bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-UAVs Formation Autonomous Control Method Based on RQPSO-FSM-DMPC
Authors: Zhou Shao-lei , Kang Yu-hang , Dai Hong-de , Chao Zhou
Published: September 2016

For various threats in the enemy defense area, in order to achieve covert penetration and implement effective combat against enemy, the unmanned aerial vehicles formation needs to be reconfigured in the process of penetration; the mutual collision avoidance problems and communication constraint problems among the formation also need to be considered. By establishing the virtual-leader formation model, this paper puts forward distributed model predictive control and finite state machine formation manager. Combined with distributed cooperative strategy establishing the formation reconfiguration cost function, this paper proposes that adopting the revised quantum-behaved particle swarm algorithm solves the cost function, and it is compared with the result which is solved by particle swarm algorithm. Simulation result shows that this algorithm can control multiple UAVs formation autonomous reconfiguration effectively and achieve covert penetration safely.
Dynamic Rocker-Bogie: Kinematical Analysis in a High-Speed Traversal Stability Enhancement
Authors: Wang Sunxin , Li Yan
Published: September 2016

The rocker-bogie suspension system has robust capabilities to deal with uneven terrain because of its distributing of the payload over its six wheels uniformly, while there is one major shortcoming to high-speed traversal over the planar terrain. This paper proposes a new dynamic rocker-bogie suspension system with two modes of operation: it can expand the span of the rocker-bogie support polygon to increase travel rate when the terrain is planar; and it can switch to its original configuration to move by low speed when it is faced with rough terrain. The analysis on dynamic stability margin and kinematical simulation on the two operating modes of rocker-bogie are employed to analyze and verify the rationality and effectiveness of the modification in the structure.
Analysis of Different Classification Techniques for Two-Class Functional Near-Infrared Spectroscopy-Based Brain-Computer Interface
Authors: Naseer Noman , Qureshi Nauman Khalid , Noori Farzan Majeed , Hong Keum-Shik
Published: September 2016

We analyse and compare the classification accuracies of six different classifiers for a two-class mental task (mental arithmetic and rest) using functional near-infrared spectroscopy (fNIRS) signals. The signals of the mental arithmetic and rest tasks from the prefrontal cortex region of the brain for seven healthy subjects were acquired using a multichannel continuous-wave imaging system. After removal of the physiological noises, six features were extracted from the oxygenated hemoglobin (HbO) signals. Two- and three-dimensional combinations of those features were used for classification of mental tasks. In the classification, six different modalities, linear discriminant analysis (LDA), quadratic discriminant analysis (QDA),k-nearest neighbour (kNN), the Naïve Bayes approach, support vector machine (SVM), and artificial neural networks (ANN), were utilized. With these classifiers, the average classification accuracies among the seven subjects for the 2- and 3-dimensional combinations of features were 71.6, 90.0, 69.7, 89.8, 89.5, and 91.4% and 79.6, 95.2, 64.5, 94.8, 95.2, and 96.3%, respectively. ANN showed the maximum classification accuracies: 91.4 and 96.3%. In order to validate the results, a statistical significance test was performed, which confirmed that thepvalues were statistically significant relative to all of the other classifiers (p< 0.005) using HbO signals.
Fish Collagen Promotes the Expression of Genes Related to Osteoblastic Activity
Authors: Capati Mark Luigi Fabian , Nakazono Ayako , Yamamoto Kohei , Sugimoto Kouji , Yanagiguchi Kajiro , Yamada Shizuka , Hayashi Yoshihiko
Published: September 2016

Tilapia type I atelocollagen (TAC) is a strong candidate for clinical application as its biological scaffold due to a high degeneration temperature and biologically safe properties. The aim of this study was to confirm the biological effects of TACin vitroon osteoblastic cells, simulating its clinical application. The proliferation and differentiation of typical preosteoblasts, MC3T3-E1 cells, were investigated using a microarray analysis, staining assay for mineralization, and real-time PCR analysis of the expression of mineralization-related genes. The mRNA expression of 10 genes involved in proliferation and differentiation increased after 3-day culture on an TAC gel, with an average balanced score ratio exceeding 1.5 compared to the control. After two weeks of culture, all three experimental groups showed stronger alkaline phosphatase staining than after one week. The genes expression of alkaline phosphatase, osteocalcin, and bone sialoprotein increased under the experimental conditions. The gene expression of osteopontin did not increase, and no statistical differences were noted among the three experimental groups. The present and previous findings suggest that TAC is not only a suitable alternative to collagen products originating from mammals but also a novel biomaterial with cell differentiation ability for regenerative medicine.
The Fluid-Solid Interaction Dynamics between Underwater Explosion Bubble and Corrugated Sandwich Plate
Authors: Wang Hao , Cheng Yuan Sheng , Liu Jun , Gan Lin
Published: September 2016

Lightweight sandwich structures with highly porous 2D cores or 3D (three-dimensional) periodic cores can effectively withstand underwater explosion load. In most of the previous studies of sandwich structure antiblast dynamics, the underwater explosion (UNDEX) bubble phase was neglected. As the UNDEX bubble load is one of the severest damage sources that may lead to structure large plastic deformation and crevasses failure, the failure mechanisms of sandwich structures might not be accurate if only shock wave is considered. In this paper, detailed 3D finite element (FE) numerical models of UNDEX bubble-LCSP (lightweight corrugated sandwich plates) interaction are developed by using MSC.Dytran. Upon the validated FE model, the bubble shape, impact pressure, and fluid field velocities for different stand-off distances are studied. Based on numerical results, the failure modes of LCSP and the whole damage process are obtained. It is demonstrated that the UNDEX bubble collapse jet local load plays a more significant role than the UNDEX shock wave load especially in near-field underwater explosion.
Ensemble Deep Learning for Biomedical Time Series Classification
Authors: Jin Lin-peng , Dong Jun
Published: September 2016

