bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrocatalytic Enhancement Effects at Platinized Nanoporous Substrates: Oxidation of Ethanol at PtRu Nanoparticles Dispersed over Rh-Containing ZrO2 Support
Authors: Rutkowska Iwona Agnieszka , Koster Margaretta D. , Blanchard Gary J. , Kulesza Pawel J.
Published: October 2014

The presence of a large population of hydroxyl groups (originating from zirconia) in the vicinity of PtRu, in addition to possible specific interactions between zirconia and the ruthenium component, most likely induced oxidative removal (from Pt) of otherwise passivating CO adsorbates. Although Rh itself did not show directly any activity toward the ethanol oxidation, the metal is expected to facilitate C-C bond splitting in C2H5OH molecule. Codeposition and introduction of metallic rhodium particles to ZrO2 also improved the overall conductivity of the matrix and charge distribution at the electrocatalytic interface. Application of the nanoporous platinum electrode substrate together with Rh and ZrO2 components as well as PtRu electrocatalytic sites led to enhancement of the electrocatalytic currents larger than one would expect from simple addition of activities of single components.
Effect of La Doping of Ceria Abrasives for STI CMP
Authors: Praveen B V S , Park Jin-Goo , Ramanathan S
Published: October 2014

The nitride removal rate by ceria abrasives in presence of amino acids is altered by the purity of ceria. Commercial ceria obtained from Sigma-Aldrich with low purity (<90%) and with high purity (99.95%) were employed in the study. Polishing experiments showed that in presence of lanthanum in the abrasive, proline does not suppress nitride removal. In order to verify that the effect is mainly due to presence of lanthanum, ceria particles were synthesized with and without lanthanum doping. Three types of amino acids viz. proline, alanine and glutamic acid were used with the ceria particles. The removal rate results show that proline is sensitive to presence of lanthanum impurity in abrasive, while alanine and glutamic acid suppress the nitride removal irrespective of the purity of the abrasives. The abrasives were characterized using XRD. The adsorption of amino acids on abrasive was characterized by differential thermal analysis
Quantum Dot Based Sensing Platform for Selective Detection of Volatile Organic Compounds and Biomarkers
Authors: Sarswat Prashant , Free Michael L
Published: October 2014

Diagnosing and monitoring diseases such as lung cancer often involves expensive testing in advanced stages of development. An inexpensive method is desired for earlier detection and improved prognosis. Such diseases cause changes in body chemistry that result in the release of volatile organic biomarkers (VOBs) that are often different than those of healthy patients. Therefore, appropriate analysis of patients’ breath can lead to early diagnosis and monitoring. The objective of this research is to understand and improve new non-invasive selective sensors to quantify specific VOBs. These sensors consist of mixture of quantum dots and dye. The dye becomes colored when exposed to volatile organic biomarkers without a significant difference in color for different biomarkers. However, when the dye is tethered to quantum dots and exposed to light, the color for each biomarker is quantifiably different. Such a combination creates a sensitive and selective sensor for disease specific VOBs.
Surface Engineered Pyrolyzed Carbon Electrode Arrays for Bio-Sensing
Authors: Song Yin , Penmatsa Varun , Yang jung Hoon , Wang Chunlei
Published: October 2014

There is an urgent need to develop highly selective, sensitive and reproducible miniaturized bio-sensing platforms based on reliable interfaces is compatible with microfabrication processing.. Our objective is to first create pyrolyzed carbon micropillar arrays with high surface area as bio-sensing electrodes, second to develop functionalization methods in order to improve the biomolecule immobilization efficiency and finally to understand the electrochemical phenomena occurring at the biomolecule/carbon interface. The carbon micropillar arrays with high aspect ratios and hierarchical porous surface have been fabricated by carbon microelectromechanical systems (C-MEMS). Nanomaterials have been integrated onto the micropillar arrays to further increase the accessible surface area and in order to achieve efficient covalent immobilization of biomolecules, various functionalization methods have been investigated. The developed bio-sensing platform was then applied to several applications including DNA sensors; H2O2 sensors, aptamer sensors and HIV sensors.
Electrodeposition of Cu-Ni Incorporated with Layered Silicates for Corrosion Protection
Authors: Thurber Casey R. , Calhoun Margaret C. , Ahmad Yahia H. , D'Souza Nandika , Mohamed Adel , Golden Teresa D.
Published: October 2014

Electrodeposition of different metals and alloys is popular for corrosion resistance because of the major problems that persist with corrosion. Two major alloys of Cu-Ni, 70-30 and 90-10, have been evaluated for corrosion protection on a stainless steel substrate. Copper and copper alloys are commonly used in marine environments to resist biofouling of materials by inhibiting microbial growth. The results show that the incorporated montmorillonite in the Cu-Ni matrix at 0.05% (238.1-297.5 kΩ cm2) and 0.1% (138.2-102.9 kΩ cm2) improved the overall corrosion resistance versus the pure alloy film (71.9-68.5 kΩ cm2). These coatings hold promise for the off-shore drilling environment in the oil and gas industry.
Membrane Assisted Capacitive Deionization with Binder-Free Carbon Xerogel Electrodes
Authors: Omosebi Ayokunle , Gao Xin , Landon James , Liu Kunlei
Published: October 2014

