bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation of Highly Active Au/Pd Nanocatalysts for Self-Powered Sensing Applications
Authors: Chang Ting-Wei , Rao Yun-Ting , Lin Zong-Hong
Published: May 2016

Self-powered sensing systems that can work without external power sources have recently been demonstrated to detect various different targets. By harvesting energy directly from the environment, these self-powered sensing systems are advantageous in minimizing their size, working for a long time, and avoiding the use of toxic materials in battery. In this paper, we prepared Se-supported Au/Pd nanoparticles as the catalysts in the self-powered sensing systems. Au nanoparticles were synthesized first and served as the seeds for the growth of Pd component. The concentration of Pd component was varied by reacting with different concentrations of Pd2+ ions. Cyclic voltammetry results indicate that the Se/Au/Pd nanoparticles have excellent catalytic activity toward ethanol oxidation. Finally, The Se/Au/Pd nanoparticles were integrated with a self-powered sensing system for ethanol detection. We believe the self-powered ethanol sensor developed here will become a real sensing product in the near future.
Development of Biocompatible Triboelectric Nanogenerators by Using Polypeptides As the Contact Materials
Authors: Chen Chuan-Hua , Tsao Yu-Hsiang , Lin Zong-Hong
Published: May 2016

Since the first triboelectric nanogenerator (TENG) was developed in 2012, it has now become a new energy technology. TENG has been applied to efficiently convert the mechanical vibration energy into electricity. The fundamental mechanism of TENG is based on the contact electrification and electrostatic effect. Among these two effects, surface charge transfer happened during the contact electrification process is the main factor to affect the electric output of TENG. The electric output of most TENG would decrease in environment with high relative humidity, which restricts their application. By using the polypeptide as contact material to construct a biocompatible TENG, we found that the electric output of the TENG can be maintained or even enhanced at a higher relative humidity.
Measuring Thermochemical Energy Storage Capacity with Redox Cycles of Doped-CaMnO3
Authors: Imponenti Luca , Albrecht Kevin J , Braun Robert J. , Jackson Gregory S
Published: May 2016

Doped CaMnO3 perovskites can store energy thermochemically via reversible redox cycles with endothermic reduction at high temperature and intermediate oxygen partial pressures (P
O2 ≈ 10-4 bar). Reoxidation in air and cooling to lower temperatures can release the stored energy. This study presents measurements of specific thermochemical energy storage in doped CaMnO3, notably CaCryMn1-yO3-δ and Ca1-xSrxMnO3-δ. Thermogravimetric measurements of equilibrium O non-stoichiometry (δ) at various temperatures and P
O2 are fit to point-defect thermodynamic models to derive reaction enthalpy as a function of δ. Comparison of these models to calorimetry show specific thermochemical energy storage above 750 kJ/kg for cycles between 500 and 1000 °C with Ca0.95Sr0.05MnO3-δ having the highest specific energy. Kinetic experiments in a packed bed reactor give a measure of how rapidly energy can be incorporated into particles and provide a basis for developing future reactor models for energy storage or release in solar power plants and other applications.
Mixed Conductors under Light: On the Way to Solid Oxide Photo-Electrochemical Cells
Authors: Fleig Juergen , Walch Gregor , Brunauer Georg Christoph , Rotter Bernhard , Esmaeli Esmaeil , Summhammer Johann , Opitz Alexander Karl , Ponweiser Karl
Published: May 2016

Photo-electrochemical cells based on aqueous electrolytes have been heavily investigated for their potential to convert light into chemical energy. In contrast, very little is known on the possibility of transferring photon energy into chemical energy in high temperature solid state electrochemical cells. This is true despite the fact that solid electrolyte based systems can be operated very successfully as fuel and electrolysis cells (SOFCs/SOECs). Here, we report results on the interaction of mixed conducting oxides with light in cells using oxide ion conductors and operating at 350-500°C. One type of system contains a high temperature solar cell based on SrTiO3 and LaCrO3. It allows oxygen pumping and thus chemical energy storage under UV light. In another type of system UV light produces a time dependent voltage that includes two processes potentially also enabling energy storage: First, again a photovoltaic effect is present; second, the illuminated mixed conducting oxide changes its stoichiometry and thus leads to a battery type (Nernstian) voltage.
Influence of a La0.6Sr0.4CoO3-δ Functional Layer on (Ba0.5Sr0.5)(Co0.8Fe0.2)O3-δ Oxygen Transport Membranes (OTMs)
Authors: Unger Lana-Simone , Meffert Matthias , Wilde Virginia , Störmer Heike , Niedrig Christian , Menesklou Wolfgang , Wagner Stefan F. , Gerthsen Dagmar , Ivers-Tiffée Ellen
Published: May 2016

Nanoporous La0.6Sr0.4CoO3-δ (LSC) thin films with a thickness between 100 and 500 nm were derived from metal-organic precursors. These layers were applied onto a thin Ba0.
5Sr0.
5Co0.8Fe0.2O3-δ
substrate (thickness ≈ 400 µm) in order to enhance oxygen surface exchange. The surface exchange coefficient k
δ of uncoated and LSC-coated dense BSCF ceramic bulk samples were determined by electrical conductivity relaxation (ECR) measurements. By combining the results from these ECR measurements under varying oxygen partial pressures with transmission electron microscopy (TEM) analyses the influence of the nanostructured functional LSC layer on the dense BSCF ceramic membrane was investigated and discussed. Elemental distributions before and after aging obtained by analytical scanning TEM were carried out to address cation interdiffusion between LSC and BSCF.
Effect of Porous Layer on Oxygen Semi Permeation and Surface Exchange of CaTi0.9Fe0.1O3-δ Membranes
Authors: Salles Corinne , Steil M. C. , Fouletier Jacques , Marinha Daniel
Published: May 2016