Ensemble learning has been proved to improve the generalization ability effectively in both theory and practice. In this paper, we briefly outline the current status of research on it first. Then, a new deep neural network-based ensemble method that integrates filtering views, local views, distorted views, explicit training, implicit training, subview prediction, and Simple Average is proposed for biomedical time series classification. Finally, we validate its effectiveness on the Chinese Cardiovascular Disease Database containing a large number of electrocardiogram recordings. The experimental results show that the proposed method has certain advantages compared to some well-known ensemble methods, such asBaggingandAdaBoost.
Impact of Some Ecological Factors on Fecal Contamination of Drinking Water by Diarrheagenic Antibiotic-ResistantEscherichia coliin Zagazig City, Egypt
Authors: Fakhr Ahmed Elsadek , Gohar Maha Kamal , Atta Amal Hassan
Published: September 2016

Fecal contamination of drinking water is a major health problem which accounts for many cases of diarrhea mainly in infants and foreigners. This contamination is a complex interaction of many parameters. Antibiotic resistance among bacterial isolates complicates the problem. The study was done to identify fecal contamination of drinking water by Diarrheagenic Antibiotic-ResistantEscherichia coliin Zagazig city and to trace reasons for such contamination, three hundred potable water samples were investigated forE. coliexistence. Locations ofE. colipositive samples were investigated in relation to population density, water source, and type of water pipe. SixteenE. colistrains were isolated. Antibiotic sensitivity was done and enterotoxigenic, enteropathogenic, and enterohaemorrhagic virulence genes were investigated by PCR. Probability of fecal contamination correlated with higher population density, with increased distance from Zagazig water plant, and with asbestos cement water pipes. Resistance to at least one antimicrobial drug was found in all isolates. Virulence genes were detected in a rate of 26.27%, 13.13%, 20%, 6.67%, and 33.33% for LT, ST, stx1, stx2, and eae genes, respectively. This relatively high frequency of fecal contamination points towards the high risk of developing diarrhea by antibiotic resistant DEC in low socioeconomic communities particularly with old fashion distribution systems.
Shear Stress-Relative Slip Relationship at Concrete Interfaces
Authors: Yang Keun-Hyeok
Published: September 2016

This study develops a simple and rational shear stress-relative slip model of concrete interfaces with monolithic castings or smooth construction joints. In developing the model, the initial shear cracking stress and relative slip amount at peak stress were formulated from a nonlinear regression analysis using test data for push-off specimens. The shear friction strength was determined from the generalized equations on the basis of the upper-bound theorem of concrete plasticity. Then, a parametric fitting analysis was performed to derive equations for the key parameters determining the shapes of the ascending and descending branches of the shear stress-relative slip curve. The comparisons of predictions and measurements obtained from push-off tests confirmed that the proposed model provides superior accuracy in predicting the shear stress-relative slip relationship of interfacial shear planes. This was evidenced by the lower normalized root mean square error than those in Xu et al.’s model and the CEB-FIB model, which have many limitations in terms of the roughness of the substrate surface along an interface and the magnitude of equivalent normal stress.
Exploring and Promoting Prosocial Vaccination: A Cross-Cultural Experiment on Vaccination of Health Care Personnel
Authors: Böhm Robert , Betsch Cornelia , Korn Lars , Holtmann Cindy
Published: September 2016

Influenza vaccination for health care personnel (HCP) is recommended particularly because it indirectly protects patients from contracting the disease. Vaccinating can therefore be interpreted as a prosocial act. However, HCP vaccination rates are often far too low to prevent nosocomial infections. Effective interventions are needed to increase HCP’s influenza vaccine uptake. Here we devise a novel tool to experimentally test interventions that aim at increasing prosocially motivated vaccine uptake under controlled conditions. We conducted a large-scale and cross-cultural experiment with participants from countries with either a collectivistic (South Korea) or an individualistic (USA) cultural background. Results showed that prosocially motivated vaccination was more likely in South Korea compared to the US, mediated by a greater perception of vaccination as a social act. However, changing the default of vaccination, such that participants had to opt out rather than to opt in, increased vaccine uptake in the US and therefore compensated for the lower level of prosocial vaccination. In sum, the present study provides both a novel method to investigate HCP influenza vaccination behavior and interventions to increase their vaccine uptake.
Tax Arrangement and Regional Industrial Restructuring: Evidence from Panel Data in China
Authors: Ma Jinying , Zhang Xi , Tao Feng , Luo Fuzheng
Published: September 2016