Performance results from the extended operation of CDI and MCDI single cells configured with binder-free mesoporous CX electrodes are presented. A Randle’s equivalent circuit consisting of capacitive and resistive impedances was used to simulate the current response of the CDI and MCDI cells. The CDI cell had a lower initial resistance (RS) but also a lower resistance to current leakage (RL), and a lower effective capacitance (CDL) in comparison to the MCDI cell. The simulation model showed good agreement with experimental data, but overestimated the prediction of RS values. Performance data from conductivity profiles showed improved performance for the MCDI cell, but also inversion spiking for the CDI cell after extended operation. The results suggest that the lower RL, led to faster oxidation of the electrodes and a degraded CDI performance. In contrast, the MCDI cell showed preserved behavior with extended operation.
Investigating the Composition and Electrochemical Activity of Ti/SnO2-Sb2O5 Anodes Fabricated by Thermal Decomposition
Authors: Ni Qing , Kirk Donald W. , Thorpe Steven J.
Published: October 2014

Antimony-doped tin oxide anodes were fabricated from the thermal decomposition of tin chloride and antimony chloride. The surface and in-depth distribution of elemental compositions were analyzed using photoelectron spectroscopy. The results suggested that during the thermal treatment of the anodes, antimony preferentially was lost by evaporation, resulting in a composition that deviated from that nominally expected. Further electrochemical tests revealed that the composition in the antimony-doped tin oxide coatings had an impact on the conductivity of the anodes. Therefore, this study reveals that the evaporation loss of the precursor had an impact on the electrochemical activity of the antimony-doped tin oxide anodes.
Modeling and Experimental Validation of Electroplating Deposit Distributions from Copper Sulfate Solutions
Authors: Robison Mark , Free Michael L
Published: October 2014

3-D Modeling of copper electrodeposition in a copper sulfate solutions was carried out using COMSOL Multiphysics. The results of the model were validated using experimental plating cells of different geometries. A new empirical equation was developed to predict deposit thickness on protruding or recessed features in a plating cell with accuracy comparable to the COMSOL model.
Estimation of Leakage Current in Proton Exchange Membrane Fuel Cells
Authors: Rezaei Niya Seyed Mohammad , Phillips Ryan , Hoorfar Mina
Published: October 2014

In this study, the leakage current of a proton exchange membrane fuel cell is determined from the polarization curve and impedance measurements. The ohmic loss is specified from the high frequency resistance in the Nyquist plot. The polarization curve is then rotated counter-clockwise to nullify the effects of the ohmic loss. Considering the negligible mass transport loss in low current densities, the activation loss is then determined as a function of the current density. Employing the Tafel assumption, the leakage current can be determined from the best logarithmic fit. The method is then experimentally verified by measuring the polarization curves and Nyquist plots of a cell including the Nafion 212 as the membrane. Tests are conducted using four different gas diffusion layers for all of which the same current leakage is obtained.
Mathematical Modeling of the Electrodeposition Process
Authors: Mahapatro Anil , Suggu Santosh Kumar
Published: October 2014

Electroplating or electrodeposition is a process which produces a dense, uniform and adherent coating on a metal surface using electric current in an electrolytic cell. This process is mainly used to change the surface properties of a material. It is used for many technological applications, like automotive industries, electrical industries, corrosion protection of metals etc. Modeling of the electrodeposition process will assist in minimizing experimental trials for optimization of these coating strategies. In this manuscript we report the development of a mathematical model to simulate the electrodeposition of copper on cobalt-chrome alloy. The developed model was validated using experiments
Systematic Characterization of Ionic Liquid Electrolyte Systems for Lithium Ion Batteries
Authors: Cama Christina , DiLeo Roberta A. , Takeuchi Kenneth J , Marschilok Amy C , Takeuchi Esther S
Published: October 2014

Next generation high energy density battery materials for application in lithium – ion batteries (LIBs) may require operating voltages beyond the limits of conventional electrolytes. Ionic liquids (ILs) are an appealing potential replacement for conventional electrolyte, offering the opportunity for higher voltage stability and appropriate conductivity when used to generate hybrid IL-solvent based electrolytes. However, few systematic studies on the physical properties of IL electrolytes are available. The effect of the structure of the IL, composition of electrolyte, and the addition of salt to the IL electrolyte was studied to determine hybrid IL electrolytes suitable for use within lithium – ion batteries.
Electrothermal and Electrochemical Modeling of Lithium-ion Batteries: 3D Simulation with Experimental Validation
Authors: Fink Clemens , Kaltenegger Bernhard
Published: October 2014

This work presents two lithium-ion battery models which are implemented in the multiphysics software package FIRE®, developed by AVL List GmbH: an efficient electrothermal model based on an empirical voltage/current relationship and a physically based, non-isothermal electrochemical model. The models are applied to a 3D simulation of a high energy lithium-ion pouch battery. Both models are adjusted to measured discharge curves for various currents and temperatures. Then their results are compared and a deep insight into the electrodes is given by the electrochemical model. Here, the importance of 3D effects and temperature influence are pointed out – both effects which are often neglected in electrochemical models presented in literature. Finally, both models are compared to voltage and temperature measurements using a realistic, strongly dynamic driving profile. A highly accurate prediction of the experimental data can be achieved with both models.
Effect of Heat Treatment on Activity of Fe/N/C Catalyst Prepared by Hemin for Oxygen Reduction Reaction
Authors: Tei Go , Kamai Ryo , Gyoten Hisaaki , Hayashi Takao , Aizawa Masato
Published: October 2014