Oxygen transport membranes are dense ceramic oxides that allow oxygen diffusion along a chemical potential gradient. CaTi0.9Fe0.1O3−δ(CTF) exhibits an interesting tradeoff between performance and stability; despite a lower oxygen flux, it exhibits a superior thermal, mechanical, and chemical stability. To optimize the performance of CTF, it is important to establish the rate-limiting step of oxygen transport mechanism, either surface oxygen exchange reactions, or bulk diffusion. We prepared CTF membranes with and without a porous layer. The limiting step was determined using the ratio between chemical potential drop of oxygen near the surface and across the bulk. We find that bare CTF membranes exhibit a mixed-control below 750 °C, changing to a bulk-limited process with increasing temperature. The porous layer mitigates surface limitation and increases the flux by 35% at lower temperature.
(Invited) Effects of Microstructure on Surface Segregation: Role of Grain Boundaries
Authors: Téllez Helena , Druce John , Ishihara Tatsumi , Kilner John A.
Published: May 2016

The effects of microstructure on the kinetics of strontium segregation in La0.6Sr0.4CoO3-δ ceramic samples are investigated. A faster segregation of the Sr cations towards the surface was observed after annealing for 1 h at 600 °C in dry oxygen (pO2= 200 mbar) as the density of grain boundaries at the surface increases (i.e. with a decrease of the grain size). The presence of surface impurities, such as Na, partially inhibits the Sr segregation towards the surface. Optical micrographs and ToF-SIMS chemical imaging showed that the segregation and precipitation of Sr starts at the grain boundaries, with an apparent enrichment of the surface around the grain boundary via Sr surface diffusion.
A Coupled Experimental/Numerical Approach for Tuning High-Performing SOFC-Cathode
Authors: Celikbilek Ozden , Jauffres David , Dessemond Laurent , Burriel Mónica , Martin Christophe L , Djurado Elisabeth
Published: May 2016

In this paper, a coupled experimental and numerical approach is used to assess the influence of electrode micro/nano-structure and composition on electrochemical performance. First, the area-specific resistance (ASRchem) of 100 vol. % La0.6Sr0.4Co0.2Fe0.8O3−
δ (LSCF) and 60:40 vol. %LSCF:CGO (Ce0.9Gd0.1O2-
δ) composite cathode operating at intermediate temperature range (550-650 ˚C) was investigated by impedance spectroscopy. Despite positive expectations based on the literature, the composite in this work showed ASRchem values almost twice as high as those of the pure LSCF cathode. It is believed that the beneficial effect of the addition of CGO on the bulk transport is lost by a drastic reduction of the specific surface area. Next, a 3D finite element method (FEM) cube model is implemented to study the influence of the CGO addition and to relate microstructural modifications to the ASRchem. The model successfully calculates the performance of randomly-distributed constituent phases.
Effect of Cobalt-Doped Electrolyte on the Electrochemical Performance of LSCFO/CGO Interfaces
Authors: Baqué Laura Cecilia , Padmasree Karinjilottu , Ceniceros Reyes Mónica Aimee , Troiani Horacio , Arce Mauricio Damian , Serquis Adriana , Soldati Analía
Published: May 2016

In this work, we have studied La0.4Sr0.6Co0.8Fe0.2O3-δ/Ce0.8Gd0.2O2-δ/La0.4Sr0.6Co0.8Fe0.2O3-δ symmetrical cells containing Ce0.8Gd0.2O2-δ electrolytes synthetized with and without the addition of cobalt as sintering aid. Electrochemical impedance spectroscopy results indicate that both electrolyte and cathode impedance response are affected by the addition of Co to the electrolyte, despite using cathodes with similar nano/microstructure according to scanning electron microscopy observations. Transmission electron microscopy characterization revealed the formation of columnar structures at the cathode/electrolyte interface of the cell with Co-doped electrolyte. These columnar structures would negatively affect the cell performance hindering the diffusion of oxide ions from the cathode to the electrolyte.
(High Temperature Materials Division J. Bruce Wagner, Jr. Award) Oxygen Non-Stoichiometry of La, Yb, Y, and Ca Doped Cerium Oxide and the Stoichiometric Expansion Coefficient of Yb, Y, and Ca Doped Cerium Oxide
Authors: Bishop Sean R.
Published: May 2016

The oxygen non-stoichiometry (δ) for M0.1Ce0.9O1.95-δ (M = La, Yb, and Y), Ca0.1Ce0.9O1.9-δ, and undoped ceria are reported at 800 oC and compared with literature results for undoped and Gd doped ceria. Reducibility shows an increasing trend with increasing amount of oxygen vacancies introduced by the dopant. The stoichiometric expansion coefficient for the Yb, Y, and Ca doped samples was evaluated and found to be approximately equal and within the range typically found for ceria. A clear dependence of stoichiometric expansion coefficient on ionic radius or oxygen vacancy concentration was not observed.
The Fabrication of Garnet-Type Li7La3Zr2O12 Solid Electrolyte Materials
Authors: Zhang Xingxing , Fergus Jeff W.
Published: May 2016

Garnet-type Li7La3Zr2O12 (LLZO) was prepared by the sol-gel method. X-ray diffraction results showed that aluminum additions led to the formation of the cubic-phase. La2Zr2O7 was present at a sintering temperature 1000°C but not after sintering at higher temperatures. The amount of aluminum addition influenced the final garnet-type LLZO structure. An aluminum content of 0.67 mole fraction led to the formation of LaAlO3 even at 1100°C, indicating that the solubility limit of aluminum in the cubic LLZO structure had been exceeded.
(Invited) Probing Oxide Ion Transport in Fluorite and Perovskite Oxides for Solid Oxide Fuel Cells
Authors: Bagarinao Katherine Develos- , Kishimoto Haruo , Ishiyama Tomohiro , Horita Teruhisa , Yokokawa Harumi , Yamaji Katsuhiko
Published: May 2016

