBD stones on ERCP. Among 76 patients without CBD stones, no false-negative cases were identified during the mean 6-month follow-up. Linear EUS had sensitivity, specificity, and positive and negative predictive values for the detection of CBD stones of 100%, 92.88%, 98.21%, and 100%, respectively.Conclusions. Linear EUS is a safe and efficacious diagnostic tool for evaluating clinically suggestive CBD stones with high risk of choledocholithiasis. Performing linear EUS prior to ERCP in patients with symptoms suggestive of CBD stones can reduce unnecessary ERCP procedures.
The Effect of Dexmedetomidine on Lumbar Epidural Injection for Failed Back Surgery Syndrome
Authors: Eskandr Ashraf , Abdel Maseeh Sadik
Published: August 2016

Purpose. Failed back surgery syndrome is a chronic pain condition requiring rapid, effective, and efficient management. This study evaluates the effect of adding dexmedetomidine to lumbar epidural steroids in patients with failed back surgery syndrome.Methods. Fifty patients suffering from failed back surgery syndrome were randomly assigned to one of two groups, receiving an epidural injection of 20 mL of either a mixture of betamethasone (14 mg) and bupivacaine 0.5 mg (group C) or a mixture of betamethasone (14 mg), bupivacaine 0.5 mg, and dexmedetomidine (0.5 μg/kg) (group D) adjusted to the volume with normal saline. The effect was evaluated using visual analogue scale (VAS), analgesic requirement, and Oswestry disability index 2 weeks, 4 weeks, 8 weeks, and 12 weeks after injection.Results. VAS and ibuprofen consumption showed a significant reduction in group D. The Oswestry disability index was significantly improved in group D. There were no records of hypotension, bradycardia, sedation, or hypoxemia in both groups.Conclusion. The present study demonstrated potential safe and effective usage of adding dexmedetomidine to epidural steroid to control pain in patients with failed back surgery syndrome.
A Gel Formulation Containing a New Recombinant Form of Manganese Superoxide Dismutase: A Clinical Experience Based on Compassionate Use-Safety of a Case Report
Authors: Grumetto Lucia , Prete Antonio Del , Ortosecco Giovanni , Borrelli Antonella , Prete Salvatore Del , Mancini Aldo
Published: August 2016

Background. We report a case of bilateral posterior subcapsular cataracts (PSCs) in a 24-year-old man with an allergic conjunctivitis history caused by a long-term therapy with glucocorticoids.Case Presentation. The patient showed a visual acuity of 9/10 for both eyes. He followed a therapy with ketotifen and bilastine for four years. During the last six months before our evaluation, he was treated with chloramphenicol and betamethasone, interrupted for onset of cataracts and increased intraocular pressure. We treated him with ophthalmic gel preparation containing a new recombinant form of manganese superoxide dismutase (rMnSOD) at a concentration of 12.5 μg/mL, only for the right eye, while left eye was treated with standard protocol of Bendazac-lysine g 0.5.Conclusion. This case report shows the protective effects of rMnSOD versus PSC disease, probably due to the capacity of rMnSOD of countering free radical species.
A Natural Generalization of Linear Isotropic Relations with Seth-Hill Strain Tensors to Transversely Isotropic Materials at Finite Strains
Authors: Wang Zhi-Qiao , Wang Yu
Published: August 2016

Hooke’s law was naturally generalized to finite strains by Hill in 1978, by introducing the Seth-Hill strain and its conjugate stress. This paper presents the transversely isotropic relations, which are not only a natural extension of Hill’s theory from isotropic materials to transversely isotropic materials, but also the natural generalization of the transversely isotropic Hooke’s law from infinitesimal strains to moderate strains. This generalization introduces a class of transversely isotropic hyperelastic models, which are adopted to investigate the uniaxial stretch and the simple shear problems. Results show that the material responses for different constitutive equations are significantly different; the stiffening or softening behaviors of materials at moderate deformations can be described by the appropriate model with proper material parameters.
The Progress and Prospects of Putative Biomarkers for Liver Cancer Stem Cells in Hepatocellular Carcinoma
Authors: Xiang Yan , Yang Ting , Pang Bing-yao , Zhu Ying , Liu Yong-ning
Published: August 2016

