bluuebunny/crossref_metadata_2025 huggingface dataset:
Cooperative Communication in Cognitive Radio Networks under Asymmetric Information: A Contract-Theory Based Approach
Authors: Zhao Nan , Wu Minghu , Xiong Wei , Liu Cong
Published: October 2015

By exploiting the spatial diversity of multiple wireless nodes, cooperative communication technique is a promising technique for spectrum sharing to improve spectrum efficiency. In this paper, the incentive issue between relay nodes’ (RNs’) service and source’s relay selection is investigated in the presence of the asymmetric information scenario. Multiuser cooperative communication is modelled as a labour market, where the source designs a contract and each relay node decides to select a contract item according to hidden information in order to obtain the best profit. The optimal contract design under both symmetric information and asymmetric information is presented based on contract theory. The contract-theoretic model for ability discrimination relay selection is formulated as an optimization problem to maximize the source’s utility. A sequential optimization algorithm is proposed to obtain the optimalrelay-rewardstrategy. Simulation results show that the optimal contract design scheme is effective in improving system performance for cooperative communication. This paper establishes a valuable cooperative communication mechanism in cognitive radio networks.
Fault Line Selection Method of Small Current to Ground System Based on Atomic Sparse Decomposition and Extreme Learning Machine
Authors: Wang Xiaowei , Wei Yanfang , Zeng Zhihui , Hou Yaxiao , Gao Jie , Wei Xiangxiang
Published: October 2015

This paper proposed a fault line voting selection method based on atomic sparse decomposition (ASD) and extreme learning machine (ELM). Firstly, it adopted ASD algorithm to decompose zero sequence current of every feeder line at first two cycles and selected the first four atoms to construct main component atom library, fundamental atom library, and transient characteristic atom libraries 1 and 2, respectively. And it used information entropy theory to calculate the atom libraries; the measure values of information entropy are got. It constructed four ELM networks to train and test atom sample and then obtained every network accuracy. At last, it combined the ELM network output and confidence degree to vote and then compared the vote number to achieve fault line selection (FLS). Simulation experiment illustrated that the method accuracy is 100%, it is not affected by fault distance and transition resistance, and it has strong ability of antinoise interference.
Feature Selection Tracking Algorithm Based on Sparse Representation
Authors: Lou Hui-dong , Li Wei-guang , Hou Yue-en , Yao Qing-he , Ye Guo-qiang , Wan Hao
Published: October 2015

In order to enhance the robustness of visual tracking algorithm in complex environment, a novel visual tracking algorithm based on multifeature selection and sparse representation is proposed. In the framework of particles filter, particles with low target similarity are first filtered out by a fast algorithm; then, based on the principle of sparsely reconstructing the sample label, the features with high differentiation against the background are involved in the computation so as to reduce the disturbance of occlusions and noises. Finally, candidate targets are linearly reconstructed via sparse representation and the sparse equation is solved by using APG method to obtain the state of the target. Four comparative experiments demonstrate that the proposed algorithm in this paper has effectively improved the robustness of the target tracking algorithm.
Lico A Enhances Nrf2-Mediated Defense Mechanisms againstt-BHP-Induced Oxidative Stress and Cell Death via Akt and ERK Activation in RAW 264.7 Cells
Authors: Lv Hongming , Ren Hua , Wang Lidong , Chen Wei , Ci Xinxin
Published: October 2015

Licochalcone A (Lico A) exhibits various biological properties, including anti-inflammatory and antioxidant activities. In this study, we investigated the antioxidative potential and mechanisms of Lico A againsttert-butyl hydroperoxide- (t-BHP-) induced oxidative damage in RAW 264.7 cells. Our results indicated that Lico A significantly inhibitedt-BHP-induced cytotoxicity, apoptosis, and reactive oxygen species (ROS) generation and reduced glutathione (GSH) depletion but increased the glutamate-cysteine ligase modifier (GCLM) subunit and the glutamate-cysteine ligase catalytic (GCLC) subunit genes expression. Additionally, Lico A dramatically upregulated the antioxidant enzyme heme oxygenase 1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2), which were associated with inducing Nrf2 nuclear translocation, decreasing Keap1 protein expression and increasing antioxidant response element (ARE) promoter activity. Lico A also obviously induced the activation of serine/threonine kinase (Akt) and extracellular signal-regulated kinase (ERK), but PI3K/Akt and ERK inhibitors treatment displayed clearly decreased levels of LicoA-induced Nrf2 nuclear translocation and HO-1 expression, respectively. Furthermore, Lico A treatment markedly attenuatedt-BHP-induced oxidative damage, which was reduced by treatment with PI3K/Akt, ERK, and HO-1 inhibitors. Therefore, Lico A might have a protective role againstt-BHP-induced cytotoxicity by modulating HO-1 and by scavenging ROS via the activation of the PI3K/Akt and ERK/Nrf2 signaling pathways.
High-Throughput Quantification of Phenotype Heterogeneity Using Statistical Features
Authors: Chaddad Ahmad , Tanougast Camel
Published: October 2015