Oxygen surface exchange reactions occurring at the solid cathode surface, and subsequent incorporation and transport of oxygen species across heterostructures strongly affect the performance of solid oxide fuel cells (SOFCs). Using isotopic exchange in conjunction with secondary ion mass spectroscopy (SIMS) depth profile analysis, we examined some technologically relevant fluorite and perovskite thin film oxides commonly utilized as component materials for intermediate-temperature SOFCs. In general, nanograined thin films exhibited improved oxygen surface exchange kinetics as compared to quasi-single-crystalline thin films, indicating enhancement of oxygen incorporation facilitated via highly dense grain boundaries. Furthermore, results indicated strong dependence of oxygen surface exchange properties on crystalline orientation. These results demonstrate the versatility of the technique to further our understanding of oxide ion transport occurring across various heterostructures and heterointerfaces, which hopefully would lead towards envisaging new structures and interfaces for high-performance SOFCs.
Investigation of Heterogeneous Catalysts by an Electrochemical Method: Ceria and Titania-Supported Iridium Nanoparticles for Ethylene Oxidation
Authors: Hajar Yasmine , Dole Holly Andrea Eva , Couillard Martin , Baranova Elena A.
Published: May 2016

Recently, metal support interaction (MSI) has been demonstrated to be closely related to electrochemical promotion of catalysis (EPOC) in the functionality of the process through spillover/backspillover of ionic species to/from the conductive support. In the present work, the interaction that iridium oxide (IrOx) nanoparticles have with two mixed ionic-electronic conducting (MIEC) materials (i.e., ceria, CeO2 and titania, TiO2) for ethylene oxidation is evaluated. To this end, the open circuit catalytic oxidation of ethylene as well as steady-state polarization measurements were carried out for free-standing (unsupported) IrOx and ceria- and titania-supported IrOx (~1 nm). The presence of these two supports was found to increase the catalytic reaction rate when compared to the free-standing IrOx, and decrease the electrochemical reaction rate at the three-phase boundary, as confirmed by the exchange current density (i0). In the light-off experiments, the IrOx/CeO2 catalyst showed a higher reaction rate until 3000C; however IrOx/TiO2 was superior at 3500C. It was also shown that the catalysts with lower i0 resulted in higher open-circuit reaction rates due to the larger amount of thermally-induced backspillover promoters to the gas exposed catalyst surface, in agreement with the EPOC phenomenon.
Carbon and Redox Tolerant Infiltrated Oxide Fuel-Electrodes for Solid Oxide Cells
Authors: Skafte Theis Løye , Sudireddy Bhaskar Reddy , Blennow Peter , Graves Christopher
Published: May 2016

To solve issues of coking and redox instability related to the presence of nickel in typical fuel electrodes in solid oxide cells, Gd-doped CeO2 (CGO) electrodes were studied using symmetric cells. These electrodes showed high electro-catalytic activity, but low electronic conductivity. When infiltrated with Sr0.99Fe0.75Mo0.25O3-δ
(SFM), the electronic conductivity was enhanced. However, polarization resistance of the cells increased, suggesting that the infiltrated material is less electro-catalytically active and was partly blocking the CGO surface reaction sites. The activity could be regained by infiltrating nano-sized CGO or NiCGO on top of SFM, while still sustaining the high electronic conductivity. Ohmic resistance of the electrodes was thus practically eliminated and performance comparable to, or better than, state-of-the-art fuel electrodes has been achieved. The Ni containing cells were damaged by carbon deposition in a CO/CO2-atmosphere, while none of the non-nickel cells catalyzed carbon. Stability towards redox cycles was also proven.
A human model of restricted upper esophageal sphincter opening and its pharyngeal and UES deglutitive pressure phenomena
Authors: Jiao Hongmei , Mei Ling , Sharma Tarun , Kern Mark , Sanvanson Patrick , Shaker Reza
Published: May 2016

Oropharyngeal dysphagia due to upper esophageal sphincter (UES) dysfunction is commonly encountered in the clinical setting. Selective experimental perturbation of various components of the deglutitive apparatus can provide an opportunity to improve our understanding of the swallowing physiology and pathophysiology. The aim is to characterize the pharyngeal and UES deglutitive pressure phenomena in an experimentally induced restriction of UES opening in humans. We studied 14 volunteers without any dysphagic symptoms (7 men, 66 ± 11 yr) but with various supraesophageal reflux symptoms. To induce UES restriction, we used a handmade device that with adjustment could selectively apply 0, 20, 30, or 40 mmHg pressure perpendicularly to the cricoid cartilage. Deglutitive pharyngeal and UES pressure phenomena were determined during dry and 5- and 10-ml water swallows × 3 for each of the UES perturbations. External cricoid pressure against the UES resulted in a significant increase in hypopharyngeal intrabolus pressure and UES nadir deglutitive relaxation pressure for all tested swallowed volumes ( P < 0.05). Application of external cricoid pressure increased the length of the UES high pressure zone from 2.5 ± 0.2 to 3.1 ± 0.2, 3.5 ± 0.1, and 3.7 ± 0.1 cm for 20, 30, and 40 mmHg cricoid pressure, respectively ( P < 0.05). External cricoid pressure had no significant effect on pharyngeal peristalsis. On the other hand, irrespective of external cricoid pressure deglutitive velopharyngeal contractile integral progressively increased with increased swallowed volumes ( P < 0.05). In conclusion, acute experimental restriction of UES opening by external cricoid pressure manifests the pressure characteristics of increased resistance to UES transsphincteric flow observed clinically without affecting the pharyngeal peristaltic contractile function.
Sourcing for Quality: Cooperating with a Single Supplier or Developing Two Competing Suppliers?
Authors: Chen Jingxian
Published: May 2016