Accumulating evidence suggests that hepatocellular carcinoma (HCC) is organized by liver cancer stem cells (LCSCs), which are a subset of cells with “stem‐like” characteristics. Identification of the LCSCs is a fundamental and important problem in HCC research. LCSCs have been investigated by various stem cell biomarkers. There is still lack of consensus regarding the existence of a “global” marker for LCSCs in HCC. In this review article, we summarize the progress and prospects of putative biomarkers for LCSCs in the past decades, which is essential to develop future therapies targeting CSCs and to predict prognosis and curative effect of these therapies.
Immediate Postpartum Intrauterine Contraceptive Device Insertions in Caesarean and Vaginal Deliveries: A Comparative Study of Follow-Up Outcomes
Authors: Hooda Reetu , Mann Sonika , Nanda Smiti , Gupta Anjali , More Hemant , Bhutani Jaikrit
Published: August 2016

Background. Immediate postpartum intrauterine contraceptive device (IPPIUCD) is a lucrative postpartum family planning method which provides effective reversible contraception to women in the delivery setting. Our aim was to study the clinical outcomes of IPPIUCD insertions and compare them as a factor of route of insertion (vaginal versus caesarean).Methods. This is a retrospective analytical study done in a tertiary care teaching institute. A Cohort of 593 vaginal and caesarean deliveries with IPPIUCD insertions, over a two-year period, was studied and compared for follow-up results. Outcome measures were safety (perforation, irregular bleeding, unusual vaginal discharge, and infection), efficacy (pregnancy, expulsions, and discontinuations), and incidence of undescended IUCD strings. Descriptives were calculated for various outcomes and chi square tests were used for comparison in between categorical variables.Results. Overall complication rates were low. No case of perforation or pregnancy was reported. Spontaneous expulsions were present in 5.3% cases and were significantly higher in vaginal insertions (p=0.042). The incidence of undescended strings was high (38%), with highly significant difference between both groups (p=0.000).Conclusion. IPPIUCD is a strong weapon in the family planning armoury and should be encouraged in both vaginal and caesarean deliveries. Early follow-up should be encouraged to detect expulsions and tackle common problems.
Triptans Use for Migraine Headache among Nonelderly Adults with Cardiovascular Risk
Authors: Alwhaibi Monira , Deb Arijita , Sambamoorthi Usha
Published: August 2016

Objective. To examine the association between the cardiovascular (CV) risk factors and triptans use among adults with migraine. Methods. A retrospective cross-sectional study design was used. Data were derived from 2009–2013 Medical Expenditure Panel Survey (MEPS). The study sample consisted of adults (age > 21 years) with migraine headache (N = 1,652). Multivariable logistic regression was used to examine the relationship between CV risk factors and triptans use. Results. Overall, 21% adults with migraine headache used triptans. Nearly two-thirds (61%) of adults with migraine had at least one CV risk factor. A significantly lower percentage of adults with CV risk (18.1%) used triptans compared to those without CV risk factors (25.5%). After controlling for demographic, socioeconomic status, access to care, and health status, adults with no CV risk factors were more likely to use triptans as compared to those with one CV risk factor (AOR = 1.83, 95% CI = 1.17–2.87). There were no statistically significant differences in triptans use between those with two or more CV risk factors and those with one CV risk factor. Conclusion. An overwhelming majority of adults with migraine had a contraindication to triptans based on their CV risk factors. The use of triptans among adults with migraine and multiple CV risk factors warrants further investigation.
Transitioning to a Data Driven Mental Health Practice: Collaborative Expert Sessions for Knowledge and Hypothesis Finding
Authors: Menger Vincent , Spruit Marco , Hagoort Karin , Scheepers Floor
Published: August 2016