Statistical features are widely used in radiology for tumor heterogeneity assessment using magnetic resonance (MR) imaging technique. In this paper, feature selection based on decision tree is examined to determine the relevant subset of glioblastoma (GBM) phenotypes in the statistical domain. To discriminate between active tumor (vAT) and edema/invasion (vE) phenotype, we selected the significant features using analysis of variance (ANOVA) with p value < 0.01. Then, we implemented the decision tree to define the optimal subset features of phenotype classifier. Naïve Bayes (NB), support vector machine (SVM), and decision tree (DT) classifier were considered to evaluate the performance of the feature based scheme in terms of its capability to discriminate vAT from vE. Whole nine features were statistically significant to classify the vAT from vE with p value < 0.01. Feature selection based on decision tree showed the best performance by the comparative study using full feature set. The feature selected showed that the two features Kurtosis and Skewness achieved a highest range value of 58.33–75.00% accuracy classifier and 73.88–92.50% AUC. This study demonstrated the ability of statistical features to provide a quantitative, individualized measurement of glioblastoma patient and assess the phenotype progression.
Current Approach in the Diagnosis and Management of Uveitic Glaucoma
Authors: Muñoz-Negrete Francisco J. , Moreno-Montañés Javier , Hernández-Martínez Paula , Rebolleda Gema
Published: October 2015

Uveitic glaucoma (UG) typically is associated with very high intraocular pressure (IOP) and more intense optic nerve damage than other glaucoma types. This secondary glaucoma requires an early diagnosis and adequate management of both uveitis and glaucoma. It is mandatory to identify the mechanisms of IOP elevation that in many eyes have multiple combined mechanisms. Management of these patients commonly requires an interdisciplinary approach that includes a glaucoma specialist and rheumatologist to control the inflammation and IOP. Glaucoma surgery is required early in these patients due to the high IOP usually present and is less successful than in primary open-angle glaucoma. Recurrent uveitic episodes, multiple mechanism, and the complications associated with uveitis make surgical management of UG challenging. In this review, the management and treatment of UG are updated to clarify the pathogenesis and prevent optic nerve damage.
The Metabonomic Studies of Tongue Coating inH. pyloriPositive Chronic Gastritis Patients
Authors: Liu Xuan , Sun Zhu-Mei , Liu Yan-Na , Ji Qing , Sui Hua , Zhou Li-Hong , Li Fu-Feng , Li Qi
Published: October 2015

In Traditional Chinese Medicine (TCM), tongue diagnosis (TD) has been an important diagnostic method for the last 3000 years. Tongue coating can be used as a very sensitive marker to determine the progress of chronic gastritis. Therefore, the scientific, qualitative, and quantitative study for the pathophysiologic basis of tongue coating (TC) emerged as a major direction for the objective research of TD. In our current report, we used GC/MS technology to determine the potential changes of metabolites and identify special metabolic biomarkers in the TC ofH. pyloriinfected chronic gastritis patients. Four discriminative metabolites were identified by GC/MS between the TC ofH. pyloriinfection (G+H) and withoutH. pyloriinfection (G-H) patients: ethylene, cephaloridine,γ-aminobutyric acid, and 5-pyroglutamic acid, indicating that changes in amino acid metabolism are possibly involved in the formation of TC, and the amino acid metabolites are part of the material components of TC inG+Hpatients.
Modeling the Effects of Land-Cover Change on Rainfall-Runoff Relationships in a Semiarid, Eastern Mediterranean Watershed
Authors: Ohana-Levi Noa , Karnieli Arnon , Egozi Roey , Givati Amir , Peeters Aviva
Published: October 2015

Temporal changes and spatial patterns are often studied by analyzing land-cover changes (LCCs) using spaceborne images. LCC is an important factor, affecting runoff within watersheds. The objective was to estimate the effects of 20 years of LCCs on rainfall-runoff relations in an extreme rainfall event. A 1989 Landsat TM-derived classification map was used as input for a Kinematic Runoff and Erosion (KINEROS) hydrological model along with the precipitation data of an extreme rainfall event. Model calibration was performed using measured runoff volume data. Validation of the model performance was conducted by comparing the model results to measured data. A similar procedure was used with a 2009 land-cover classification map as an input to the KINEROS model, along with similar precipitation data and calibration parameters, in order to understand the possible outcomes of a rainfall event of such a magnitude and duration after 20 years of LCCs. The results show an increase in runoff volume and peak discharge between the time periods as a result of LCCs. A strong relationship was detected between vegetation cover and the runoff volume. The LCCs with most pronounced effects on runoff volumes were related to urbanization and vegetation removal.
Towards Noncommutative Linking Numbers via the Seiberg-Witten Map
Authors: García-Compeán H. , Obregón O. , Santos-Silva R.
Published: October 2015

Some geometric and topological implications of noncommutative Wilson loops are explored via the Seiberg-Witten map. In the abelian Chern-Simons theory on a three-dimensional manifold, it is shown that the effect of noncommutativity is the appearance of6nnew knots at thenth order of the Seiberg-Witten expansion. These knots are trivial homology cycles which are Poincaré dual to the higher-order Seiberg-Witten potentials. Moreover the linking number of a standard 1-cycle with the Poincaré dual of the gauge field is shown to be written as an expansion of the linking number of this 1-cycle with the Poincaré dual of the Seiberg-Witten gauge fields. In the process we explicitly compute the noncommutative “Jones-Witten” invariants up to first order in the noncommutative parameter. Finally in order to exhibit a physical example, we apply these ideas explicitly to the Aharonov-Bohm effect. It is explicitly displayed at first order in the noncommutative parameter; we also show the relation to the noncommutative Landau levels.
Enhanced Photocatalytic Property of Cu Doped Sodium Niobate
Authors: Xu Jianbin , Zhang Feng , Sun Bingyang , Du Yingge , Li Guoqiang , Zhang Weifeng
Published: October 2015