Supplier efforts regarding product quality are an important issue in outsourcing and play a critical role in a manufacturer’s choice of sourcing strategy. Consider a manufacturer that wants to outsource the manufacturing of two substitute products to external suppliers. This paper studies the strategic interactions under two sourcing strategies: single and dual sourcing. A four-stage noncooperative game model is established to describe each member’s decisions. We further propose four decision scenarios: single sourcing with and without manufacturer quality investment sharing and dual sourcing when suppliers cooperate or do not cooperate on quality decisions. By the backward induction approach, we obtain analytical equilibrium solutions for each decision scenario. By comparing each pair of equilibrium profiles, we find that an appropriate proportion of quality investment sharing by the manufacturer can enable a cooperating strategy with a single supplier to be the dominant strategy. When the manufacturer does not want to share or does not want to share a relatively large portion of its supplier’s quality investment, it will always prefer to develop two competing suppliers when the cost of dual sourcing is sufficiently low. However, dual sourcing can be extremely risky for the manufacturer because the suppliers could provide a relatively low product quality level by cooperating on the quality decision to extract the manufacturer’s profit.
How to Surgically Remove the Permanent Mesh Ring after the Onstep Procedure for Alleviation of Chronic Pain following Inguinal Hernia Repair
Authors: Öberg Stina , Andresen Kristoffer , Rosenberg Jacob
Published: May 2016

A promising open inguinal hernia operation called Onstep was developed in 2005. The technique is without sutures to the surrounding tissue, causing minimal tension. A specific mesh is used with a memory recoil ring in the border, which may cause pain superficial to the lateral part of the mesh for slender patients. The aim of this study was to illustrate an easy procedure that alleviates/removes the pain. A male patient had persistent pain six months after the Onstep operation and therefore had a ring removal operation. The procedure is presented as a video and a protocol. At the eleven-month follow-up, the patient was free of pain, without a recurrence. It is advised to wait some months after the initial hernia repair before removing the ring, since the mesh needs time to become well integrated into the surrounding tissue. The operation is safe and easy to perform, which is demonstrated in a video.
Increased Oxidative Stress and Inflammation Independent of Body Adiposity in Diabetic and Nondiabetic Controls infalciparumMalaria
Authors: Acquah Samuel , Boampong Johnson Nyarko , Eghan Jnr Benjamin Ackon
Published: May 2016

Information on the extent to which oxidative stress and inflammation occur in the presence offalciparummalaria and type 2 diabetes mellitus in the same individual is limited. This study sought to investigate the extent of inflammation and oxidative stress in adult uncomplicated malaria by measuring fasting levels of lipid peroxides, C-reactive protein (CRP), and total antioxidant power (TAP) before and duringfalciparummalaria, in 100 respondents with type 2 diabetes and 100 age-matched controls in the Cape Coast metropolis of Ghana. Also, body adiposity index, body mass index, and waist-to-hip ratio were computed. Before and duringfalciparummalaria, diabetes patients exhibited higher (P<0.05) levels of CRP and peroxides than controls but TAP and BAI were comparable (P>0.05) between the two groups. Baseline CRP correlated positively (r=0.341,P=0.002) with peroxide only in the diabetic group. During malaria, TAP level in both study groups declined (P<0.05) by 80% of their baseline levels. CRP correlated negatively (r=-0.352,P=0.011) with TAP in the control but not the diabetic group. Uncomplicatedfalciparummalaria elevated inflammation and peroxidation but decreased antioxidant power independent of adiposity. This finding may have implication on cardiovascular health.
Secondary Structure and Subunit Composition of Soy ProteinIn VitroDigested by Pepsin and Its Relation with Digestibility
Authors: Yang Yong , Wang Zhongjiang , Wang Rui , Sui Xiaonan , Qi Baokun , Han Feifei , Li Yang , Jiang Lianzhou
Published: May 2016

In the present study,in vitrodigestibility and structure of soybean protein isolates (SPIs) prepared from five soybean varieties were investigated in simulated gastric fluid (SGF), using FT-IR microspectroscopy and SDS-PAGE. The result indicated thatβ-conformations were prone to be hydrolyzed by pepsin preferentially and transformed to unordered structure duringin vitrodigestion, followed by the digestion ofα-helix and unordered structure. A negative linear correlation coefficient was found between theβ-conformation contents of five SPIs and theirin vitrodigestibility values. The intensities of the protein bands corresponding to 7S and 11S fractions were decreased and many peptide bands appeared at 11~15 kDa during enzymatic hydrolysis.β-conglycinin was poorly hydrolyzed with pepsin, especially theβ-7S subunit. On the other hand, basic polypeptides of glycinin degraded slower than acidic polypeptides and represented a large proportion of the residual protein after digestion. 11S-A3of all SPIs disappeared after 1 h digestion. Moreover, a significant negative linear correlation coefficient (r=-0.89) was found between theβ-7S contents of five SPIs and theirin vitrodigestibility values. These results are useful for further studies of the functional properties and bioactive properties of these varieties and laid theoretical foundations for the development of the specific functional soy protein isolate.
An Improved Focused Crawler: Using Web Page Classification and Link Priority Evaluation
Authors: Lu Houqing , Zhan Donghui , Zhou Lei , He Dengchao
Published: May 2016