Regional industrial restructuring has been one of the major items in the transformation of economic development mode. An exploration was made into the influence of tax arrangement on the regional industrial structure by setting up a panel data econometric model based on the evaluation and analysis of the regional industrial structure in China. It was shown that tax arrangement influenced the regional industrial restructuring in terms of three aspects. Microlevel: the turnover tax and income tax appeared with a U-path of influence on upgrading of the industrial structure while appearing with an inverted U-path of influence on rationalization of the industrial structure. In addition, the levy of resource tax had a negative impact on both upgrading and rationalization of the industrial structure. Mesolevel: taxation in the secondary and tertiary industries appeared with a U-path of influence on upgrading of the industrial structure. An increase of taxation in the secondary industry had a negative impact on rationalization of the industrial structure. The taxation in the tertiary industry appeared with an inverted U-path of influence on rationalization of the industrial structure. Macrolevel: the macrotax burden had a U-path of influence on both upgrading and rationalization of the industrial structure.
In VitroAdherence of Oral Bacteria to Different Types of Tongue Piercings
Authors: Borges Lucas Pereira , Ferreira-Filho Julio Cesar Campos , Martins Julia Medeiros , Alves Caroline Vieira , Santiago Bianca Marques , Valença Ana Maria Gondim
Published: September 2016

The purpose of this work was to verifyin vitroadherence ofE. corrodensandS. oralisto the surface of tongue piercings made of surgical steel, titanium, Bioplast, and Teflon. For this, 160 piercings were used for the count of Colony Forming Units (CFU) and 32 piercings for analysis under scanning electron microscopy. Of these, 96 (24 of each type) were individually incubated in 5 mL of BHI broth and 50 μL of inoculum at 37°C/24 h. The other 96 piercings formed the control group and were individually incubated in 5 mL of BHI broth at 37°C/24 h. Plates were incubated at 37°C/48 h for counting of CFU/mL and data were submitted to statistical analysis (pvalue<0.05). ForE. corrodens, difference among types of material was observed (p<0.001) and titanium and surgical steel showed lower bacterial adherence. The adherence ofS. oralisdiffered among piercings, showing lower colonization (p<0.007) in titanium and surgical steel piercings. The four types of piercings were susceptible to colonization byE. corrodensandS. oralis, and bacterial adhesion was more significant in those made of Bioplast and Teflon. The piercings presented bacterial colonies on their surface, being higher in plastic piercings probably due to their uneven and rough surface.
Defensins: The Case for Their Use against Mycobacterial Infections
Authors: Dong Haodi , Lv Yue , Zhao Deming , Barrow Paul , Zhou Xiangmei
Published: September 2016

Human tuberculosis remains a huge global public health problem with an estimated 1/3rd of the population being infected. Defensins are antibacterial cationic peptides produced by a number of cell types, most notably neutrophil granulocytes and epithelial cells. All three defensin types (α-,β-, andθ-defensins) have antibacterial activities, mainly through bacterial membrane permeabilization. Defensins are effective against Gram-negative and Gram-positive bacteria including mycobacteria and are active both intra- and extracellularly. Mycobacterial resistance has never been demonstrated although themprFgene encoding resistance inStaphylococcus aureusis present in theMycobacterium tuberculosisgenome. In addition to their antibacterial effect, defensins are chemoattractants for macrophages and neutrophils. There are many cases for their use for therapy or prophylaxis in tuberculosis as well. In conclusion, we propose that there is considerable scope and potential for exploring their use as therapeutic/prophylactic agents and more comprehensive survey of defensins from different species and their bioactivity is timely.
Supporting Business Privacy Protection in Wireless Sensor Networks
Authors: Feng Nan , Hao Zhiqi , Yang Sibo , Wu Harris
Published: September 2016

With the pervasive use of wireless sensor networks (WSNs) within commercial environments, business privacy leakage due to the exposure of sensitive information transmitted in a WSN has become a major issue for enterprises. We examine business privacy protection in the application of WSNs. We propose a business privacy-protection system (BPS) that is modeled as a hierarchical profile in order to filter sensitive information with respect to enterprise-specified privacy requirements. The BPS aims at solving a tradeoff between metrics that are defined to estimate the utility of information and the business privacy risk. We design profile, risk assessment, and filtration agents to implement the BPS based on multiagent technology. The effectiveness of our proposed BPS is validated by experiments.
A Case Study of Deep Vein Thrombosis of the Right Internal Jugular Vein in a Healthy 21-Year-Old Male
Authors: Corral Javier , Villanueva Geri
Published: September 2016

We are reporting a case of a healthy 21-year-old male, with no significant past medical history, who was found to have an incidental nonocclusive deep vein thrombosis in the right internal jugular vein detected on a head MRI previously ordered for work-up of headaches. A follow-up upper extremity venous Doppler ultrasound confirmed the presence of a partially occlusive deep vein thrombosis in the right jugular vein. The case presented is unique for the reason that the patient is young and has no prior risk factor, personal or familial, for venous thrombosis except for associated polycythemia on clinical presentation.
Feature Selection for Intelligent Firefighting Robot Classification of Fire, Smoke, and Thermal Reflections Using Thermal Infrared Images
Authors: Kim Jong-Hwan , Jo Seongsik , Lattimer Brian Y.
Published: September 2016

Locating a fire inside of a structure that is not in the direct field of view of the robot has been researched for intelligent firefighting robots. By classifying fire, smoke, and their thermal reflections, firefighting robots can assess local conditions, decide a proper heading, and autonomously navigate toward a fire. Long-wavelength infrared camera images were used to capture the scene due to the camera’s ability to image through zero visibility smoke. This paper analyzes motion and statistical texture features acquired from thermal images to discover the suitable features for accurate classification. Bayesian classifier is implemented to probabilistically classify multiple classes, and a multiobjective genetic algorithm optimization is performed to investigate the appropriate combination of the features that have the lowest errors and the highest performance. The distributions of multiple feature combinations that have 6.70% or less error were analyzed and the best solution for the classification of fire and smoke was identified.
Geochemical and Isotopic Characterisation of Actual Lacustrine Sediments from the Hydrothermal LakeSpecchio di Venere, Pantelleria Island (Italy)
Authors: Cangemi Marianna , Madonia Paolo , Bellomo Sergio , Oliveri Ygor
Published: September 2016