We investigate the photocatalytic activity of Cu doped NaNbO3powder sample prepared by the modified polymer complex method. The photocatalytic activity of hydrogen evolution from methanol aqueous solution was improved by Cu 2.6 at% doping. The photocatalytic degradation of rhodamine B (RhB) under visible light irradiation was enhanced in comparison with pristine NaNbO3. Cu introduction improved the adsorption property of NaNbO3, judging from the Fourier transform infrared spectra. Moreover, the ultraviolet light excitation in Cu doped sample would accelerate the mineralized process.
Body Size of the Monomorphic AntLasius niger: Young Colonies along a Metal Pollution Gradient
Authors: Grześ Irena M. , Okrutniak Mateusz , Antosik Gracjan
Published: October 2015

Metal pollution may cause the decrease in the individual body size. In ants, the morphological diversity within and between colonies may be much higher than that considered before, even in monomorphic ants. In this study we measured the body size, expressed as head width, ofLasius nigerworkers collected from 44 young colonies in their ergonomic stage along a well-known gradient exhibiting chronic metal pollution. We calculated statistics describing the body size distribution curve, namely, average, median, data range, skewness, and kurtosis. None of these statistics correlated with the pollution level. Contrary to our previous study performed on mature colonies, workers from young colonies do not display pollution-related morphological changes. The results stress the importance of developmental stage of colony on diversifying body size of the worker cast, in monomorphic ants living in metal-polluted areas.
Physical, Mechanical, and Morphological Properties of Woven Kenaf/Polymer Composites Produced Using a Vacuum Infusion Technique
Authors: Salman Suhad D. , Sharba Mohaiman J. , Leman Z. , Sultan M. T. H. , Ishak M. R. , Cardona F.
Published: October 2015

Nowadays, due to renewable issues, environmental concerns, and the financial problems of synthetic fibres, the development of high-performance engineering products made from natural resources is increasing all over the world. Lately, kenaf fibre has been used among many different types of natural resources in various shapes. Unidirectional long fibres or randomly oriented short fibre shapes are the most common type of kenaf fibres that have been investigated in previous works. This work characterises and evaluates the physical, mechanical, and morphological properties of plain woven kenaf fabric and its composites with three types of thermoset resin at 0°/90° and 45°/−45° orientation, in order to assess their suitability as lignocellulosic reinforced polymer composites. A vacuum infusion manufacturing technique was used to prepare the specimens with fibre weight content of 35% ± 2%. Eight specimens were prepared for each test, and five replications were adopted. A total of 78 samples were tested in this study. The results show that the composites with 0°/90° had the highest tensile, flexural strengths, and modulus. The morphological properties of composite samples were analysed through scanning electron microscopy (SEM) images and these clearly demonstrated the better interfacial adhesion between the woven kenaf and the epoxy matrix.
Study on the Optical Properties of Triangular Cavity Absorber for Parabolic Trough Solar Concentrator
Authors: Chen Fei , Li Ming , Hassanien Emam Hassanien Reda , Luo Xi , Hong Yongrui , Feng Zhikang , Ji Mengen , Zhang Peng
Published: October 2015

A theoretical analytical method for optical properties of cavity absorber was proposed in this paper and the optical design software TracePro was used to analyze the optical properties of triangular cavity absorber. It was found that the optimal optical properties could be achieved with appropriate aperture width, depth-to-width ratio, and offset distance from focus of triangular cavity absorber. Based on the results of orthogonal experiment, the optimized triangular cavity absorber was designed. Results showed that the standard deviation of irradiance and optical efficiency of optimized designed cavity absorber were 30528 W/m2and 89.23%, respectively. Therefore, this study could offer some valuable references for designing the parabolic trough solar concentrator in the future.
The Accordion Maneuver: A Noninvasive Strategy for Absent or Delayed Callus Formation in Cases of Limb Lengthening
Authors: Makhdom Asim M. , Cartaleanu Adrian Sever , Rendon Juan Sebastian , Villemure Isabelle , Hamdy Reggie C.
Published: October 2015

The distraction osteogenesis (DO) technique has been used worldwide to treat many orthopaedic conditions. Although successful, absent or delayed callus formation in the distraction gap can lead to significant morbidities. An alternate cycle of distraction-compression (accordion maneuver) is one approach to accelerate bone regeneration. The primary aim of our study is to report our experience with the accordion maneuver during DO and to provide a detailed description of this technique, as performed in our center. The secondary aim is to present a review of the literature regarding the use of accordion maneuver. We reviewed the database of all patients undergoing limb lengthening from the year of 1997 to 2012. Four patients (6.15%) out of 65 showed poor bone regenerate in their tibiae and therefore accordion maneuver was applied for a mean of 6.75 weeks. Of these, three patients have had successful outcome with this technique. The literature showed that this technique is successful approach to trigger bone healing. However, details of how and when to apply this combination of distraction-compression forces were lacking. In conclusion, the accordion technique is safe noninvasive approach to promote bone formation, thus avoiding more invasive surgical procedures in cases of poor callus formation in limb lengthening.
Superresolution of Hyperspectral Image Using Advanced Nonlocal Means Filter and Iterative Back Projection
Authors: Wang Jin , Wu Zhensen , Lee Young-Sup
Published: October 2015