A focused crawler is topic-specific and aims selectively to collect web pages that are relevant to a given topic from the Internet. However, the performance of the current focused crawling can easily suffer the impact of the environments of web pages and multiple topic web pages. In the crawling process, a highly relevant region may be ignored owing to the low overall relevance of that page, and anchor text or link-context may misguide crawlers. In order to solve these problems, this paper proposes a new focused crawler. First, we build a web page classifier based on improved term weighting approach (ITFIDF), in order to gain highly relevant web pages. In addition, this paper introduces an evaluation approach of the link, link priority evaluation (LPE), which combines web page content block partition algorithm and the strategy of joint feature evaluation (JFE), to better judge the relevance between URLs on the web page and the given topic. The experimental results demonstrate that the classifier using ITFIDF outperforms TFIDF, and our focused crawler is superior to other focused crawlers based on breadth-first, best-first, anchor text only, link-context only, and content block partition in terms of harvest rate and target recall. In conclusion, our methods are significant and effective for focused crawler.
Involvement of 5‐HT1A Receptors in the Anxiolytic‐Like Effects of Quercitrin and Evidence of the Involvement of the Monoaminergic System
Authors: Li Jian , Liu Qian-tong , Chen Yi , Liu Jie , Shi Jin-li , Liu Yong , Guo Jian-you
Published: May 2016

Quercitrin is a well‐known flavonoid that is contained in Flos Albiziae, which has been used for the treatment of anxiety. The present study investigated the anxiolytic‐like effects of quercitrin in experimental models of anxiety. Compared with the control group, repeated treatment with quercitrin (5.0 and 10.0 mg/kg/day, p.o.) for seven days significantly increased the percentage of entries into and time spent on the open arms of the elevated plus maze. In the light/dark box test, quercitrin exerted an anxiolytic‐like effect at 5 and 10 mg/kg. In the marble‐burying test, quercitrin (5.0 and 10.0 mg/kg) also exerted an anxiolytic‐like effect. Furthermore, quercitrin did not affect spontaneous locomotor activity. The anxiolytic‐like effects of quercitrin in the elevated plus maze and light/dark box test were blocked by the serotonin‐1A (5‐hydroxytryptamine‐1A (5‐HT1A)) receptor antagonist WAY‐100635 (3.0 mg/kg, i.p.) but not by the γ‐aminobutyric acid‐A (GABAA) receptor antagonist flumazenil (0.5 mg/kg, i.p.). The levels of brain monoamines (5‐HT and dopamine) and their metabolites (5‐hydroxy‐3‐indoleacetic acid, 3,4‐dihydroxyphenylacetic acid, and homovanillic acid) were decreased after quercitrin treatment. These data suggest that the anxiolytic‐like effects of quercitrin might be mediated by 5‐HT1A receptors but not by benzodiazepine site of GABAA receptors. The results of the neurochemical studies suggest that these effects are mediated by modulation of the levels of monoamine neurotransmitters.
The Size of the Human Proteome: The Width and Depth
Authors: Ponomarenko Elena A. , Poverennaya Ekaterina V. , Ilgisonis Ekaterina V. , Pyatnitskiy Mikhail A. , Kopylov Arthur T. , Zgoda Victor G. , Lisitsa Andrey V. , Archakov Alexander I.
Published: May 2016

This work discusses bioinformatics and experimental approaches to explore the human proteome, a constellation of proteins expressed in different tissues and organs. As the human proteome is not a static entity, it seems necessary to estimate the number of different protein species (proteoforms) and measure the number of copies of the same protein in a specific tissue. Here, meta-analysis of neXtProt knowledge base is proposed for theoretical prediction of the number of different proteoforms that arise from alternative splicing (AS), single amino acid polymorphisms (SAPs), and posttranslational modifications (PTMs). Three possible cases are considered:(1)PTMs and SAPs appear exclusively in the canonical sequences of proteins, but not in splice variants;(2)PTMs and SAPs can occur in both proteins encoded by canonical sequences and in splice variants;(3)all modification types (AS, SAP, and PTM) occur as independent events. Experimental validation of proteoforms is limited by the analytical sensitivity of proteomic technology. A bell-shaped distribution histogram was generated for proteins encoded by a single chromosome, with the estimation of copy numbers in plasma, liver, and HepG2 cell line. The proposed metabioinformatics approaches can be used for estimation of the number of different proteoforms for any group of protein-coding genes.
Combination of Photodynamic Therapy with Radiotherapy for Cancer Treatment
Authors: Xu Jing , Gao Jianqing , Wei Qichun
Published: May 2016

Photodynamic therapy (PDT) is a promising treatment modality for the management of malignant diseases. However, general acceptance of PDT has been hampered due to the limited tissue penetration of light and unavailability of suitable photosensitizers (PSs). The innovative combination of the conventional radiotherapy (RT) with PDT might reduce the unacceptable normal tissue toxicity while maintaining the desired tumor suppression effect. There have been a number of attempts to examine the interaction of PDT and RT; however, the previous results presented are ambiguous. The exact mechanisms for the variable responses of diverse panel of cell lines to the combination therapeutic regimen are still unclear. Novel ways are being explored to overcome the weaknesses of the conventional PDT and RT treatment regimen. The novel application to enable PDT of deep cancers is the utilization of scintillating nanoparticles as an intracellular light source for PDT activation. Upon simulation by X-rays, the nanoparticles emit scintillation or persistent luminescence to activate the PS to generate singlet oxygen. For future clinical applications, several questions are worthy of further elucidation, including the specific light dose, PS dose, radiation dose, the risk of complications, and the accurate time interval between administration of PDT and administration of RT.
GNE Myopathy in Turkish Sisters with a Novel Homozygous Mutation
Authors: Diniz Gulden , Secil Yaprak , Ceylaner Serdar , Tokucoglu Figen , Türe Sabiha , Celebisoy Mehmet , İncesu Tülay Kurt , Akhan Galip
Published: May 2016