Carbon-supported Fe/N/C catalysts synthesized from hemin have recently shown high oxygen reduction reaction (ORR) activity for the cathode use of fuel cells. In previous studies, such hemin-based catalysts were usually prepared by heat treatment at temperatures ranging from 600 to 900°C at a fixed calcination time of about 2 hours. In this study, we compare the ORR activity of hemin-based catalyst prepared by different calcination times: 100 s, 30 min, or 2 hrs. The results show that the calcination time dependence of ORR activity dynamically changes depending on the calcination temperature. When the heat treatment temperature is 600°C, the ORR activity consistently improves as the calcination time increases from 100 s to 2 hrs. At 750 and 900°C, first the ORR activity improves and then plateaus or decreases with the increase of the calcination time. The optimum calcination time of our catalyst seems to exist below 30 minutes at 750°C. These calcination time dependences are explained by the different rate of the formation of FeNx ORR active site and its extinction depending on the calcination temperature.
Synthesis of Ordered Mesoporous Carbon as Support for Pt-Co Alloys: Evaluation as an Alcohol-Tolerant ORR Catalyst for Direct Oxidation Fuel Cells
Authors: Morales-Acosta D. , Sanchez-Padilla N. M. , Rodriguez-Varela F.J.
Published: October 2014

In this work the Pt-Co/OMC as oxygen reduction reaction (ORR) cathode was evaluated under fuel-free and fuel-propanol in acid electrolyte conditions. By RDE measurements the ORR on the alloy seems to proceed via 4 e- transfer mechanism in acid media. In presence of 2-Propanol the alloy shows a high degree of tolerance. The results obtained from the Pt-Co/OMC alloy were compared to those of a Pt/OMC cathode.
Steric Effects in the Reaction of Electrogenerated Ligand-Reduced Nickel Salen with Organic Halides
Authors: Nguyen Minh-Anh N , Tomasso Maria E , Ji Chang
Published: October 2014

Cyclic voltammetry (CV) and controlled-potential electrolysis were employed to examine the reactions of electrogenerated ligand-reduced nickel salen with four different organic halides (1-bromooctane, benzyl bromide, 1-bromomethylnaphthalene, and a-bromodiphenylmethane). CVs for nickel(II) salen in the presence of benzyl bromide or 1-bromomethylnaphthalene exhibit characteristic features for the catalytic reduction of substrates involving radical intermediates. Bulk electrolyses of benzyl bromide and 1-bromomethylnaphthalene at carbon cathodes catalyzed by nickel salen were also carried out at selected potentials to afford various products. Comparison of the CVs for nickel salen before and after reactions with these four organic halides further reveals that steric effect could play an important role in the corresponding nucleophilic attack of the substrates by ligand-reduced catalyst (a radical-anion), which follows the sequence of 1-bromooctane > benzyl bromide > 1-bromomethylnaphthalene > α-bromodiphenylmethane in terms of reaction efficiency. A proposed mechanism for the electrochemical reactions was also discussed on the basis of previous studies.
Effect of Pretreatment on the Rate of the VO2+/VO2
+ and V2+/V3+ Reactions at a Carbon Electrode
Authors: Bourke Andrea , Quill Nathan , Lynch Robert P. , Buckley D. Noel
Published: October 2014

It was shown by cyclic voltammetry, current measurements at constant potential and electrochemical impedance spectroscopy that polarization pretreatment of glassy carbon electrodes affects the kinetics of the VO2+/VO2
+ and V2+/V3+ redox reactions. After pretreatment at potentials more positive than ~0.7 V (sat. Hg/Hg2SO4), electrodes were less active both for oxidation of VO2+ and for reduction of VO2
+. The activity of the electrode remained depressed indefinitely but was recovered by pretreatment at negative potentials. However, the converse was observed for the V2+/V3+ redox reactions: after pretreatment at positive potentials electrodes were more active for oxidation of V2+ and reduction of V3+ than after pretreatment at negative potentials. Both activation and deactivation (for VO2+/VO2
+) occurred relatively quickly, typically within ~60 s. and eventually approached a steady state characteristic of the particular pretreatment potential. It is suggested that oxygen species formed on the electrode during anodization inhibit the VO2+/VO2
+ electrode reaction but enhance the V2+/V3+ electrode reaction.
Effect of Sub 1-Nm Pt Nanoparticle on the Conduction Properties of Graphene Based Field Effect Transistor
Authors: Zheng Haisheng , Mukherjee Somik , Gangopadhyay Keshab , Gangopadhyay Shubhra
Published: October 2014

We have developed a low-power tilted-target sputtering process for achieving sub-1 nm metal nanoparticles (NPs) with controlled sizes and number densities and narrow size distributions on graphene. In this report, the unique properties of Pt NPs and their applications in graphene-based field-effect transistor by modifying the conduction channel with sub 1-nm Pt NPs has been studied. By using ultra-small size Pt NPs with quantized energy levels, we influence the electrical properties of large-area single-layer graphene by both electron transfer, carrier scattering and strain, resulting in substantial Dirac point shifting in the I-V characteristics and change in conductivity, respectively, which could be helpful to better understand the metal NP-graphene interaction. We also show that the plasma damage created on the graphene surface from the sputter deposition of metal NPs can be removed by 250 °C annealing in hydrogen.
Gastric dysregulation induced by microinjection of 6-OHDA in the substantia nigra pars compacta of rats is determined by alterations in the brain-gut axis
Authors: Toti Luca , Travagli R. Alberto
Published: October 2014