The surge in the amount of available data in health care enables a novel, exploratory research approach that revolves around finding new knowledge and unexpected hypotheses from data instead of carrying out well-defined data analysis tasks. We propose a specification of the Cross Industry Standard Process for Data Mining (CRISP-DM), suitable for conducting expert sessions that focus on finding new knowledge and hypotheses in collaboration with local workforce. Our proposed specification that we name CRISP-IDM is evaluated in a case study at the psychiatry department of the University Medical Center Utrecht. Expert interviews were conducted to identify seven research themes in the psychiatry department, which were researched in cooperation with local health care professionals using data visualization as a modeling tool. During 19 expert sessions, two results that were directly implemented and 29 hypotheses for further research were found, of which 24 were not imagined during the initial expert interviews. Our work demonstrates the viability and benefits of involving work floor people in the analyses and the possibility to effectively find new knowledge and hypotheses using our CRISP-IDM method.
Electrical Properties of Polytypic Mg Doped GaAs Nanowires
Authors: Cifuentes N. , Viana E. R. , Limborço H. , Roa D. B. , Abelenda A. , da Silva M. I. N. , Moreira M. V. B. , Ribeiro G. M. , de Oliveira A. G. , González J. C.
Published: August 2016

The electrical transport properties of individual Mg doped GaAs nanowires are investigated. It is shown that Mg can be successfully used as a nontoxic p-type dopant in GaAs nanowires. The doping levels, expanding over two orders of magnitude, and free holes mobility in the NW were obtained by the analysis of field effect transistors transfer curves. The temperature dependence of the electrical resistivity above room temperature shows that the polytypic structure of the NWs strongly modifies the NWs charge transport parameters, like the resistivity activation energy and holes mobility. At lower temperatures the NWs exhibit variable range hopping conduction. Both Mott and Efros-Shklovskii variable range hopping mechanisms were clearly identified in the nanowires.
Tobacco and Alcohol Use and the Impact of School Based Antitobacco Education for Knowledge Enhancement among Adolescent Students of Rural Kerala, India
Authors: Jayakrishnan Radhakrishnan , Geetha Seema , Mohanan Nair Jagathnath Krishna Kumara Pillai , Thomas Gigi , Sebastian Paul
Published: August 2016

Objectives. Limited information is available on adolescent tobacco and alcohol use in rural Kerala, the southernmost state in India. The study was conducted to estimate the prevalence of tobacco and alcohol use among adolescent school students and further to understand the extent of knowledge pertaining to tobacco before and after conducting awareness programmes in schools.Methods. A cross-sectional study was conducted in 10 government schools of rural Thiruvananthapuram district of Kerala state based on a multistaged sampling design. Using a pretested semistructured questionnaire, prevalence and patterns of tobacco use by students and their households, as well as students’ knowledge on tobacco hazards before and after delivering antitobacco messages, were collected.Results.The overall prevalence of self-reported ever users of tobacco in the current academic year was 7.4% (95% CI 5.86–8.94), while that of ever alcohol users was 5.6% (95% CI 4.25–6.95). Knowledge assessment scores revealed a significant increase in the mean knowledge scores after posttraining evaluation (mean score = 10.34) when compared to pretraining evaluation (mean score = 9.26) (p<0.0001).Conclusion. Apart from antitobacco awareness programmes, strict monitoring of trade of tobacco and alcohol products near educational institutions has to be conducted consistently to curb the problem.
Prediction Intervals for the Failure Time of Prestressed Concrete Beams
Authors: Szugat Sebastian , Heinrich Jens , Maurer Reinhard , Müller Christine H.
Published: August 2016

The aim is the prediction of the failure time of prestressed concrete beams under low cyclic load. Since the experiments last long for low load, accelerated failure tests with higher load are conducted. However, the accelerated tests are expensive so that only few tests are available. To obtain a more precise failure time prediction, the additional information of time points of breakage of tension wires is used. These breakage time points are modeled by a nonlinear birth process. This allows not only point prediction of a critical number of broken tension wires but also prediction intervals which express the uncertainty of the prediction.
Significant Contribution of Mouse Mast Cell Protease 4 in Early Phases of Experimental Autoimmune Encephalomyelitis
Authors: Desbiens Louisane , Lapointe Catherine , Gharagozloo Marjan , Mahmoud Shaimaa , Pejler Gunnar , Gris Denis , D’Orléans-Juste Pedro
Published: August 2016