Background. Hereditary inclusion body myopathy is caused by biallelic defects in the GNE gene located on chromosome 9p13. It generally affects adults older than 20 years of age.Methods and Results. In this study, we present two Turkish sisters with progressive myopathy and describe a novel mutation in the GNE gene. Both sisters had slightly higher levels of creatine kinase (CK) and muscle weakness. The older sister presented at 38 years of age with an inability to climb steps, weakness, and a steppage gait. Her younger sister was 36 years old and had similar symptoms. The first symptoms of the disorder were seen when the sisters were 30 and 34 years old, respectively. The muscle biopsy showed primary myopathic features and presence of rimmed vacuoles. DNA analysis demonstrated the presence of previously unknown homozygous mutations [c.2152 G>A (p.A718T)] in the GNE genes.Conclusion. Based on our literature survey, we believe that ours is the first confirmed case of primary GNE myopathy with a novel missense mutation in Turkey. These patients illustrate that the muscle biopsy is still an important method for the differential diagnosis of vacuolar myopathies in that the detection of inclusions is required for the definitive diagnosis.
Hepcidin Plays a Key Role in 6-OHDA Induced Iron Overload and Apoptotic Cell Death in a Cell Culture Model of Parkinson’s Disease
Authors: Xu Qi , Kanthasamy Anumantha G. , Jin Huajun , Reddy Manju B.
Published: May 2016

Background. Elevated brain iron levels have been implicated in the pathogenesis of Parkinson’s disease (PD). However, the precise mechanism underlying abnormal iron accumulation in PD is not clear. Hepcidin, a hormone primarily produced by hepatocytes, acts as a key regulator in both systemic and cellular iron homeostasis.Objective. We investigated the role of hepcidin in 6-hydroxydopamine (6-OHDA) induced apoptosis in a cell culture model of PD.Methods. We downregulated hepcidin using siRNA interference in N27 dopaminergic neuronal cells and made a comparison with control siRNA transfected cells to investigate the role of hepcidin in 6-OHDA induced neurodegeneration.Results. Hepcidin knockdown (32.3%,P<0.0001) upregulated ferroportin 1 expression and significantly (P<0.05) decreased intracellular iron by 25%. Hepcidin knockdown also reduced 6-OHDA induced caspase-3 activity by 42% (P<0.05) and DNA fragmentation by 29% (P=0.086) and increased cell viability by 22% (P<0.05). In addition, hepcidin knockdown significantly attenuated 6-OHDA induced protein carbonyls by 52% (P<0.05) and intracellular iron by 28% (P<0.01), indicating the role of hepcidin in oxidative stress.Conclusions. Our results demonstrate that hepcidin knockdown protected N27 cells from 6-OHDA induced apoptosis and that hepcidin plays a major role in reducing cellular iron burden and oxidative damage by possibly regulating cellular iron export mediated by ferroportin 1.
ESP‐102, a Combined Herbal Extract of Angelica gigas, Saururus chinensis, and Schisandra chinensis, Changes Synaptic Plasticity and Attenuates Scopolamine‐Induced Memory Impairment in Rat Hippocampus Tissue
Authors: Kim Hyun-Bum , Hwang Eun-Sang , Choi Ga-Young , Lee Seok , Park Tae-Suk , Lee Cheol-Won , Lee Eun-Suk , Kim Young-Choong , Kim Sang Seong , Lee Sung-Ok , Park Ji-Ho
Published: May 2016

ESP‐102, an extract from Angelica gigas, Saururus chinensis, and Schisandra chinensis, has been used as herbal medicine and dietary supplement in Korea. Despite the numerous bioactivities in vitro and in vivo studies, its effects on neuronal networks remain elusive. To address the neuronal effect, we examined synaptic plasticity in organotypic hippocampal slice culture with multielectrode array. Our results showed an increase in excitatory postsynaptic potential (EPSP), indicating the induction of long‐term potentiation (LTP), in the presence of ESP‐102. In addition, the neuroprotective effect of ESP‐102 was also tested by application of scopolamine to the hippocampal slice. Interestingly, ESP‐102 competitively antagonized the preventative LTP effect induced by scopolamine. The scopolamine‐induced reduction in brain‐derived neurotrophic factor (BDNF) and GluR‐2 expression was also rescued by ESP‐102. In terms of mode of action, ESP‐102 appears to act on the presynaptic region independent of AMPA/NMDA receptors. Based on these findings, ESP‐102 can be suggested as a novel herbal ingredient with memory enhancing as well as neuroprotective effects.
Abstract A119: Investigating PIK3CA mutational status on cisplatin and radiation sensitivity in cervical cancer cell lines: Implications for PI3K inhibitor therapy
Authors: WANI ARJUMAND , MERRY COLE , WANG CHEN , FANG SHUJUAN , KORNAGA ELIZABETH , MCINTYRE Jb , GHATAGE PRAFULL , KöBEL MARTIN , DOLL CORINNE M. , LEES-MILLER SUSAN P.
Published: May 2016