Idiopathic Parkinson's disease (PD) is a late-onset, chronic, and progressive motor dysfunction attributable to loss of nigrostriatal dopamine neurons. Patients with PD experience significant gastrointestinal (GI) issues, including gastroparesis. We aimed to evaluate whether 6-hydroxy-dopamine (6-OHDA)-induced degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) induces gastric dysmotility via dysfunctions of the brain-gut axis. 6-OHDA microinjection into the SNpc induced a >90% decrease in tyrosine hydroxylase-immunoreactivity (IR) on the injection site. The [13C]-octanoic acid breath test showed a delayed gastric emptying 4 wk after the 6-OHDA treatment. In control rats, microinjection of the indirect sympathomimetic, tyramine, in the dorsal vagal complex (DVC) decreased gastric tone and motility; this inhibition was prevented by the fourth ventricular application of either a combination of α1- and α2- or a combination of D1 and D2 receptor antagonists. Conversely, in 6-OHDA-treated rats, whereas DVC microinjection of tyramine had reduced effects on gastric tone or motility, DVC microinjection of thyrotropin-releasing hormone induced a similar increase in motility as in control rats. In 6-OHDA-treated rats, there was a decreased expression of choline acetyl transferase (ChAT)-IR and neuronal nitric oxide synthase (NOS)-IR in DVC neurons but an increase in dopamine-β-hydroxylase-IR in the A2 area. Within the myenteric plexus of the esophagus, stomach, and duodenum, there were no changes in the total number of neurons; however, the percentage of NOS-IR neurons increased, whereas that of ChAT-IR decreased. Our data suggest that the delayed gastric emptying in a 6-OHDA rat model of PD may be caused by neurochemical and neurophysiological alterations in the brain-gut axis.
The extraction of neural strategies from the surface EMG: an update
Authors: Farina Dario , Merletti Roberto , Enoka Roger M.
Published: October 2014

A surface EMG signal represents the linear transformation of motor neuron discharge times by the compound action potentials of the innervated muscle fibers and is often used as a source of information about neural activation of muscle. However, retrieving the embedded neural code from a surface EMG signal is extremely challenging. Most studies use indirect approaches in which selected features of the signal are interpreted as indicating certain characteristics of the neural code. These indirect associations are constrained by limitations that have been detailed previously (Farina D, Merletti R, Enoka RM. J Appl Physiol 96: 1486–1495, 2004) and are generally difficult to overcome. In an update on these issues, the current review extends the discussion to EMG-based coherence methods for assessing neural connectivity. We focus first on EMG amplitude cancellation, which intrinsically limits the association between EMG amplitude and the intensity of the neural activation and then discuss the limitations of coherence methods (EEG-EMG, EMG-EMG) as a way to assess the strength of the transmission of synaptic inputs into trains of motor unit action potentials. The debated influence of rectification on EMG spectral analysis and coherence measures is also discussed. Alternatively, there have been a number of attempts to identify the neural information directly by decomposing surface EMG signals into the discharge times of motor unit action potentials. The application of this approach is extremely powerful, but validation remains a central issue.
A virtual rat for simulating environmental and exertional heat stress
Authors: Rakesh Vineet , Stallings Jonathan D. , Reifman Jaques
Published: October 2014

Severe cases of environmental or exertional heat stress can lead to varying degrees of organ dysfunction. To understand heat-injury progression and develop efficient management and mitigation strategies, it is critical to determine the thermal response in susceptible organs under different heat-stress conditions. To this end, we used our previously published virtual rat, which is capable of computing the spatiotemporal temperature distribution in the animal, and extended it to simulate various heat-stress scenarios, including 1) different environmental conditions, 2) exertional heat stress, 3) circadian rhythm effect on the thermal response, and 4) whole body cooling. Our predictions were consistent with published in vivo temperature measurements for all cases, validating our simulations. We observed a differential thermal response in the organs, with the liver experiencing the highest temperatures for all environmental and exertional heat-stress cases. For every 3°C rise in the external temperature from 40 to 46°C, core and organ temperatures increased by ∼0.8°C. Core temperatures increased by 2.6 and 4.1°C for increases in exercise intensity from rest to 75 and 100% of maximal O2 consumption, respectively. We also found differences as large as 0.8°C in organ temperatures for the same heat stress induced at different times during the day. Even after whole body cooling at a relatively low external temperature (1°C for 20 min), average organ temperatures were still elevated by 2.3 to 2.5°C compared with normothermia. These results can be used to optimize experimental protocol designs, reduce the amount of animal experimentation, and design and test improved heat-stress prevention and management strategies.
BET Protein Inhibitor JQ1 Attenuates Myc-Amplified MCC Tumor Growth In Vivo
Authors: Shao Qiang , Kannan Aarthi , Lin Zhenyu , Stack Brendan C. , Suen James Y. , Gao Ling
Published: October 2014

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin currently with no cure. In this study, we have first demonstrated that c-Myc overexpression is common in MCC. By targeting c-Myc, bromodomain inhibitors have demonstrated antitumor efficacy in several preclinical human cancer models. Thus, we interrogated the role of c-Myc inhibition in MCC with c-Myc amplification by using the BET inhibitor JQ1. We have uncovered that c-Myc can be regulated by JQ1 in MCC cells with pathologic c-Myc activation. Moreover, JQ1 potently abrogates c-Myc expression in MCC cells and causes marked G1 cell-cycle arrest. Mechanistically, JQ1-induced cell-cycle arrest coincides with downregulation of cyclin D1 and upregulation of p21, p27, and p57, whereas JQ1 exerts no effect on apoptosis in MCC cells. Further knockdown of p21, p27, or p57 by shRNA partially protects cells from JQ1-induced cell-cycle arrest. In addition, c-Myc knockdown by shRNA generates significant cell-cycle arrest, suggesting that c-Myc overexpression plays a role in MCC pathogenesis. Most importantly, JQ1 significantly attenuates tumor growth in xenograft MCC mouse models. Our results provide initial evidence, indicating the potential clinical utility of BET protein inhibitors in the treatment of MCC with pathologic activation of c-Myc. Cancer Res; 74(23); 7090–102. ©2014 AACR.
Challenges and Opportunities in International Molecular Cancer Prevention Research: An ASPO Molecular Epidemiology and the Environment and International Cancer Prevention Interest Groups Report
Authors: Epplein Meira , Bostick Roberd M. , Mu Lina , Ogino Shuji , Braithwaite Dejana , Kanetsky Peter A.
Published: October 2014