Hydrothermal lakes are a very common feature in volcanic environments, and among these lake Specchio di Venere (Pantelleria island, Italy) has attracted the interest of several researchers due to its peculiar characteristics. With the aim of improving the knowledge of its mineralogy, our work pointed out the characterisation of the bottom lake sediments. We collected and analysed 5 sediments cores around the shoreline, determining the mineralogical phases, concentration of major, minor, and trace elements, and the isotopic composition of carbon and oxygen in the carbonate phases. Our findings remarked a general compositional homogeneity in both the vertical and horizontal distribution of mineral phases, with the exception of peculiar geological niches connoted by biological and hydrothermal activities.
Insulin-Sensitizers, Polycystic Ovary Syndrome and Gynaecological Cancer Risk
Authors: Lauretta Rosa , Lanzolla Giulia , Vici Patrizia , Mariani Luciano , Moretti Costanzo , Appetecchia Marialuisa
Published: September 2016

Preclinical, early phase clinical trials and epidemiological evidence support the potential role of insulin-sensitizers in cancer prevention and treatment. Insulin-sensitizers improve the metabolic and hormonal profile in PCOS patients and may also act as anticancer agents, especially in cancers associated with hyperinsulinemia and oestrogen dependent cancers. Several lines of evidence support the protection against cancer exerted by dietary inositol, in particular inositol hexaphosphate. Metformin, thiazolidinediones, and myoinositol postreceptor signaling may exhibit direct inhibitory effects on cancer cell growth. AMPK, the main molecular target of metformin, is emerging as a target for cancer prevention and treatment. PCOS may be correlated to an increased risk for developing ovarian and endometrial cancer (up to threefold). Several studies have demonstrated an increase in mortality rate from ovarian cancer among overweight/obese PCOS women compared with normal weight women. Long-term use of metformin has been associated with lower rates of ovarian cancer. Considering the evidence supporting a higher risk of gynaecological cancer in PCOS women, we discuss the potential use of insulin-sensitizers as a potential tool for chemoprevention, hypothesizing a possible rationale through which insulin-sensitizers may inhibit tumourigenesis.
In Situ Measurement of Wind-Induced Pulse Response of Sound Barrier Based on High-Speed Imaging Technology
Authors: Zhu Chunli , Guo Jie , Zhang Dashan , Shen Yuan , Liu Dongcai
Published: September 2016

The lifetime of the sound barrier is threatened by high-speed train-induced impulsive wind pressure as it passes by. The vibration response of the sound barrier during the process of train passing is difficult to be measured using conventional measurement methods because of the inconvenience of the installation of markers on the sound barrier. In this paper, the high-speed camera is used to record the whole process of the train passing by the sound barrier. Then, a displacement extraction algorithm based on the theory of Taylor expansion is proposed to obtain the vibration response curve. Compared with the result simulated by using the finite element method, the video extraction result shows the same head wave and tail wave phenomenon, demonstrating that the vibration measurement by using the high-speed imaging technology is an effective measuring way. It can achieve noncontact and remote vibration measurement and has important practical value.
Strategies for Lipid Production Improvement in Microalgae as a Biodiesel Feedstock
Authors: Zhu L. D. , Li Z. H. , Hiltunen E.
Published: September 2016

In response to the energy crisis, global warming, and climate changes, microalgae have received a great deal of attention as a biofuel feedstock. Due to a high lipid content in microalgal cells, microalgae present as a promising alternative source for the production of biodiesel. Environmental and culturing condition variations can alter lipid production as well as chemical compositions of microalgae. Therefore, application of the strategies to activate lipid accumulation opens the door for lipid overproduction in microalgae. Until now, many original studies regarding the approaches for enhanced microalgal lipid production have been reported in an effort to push forward the production of microalgal biodiesel. However, the current literature demonstrates fragmented information available regarding the strategies for lipid production improvement. From the systematic point of view, the review highlights the main approaches for microalgal lipid accumulation induction to expedite the application of microalgal biodiesel as an alternative to fossil diesel for sustainable environment. Of the several strategies discussed, the one that is most commonly applied is the design of nutrient (e.g., nitrogen, phosphorus, and sulfur) starvation or limitation. Other viable approaches such as light intensity, temperature, carbon dioxide, salinity stress, and metal influence can also achieve enhanced microalgal lipid production.
A Linear Analysis of Coupled Wilson-Cowan Neuronal Populations
Authors: Neves L. L. , Monteiro L. H. A.
Published: September 2016

Let a neuronal population be composed of an excitatory group interconnected to an inhibitory group. In the Wilson-Cowan model, the activity of each group of neurons is described by a first-order nonlinear differential equation. The source of the nonlinearity is the interaction between these two groups, which is represented by a sigmoidal function. Such a nonlinearity makes difficult theoretical works. Here, we analytically investigate the dynamics of a pair of coupled populations described by the Wilson-Cowan model by using a linear approximation. The analytical results are compared to numerical simulations, which show that the trajectories of this fourth-order dynamical system can converge to an equilibrium point, a limit cycle, a two-dimensional torus, or a chaotic attractor. The relevance of this study is discussed from a biological perspective.
Influence of Nutrition Claims on Appetite Sensations according to Sex, Weight Status, and Restrained Eating
Authors: Painchaud Guérard Geneviève , Lemieux Simone , Doucet Éric , Pomerleau Sonia , Provencher Véronique
Published: September 2016