Experimental autoimmune encephalomyelitis (EAE) is a mouse model that reproduces cardinal signs of clinical, histopathological, and immunological features found in Multiple Sclerosis (MS). Mast cells are suggested to be involved in the main inflammatory phases occurring during EAE development, possibly by secreting several autacoids and proteases. Among the latter, the chymase mouse mast cell protease 4 (mMCP-4) can contribute to the inflammatory response by producing endothelin-1 (ET-1). The aim of this study was to determine the impact of mMCP-4 on acute inflammatory stages in EAE. C57BL/6 wild type (WT) or mMCP-4 knockout (KO) mice were immunized withMOG35–55plus complete Freund’s adjuvant followed by pertussis toxin. Immunized WT mice presented an initial acute phase characterized by progressive increases in clinical score, which were significantly reduced in mMCP-4 KO mice. In addition, higher levels of spinal myelin were found in mMCP-4 KO as compared with WT mice. Finally, whereas EAE triggered significant increases in brain levels of mMCP-4 mRNA and immunoreactive ET-1 in WT mice, the latter peptide was reduced to basal levels in mMCP-4 KO congeners. Together, the present study supports a role for mMCP-4 in the early inflammatory phases of the disease in a mouse model of MS.
Isolation and Analysis of Phospholipids in Dairy Foods
Authors: Pimentel Lígia , Gomes Ana , Pintado Manuela , Rodríguez-Alcalá Luis Miguel
Published: August 2016

The lipid fraction of milk is one of the most complex matrixes in foodstuffs due to the presence of a high number of moieties with different physical and chemical properties. Glycerolipids include glycerol and two fatty acids esterified in positions sn-1 and sn-2 with higher concentration of unsaturated fatty acids than in the triglyceride fraction of milk. Sphingolipids consist of a sphingoid base linked to a fatty acid across an amide bond. Their amphiphilic nature makes them suitable to be added into a variety of foods and recent investigations show that phospholipids, mainly phosphatidylserine and sphingomyelin, can exert antimicrobial, antiviral, and anticancer activities as well as positive effects in Alzheimer’s disease, stress, and memory decline. Polar lipids can be found as natural constituents in the membranes of all living organisms with soybean and eggs as the principal industrial sources, yet they have low contents in phosphatidylserine and sphingomyelin. Animal products are rich sources of these compounds but since there are legal restrictions to avoid transmission of prions, milk and dairy products are gaining interest as alternative sources. This review summarizes the analysis of polar lipids in dairy products including sample preparation (extraction and fractionation/isolation) and analysis by GC or HPLC and the latest research works using ELSD, CAD, and MS detectors.
NUDT15 Hydrolyzes 6-Thio-DeoxyGTP to Mediate the Anticancer Efficacy of 6-Thioguanine
Authors: Valerie Nicholas C.K. , Hagenkort Anna , Page Brent D.G. , Masuyer Geoffrey , Rehling Daniel , Carter Megan , Bevc Luka , Herr Patrick , Homan Evert , Sheppard Nina G. , Stenmark Pål , Jemth Ann-Sofie , Helleday Thomas
Published: August 2016

Thiopurines are a standard treatment for childhood leukemia, but like all chemotherapeutics, their use is limited by inherent or acquired resistance in patients. Recently, the nucleoside diphosphate hydrolase NUDT15 has received attention on the basis of its ability to hydrolyze the thiopurine effector metabolites 6-thio-deoxyGTP (6-thio-dGTP) and 6-thio-GTP, thereby limiting the efficacy of thiopurines. In particular, increasing evidence suggests an association between the NUDT15 missense variant, R139C, and thiopurine sensitivity. In this study, we elucidated the role of NUDT15 and NUDT15 R139C in thiopurine metabolism. In vitro and cellular results argued that 6-thio-dGTP and 6-thio-GTP are favored substrates for NUDT15, a finding supported by a crystallographic determination of NUDT15 in complex with 6-thio-GMP. We found that NUDT15 R139C mutation did not affect enzymatic activity but instead negatively influenced protein stability, likely due to a loss of supportive intramolecular bonds that caused rapid proteasomal degradation in cells. Mechanistic investigations in cells indicated that NUDT15 ablation potentiated induction of the DNA damage checkpoint and cancer cell death by 6-thioguanine. Taken together, our results defined how NUDT15 limits thiopurine efficacy and how genetic ablation via the R139C missense mutation confers sensitivity to thiopurine treatment in patients. Cancer Res; 76(18); 5501–11. ©2016 AACR.
CRISPR/Cas9-Mediated Trp53 and Brca2 Knockout to Generate Improved Murine Models of Ovarian High-Grade Serous Carcinoma
Authors: Walton Josephine , Blagih Julianna , Ennis Darren , Leung Elaine , Dowson Suzanne , Farquharson Malcolm , Tookman Laura A. , Orange Clare , Athineos Dimitris , Mason Susan , Stevenson David , Blyth Karen , Strathdee Douglas , Balkwill Frances R. , Vousden Karen , Lockley Michelle , McNeish Iain A.
Published: August 2016