We introduce an efficient superresolution algorithm based on advanced nonlocal means (NLM) filter and iterative back projection for hyperspectral image. The nonlocal means method achieves the to-be-interpolated pixel by the weighted average of all pixels within an image, and the unrelated neighborhoods are automatically eliminated by the trivial weights. However, spatial location distance is also an important issue to reconstruct the missing pixel. Therefore, we proposed an advanced NLM (ANLM) filter considering both neighborhood similarity and patch distance. In the conventional NLM method, the search region was the whole image, while the proposed ANLM utilizes the limited search to reduce the complexity. The iterative back projection (IBP) is a very famous method to deal with the image restoration. In the superresolution issue, IBP is able to recover the high-resolution image iteratively from the given low-resolution image which is blurred due to the noise by minimizing the reconstruction error, while, because the reconstruction error of IBP is back projection and isotropic, the conventional IBP suffers from jaggy and ringing artifacts. Introducing the ANLM method to improve the visual quality is necessary.
Temperature Effect on Electrical Treeing and Partial Discharge Characteristics of Silicone Rubber‐Based Nanocomposites
Authors: Ahmad Mohd Hafizi , Bashir Nouruddeen , Buntat Zolkafle , Arief Yanuar Z. , Abd Jamil Abdul Azim , Mohamed Piah Mohamed Afendi , Suleiman Abubakar A. , Dodd Steve , Chalashkanov Nikola
Published: October 2015

This study investigated electrical treeing and its associated phase‐resolved partial discharge (PD) activities in room‐temperature, vulcanized silicone rubber/organomontmorillonite nanocomposite sample materials over a range of temperatures in order to assess the effect of temperature on different filler concentrations under AC voltage. The samples were prepared with three levels of nanofiller content: 0% by weight (wt), 1% by wt, and 3% by wt. The electrical treeing and PD activities of these samples were investigated at temperatures of 20°C, 40°C, and 60°C. The results show that the characteristics of the electrical tree changed with increasing temperature. The tree inception times decreased at 20°C due to space charge dynamics, and the tree growth time increased at 40°C due to the increase in the number of cross‐link network structures caused by the vulcanization process. At 60°C, more enhanced and reinforced properties of the silicone rubber‐based nanocomposite samples occurred. This led to an increase in electrical tree inception time and electrical tree growth time. However, the PD characteristics, particularly the mean phase angle of occurrence of the positive and negative discharge distributions, were insensitive to variations in temperature. This reflects an enhanced stability in the nanocomposite electrical properties compared with the base polymer.
Crystallization Behavior of Phosphate Glasses with Hydrophobic Coating Materials
Authors: Chung Jaeyeop , Ryu Bongki
Published: October 2015

We analyzed the effect of the addition of Li2O3, TiO2, and Fe2O3 on the crystallization behavior of P2O5–CaO–SiO2–K2O glasses and the effect of the crystallization behavior on the roughness and hydrophobicity of the coated surface. Exothermic behavior, including a strong exothermic peak in the 833–972 K temperature range when Fe2O3, TiO2, or Li2O3 was added, was confirmed by differential thermal analysis. The modified glass samples (PFTL1–3) showed diffraction peaks when heated at 1073 and 1123 K for 5 min; the crystallized phase corresponds to Fe3(PO4)2, that is, graftonite. We confirmed that the intensity of the diffraction peaks increases at high temperatures and with increasing Li2O3 content. In the case of the PFTL3 glass, a Li3Fe2(PO4)2 phase, that is, trilithium diiron(III) tris[phosphate(V)], was observed. Through scanning electron microscopy and the contact angles of the surfaces with water, we confirmed that the increase in surface roughness, correlated to the crystallization of the glass frit, increases hydrophobicity of the surface. The calculated values of the local activation energies for the growth of Fe3(PO4)2 on the PTFL1, PTFL2, and PFTL3 glass were 237–292 kJ mol−1, 182–258 kJ mol−1, and 180–235 kJ mol−1.
Prevalence of Pathogenic Mutations in Cancer Predisposition Genes among Pancreatic Cancer Patients
Authors: Hu Chunling , Hart Steven N. , Bamlet William R. , Moore Raymond M. , Nandakumar Kannabiran , Eckloff Bruce W. , Lee Yean K. , Petersen Gloria M. , McWilliams Robert R. , Couch Fergus J.
Published: October 2015

The prevalence of germline pathogenic mutations in a comprehensive panel of cancer predisposition genes is not well-defined for patients with pancreatic ductal adenocarcinoma (PDAC). To estimate the frequency of mutations in a panel of 22 cancer predisposition genes, 96 patients unselected for a family history of cancer who were recruited to the Mayo Clinic Pancreatic Cancer patient registry over a 12-month period were screened by next-generation sequencing. Fourteen pathogenic mutations in 13 patients (13.5%) were identified in eight genes: four in ATM, two in BRCA2, CHEK2, and MSH6, and one in BARD1, BRCA1, FANCM, and NBN. These included nine mutations (9.4%) in established pancreatic cancer genes. Three mutations were found in patients with a first-degree relative with PDAC, and 10 mutations were found in patients with first- or second-degree relatives with breast, pancreas, colorectal, ovarian, or endometrial cancers. These results suggest that a substantial proportion of patients with PDAC carry germline mutations in predisposition genes associated with other cancers and that a better understanding of pancreatic cancer risk will depend on evaluation of families with broad constellations of tumors. These findings highlight the need for recommendations governing germline gene-panel testing of patients with pancreatic cancer. Cancer Epidemiol Biomarkers Prev; 25(1); 207–11. ©2015 AACR.
MAPK Activation Predicts Poor Outcome and the MEK Inhibitor, Selumetinib, Reverses Antiestrogen Resistance in ER-Positive High-Grade Serous Ovarian Cancer
Authors: Hew Karina E. , Miller Philip C. , El-Ashry Dorraya , Sun Jun , Besser Alexandra H. , Ince Tan A. , Gu Mengnan , Wei Zhi , Zhang Gao , Brafford Patricia , Gao Wei , Lu Yiling , Mills Gordon B. , Slingerland Joyce M. , Simpkins Fiona
Published: October 2015

Purpose: Although 67% of high-grade serous ovarian cancers (HGSOC) express the estrogen receptor (ER), most fail antiestrogen therapy. Because MAPK activation is frequent in ovarian cancer, we investigated if estrogen regulates MAPK and if MEK inhibition (MEKi) reverses antiestrogen resistance.