The phosphatidylinositol-3 kinase (PI3K)/AKT/ mTOR signaling pathway is activated in many different human cancers. Activation is frequently mediated by “hotspot” mutations including E542K, E545K and H1047R in the PIK3CA gene, which encodes the catalytic subunit of PI3Kα. We previously reported PIK3CA mutation in patients with early stage (IB/II) cervical cancer was associated with poor survival (McIntyre et al. Gynecol Oncol. 2013, 128(3): 409-14). The purpose of this study was to determine whether PIK3CA mutation renders cervical cancer cells more resistant to conventional therapy (cisplatin chemotherapy and/or radiation), and whether PI3K inhibition enhances cell kill and/or reverse this phenotype. Here, we report that the cervical cancer cell line CaSki, which expresses the PIK3CA-E545K mutation, is more resistant to cisplatin than cervical cancer cells with wild-type PIK3CA. To validate our findings, we depleted endogenous PIK3CA from HeLa cells using shRNA and stably expressed either shRNA resistant wild-type PIK3CA or PIK3CA-E545K. Cells expressing PIK3CA-E545K were more resistant to cisplatin and cisplatin plus ionizing radiation than cells expressing either wild-type PIK3CA or lacking PIK3CA. Preliminary results also suggest that cells expressing PIK3CA-E545K have an enhanced migratory phenotype. We are currently testing whether treatment with the PI3K inhibitor GDC-0941 restores sensitivity to cisplatin and reverts this aggressive phenotype. Together, these experiments will determine whether inhibition of the PI3K pathway in cervical cancers with PIK3CA activating mutation has potential for therapeutic benefit.

Citation Format: ARJUMAND WANI, COLE MERRY, CHEN WANG, SHUJUAN FANG, ELIZABETH KORNAGA, Jb MCINTYRE, PRAFULL GHATAGE, MARTIN KöBEL, CORINNE M. DOLL, SUSAN P. LEES-MILLER. Investigating PIK3CA mutational status on cisplatin and radiation sensitivity in cervical cancer cell lines: Implications for PI3K inhibitor therapy. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A119.
Abstract A133: Activating ERBB4 mutations in non-small cell lung cancer
Authors: Kurppa Kari J. , Denessiouk Konstantin , Johnson Mark S. , Elenius Klaus
Published: May 2016

Genes encoding the ErbB receptor tyrosine kinases (EGFR/ERBB1, ERBB2, ERBB3, and ERBB4) are key regulators of cellular proliferation, survival, and differentiation, and thus represent potent proto-oncogenes. In particular, mutations or copy number variations of EGFR or ERBB2 are present in human malignancies and serve as predictive markers for targeted therapies. Recent efforts to comprehensively characterize the mutational landscape of human cancers have identified frequent somatic mutations in ERBB4 in various cancer types, such as non-small cell lung cancer (NSCLC), melanoma, and colorectal cancer. However, the significance of mutated ERBB4 in cancer remains elusive.

Here, we have functionally characterized nine ERBB4 mutations previously identified in lung adenocarcinoma. Four out of the nine mutations, Y285C, D595V, D931Y and K935I, were found to be activating, increasing both basal and ligand-induced ErbB4 phosphorylation. According to structural analysis, the four activating mutations were located at critical positions at the dimerization interfaces of the ErbB4 extracellular (Y285C, D595V) and kinase (D931Y and K935I) domains. Consistently, the mutations enhanced ErbB4 dimerization and increased the trans activation in ErbB4 homodimers and ErbB4/ErbB2 heterodimers. The expression of the activating ERBB4 mutants promoted survival of NIH 3T3 cells in the absence of serum. Interestingly, serum starvation of NIH 3T3 cells expressing the ERBB4 mutants only moderately increased the phosphorylation of canonical ErbB signaling pathway effectors Erk1/2 and Akt as compared to wild-type ERBB4. In contrast, the mutations clearly enhanced the proteolytic release of signaling-competent ErbB4 intracellular domain.

These results suggest the presence of activating, oncogenic mutations of ERBB4 in non-small cell lung cancer.

Citation Format: Kari J. Kurppa, Konstantin Denessiouk, Mark S. Johnson, Klaus Elenius. Activating ERBB4 mutations in non-small cell lung cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A133.
Abstract A134: MiR-875-5p impairs prostate cancer metastasis by remodeling tumor secretome and enhances tumor radiation response via EGFR suppression
Authors: Fenderico Nicola , Cominetti Denis , El Bezawy Rihan , Tortoreto Monica , Dugo Matteo , Valdagni Riccardo , Gandellini Paolo , Zaffaroni Nadia
Published: May 2016

Acquisition of mesenchymal features by carcinoma cells through the epithelial-mesenchymal transition (EMT) is responsible for the initiation and sustainment of the metastatic cascade, as well as the establishment of a chemo- and radio-resistant phenotype. In prostate cancer (PCa), metastatic disease remains incurable despite the approval of several new drugs for clinical use in recent years. In addition, emergence of resistance to radiotherapy, which is one of the mostly used therapeutic options for PCa, still represents a clinical challenge. In the study, we reported for the first time on the possible therapeutic utility of miR-875-5p, a microRNA the role of which in human cancer has not been so far investigated. By exploiting the correlation with E-cadherin levels in a series of PCa clinical specimens, we identified miR-875-5p as a novel microRNA able to impair metastasis in PCa experimental models by repressing EMT and remodeling tumor secretome, mainly reducing cytokine secretion. Indeed, the sole intratumoral administration of the culture media obtained from PCa cells ectopically overexpressing miR-875-5p showed antitumor (max tumor volume inhibition: 49%, P<0.01) and antimetastatic (significant reduction of spontaneous dissemination to the lung) effects in SCID mice subcutaneously xenotransplanted with PCa cells. We additionally found that the reversion of EMT operated by miR-875-5p depends at least in part on the repression of epidermal growth factor receptor (EGFR), a direct target of the microRNA as confirmed in a luciferase assay, and consequent reduction of interleukin-8 secretion. Consistent with the known role of EGFR in determining response to ionizing radiation, we found that miR-875-5p overexpression increased the radiosensitivity of PCa cells, in terms of reduced clonogenic cell survival and decreased DNA damage repair, as assessed by γH2AX foci and DNA comet tail in individual cells. Overall, our data support the clinical interest in developing a novel therapeutic approach for PCa based on miR-875-5p reconstitution to counteract tumor dissemination and increase response to radiotherapy.