There is a need for transplantable murine models of ovarian high-grade serous carcinoma (HGSC) with regard to mutations in the human disease to assist investigations of the relationships between tumor genotype, chemotherapy response, and immune microenvironment. In addressing this need, we performed whole-exome sequencing of ID8, the most widely used transplantable model of ovarian cancer, covering 194,000 exomes at a mean depth of 400× with 90% exons sequenced >50×. We found no functional mutations in genes characteristic of HGSC (Trp53, Brca1, Brca2, Nf1, and Rb1), and p53 remained transcriptionally active. Homologous recombination in ID8 remained intact in functional assays. Further, we found no mutations typical of clear cell carcinoma (Arid1a, Pik3ca), low-grade serous carcinoma (Braf), endometrioid (Ctnnb1), or mucinous (Kras) carcinomas. Using CRISPR/Cas9 gene editing, we modeled HGSC by generating novel ID8 derivatives that harbored single (Trp53–/–) or double (Trp53–/–;Brca2–/–) suppressor gene deletions. In these mutants, loss of p53 alone was sufficient to increase the growth rate of orthotopic tumors with significant effects observed on the immune microenvironment. Specifically, p53 loss increased expression of the myeloid attractant CCL2 and promoted the infiltration of immunosuppressive myeloid cell populations into primary tumors and their ascites. In Trp53–/–;Brca2–/– mutant cells, we documented a relative increase in sensitivity to the PARP inhibitor rucaparib and slower orthotopic tumor growth compared with Trp53–/– cells, with an appearance of intratumoral tertiary lymphoid structures rich in CD3+ T cells. This work validates new CRISPR-generated models of HGSC to investigate its biology and promote mechanism-based therapeutics discovery. Cancer Res; 76(20); 6118–29. ©2016 AACR.
Polarization of Tissue-Resident TFH-Like Cells in Human Hepatoma Bridges Innate Monocyte Inflammation and M2b Macrophage Polarization
Authors: Chen Min-Min , Xiao Xiao , Lao Xiang-Ming , Wei Yuan , Liu Rui-Xian , Zeng Qiu-Hui , Wang Jun-Cheng , Ouyang Fang-Zhu , Chen Dong-Ping , Chan Ka-Wo , Shi Dai-Chao , Zheng Limin , Kuang Dong-Ming
Published: August 2016

The existence, regulation, and functions of IL21+ immune cells are poorly defined in human cancers. Here, we identified a subset of protumorigenic IL21+ TFH-like cells in human hepatocellular carcinoma. These cells were the major source of IL21 in tumors and represented about 10% of the CD4+ T-cell population at levels comparable with the TFH cells present in lymph nodes. However, these TFH-like cells displayed a unique CXCR5−PD-1lo/−BTLA−CD69hi tissue-resident phenotype with substantial IFNγ production, which differed from the phenotype of TFH cells. Toll-like receptor 4 (TLR4)–elicited innate monocyte inflammation was important for IL21+ TFH-like cell induction in tumors, and activation of STAT1 and STAT3 was critical for TFH-like cell polarization in this process. Importantly, the TFH-like cells operated in IL21–IFNγ-dependent pathways to induce plasma cell differentiation and thereby create conditions for protumorigenic M2b macrophage polarization and cancer progression. Thus, induction of TFH-like cells links innate inflammation to immune privilege in tumors.