Experimental Design: Effects of MEKi (selumetinib), antiestrogen (fulvestrant), or both were assayed in ER-positive HGSOC in vitro and in xenografts. Response biomarkers were investigated by gene expression microarray and reverse phase protein array (RPPA). Genes differentially expressed in two independent primary HGSOC datasets with high versus low pMAPK by RPPA were used to generate a “MAPK-activated gene signature.” Gene signature components that were reversed by MEKi were then identified.

Results: High intratumor pMAPK independently predicts decreased survival (HR, 1.7; CI > 95%,1.3–2.2; P = 0.0009) in 408 HGSOC from The Cancer Genome Atlas. A differentially expressed “MAPK-activated” gene subset was also prognostic. “MAPK-activated genes” in HGSOC differ from those in breast cancer. Combined MEK and ER blockade showed greater antitumor effects in xenografts than monotherapy. Gene set enrichment analysis and RPPA showed that dual therapy downregulated DNA replication and cell-cycle drivers, and upregulated lysosomal gene sets. Selumetinib reversed expression of a subset of “MAPK-activated genes” in vitro and/or in xenografts. Three of these genes were prognostic for poor survival (P = 0.000265) and warrant testing as a signature predictive of MEKi response.

Conclusions: High pMAPK is independently prognostic and may underlie antiestrogen failure. Data support further evaluation of fulvestrant and selumetinib in ER-positive HGSOC. The MAPK-activated HGSOC signature may help identify MEK inhibitor responsive tumors. Clin Cancer Res; 22(4); 935–47. ©2015 AACR.
Well-Differentiated Neuroendocrine Tumors with a Morphologically Apparent High-Grade Component: A Pathway Distinct from Poorly Differentiated Neuroendocrine Carcinomas
Authors: Tang Laura H. , Untch Brian R. , Reidy Diane L. , O'Reilly Eileen , Dhall Deepti , Jih Lily , Basturk Olca , Allen Peter J. , Klimstra David S.
Published: October 2015

Purpose: Most well-differentiated neuroendocrine tumors (WD-NET) of the enteropancreatic system are low-intermediate grade (G1, G2). Elevated proliferation demonstrated by either a brisk mitotic rate (>20/10 high power fields) or high Ki-67 index (>20%) defines a group of aggressive neoplasms designated as high-grade (G3) neuroendocrine carcinoma (NEC). High-grade NEC is equated with poorly differentiated NEC (PD-NEC) and is associated with a dismal outcome. Progression of WD-NETs to a high-grade neuroendocrine neoplasm very rarely occurs and their clinicopathologic and molecular features need to be characterized.

Experimental Design: We investigated 31 cases of WD-NETs with evidence of a component of a high-grade neoplasm. The primary sites included pancreas, small bowel, bile duct, and rectum. Histopathology of the cases was retrospectively reviewed and selected IHC and gene mutation analyses performed.

Results: The high-grade component occurred either within the primary tumor (48%) or at metastatic sites (52%). The clinical presentation, radiographic features, biomarkers, and the genotype of these WD-NETs with high-grade component remained akin to those of G1–G2 WD-NETs. The median disease-specific survival (DSS) was 55 months (16–119 months), and 2-year and 5-year DSS was 88% and 49%, respectively—significantly better than that of a comparison group of true PD-NEC (DSS 11 months).

Conclusions: Mixed grades can occur in WD-NETs, which are distinguished from PD-NECs by their unique phenotype, proliferative indices, and the genotype. This phenomenon of mixed grade in WD-NET provides additional evidence to the growing recognition that the current WHO G3 category contains both WD-NETs as well as PD-NECs. Clin Cancer Res; 22(4); 1011–7. ©2015 AACR.
Abstract B03: Pin1 is required for sustained B cell proliferation upon oncogenic activation of Myc
Authors: D'Artista Luana , Piontini Andrea , Kress Theresia , Morelli Marco , Verrecchia Alessandro , Doni Mirko , Campaner Stefano , Amati Bruno
Published: October 2015

The c-myc proto-oncogene is activated by translocation in Burkitt's lymphoma, where it is also frequently subject to secondary mutations. Substitutions in codon 58, in particular, stabilize the Myc protein and augment its oncogenic potential. In wild-type Myc, phosphorylation of Ser 62 primes phosphorylation of Thr 58, providing a landing pad for the peptidyl prolyl-isomerase Pin1, which in turn promotes Ser 62 dephosphorylation and Myc degradation. However, genetic data are missing to address whether Pin1 influences Myc-induced lymphomagenesis. Here, we show that genetic ablation of Pin1 in Eµ-myc transgenic mice starkly reduced lymphoma onset and penetrance. In pre-malignant Pin1 deficient B cells, the proliferative response to Myc was selectively impaired, while Myc-induced apoptosis was intact. This phenotype was not the result of deregulated levels of Ser 62 phosphorylation in the Pin1-/- background. Similar results were observed in Pin1-/- mouse embryo fibroblasts (MEFs), where prolonged Myc activation inhibited proliferation. In either B cells or MEFs, loss of Pin1 did not affect mitogen-induced cell cycle entry, an effect that relies on endogenous Myc activity. Thus, our data unravel the existence of a synthetic-lethal interaction between deletion of Pin1 and oncogenic activation of Myc. Myc-induced oncogenic stress is linked to the induction of the Arf/p53 pathway, which is critical for tumor suppression in Eµ-myc mice. The selective pressure to inactivate Arf/p53 axis was preserved in Eµ-myc Pin1-/- lymphomas. In the absence of Arf or p53, the Pin1 deletion no longer reduced Myc-induced tumorigenesis or proliferation. Thus the proliferative arrest of pre-tumoral Eµ-myc Pin1-/- B cells required an active ARF-p53 dependent cytostatic response. Our data demonstrate that Pin1 is required to support the oncogenic activity of Myc in B cells and warrant further assessment of Pin1 as a therapeutic target in Myc-dependent malignancies.