The International Agency for Research on Cancer estimates that over half of the new cancer cases and almost two-thirds of the cancer deaths in 2012 occurred in low and middle income countries. To discuss the challenges and opportunities to reducing the burden of cancer worldwide, the Molecular Epidemiology and the Environment and the International Issues in Cancer Special Interest Groups joined forces to hold a session during the 38th Annual Meeting of the American Society of Preventive Oncology (March 2014, Arlington, Virginia). The session highlighted three topics of particular interest to molecular cancer prevention researchers working internationally, specifically: 1) biomarkers in cancer research; 2) environmental exposures and cancer; and 3) molecular pathological epidemiology. A major factor for successful collaboration illuminated during the discussion was the need for strong, committed, and reliable international partners. A key element of establishing such relationships is to thoroughly involve individual international collaborators in the development of the research question; engaged international collaborators are particularly motivated to champion and shepherd the project through all necessary steps, including issues relating to institutional review boards, political sensitivity, laboratory-based assays, and tumor subtyping. Also essential is allotting time for the building, maintaining, and investing in such relationships so that successful international collaborations may take root and bloom. While there are many challenges inherent to international molecular cancer research, the opportunities for furthering the science and prevention of cancer worldwide are great, particularly at this time of increasing cancer incidence and prevalence in low and middle income countries. Cancer Epidemiol Biomarkers Prev; 23(11); 2613–7. ©2014 AACR.
Epidemiology of Gastrointestinal Stromal Tumors in the Era of Histology Codes: Results of a Population-Based Study
Authors: Ma Grace L. , Murphy James D. , Martinez Maria E. , Sicklick Jason K.
Published: October 2014

To date, all population-based epidemiologic data on gastrointestinal stromal tumor (GIST) in the United States predate the 2001 implementation of GIST-specific histology coding. As such, results from previous studies were limited because of inclusion of non-GIST abdominal or gastrointestinal sarcomas. We used a national cancer registry with modern day histologic codes to gain greater insight into the true epidemiology of GIST in the United States. We identified 6,142 patients diagnosed with GIST between 2001 and 2011 in the Surveillance, Epidemiology, and End Results database. Incidence, survival, demographic risk factors, and prognostic factors were analyzed. Annual age-adjusted incidence rose from 0.55/100,000 in 2001 to 0.78/100,000 in 2011 and increased with age, peaking among 70- to 79-year-olds (3.06/100,000). GIST was also more common in males than females [rate ratio (RR), 1.35], non-Hispanics than Hispanics (RR, 1.23), and blacks (RR, 2.07) or Asians/Pacific Islanders (RR, 1.50) than whites. The study period had 5-year overall and GIST-specific survival rates of 65% and 79%, respectively. The 5-year overall survival rates for those with localized, regional, and metastatic disease at diagnosis were 77%, 64%, and 41%, respectively. Multivariate analyses demonstrated that older age at diagnosis, male sex, black race, and advanced stage at diagnosis were independent risk factors for worse overall survival. Multivariate analysis also showed the four aforementioned characteristics, along with earlier year of diagnosis, to be independent risk factors for worse GIST-specific survival. As the first population-based, epidemiologic study of histologically confirmed disease, our findings provide a robust representation of GIST in the era of immunohistochemical diagnoses. Cancer Epidemiol Biomarkers Prev; 24(1); 298–302. ©2014 AACR.
Genome-wide DNA Methylation Analysis of Lung Carcinoma Reveals One Neuroendocrine and Four Adenocarcinoma Epitypes Associated with Patient Outcome
Authors: Karlsson Anna , Jönsson Mats , Lauss Martin , Brunnström Hans , Jönsson Per , Borg Åke , Jönsson Göran , Ringnér Markus , Planck Maria , Staaf Johan
Published: October 2014

Purpose: Lung cancer is the worldwide leading cause of death from cancer. DNA methylation in gene promoter regions is a major mechanism of gene expression regulation that may promote tumorigenesis. However, whether clinically relevant subgroups based on DNA methylation patterns exist in lung cancer remains unclear.

Experimental Design: Whole-genome DNA methylation analysis using 450K Illumina BeadArrays was performed on 12 normal lung tissues and 124 tumors, including 83 adenocarcinomas, 23 squamous cell carcinomas (SqCC), 1 adenosquamous cancer, 5 large cell carcinomas, 9 large cell neuroendocrine carcinomas (LCNEC), and 3 small-cell carcinomas (SCLC). Unsupervised bootstrap clustering was performed to identify DNA methylation subgroups, which were validated in 695 adenocarcinomas and 122 SqCCs. Subgroups were characterized by clinicopathologic factors, whole-exome sequencing data, and gene expression profiles.

Results: Unsupervised analysis identified five DNA methylation subgroups (epitypes). One epitype was distinctly associated with neuroendocrine tumors (LCNEC and SCLC). For adenocarcinoma, remaining four epitypes were associated with unsupervised and supervised gene expression phenotypes, and differences in molecular features, including global hypomethylation, promoter hypermethylation, genomic instability, expression of proliferation-associated genes, and mutations in KRAS, TP53, KEAP1, SMARCA4, and STK11. Furthermore, these epitypes were associated with clinicopathologic features such as smoking history and patient outcome.