Significance: We identified a novel protumorigenic IL21+ TFH-like cell subset with a CXCR5−PD-1− BTLA−CD69hi tissue-resident phenotype in hepatoma. TLR4-mediated monocyte inflammation and subsequent T-cell STAT1 and STAT3 activation are critical for TFH-like cell induction. TFH-like cells operate via IL21–IFNγ pathways to induce plasma cells and create conditions for M2b macrophage polarization. Cancer Discov; 6(10); 1182–95. ©2016 AACR.

This article is highlighted in the In This Issue feature, p. 1069
Smoking and New-Onset Asthma in a Prospective Study on Italian Adults
Authors: Verlato Giuseppe , Nguyen Giang , Marchetti Pierpaolo , Accordini Simone , Marcon Alessandro , Marconcini Roberto , Bono Roberto , Fois Alessandro , Pirina Pietro , de Marco Roberto
Published: August 2016

Background: The existence of a cause-effect relation between active smoking and new-onset asthma in adults, although supported by several studies, has not been proven yet. Aims: We aimed to prospectively study asthma incidence as a function of smoking habits in the Italian adult population. Methods: A population-based cohort of 5,241 non-asthmatics was enrolled in Verona and Sassari in 1998-2000. The cohort was contacted again in 2007-2009 within the Gene-Environment Interactions in Respiratory Diseases study, and 3,187 subjects (60.8%) answered a screening questionnaire on smoking habits and respiratory disorders. The relation between smoking habits and self-reported new-onset asthma, defined as asthma attacks/use of medicines for asthma, was investigated by a multivariable logistic model. Results: During follow-up, 145 new cases of asthma were observed, yielding a cumulative incidence of 4.6% (95% CI 3.9-5.4); cumulative incidence of asthma did not significantly differ among never-smokers (76/1,666 = 4.6%), ex-smokers (30/554 = 5.4%) and current smokers (39/883 = 4.4%) (p = 0.641). In a multivariable analysis, the most important risk factor for asthma onset was allergic rhinitis (OR = 4.00, 95% CI 3.68-4.35). Compared to never-smokers, the risk of asthma onset was slightly increased in ex-smokers (OR = 1.28, 1.09-1.49) but not in current smokers (OR 1.01, 0.66-1.53). Current smoking became a significant predictor only when both new-onset wheezing and new-onset asthma were considered as the outcome (OR = 2.03, 1.35-3.05). Conclusions: In this prospective study, current smoking was not a risk factor for new-onset asthma, unless new-onset wheezing was also considered. The increase in asthma incidence among ex-smokers was likely due to reverse causation.
Prevention of Hepatocellular Carcinoma
Authors: Schütte Kerstin , Balbisi Fathi , Malfertheiner Peter
Published: August 2016

The epidemiology of hepatocellular carcinoma (HCC) has significantly changed throughout the past decade and will continue to do so in the future as a consequence of effective primary prevention and treatment of virus-related liver diseases. However, other risk factors for HCC are constantly on the rise, including alcoholic liver disease and nonalcoholic fatty liver disease. The knowledge on these and further risk factors associated with an increased risk of HCC provide the opportunity and chance for the development and implementation of successful preventive strategies to decrease the worldwide burden of HCC. This mini-review gives a short overview on current strategies in primary, secondary, and tertiary prevention of HCC.
Extra- and Intraluminal Elastase Induce Morphologically Distinct Abdominal Aortic Aneurysms in Mice and Thus Represent Specific Subtypes of Human Disease
Authors: Busch Albert , Holm Amina , Wagner Nicole , Ergün Süleyman , Rosenfeld Mathias , Otto Christoph , Baur Johannes , Kellersmann Richard , Lorenz Udo
Published: August 2016