Citation Format: Luana D'Artista, Andrea Piontini, Theresia Kress, Marco Morelli, Alessandro Verrecchia, Mirko Doni, Stefano Campaner, Bruno Amati. Pin1 is required for sustained B cell proliferation upon oncogenic activation of Myc. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr B03.
Abstract B28: Determining the apoptotic mechanisms of bromodomain and extraterminal (BET) inhibitors
Authors: Lasorsa Elena , Ellis Leigh
Published: October 2015

Inhibitors of the bromodomain and extraterminal domain family (BETi), represent a novel class of targeted therapy to treat aggressive B-cell lymphomas. Specifically, BETi are shown to inhibit proliferation and induce apoptosis in lymphoma cells arising from Myc transgenic mice. However, the underlying apoptotic mechanisms are still not well understood. Dissecting apoptotic mechanisms required by BETi could provide strong rationale on how to best utilize BETi to treat patients with aggressive B-cell lymphomas.

It was the primary purpose of this study to delineate the molecular mechanisms underlying BETi induced apoptosis. Secondly, by determining critical apoptotic proteins/pathways, investigate the potential of BETi in novel combination therapy strategies. For this, we conducted in vitro studies utilizing primary and compound mutant lymphomas derived from the Eµ-myc murine model of B-cell lymphoma. The BETi IBET762 was used to treat lymphomas, and over all cell death, apoptosis, mitochondria damage, cell cycle distribution were assessed by flow cytometry. Protein expression of Myc, bromodomain 3 and 4 (BRD 3 and BRD4), Bcl-2 and activated caspase 3 were assessed by western blot.

IBET762 induces apoptosis in Eµ-myc lymphomas in a time and dose dependent manner at low nanomolar concentrations. Apoptosis was dependent on the intrinsic apoptotic pathway, but independent of p53 or p19arf. Loss of apoptosome function delayed the kinetics of BETi mediated cell death. Analysis of BRD3, BRD4, Bcl-2 and Myc protein expression is ongoing. Because apoptosis induction by BETi was blocked by the overexpression of Bcl-2, we tested the efficacy of the small molecule Bcl-2 inhibitor, ABT-263. Combining low dose ABT-263 with IBET762 resulted in induction of apoptosis in Eµ-myc/Bcl-2 lymphomas.

These data indicate mitochondrial damage to be critical for BETi mediated apoptosis. Finally, our current studies will provide vision and strong rationale on how best to apply BET inhibitors to the clinic to provide maximum benefit to patients with aggressive B-cell lymphomas.

Citation Format: Elena Lasorsa, Leigh Ellis. Determining the apoptotic mechanisms of bromodomain and extraterminal (BET) inhibitors. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr B28.
Phase I/II Study of Sorafenib in Combination with Hepatic Arterial Infusion Chemotherapy Using Low-Dose Cisplatin and 5-Fluorouracil
Authors: Ueshima Kazuomi , Kudo Masatoshi , Tanaka Masatoshi , Kumada Takashi , Chung Hobyung , Hagiwara Satoru , Inoue Tatsuo , Yada Norihisa , Kitai Satoshi
Published: October 2015

We conducted a phase I/II study in patients with advanced hepatocellular carcinoma (HCC) to determine the recommended dose, as well as the safety and efficacy, of combination therapy of sorafenib with hepatic arterial infusion chemotherapy (HAIC) using low dose cisplatin (CDDP) and 5-fluorouracil (5FU). Cohorts consisting of 3-6 patients with HCC received an escalated dose of CDDP and 5-FU until a maximum-tolerated dose was achieved. The treatment regimen was as follows: oral administration of sorafenib (400 mg twice daily for 28 days) combined with HAIC using CDDP (14-20 mg/m2, on days 1 and 8) and 5-FU (170-330 mg/m2, continuously on days 1-5 and 8-12) via an implanted catheter system). Each treatment cycle consisted of 28 days and three cycles of combination therapy. At the end of the first cycle, adverse events were evaluated and future dose escalation was determined. Eighteen patients with advanced HCC were enrolled. Dose-limiting toxicity was observed in two patients from cohort 1 (erythema multiforme and grade 4 thrombocytopenia) and in one patient from cohort 2 (erythema multiforme). Seven of the 18 patients achieved a partial response, seven showed stable disease, two were diagnosed as progressive disease, and two were not assessable. The response rate was 38.9% and the disease control rate was 77.8%. The time-to-progression was 9.7 months and the 1-year survival rate was 88.2%. Oral administration of 400 mg of sorafenib twice daily, 20 mg/m2 of intra-arterial infusion of CDDP, and 5-FU at 330 mg/m2 are the recommended doses for combination therapy, which was well tolerated and efficacious. This combination therapy may be a promising treatment for patients with advanced HCC. A large prospective randomized multicenter study (ClinicalTrials.gov Identifier NCT01214343) is ongoing.
Scleral Buckling versus Vitrectomy for Retinal Detachment Repair: Comparison of Visual Fields and Nerve Fiber Layer Thickness
Authors: Koutsandrea Chryssanthi , Kanakis Menelaos , Papaconstantinou Dimitrios , Brouzas Dimitrios , Ladas Ioannis , Petrou Petros , Georgalas Ilias
Published: October 2015