Citation Format: Nicola Fenderico, Denis Cominetti, Rihan El Bezawy, Monica Tortoreto, Matteo Dugo, Riccardo Valdagni, Paolo Gandellini, Nadia Zaffaroni. MiR-875-5p impairs prostate cancer metastasis by remodeling tumor secretome and enhances tumor radiation response via EGFR suppression. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A134.
Abstract A171: Targeting tumor metabolism by novel EGFR inhibitor in head and neck cancer
Authors: Kuo Ching-Chuan , Hsieh Hsing-Pang , Kung Hsing-Jien
Published: May 2016

Cellular metabolism is substantially altered during tumor progression, and associated with poor prognosis and therapeutic resistance of human cancers. Therefore, the metabolic rewiring of cancer cells has been viewed as a promising source for novel drug targets, and being actively pursued in the development of selective antineoplastic agents. EGFR targeted agents currently approved or under investigation for head and neck squamous cell carcinoma (HNSCC) include EGFR monoclonal antibodies or EGFR tyrosine kinase inhibitors (EGFR-TKI). However, HNSCC patients failing to these agents treatment, due to the development of acquired tumor resistance, will have a compromised survival. We have identified a novel EGFR-TKI, BPR3K007S0. Based on the EC50 in enzyme-based assay of wild-type EGFR & EGFR mutant L858R protein, BPR3K007S0 is more effective than that of clinical used EGFR-TKI gefitinib (Iressa). We further evaluated the drug effects on EGFR phosphorylation in HNSCC cells, and found that BPR3K007S0 inhibited phosphorylation of EGFR in a time-dependent manner. Further study demonstrated that BPR3K007S0 decreased HNSCC cell proliferation and colony formation by causing G1-phase arrest, which was strongly associated with a marked decrease of the level of cyclin E and cdk2 with concomitant induction of p21 and p27. Notably, BPR3K007S0 showed much potent effect toward cell growth in vitro and in vivo than that of gefitinib in HNSCC cells, implicating that the anticancer effect of BPR3K007S0 is not limited to EGFR inhibition. More importantly, we found that BPR3K007S0 significantly suppressed the expression of a wide range of metabolic genes. Among them, the levels of c-Myc and hexokinase 2 were significantly decreased in a time-dependent manner by treatment with BPR3K007S0. Gene manipulation study demonstrated that knockdown of c-Myc leads to a decreased level of hexokinase 2. In this system, silence of EGFR did not affect c-Myc expression, suggesting that c-Myc may not be the EGFR downstream target in used HNSCC cells. Taken together, these results revealed that BPR3K007S0 has added benefits by targeting of EGFR and cancer metabolism, and are likely to be superior to gefitinib in HNSCC models. Thus, development of multi-kinase and metabolic inhibitors holds promises for overcoming treatment resistance of HNSCC. (Grant support: DOH102-TD-M-111-102001)

Citation Format: Ching-Chuan Kuo, Hsing-Pang Hsieh, Hsing-Jien Kung. Targeting tumor metabolism by novel EGFR inhibitor in head and neck cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A171.
Abstract A176: RET inhibition: Development of novel compounds and a personalized medicine strategy in lung adenocarcinoma
Authors: Watson Mandy , Small Helen , Chapman Phil , Hopkins Gemma , Begum Habiba , Waddell Ian D. , Ashton Garry , Abbey Caron , Harris Jade , Ayub Mahmood , Mohan Sumitra , Rothwell Dominic , Brady Ged , Dive Caroline , Jordan Allan , Ogilvie Donald
Published: May 2016

Background:RET is a receptor tyrosine kinase (RTK) and forms part of a macromolecular receptor complex containing dimerised RET receptor, two co-receptors and a bound ligand. Signalling networks downstream of RET play an important role in regulating cell survival, differentiation, proliferation, migration and chemotaxis. Activating mutations in RET (e.g. C634W and M918T) are known drivers in medullary thyroid carcinomas (MTC). More recently, oncogenic RET fusions (e.g. CCDC6-RET and KIF5B-RET) have been identified in 1-2% of lung adenocarcinoma patients. We are currently developing novel, selective inhibitors of RET, and at the same time, investigating a number of biomarker approaches for the stratification of RET fusion-positive lung cancer patients who might benefit from such therapy.

Methods: We have undertaken collaborative studies using established techniques including immunohistochemistry (IHC) and FISH (DNA break apart and RNA). In addition, we have investigated hybrid capture DNA sequencing of both biopsy material and circulating tumour DNA in the blood. Here we, compare and contrast the benefits of each biomarker assay evaluated and consider how these approaches could be translated for use in Phase I clinical trials at The Christie.

Conclusion: Our data supports the successful implementation of predictive biomarkers to identify patients who might benefit from treatment with selective RET inhibitors.

Acknowledgements:This work was funded by Cancer Research UK (Grant numbers C480/A1141 and C5759/A17098).

Citation Format: Mandy Watson, Helen Small, Phil Chapman, Gemma Hopkins, Habiba Begum, Ian D. Waddell, Garry Ashton, Caron Abbey, Jade Harris, Mahmood Ayub, Sumitra Mohan, Dominic Rothwell, Ged Brady, Caroline Dive, Allan Jordan, Donald Ogilvie. RET inhibition: Development of novel compounds and a personalized medicine strategy in lung adenocarcinoma. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A176.