Conclusions: Our findings highlight one neuroendocrine and four adenocarcinoma epitypes associated with molecular and clinicopathologic characteristics, including patient outcome. This study demonstrates the possibility to further subgroup lung cancer, and more specifically adenocarcinomas, based on epigenetic/molecular classification that could lead to more accurate tumor classification, prognostication, and tailored patient therapy. Clin Cancer Res; 20(23); 6127–40. ©2014 AACR.
In vitro Effects of the Organophosphorus Pesticide Malathion on the Reactivity of Rat Aorta
Authors: Menezes de Carvalho Marco Tulio , Celotto Andrea Carla , Sumarelli Albuquerque Agnes Afrodite , Garros Ferreira Luciana , Capellini Verena Kise , Cassiano Silveira Ana Paula , Rubens de Nadai Tales , Evora Paulo Roberto Barbosa
Published: October 2014

Background and Purpose: There is a remarkable paucity of studies analyzing the role of the endothelium-derived relaxing factors on the vascular effects of organophosphates. This study was carried out to evaluate the vascular effects of malathion and the role of nitric oxide (NO) and prostacyclin (PGI2). Methods: Vascular reactivity measuring isometric forces in vitro (‘organ chambers') and flow cytometry (cells loaded with DAF-FM DA) were used. Results: In rat thoracic aorta segments contracted with phenylephrine (Phe) (10-7 mol/l), malathion (10-10 to 10-5 mol/l) induced concentration-dependent relaxation in arteries with intact endothelium (n = 7; p < 0.05). Malathion-mediated relaxation was blocked by N-nitro-L-arginine methyl ester (L-NAME; 10-4 mol/l), a nonspecific NO synthase inhibitor, and/or indomethacin (10-5 mol/l), a nonspecific cyclooxygenase inhibitor (n = 10, p < 0.05). In thoracic aorta rings, with and without endothelium, Phe (10-10 to 10-5 mol/l) evoked concentration-dependent contraction, which was reduced in the presence of malathion. In rings with or without endothelium, incubated with malathion, L-NAME and indomethacin, the Phe-induced contraction was restored. The role of NO was confirmed using flow cytometry. Malathion evokes endothelium-dependent relaxation through the M1 muscarinic receptor, since this relaxation was clearly blocked by atropine (M1 and M2 blocker) and pirenzepine (M1 blocker), but was less blocked by gallamine (M2 blocker) or 4-DAMP (M3 blocker). Conclusions: These findings suggest that the organophosphate compound effects on vascular reactivity depend of NO and PGI2.
Hemoglobin α/eNOS Coupling at Myoendothelial Junctions Is Required for Nitric Oxide Scavenging During Vasoconstriction
Authors: Straub Adam C. , Butcher Joshua T. , Billaud Marie , Mutchler Stephanie M. , Artamonov Mykhaylo V. , Nguyen Anh T. , Johnson Tyler , Best Angela K. , Miller Megan P. , Palmer Lisa A. , Columbus Linda , Somlyo Avril V. , Le Thu H. , Isakson Brant E.
Published: October 2014

Objective—

Hemoglobin α (Hb α) and endothelial nitric oxide synthase (eNOS) form a macromolecular complex at myoendothelial junctions; the functional role of this interaction remains undefined. To test if coupling of eNOS and Hb α regulates nitric oxide signaling, vascular reactivity, and blood pressure using a mimetic peptide of Hb α to disrupt this interaction.

Approach and Results—

In silico modeling of Hb α and eNOS identified a conserved sequence of interaction. By mutating portions of Hb α, we identified a specific sequence that binds eNOS. A mimetic peptide of the Hb α sequence (Hb α X) was generated to disrupt this complex. Using in vitro binding assays with purified Hb α and eNOS and ex vivo proximity ligation assays on resistance arteries, we have demonstrated that Hb α X significantly decreased interaction between eNOS and Hb α. Fluorescein isothiocyanate labeling of Hb α X revealed localization to holes in the internal elastic lamina (ie, myoendothelial junctions). To test the functional effects of Hb α X, we measured cyclic guanosine monophosphate and vascular reactivity. Our results reveal augmented cyclic guanosine monophosphate production and altered vasoconstriction with Hb α X. To test the in vivo effects of these peptides on blood pressure, normotensive and hypertensive mice were injected with Hb α X, which caused a significant decrease in blood pressure; injection of Hb α X into eNOS
-/-
mice had no effect.

Conclusions—

These results identify a novel sequence on Hb α that is important for Hb α/eNOS complex formation and is critical for nitric oxide signaling at myoendothelial junctions.
Mechanism of Race-Dependent Platelet Activation Through the Protease-Activated Receptor-4 and Gq Signaling Axis
Authors: Tourdot Benjamin E. , Conaway Stanley , Niisuke Katrin , Edelstein Leonard C. , Bray Paul F. , Holinstat Michael
Published: October 2014

Objective—

Black individuals are at an increased risk of myocardial infarction and stroke, 2 vascular diseases with strong thrombotic components. Platelet activation is a key step in platelet clot formation leading to myocardial infarction and stroke, and recent work supports a racial difference in platelet aggregation through the thrombin protease-activated receptors (PARs). The underlying mechanism for this racial difference, however, has not been established. Determining where in the signaling cascade these racial differences emerge will aid in understanding why individuals of differing racial ancestry may possess an inherent difference in their responsiveness to antiplatelet therapies.