Purpose: To compare visual field loss and retinal nerve fiber layer (RNFL) defects in cases of rhegmatogenous retinal detachment (RRD) treated with scleral buckle (SB) versus pars plana vitrectomy (PPV) and C3F8 injection. Methods: This was a prospective, comparative interventional study of 50 eyes with primary RRD, treated with PPV (25 eyes) or SB (25 eyes). All measurements took place at least 9 months following successful and uncomplicated surgical treatment. The visual field total deviation (TD) values for preoperative attached and detached areas were calculated and compared separately. The optic nerve head morphology was studied with Heidelberg retinal tomography (HRT), and the RNFL using spectral-domain optical coherence tomography. Results: The preoperative detached areas demonstrated more affected TD values (in dB) compared to the preoperative attached areas (-6.9 ± 5.2 vs. -4.3 ± 3.3 for the SB group and -9.6 ± 5.2 vs. -7.8 ± 5.1 for the PPV group; p = 0.001) in both groups. The preoperative attached areas of the SB group showed better TD values (calculated mean values) compared to the preoperative attached areas of the PPV group (-4.3 ± 3.3 vs. -7.8 ± 5.1, p = 0.007). The RNFL and HRT values showed no statistically significant difference between the two groups. Conclusions: It seems that the preoperative detached retina, despite successful reattachment, suffers permanent damage as a result of the detachment, irrespective of the method of treatment. In the PPV group, the postoperative functionality of the preoperative attached areas was detected to be worse compared to the postoperative functionality of the preoperative attached areas of the SB group. We postulate that this fact could be attributed to an additional traumatizing factor (possibly fluid-air exchange or gas injection) in patients with RRD treated with PPV.
Identification and Functional Characterization of a Novel
CACNA1C
-Mediated Cardiac Disorder Characterized by Prolonged QT Intervals With Hypertrophic Cardiomyopathy, Congenital Heart Defects, and Sudden Cardiac Death
Authors: Boczek Nicole J. , Ye Dan , Jin Fang , Tester David J. , Huseby April , Bos J. Martijn , Johnson Aaron J. , Kanter Ronald , Ackerman Michael J.
Published: October 2015

Background—

A portion of sudden cardiac deaths can be attributed to structural heart diseases, such as hypertrophic cardiomyopathy (HCM) or cardiac channelopathies such as long-QT syndrome (LQTS); however, the underlying molecular mechanisms are distinct. Here, we identify a novel
CACNA1C
missense mutation with mixed loss-of-function/gain-of-function responsible for a complex phenotype of LQTS, HCM, sudden cardiac death, and congenital heart defects.

Methods and Results—

Whole exome sequencing in combination with Ingenuity variant analysis was completed on 3 affected individuals and 1 unaffected individual from a large pedigree with concomitant LQTS, HCM, and congenital heart defects and identified a novel CACNA1C mutation, p.Arg518Cys, as the most likely candidate mutation. Mutational analysis of exon 12 of
CACNA1C
was completed on 5 additional patients with a similar phenotype of LQTS plus a personal or family history of HCM-like phenotypes and identified 2 additional pedigrees with mutations at the same position, p.Arg518Cys/His. Whole cell patch clamp technique was used to assess the electrophysiological effects of the identified mutations in Ca
V
1.2 and revealed a complex phenotype, including loss of current density and inactivation in combination with increased window and late current.

Conclusions—

Through whole exome sequencing and expanded cohort screening, we identified a novel genetic substrate p.Arg518Cys/His-CACNA1C, in patients with a complex phenotype including LQTS, HCM, and congenital heart defects annotated as cardiac-only Timothy syndrome. Our electrophysiological studies, identification of mutations at the same amino acid position in multiple pedigrees, and cosegregation with disease in these pedigrees provide evidence that p.Arg518Cys/His is the pathogenic substrate for the observed phenotype.
Decrement Evoked Potential Mapping
Authors: Jackson Nicholas , Gizurarson Sigfus , Viswanathan Karthik , King Benjamin , Massé Stephane , Kusha Marjan , Porta-Sanchez Andreu , Jacob John Roshan , Khan Fakhar , Das Moloy , Ha Andrew C.T. , Pashaei Ali , Vigmond Edward , Downar Eugene , Nanthakumar Kumaraswamy
Published: October 2015

Background—

Substrate-based mapping for ventricular tachycardia (VT) ablation is hampered by its inability to determine critical sites of the VT circuit. We hypothesized that those potentials, which delay with a decremental extrastimulus (decrement evoked potentials or DEEPs), are more likely to colocalize with the diastolic pathways of VT circuits.

Methods and Results—

DEEPs were identified in intraoperative left ventricular maps from 6 patients with ischemic cardiomyopathy (total 9 VTs) and were compared with late potential (LP) and activation maps of the diastolic pathway for each VT. Mathematical modeling was also used to further validate and elucidate the mechanisms of DEEP mapping. All patients demonstrated regions of DEEPs and LPs. The mean endocardial surface area of these potentials was 18±4% and 21±6%, respectively (
P
=0.13). The mean sensitivity for identifying the diastolic pathway in VT was 50±23% for DEEPs and 36±32% for LPs (
P
=0.31). The mean specificity was 43±23% versus 20±8% for DEEP and LP mapping, respectively (
P
=0.031). The electrograms that displayed the greatest decrement in each case had a sensitivity and specificity for the VT isthmus of 29±10% and 95±1%, respectively. Mathematical modeling studies recapitulated DEEPs at the VT isthmus and demonstrated their role in VT initiation with a critical degree of decrement.