Topical application of elastase to induce arterial aneurysm formation is an emerging murine model of vascular disease. In the context of aortic abdominal aneurysm (AAA), angiotensin II infusion and porcine pancreatic elastase perfusion models are commonly used today. This study, therefore, compares matrix remodeling, inflammation, and angiogenesis as distinct features of aneurysms in two models treated with intra-/extraluminal elastase. C57BL/6 mice underwent intra-/extraluminal elastase application via laparotomy and were followed up for 4 weeks. Basic histology and immunohistochemistry were performed at different time points along with transmission electron microscopy, PCR analysis, TUNEL assays, and blood analysis. Both models did not differ in aneurysm growth rate, but they showed distinct features and results depending on the way of elastase application. Extraluminal aneurysm induction preserved endothelial cell function and elastic fibers but showed ongoing acute inflammation, mainly in the adventitia. The destruction of elastic layers followed by chronic inflammation was a characteristic of intraluminal elastase perfusion, as well as medial angiogenesis, a key feature in human AAA. Different animal models harbor different features of human AAA and must, therefore, be chosen wisely. External elastase application mimics an acute inflammatory aneurysm, whereas intraluminal elastase perfusion shows chronic inflammation with angiogenesis and endothelial destruction, thus better mimicking human disease.
Serum 25-Hydroxyvitamin D in Early Childhood Is Nonlinearly Associated with Allergy
Authors: Savilahti Emma Merike , Mäkitie Outi , Kukkonen Anna Kaarina , Andersson Sture , Viljakainen Heli , Savilahti Erkki , Kuitunen Mikael
Published: August 2016

Background: Vitamin D has several immunological functions. Data on the relation of vitamin D status and allergy are controversial. Methods: We investigated the association between serum concentrations of 25-hydroxyvitamin D (25-OHD) and allergy in childhood. The study population (n = 819) was part of a randomized, double-blind, placebo-controlled trial where the mothers of offspring with a high risk for allergy received a mixture of probiotics (or placebo) for the last 4 weeks of pregnancy, and the child received this from birth to 6 months. Study subjects were followed for the emergence of sensitization and allergic symptoms for a period of 5 years, with medical examinations at the ages of 3 and 6 months, 2 and 5 years and also in the event of allergic symptoms. Levels of 25-OHD were measured in umbilical cord blood (UCB) samples (n = 724) and serum samples drawn at the age of 2 years (n = 369); the data were categorized into tertiles (T1-T3) and quartiles (Q1-Q4). The relation between 25-OHD levels and sensitization and allergy was analyzed with multivariable logistic regression analysis. Results: 25-OHD levels in T2 in UCB were associated with a higher risk for sensitization by the age of 2 years and allergic disorders by the age of 5 years. In the serum samples, at the age of 2 years, 25-OHD levels in Q3 were associated with a higher risk of sensitization and IgE-mediated allergies by the age of 5 years. Conclusions: The 25-OHD levels in early childhood are associated with the emergence of allergy, but the association appears to be nonlinear.
Topical Treatment of Infantile Haemangiomas: A Comparative Study on the Selection of a Semi-Solid Vehicle
Authors: Casiraghi Antonella , Musazzi Umberto M. , Rocco Paolo , Franzè Silvia , Minghetti Paola
Published: August 2016

Background/Aim: Topical β-blockers have recently been proposed as a valid alternative to oral drugs for treating cutaneous infantile haemangiomas, but clinical results in the literature are inconsistent due to the empirical choice of topical preparations. The current investigation aimed to rationalize the selection of a semi-solid vehicle for a locally applied drug product containing 1% w/w propranolol hydrochloride (PR-Cl). Methods: A hydrophobic ointment of PR-Cl, two lipophilic creams, and a hydrophilic cream were prepared. In vitro release and skin permeation studies through human epidermis and full-thickness skin were performed by Franz diffusion cells. Results: The overall results highlighted that PR-Cl was able to permeate the human epidermis, and its penetration pattern was strongly influenced by the composition of the semi-solid vehicle. PR-Cl release and permeation from lipophilic vehicles were extremely limited and influenced by their composition. Best results were obtained by using the hydrophilic cream. Furthermore, the retention study evidenced that epidermis acted as a reservoir, releasing the PR-Cl accumulated after preparation removal. Conclusion: The 1% w/w PR-Cl cream resulted the most suitable formulation for improving drug permeation through the human epidermis. On the contrary, the negligible permeation profile through full-thickness skin pointed out that PR-Cl cannot diffuse significantly to reach the deeper layers of human skin.