Approach and Results—

Washed human platelets from black volunteers were hyperaggregable in response to PAR4-mediated platelet stimulation compared with whites. Interestingly, the racial difference in PAR4-mediated platelet aggregation persisted in platelets treated ex vivo with aspirin and 2MeSAMP (2-methylthioadenosine 5′-monophosphate triethylammonium salt hydrate), suggesting that the racial difference is independent of secondary feedback. Furthermore, stimulation of platelets from black donors with PAR4-activating peptide showed a potentiated level of activation through the G
q
pathway compared with platelets from white donors. Differences in signaling included increased Ca
2+
mobilization, Rap1 (Ras-related protein 1) activation, and integrin α
IIb
β
3
activation with no observed difference in platelet protein expression between the groups tested.

Conclusions—

Our study is the first to demonstrate that the G
q
pathway is differentially regulated by race after PAR4 stimulation in human platelets. Furthermore, the racial difference in PAR4-mediated platelet aggregation persisted in the presence of cyclooxygenase and P2Y
12
receptor dual inhibition, suggesting that current antiplatelet therapy may provide less protection to blacks than whites.
β-Blocker Therapy Is Not Associated With Adverse Outcomes in Patients With Pulmonary Arterial Hypertension
Authors: Thenappan Thenappan , Roy Samit S. , Duval Sue , Glassner-Kolmin Cherylanne , Gomberg-Maitland Mardi
Published: October 2014

Background—

The safety of β-blockers in patients with isolated right ventricular failure because of pulmonary arterial hypertension (PAH) is unclear.

Methods and Results—

We studied 564 PAH patients (total cohort) referred to our center from 1982 to 2013. Propensity score-matching was used to match pairs of PAH patients with and without β-blocker use (matched cohort). We compared all-cause mortality between the groups in the total cohort and the matched cohort using bootstrap validation, Kaplan–Meier, and Cox proportional hazard analyses. Seventy-one of the 564 patients in the total cohort were on β-blockers. They were older, had higher prevalence of comorbidities, and were more often on diuretics, digoxin, and angiotensin converting enzyme inhibitors. The severity of PAH and right ventricular failure was similar between those with and without β-blocker use. After propensity matching, 63 patients with β-blocker use were compared with 51 patients without β-blocker use. During a median follow-up time of 4.8 years, there were 339 (60%) deaths in the total cohort and 70 deaths (61%) in the matched cohort. There was no difference in absolute mortality between those with and without β-blockers (
P
=0.71). β-Blocker use was not associated with increased all-cause mortality in the total cohort after adjusting for propensity score (adjusted hazard ratio, 1.0; 95% confidence interval, 0.7–1.5) and in the matched cohort (hazard ratio, 1.2; 95% confidence interval, 0.8–2.0).

Conclusions—

There was no statistically significant difference in long-term mortality between propensity score-matched pairs of PAH patients with and without β-blocker use. These findings need further validation in prospective clinical trials.
Association of 10‐Year and Lifetime Predicted Cardiovascular Disease Risk With Subclinical Atherosclerosis in South Asians: Findings From the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study
Authors: Kandula Namratha R. , Kanaya Alka M. , Liu Kiang , Lee Ji Young , Herrington David , Hulley Stephen B. , Persell Stephen D. , Lloyd‐Jones Donald M. , Huffman Mark D.
Published: October 2014

Background

Ten‐year and lifetime cardiovascular risk assessment algorithms have been adopted into atherosclerotic cardiovascular disease (
ASCVD
) prevention guidelines, but these prediction models are not based on South Asian populations and may underestimate the risk in Indians, Pakistanis, Bangladeshis, Nepali, and Sri Lankans in the United States. Little is known about
ASCVD
risk prediction and intermediate endpoints such as subclinical atherosclerosis in
US
individuals of South Asian ancestry.

Methods and Results

South Asians (n=893) from the Mediators of Atherosclerosis in South Asians Living in America (
MASALA
) study who were 40 to 79 years and free of
ASCVD
were included. Ten‐year
ASCVD
predicted risk was calculated using the 2013 Pooled Cohort Equations. Lifetime predicted risk was based on risk factor burden. Baseline levels of subclinical atherosclerosis (coronary artery calcium [
CAC
] and carotid intima media thickness [
CIMT
]) were compared across 10‐year and lifetime risk strata: (1) high (≥7.5%) 10‐year and low (<7.5%) 10‐year risk; (2) high (≥39%) lifetime and low (<39%) lifetime risk. South Asian men and women with high 10‐year predicted risk had a significantly greater
CAC
burden than those with low 10‐year risk. South Asians with high lifetime predicted risk had a significantly increased odds for
CAC
higher than 0 (odds ratio: men 1.97; 95%
CI
, 1.2 to 3.2; women 3.14; 95%
CI
, 1.5, 6.6). Associations between risk strata and
CIMT
were also present.

Conclusion

This study is the first to provide evidence that contemporary
ASCVD
risk assessment algorithms derived from non‐Hispanic white and African‐American samples can successfully identify substantial differences in atherosclerotic burden in
US
South Asians.
Increased Prevalence of Posttraumatic Stress Disorder in Patients After Transient Ischemic Attack
Authors: Kiphuth Ines C. , Utz Kathrin S. , Noble Adam J. , Köhrmann Martin , Schenk Thomas
Published: October 2014

Background and Purpose—

A transient ischemic attack (TIA) involves temporary neurological symptoms but leaves a patient symptom-free. Patients are faced with an increased risk for future stroke, and the manifestation of the TIA itself might be experienced as traumatizing. We aimed to investigate the prevalence of posttraumatic stress disorder (PTSD) after TIA and its relation to patients’ psychosocial outcome.