Conclusions—

In this preliminary study, DEEP mapping was more specific than LP mapping for identifying the critical targets of VT ablation. The mechanism of DEEPs relates to conduction velocity restitution magnified by zigzag conduction within scar channels.
Hypothalamic Paraventricular and Arcuate Nuclei Contribute to Elevated Sympathetic Nerve Activity in Pregnant Rats
Authors: Shi Zhigang , Cassaglia Priscila A. , Gotthardt Laura C. , Brooks Virginia L.
Published: October 2015

Pregnancy increases sympathetic nerve activity (SNA), but the mechanisms are unknown. Here, we investigated the contributions of the hypothalamic paraventricular and arcuate nuclei in α-chloralose–anesthetized pregnant and nonpregnant rats. Baseline arterial pressure (AP) was lower, and heart rate (HR), lumbar sympathetic activity, and splanchnic SNA were higher in pregnant rats compared with nonpregnant rats. Inhibition of the paraventricular nucleus via bilateral muscimol nanoinjections decreased AP and HR more in pregnant rats than in nonpregnant rats and decreased lumbar SNA only in pregnant rats. Similarly, after arcuate muscimol nanoninjections, the decreases in AP, HR, and lumbar, renal, and splanchnic sympathetic nerve activities were greater in pregnant rats than in nonpregnant rats. Major arcuate neuronal groups that project to the paraventricular nucleus express inhibitory neuropeptide Y (NPY) and excitatory α-melanocyte–stimulating hormone. Inhibition of paraventricular melanocortin 3/4 receptors with SHU9119 also decreased AP, HR, and lumbar SNA in pregnant rats but not in nonpregnant rats. Conversely, paraventricular nucleus NPY expression was reduced in pregnant animals, and although blockade of paraventricular NPY Y1 receptors increased AP, HR, and lumbar sympathetic activity in nonpregnant rats, it had no effects in pregnant rats. Yet, the sympathoinhibitory, depressor, and bradycardic effects of paraventricular NPY nanoinjections were similar between groups. In conclusion, the paraventricular and arcuate nuclei contribute to increased basal SNA during pregnancy, likely due in part to decreased tonic NPY inhibition and increased tonic α-melanocyte–stimulating hormone excitation of presympathetic neurons in the paraventricular nucleus.
How to Merge a Root
Authors: Belder Marijke De , Craenenbroeck Jeroen van
Published: October 2015

The main goal of this article is to show that four properties of roots can be derived in a principled manner from the theory of Merge. The properties in question are the following: (a) roots have no grammatical features, (b) roots have no syntactic category, (c) roots are defined structurally rather than lexically, and (d) roots are dominated by functional material (rather than the other way around). We argue that the first Merge operation in each cyclic domain creates a radically empty structural position at the foot of the structure in which a root can be inserted at the level of Vocabulary Insertion. The four abovementioned properties of roots can then be shown to follow straightforwardly from this theory.
New Laboulbeniales parasitic on weevils from the Amazon rainforest
Authors: Rossi Walter , TORRES JUAN A. , BERNARDI MATTEO
Published: October 2015

Four new species of Laboulbenia parasitic on Curculionidae (Insecta, Coleoptera) from Ecuador are described. These are L. dichroma on Geraeus sp. (Conoderinae, Barididae, Madarini); L. elephantina on Udeus sp. (Curculioninae, Eugnomini); L. inopinata on Lechriops spp. (Conoderinae, Lechriopini) and Macrocopturus spp. (Conoderinae, Zygopini); L. microcarpa on Sicoderus sp. and Lancearius esau (Curculioninae, Erodiscini).
Phytoseiid mites (Acari: Mesostigmata) from Araucaria Forest of the State of Rio Grande do Sul, Brazil, with new records and descriptions of four new species
Authors: GONÇALVES DINARTE , CUNHA UEMERSON SILVA DA , BAMPI PAULA MARIA , MORAES GILBERTO JOSÉ DE , FERLA NOELI JUAREZ
Published: October 2015

This paper reports on the Phytoseiidae from an Araucaria forest in the State of Rio Grande do Sul, describing four new species, namely Transeius kroeffis n. sp., Typhlodromalus araucariae n. sp., Typhlodromips pompeui n. sp. and Typhlodromips salvadorii n. sp.. Iphiseiodes moraesi Ferla & Silva, Neoseiulus tunus (DeLeon), Typhlodromips japi Lofego, Demite & Feres, Typhlodromips pallinii Gonçalves, Silva & Ferla, Typhloseiopsis dorsoreticulatus Lofego, Demite & Feres are reported for the first time from this type of habitat in Rio Grande do Sul state, Brazil.
Probathylepadidae, a new family of Scalpelliformes (Thoracica: Cirripedia: Crustacea), for Probathylepas faxian gen. nov., sp. nov., from a hydrothermal vent in the Okinawa Trough
Authors: REN XIAN-QIU , SHA ZHONG-LI
Published: October 2015

A new pedunculate barnacle, Probathylepas faxian gen. and sp. nov., is described from a hydrothermal vent in the Okinawa Trough. A new scalpelliform family, Probathylepadidae, is also proposed for the new genus and species. Probathylepadidae differs from all other five families of the order Scalpelliformes by the capitulum bearing eight primal plates and two whorls of imbricating supplementary plates, and the peduncle being without scales. The relationships between the species of the new family and sessile barnacles are also discussed.