Nutrition claims may help people to adopt healthier eating habits, but little is known about the potential cognitive effects of such claims on appetite sensations. The main purpose of this study was to evaluate the impact of nutrition claims and individual factors on perceived appetite sensations. According to a three (“healthy” versus “diet” (i.e., satiating) versus “hedonic”) by two (restrained or not restrained) by two (normal-weight or overweight/obese) by two (men versus women) factorial design, 164 males and 188 females aged 18–65 were invited to taste an oatmeal-raisin snack in a blinded andad libitumcontext. Visual analog scales (150 mm) were used to evaluate appetite sensations before and over 1 h after consumption period. BMI and Restraint Scale were used to categorize participants according to their weight and restraint status. No main condition effect was observed for any of the four appetite sensations. However, subgroups analysis revealed significant differences among specific subgroups. A main effect of sex was also observed for all appetite sensations with men reporting higher levels of desire to eat, hunger and prospective food consumption, and lower levels of fullness than women. These findings highlight the importance of considering individual characteristics in interaction when studying appetite sensations.
The Behaviour of Mistuned Piezoelectric Shunt Systems and Its Estimation
Authors: Berardengo M. , Manzoni S. , Vanali M.
Published: September 2016

This paper addresses monoharmonic vibration attenuation using piezoelectric transducers shunted with electric impedances consisting of a resistance and an inductance in series. This type of vibration attenuation has several advantages but suffers from problems related to possible mistuning. In fact, when either the mechanical system to be controlled or the shunt electric impedance undergoes a change in their dynamical features, the attenuation performance decreases significantly. This paper describes the influence of biases in the electric impedance parameters on the attenuation provided by the shunt and proposes an approximated model for a rapid prediction of the vibration damping performance in mistuned situations. The analytical and numerical results achieved within the paper are validated using experimental tests on two different test structures.
UNC2025, a MERTK Small-Molecule Inhibitor, Is Therapeutically Effective Alone and in Combination with Methotrexate in Leukemia Models
Authors: DeRyckere Deborah , Lee-Sherick Alisa B. , Huey Madeline G. , Hill Amanda A. , Tyner Jeffrey W. , Jacobsen Kristen M. , Page Lauren S. , Kirkpatrick Gregory G. , Eryildiz Fatma , Montgomery Stephanie A. , Zhang Weihe , Wang Xiaodong , Frye Stephen V. , Earp H. Shelton , Graham Douglas K.
Published: September 2016

Purpose: MERTK tyrosine kinase is ectopically expressed in 30% to 50% of acute lymphoblastic leukemias (ALL) and more than 80% of acute myeloid leukemias (AML) and is a potential therapeutic target. Here, we evaluated the utility of UNC2025, a MERTK tyrosine kinase inhibitor, for treatment of acute leukemia.

Experimental Design: Preclinical in vitro and in vivo assays using cell lines and primary leukemia patient samples were used to evaluate antileukemic effects of UNC2025.

Results: UNC2025 potently inhibited prosurvival signaling, induced apoptosis, and reduced proliferation and colony formation in MERTK-expressing ALL and AML cell lines and patient samples. Approximately 30% of primary leukemia patient samples (78 of 261 total) were sensitive to UNC2025. Sensitive samples were most prevalent in the AML, T-ALL, and minimally differentiated (M0) AML subsets. UNC2025 inhibited MERTK in bone marrow leukemia cells and had significant therapeutic effects in xenograft models, with dose-dependent decreases in tumor burden and consistent two-fold increases in median survival, irrespective of starting disease burden. In a patient-derived AML xenograft model, treatment with UNC2025 induced disease regression. In addition, UNC2025 increased sensitivity to methotrexate in vivo, suggesting that addition of MERTK-targeted therapy to current cytotoxic regimens may be particularly effective and/or allow for chemotherapy dose reduction.

Conclusions: The broad-spectrum activity mediated by UNC2025 in leukemia patient samples and xenograft models, alone or in combination with cytotoxic chemotherapy, supports continued development of MERTK inhibitors for treatment of leukemia. Clin Cancer Res; 23(6); 1481–92. ©2016 AACR.
Inhibition of the Nuclear Export Receptor XPO1 as a Therapeutic Target for Platinum-Resistant Ovarian Cancer
Authors: Chen Ying , Camacho Sandra Catalina , Silvers Thomas R. , Razak Albiruni R.A. , Gabrail Nashat Y. , Gerecitano John F. , Kalir Eva , Pereira Elena , Evans Brad R. , Ramus Susan J. , Huang Fei , Priedigkeit Nolan , Rodriguez Estefania , Donovan Michael , Khan Faisal , Kalir Tamara , Sebra Robert , Uzilov Andrew , Chen Rong , Sinha Rileen , Halpert Richard , Billaud Jean-Noel , Shacham Sharon , McCauley Dilara , Landesman Yosef , Rashal Tami , Kauffman Michael , Mirza Mansoor R. , Mau-Sørensen Morten , Dottino Peter , Martignetti John A.
Published: September 2016

Purpose: The high fatality-to-case ratio of ovarian cancer is directly related to platinum resistance. Exportin-1 (XPO1) is a nuclear exporter that mediates nuclear export of multiple tumor suppressors. We investigated possible clinicopathologic correlations of XPO1 expression levels and evaluated the efficacy of XPO1 inhibition as a therapeutic strategy in platinum-sensitive and -resistant ovarian cancer.