Methods—

Patients with TIA were prospectively studied, and 3 months after the diagnosis, PTSD, anxiety, depression, quality of life, coping strategies, and medical knowledge were assessed via self-rating instruments.

Results—

Of 211 patients with TIA, data of 108 patients were complete and only those are reported. Thirty-two (29.6%) patients were classified as having PTSD. This rate is 10× as high as in the general German population. Patients with TIA with PTSD were more likely to show signs of anxiety and depression. PTSD was associated with the use of maladaptive coping strategies, subjectively rated high stroke risk, as well as with younger age. Finally, PTSD and anxiety were associated with decreased mental quality of life.

Conclusions—

The experience of TIA increases the risk for PTSD and associated anxiety, depression, and reduced mental quality of life. Because a maladaptive coping style and a subjectively overestimated stroke risk seem to play a crucial role in this adverse progression, the training of adaptive coping strategies and cautious briefing about the realistic stroke risk associated with TIA might be a promising approach. Despite the great loss of patients to follow-up, the results indicate that PTSD after TIA requires increased attention.
RNF213
Rare Variants in an Ethnically Diverse Population With Moyamoya Disease
Authors: Cecchi Alana C. , Guo Dongchuan , Ren Zhao , Flynn Kelly , Santos-Cortez Regie Lyn P. , Leal Suzanne M. , Wang Gao T. , Regalado Ellen S. , Steinberg Gary K. , Shendure Jay , Bamshad Michael J. , Grotta James C. , Nickerson Deborah A. , Pannu Hariyadarshi , Milewicz Dianna M.
Published: October 2014

Background and Purpose—

Moyamoya disease (MMD) is a rare, genetically heterogeneous cerebrovascular disease resulting from occlusion of the distal internal carotid arteries. A variant in the Ring Finger 213 gene (
RNF213
), altering arginine at position 4810 (p.R4810K), is associated with MMD in Asian populations. However, there are a lack of data on the role of
RNF213
in patients with MMD of additional ethnicities and diasporic Asian populations. We investigate the contribution of
RNF213
alterations to MMD in an ethnically diverse population based in the United States.

Methods—

We initially sequenced
RNF213
exons 43, 44, and 45 (encoding the eponymous RING finger domain) and exon 60 (encoding p.R4810K) in 86 ethnically diverse patients with MMD. Comprehensive exome sequencing data from 24 additional patients with MMD was then analyzed to identify
RNF213
variants globally. Segregation of variants with MMD and other vascular diseases was assessed in families.

Results—

RNF213
p.R4810K was identified in 56% (9/16) of patients with MMD of Asian descent and not in 94 patients of non-Asian descent. 3.6% (4/110) of patients had variants in the exons encoding the RING finger domain. Seven additional variants were identified in 29% (7/24) of patients with MMD who underwent exome sequencing. Segregation analysis supported an association with MMD for 2 variants and a lack of association with disease for 1 variant.

Conclusions—

These results confirm that alterations in
RNF213
predispose patients of diverse ethnicities to MMD, and that the p.R4810K variant predisposes individuals of Asian descent in the United States to MMD.
Legal Maxims as a Genre of Islamic Law
Authors: Musa Khadiga
Published: October 2014

Al-qawāʿid al-fiqhiyya are legal maxims or principles that are usually expressed in the form of terse adages, such as: al-umūr bi-maqāṣidihā (acts are [judged according] to the objectives behind them); and al-mashaqqa tajlub al-taysīr (hardship brings about facilitation). Most of al-qawāʿid (sg. al-qāʿida) are specific to individual schools of law, although some of them are acknowledged by all schools. The most accepted definition of al-qāʿida al-fiqhiyya is: “A predominantly valid legal determination (ḥukm aktharī) that applies to most of its particular cases (juzʾiyyāt) so that their legal determinations will be known from it”. Another designation of the genre is al-ashbāh wa’l-naẓāʾir (similitudes), referring to the similarities between cases included under the rubric of each qāʿida. The schools of law (madhāhib, sg. madhhab) are agreed on two types of qawāʿid fiqhiyya: general qawāʿid that apply to all or most fields of the law, which are therefore known as kulliyya (universal), and specific (khāṣṣa) qawāʿid that apply to one or more, rather than all, fields of fiqh; the latter are also known as ḍawābiṭ (sg. ḍābiṭ, regulators).
The Doctrinal Crisis within the Salafi-Jihadi Ranks and the Emergence of Neo-Takfirism
Authors: Alshech Eli
Published: October 2014

Salafi-jihadis, the foundation of many of today’s (most notorious) terrorist organizations, has achieved a significant impact on world affairs within less than three decades. It has given rise to many organizations such as al-Qaeda in Afghanistan, Yemen and North Africa. In this article, I argue that an important change is occurring within the Salafi-jihadi camp. Material published on jihad websites in the last few years reflects an imminent and noteworthy split within the Salafi-jihadi movement. Evidence suggests that the Salafi-jihadi community has split into two groups in Jordan (Salafi-jihadis and Neo-Takfiris), and that some of the views expressed by Neo-Takfiris coincide with those upheld by Takfiris in Egypt between the 1960s and the 1980s. A similar split may be occurring in other locations as well. I describe the emerging rift, examine its causes and assess its essence. At the root of the fragmentation observed to date, I argue, is a profound legal and ideological debate that has the potential to impact Salafi-jihadi organizations worldwide.