Experimental Design: XPO1 expression levels were analyzed to define clinicopathologic correlates using both TCGA/GEO datasets and tissue microarrays (TMA). The effect of XPO1 inhibition, using the small-molecule inhibitors KPT-185 and KPT-330 (selinexor) alone or in combination with a platinum agent on cell viability, apoptosis, and the transcriptome was tested in immortalized and patient-derived ovarian cancer cell lines (PDCL) and platinum-resistant mice (PDX). Seven patients with late-stage, recurrent, and heavily pretreated ovarian cancer were treated with an oral XPO1 inhibitor.

Results: XPO1 RNA overexpression and protein nuclear localization were correlated with decreased survival and platinum resistance in ovarian cancer. Targeted XPO1 inhibition decreased cell viability and synergistically restored platinum sensitivity in both immortalized ovarian cancer cells and PDCL. The XPO1 inhibitor–mediated apoptosis occurred through both p53-dependent and p53-independent signaling pathways. Selinexor treatment, alone and in combination with platinum, markedly decreased tumor growth and prolonged survival in platinum-resistant PDX and mice. In selinexor-treated patients, tumor growth was halted in 3 of 5 patients, including one with a partial response, and was safely tolerated by all.

Conclusions: Taken together, these results provide evidence that XPO1 inhibition represents a new therapeutic strategy for overcoming platinum resistance in women with ovarian cancer. Clin Cancer Res; 23(6); 1552–63. ©2016 AACR.
The T-cell Receptor Repertoire Influences the Tumor Microenvironment and Is Associated with Survival in Aggressive B-cell Lymphoma
Authors: Keane Colm , Gould Clare , Jones Kimberley , Hamm David , Talaulikar Dipti , Ellis Jonathan , Vari Frank , Birch Simone , Han Erica , Wood Peter , Le-Cao Kim-Anh , Green Michael R. , Crooks Pauline , Jain Sanjiv , Tobin Josh , Steptoe Raymond J. , Gandhi Maher K.
Published: September 2016

Purpose: To investigate the relationship between the intra-tumoral T-cell receptor (TCR) repertoire and the tumor microenvironment (TME) in de novo diffuse large B-cell lymphoma (DLBCL) and the impact of TCR on survival.

Experimental Design: We performed high-throughput unbiased TCRβ sequencing on a population-based cohort of 92 patients with DLBCL treated with conventional (i.e., non-checkpoint blockade) frontline “R-CHOP” therapy. Key immune checkpoint genes within the TME were digitally quantified by nanoString. The primary endpoints were 4-year overall survival (OS) and progression-free survival (PFS).

Results: The TCR repertoire within DLBCL nodes was abnormally narrow relative to non-diseased nodal tissues (P < 0.0001). In DLBCL, a highly dominant single T-cell clone was associated with inferior 4-year OS rate of 60.0% [95% confidence interval (CI), 31.7%–79.6%], compared with 79.8% in patients with a low dominant clone (95% CI, 66.7%–88.5%; P = 0.005). A highly dominant clone also predicted inferior 4-year PFS rate of 46.6% (95% CI, 22.5%–76.6%) versus 72.6% (95% CI, 58.8%–82.4%, P = 0.008) for a low dominant clone. In keeping, clonal expansions were most pronounced in the EBV+ DLBCL subtype that is known to express immunogenic viral antigens and is associated with particularly poor outcome. Increased T-cell diversity was associated with significantly elevated PD-1, PD-L1, and PD-L2 immune checkpoint molecules.

Conclusions: Put together, these findings suggest that the TCR repertoire is a key determinant of the TME. Highly dominant T-cell clonal expansions within the TME are associated with poor outcome in DLBCL treated with conventional frontline therapy. Clin Cancer Res; 23(7); 1820–8. ©2016 AACR.
Long-Term Outcome of Patients with Perimembranous Ventricular Septal Defect: Results from the Belgian Registry on Adult Congenital Heart Disease
Authors: Gabriels Charlien , De Backer Julie , Pasquet Agnes , Paelinck Bernard P. , Morissens Marielle , Helsen Frederik , Van De Bruaene Alexander , Budts Werner
Published: September 2016

Objectives: Studies evaluating the long-term outcome of adults with ventricular septal defect (VSD) are important to inform patients about prognosis. This study investigated the long-term outcome of patients with perimembranous VSD (pmVSD) followed in the Belgian Registry on Adult Congenital Heart Disease. Methods: All pmVSD patients in the registry were analyzed. Results: Two hundred and sixty-six patients were studied. Fifteen patients had Eisenmenger syndrome. One hundred and seventy-three had isolated pmVSD and 78 had pmVSD with concomitant lesions. Of the patients with isolated pmVSD, 52% were male, median age was 29 years (IQR 24-35 years) and median follow-up duration was 18 years (IQR 10-25 years). Fifty-three (31%) patients underwent VSD closure and 10 (19%) had a residual shunt. Most (93%) patients were in NYHA class I. No patients died. Two (4%) patients developed atrial arrhythmia and 2 (4%) required pacemaker implantation. Seven (14%) developed left ventricular outflow tract obstruction (LVOTO). In the unrepaired pmVSD group, 4 developed endocarditis. In the entire group, moderate or severe aortic regurgitation (AR) occurred in 9 (5%) patients. Conclusions: Long-term survival in patients with isolated pmVSD was not uneventful. Moderate or severe AR might develop and endocarditis occurred in patients without VSD repair. Complications after VSD closure included atrial arrhythmia, pacemaker implantation and LVOTO.
The Distribution and Cellular Lineages of XX and XY Cells in Gonads Associated with Ovotesticular Disorder of Sexual Development
Authors: Nishina-Uchida Noriko , Fukuzawa Ryuji , Ishii Tomohiro , Anaka Matthew R. , Hasegawa Tomonobu , Hasegawa Yukihiro
Published: September 2016

Individuals with a 46,XX/46,XY karyotype are categorized as ovotesticular disorder of sexual development (ODSD) and have gonads with either an ovary on one side and a testis on the other side or a mixed ovotestis. To examine the distribution of 46,XX and 46,XY cells in gonads of 3 patients with ODSD, FISH for X and Y chromosomes and immunohistochemistry for SOX9 and FOXL2 were carried out. FISH analysis showed that XX signals were present in Sertoli cells in the seminiferous tubules, while cells containing Y signals were seen in epithelia of ovarian follicles. The immunolabeling of SOX9 and FOXL2 in the seminiferous tubules and ovarian follicles was mutually exclusive, irrespective of the presence of reversed sex chromosomes. We therefore suggest that the fate of individual gonadal epithelial cells is determined not only by the sex chromosomes but also by local environmental factors.
NR0B1 Frameshift Mutation in a Boy with Idiopathic Central Precocious Puberty
Authors: Shima Hirohito , Yatsuga Shuichi , Nakamura Akie , Sano Shinichiro , Sasaki Takako , Katsumata Noriyuki , Suzuki Erina , Hata Kenichiro , Nakabayashi Kazuhiko , Momozawa Yukihide , Kubo Michiaki , Okamura Kohji , Kure Shigeo , Matsubara Yoichi , Ogata Tsutomu , Narumi Satoshi , Fukami Maki
Published: September 2016

NR0B1 is the causative gene for X-linked adrenal hypoplasia congenita, characterized by adrenal insufficiency, hypogonadotropic hypogonadism, and infertility. We identified an NR0B1 frameshift mutation in a boy with precocious puberty who had no signs of adrenal insufficiency. Blood examination revealed elevated testosterone levels and gonadotropin hyperresponses to gonadotropin releasing hormone (GnRH) stimulation, together with normal adrenal hormone levels. GnRH analog treatment partially ameliorated his clinical features. Molecular analysis identified a p.Glu3fsAla*16 in NR0B1. These results expand the clinical manifestations of NR0B1 mutations to include central precocious puberty without adrenal insufficiency. NR0B1 mutations likely underlie androgen overproduction via GnRH-dependent and -independent mechanisms.
Sex Reversal in Amphibians
Authors: Flament Stéphane
Published: September 2016

Amphibians have been widely used to study developmental biology due to the fact that embryo development takes place independently of the maternal organism and that observations and experimental approaches are easy. Some amphibians like Xenopus became model organisms in this field. In the first part of this article, the differentiation of the gonads in amphibians and the mechanisms governing this process are reviewed. In the second part, the state of the art about sex reversal, which can be induced by steroid hormones in general and by temperature in some species, is presented. Also information about pollutants found in the environment that could interfere with the development of the amphibian reproductive apparatus or with their reproductive physiology is given. Such compounds could play a part in the amphibian decline, since in the wild, many amphibians are endangered species.
European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2016 Update
Authors: Sweet David G. , Carnielli Virgilio , Greisen Gorm , Hallman Mikko , Ozek Eren , Plavka Richard , Saugstad Ola Didrik , Simeoni Umberto , Speer Christian P. , Vento Máximo , Visser Gerard H.A. , Halliday Henry L.
Published: September 2016

Advances in the management of respiratory distress syndrome (RDS) ensure that clinicians must continue to revise current practice. We report the third update of the European Guidelines for the Management of RDS by a European panel of expert neonatologists including input from an expert perinatal obstetrician based on available literature up to the beginning of 2016. Optimizing the outcome for babies with RDS includes consideration of when to use antenatal steroids, and good obstetric practice includes methods of predicting the risk of preterm delivery and also consideration of whether transfer to a perinatal centre is necessary and safe. Methods for optimal delivery room management have become more evidence based, and protocols for lung protection, including initiation of continuous positive airway pressure and titration of oxygen, should be implemented from soon after birth. Surfactant replacement therapy is a crucial part of the management of RDS, and newer protocols for surfactant administration are aimed at avoiding exposure to mechanical ventilation, and there is more evidence of differences among various surfactants in clinical use. Newer methods of maintaining babies on non-invasive respiratory support have been developed and offer potential for greater comfort and less chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease although minimizing the time spent on mechanical ventilation using caffeine and if necessary postnatal steroids are also important considerations. Protocols for optimizing the general care of infants with RDS are also essential with good temperature control, careful fluid and nutritional management, maintenance of perfusion and judicious use of antibiotics all being important determinants of best outcome.
Trachyonychia: Review and Update on Clinical Aspects, Histology, and Therapy
Authors: Haber Jessica S. , Chairatchaneeboon Manasmon , Rubin Adam I.
Published: September 2016

Trachyonychia is a disorder of the nail unit that most commonly presents with rough, longitudinally ridged nails (opaque trachyonychia) or less frequently, uniform, opalescent nails with pits (shiny trachyonychia). The term trachyonychia refers to ‘rough nails.' This article comprehensively reviews the clinical, histologic, and therapeutic aspects of trachyonychia. The authors' preferred evaluation and management strategies of trachyonychia are included.
Reversal of Gastric Bypass Resolves Hyperoxaluria and Improves Oxalate Nephropathy Secondary to Roux-en-Y Gastric Bypass
Authors: Agrawal Varun , Wilfong Jonathan B. , Rich Christopher E. , Gibson Pamela C.
Published: September 2016

Hyperoxaluria after Roux-en-Y gastric bypass (RYGB) increases the risk for kidney injury. Medical therapies for hyperoxaluria have limited efficacy. A 65-year-old female was evaluated for acute kidney injury [AKI, serum creatinine (Cr) 2.1 mg/dl, baseline Cr 1.0 mg/dl]. She did not have any urinary or gastrointestinal symptoms or exposure to nephrotoxic agents. Sixteen months prior to this evaluation, she underwent RYGB for morbid obesity. Her examination was unremarkable for hypertension or edema and there was no protein or blood on urine dipstick. Kidney biopsy revealed acute tubulointerstitial nephritis with oxalate crystals in tubules. The concurrent finding of severe hyperoxaluria (urine oxalate 150 mg/day) confirmed the diagnosis of oxalate nephropathy. Despite medical management of hyperoxaluria, her AKI worsened. Laparoscopic reversal of RYGB was performed and within 1 month, her hyperoxaluria resolved (urine oxalate 20 mg/day) and AKI improved (Cr 1.7 mg/dl). Surgical reversal of RYGB may be considered in patients with oxalate nephropathy at high risk of progression who fail medical therapy. Physicians need to be aware of the possibility of oxalate nephropathy after RYGB and promptly treat the hyperoxaluria to halt further kidney damage.
A Case of MECP2 Duplication Syndrome with Gonadotropin-Dependent Precocious Puberty
Authors: Tsuji-Hosokawa Atsumi , Matsuda Nozomi , Kurosawa Kenji , Kashimada Kenichi , Morio Tomohiro
Published: September 2016

Background:MECP2 duplication syndrome, which is caused by duplication of part of the Xq28 region containing the MECP2 gene, causes intellectual disability and mild dysmorphic features in males. To date, precocious puberty has not been reported as a clinical feature of MECP2 duplication syndrome. Methods: A 6-year-old male with severe intellectual disability was referred because of growth acceleration and precocious puberty. We checked his hormonal profile and conducted imaging studies and an array comparative genomic hybridization analysis. Results: His bone age (9 years and 6 months) was accelerated, and the basal level of testosterone was 8.99 ng/ml. In a luteinizing hormone (LH)-releasing hormone (LHRH) stimulation test, LH increased from 3.69 to 9.32 IU/l, and follicle-stimulating hormone increased from 0.65 to 0.90 IU/l. Chest and abdominal CTs and a brain MRI did not reveal any abnormalities. Treatment with an LHRH analogue effectively suppressed the level of testosterone to <0.03 ng/ml, consistent with the diagnosis of gonadotropin-dependent precocious puberty (GDPP). We identified a duplication of the Xq28 locus including MECP2 in the patient. Conclusion: Precocious puberty is often a benign central process in girls, but it is rarely idiopathic in boys. The present case raises the possibility that GDPP is a novel clinical feature of MECP2 duplication syndrome.
Meconium Peritonitis: Correlation of Antenatal Diagnosis and Postnatal Outcome - An Institutional Experience over 10 Years
Authors: Ping Lee May , Rajadurai Victor Samuel , Saffari Seyed Ehsan , Chandran Suresh
Published: September 2016

Objective: To identify the fetal and neonatal imaging characteristics of meconium peritonitis (MP) and their clinical outcome. We also studied the role of prenatal ultrasound (US) in antenatal diagnosis and its use in predicting the need for surgical intervention postnatally. Material and Methods: We conducted a retrospective analysis of a cohort of 18 infants with MP from April 2004 to March 2014. Results: Prenatal US detected MP-related abnormalities in 15/18 (83.3%) fetuses. The median gestational age at initial diagnosis of MP was 24 weeks (range 19-31). Fetal ascites (93.3%) was the most common prenatal US finding. Of the 18 infants, 12 (66.7%) required surgical intervention. The overall survival rate was 94.4%. All infants with a prenatal US scan showing meconium pseudocyst or bowel dilatation required surgical intervention postnatally. Discussion: A combination of ascites, intraperitoneal calcification, and echogenic bowel on fetal US raises a high suspicion of MP. Surgical intervention is indicated in the presence of meconium pseudocyst on fetal or postnatal US scan. Antenatal US has high specificity (100%) but low sensitivity (22.2%) in detecting meconium pseudocyst. A favorable outcome can be expected with early antenatal diagnosis and timely surgical intervention in a tertiary hospital.
Periungual Lesion due to Secondary Syphilis
Authors: Noriega Leandro , Gioia Di Chiacchio Nilton , Cury Rezende Flávia , Di Chiacchio Nilton
Published: September 2016

Several countries experience a new epidemic of syphilis, mainly due to the changes in risk behaviors. Dermatologists play an important role in the diagnosis, since cutaneous manifestations are frequent during disease progression. We report a rare case of secondary syphilis with periungual involvement. Syphilis, especially in the secondary form, may present with different clinical features, affecting different organs, and mimicking many diseases. Although nail apparatus lesions are more common in the primary form of the disease, they may also be present in the secondary and tertiary forms. Therefore, a comprehensive knowledge of the diverse forms of syphilis presentation is important for an early diagnosis and timely treatment.