bluuebunny/crossref_metadata_2025 huggingface dataset:
Fuel Sensitive Ignition Delay Models for a Local and Global Description of Direct Injection Internal Combustion Engines
Authors: Kwak Kyoung Hyun , Borgnakke Claus , Jung Dohoy
Published: December 2014

Models for ignition delay in a direct injection compression ignition engine are investigated and fuel specific properties are included to predict the effects of different fuels on the ignition delay. These models follow the Arrhenius type expression for the ignition delay modified with the oxygen concentration and Cetane number to extend the range of validity. In this investigation two fuel-sensitive spray ignition delay models are developed: a global model and a local model. The global model is based on the global combustion chamber charge properties including temperature, pressure and oxygen/fuel content. The local model is developed to account for temporal and spatial variations in properties of separated spray zones such as local temperature, oxidizer and fuel concentrations obtained by a quasi-dimensional multi-zone fuel spray model. These variations are integrated in time to predict the ignition delay. An ignition delay model is typically re-calibrated for a specific fuel being used. In this study, the global ignition delay model includes the Cetane number to capture ignition delay of various fuels. The local model uses Cetane number and local stoichiometric oxygen to fuel molar ratio. Due to those variables, the model is capable of predicting spray ignition delays for a set of fuels with a single calibration step. Experimental dataset of spray ignition delay in a constant volume chamber is used for model development and calibration. The models show a good accuracy for the predicted ignition delay of four different fuels: JP8, DF2, n-heptane and n-dodecane. The investigation revealed that the most accurate form of the models is from a calibration done for each individual fuel with only a slight decrease in accuracy when a single calibration is done for all fuels. The single calibration case is the more desirable outcome as it leads to general models that cover all the fuels. Of the two proposed models the local model has a slightly better accuracy compared to the global model. Results for both models demonstrate the improvements that can be obtained for the ignition delay model when additional fuel specific properties are included in the spray ignition model.

Other alternative fuels like synthetic oxygenated fuels were included in the investigation. These fuels behave differently such that the Cetane number does not provide the same explanation for the trend in ignition delay. Though of lower accuracy, the new models do improve the predictive capability when compared with existing types of ignition delay models applied to this kind of fuels.
The Observation of Cyclic Variation in Engine Simulations When Using RANS Turbulence Modeling
Authors: Richards Keith , Probst Daniel , Pomraning Eric , Senecal P. K. , Scarcelli Riccardo
Published: December 2014

State-of-the art engine technologies are susceptible to high cycle-to-cycle variability. Researchers have successfully used Large Eddy Simulations (LES) to capture this cyclic variation with CFD. However, LES is computationally expensive. The current work demonstrates that using RANS turbulence models can also exhibit cyclic variation if the simulation approach minimizes numerical viscosity. This is accomplished by using fine mesh resolution, non-morphing mesh motion, higher-order accurate numerical schemes, and small timesteps.

RANS turbulence models act to destroy time-varying smaller eddies and replace the mixing effects of these eddies with enhanced viscosity. In an IC engine, larger-scale eddies can change from cycle to cycle, and may not be small enough to be dampened out by the RANS turbulence viscosity. By minimizing the numerical viscosity, the length scale at which eddies are destroyed is reduced and more structure is seen in the simulated flowfield. If the injection and combustion strategy in an engine is susceptible to cyclic changes in these large-scale eddies, then cyclic variation will be apparent in the simulation when using a RANS model.

This work will also demonstrate that perturbations in initial conditions, boundary conditions, or numerical settings can give run-to-run variability in simulation consistent with cycle-to-cycle variability in an actual engine.

For the current work, three studies are performed to show that the use of a RANS turbulence model does not always yield an ensemble average result. One of the studies is a basic cylinder-in-cross-flow case. The other two studies are for engines. One of the engine studies focuses on global mixing parameters and compares to TCC (Transparent Combustion Chamber) experimental data. The other engine study looks at cycle-to-cycle variation in combustion predictions.
Numerical and Experimental Analysis of Ignition and Combustion Stability in EGR Dilute GDI Operation
Authors: Scarcelli Riccardo , Matthias Nicholas S. , Wallner Thomas
Published: December 2014

This paper discusses the characteristics of EGR dilute GDI engines in terms of combustion stability. A combined approach consisting of RANS numerical simulations integrated with experimental engine testing is used to analyze the effect of the ignition source on flame propagation under dilute operating conditions.

A programmable spark-based ignition system is compared to a production spark system in terms of cyclic variability and ultimately indicated efficiency. 3D-CFD simulations are carried out for multiple cycles with the goal of establishing correlations between the characteristics of the ignition system and flame propagation as well as cycle-to-cycle variations. Numerical results are compared to engine data in terms of in-cylinder pressure traces.

The results show that an improved control over the energy released to the fluid surrounding the spark domain during the ignition process has beneficial effects on combustion stability. This allows extending the dilution tolerance for fuel/air mixtures. Although affected by cyclic variability, numerical results show good qualitative agreement with experimental data. The result is a simple but promising approach for relatively quick assessment of stability improvements from advanced and alternative ignition strategies.
A Computational Study of the Mixture Preparation in a Direct Injection Hydrogen Engine
Authors: Le Moine Jerome , Senecal P. K. , Kaiser Sebastian A. , Salazar Victor M. , Anders Jon W. , Svensson K. I. , Gehrke C. R.
Published: December 2014

This paper reports the validation of a three-dimensional numerical simulation of the mixture preparation in a direct-injection hydrogen-fueled engine. Computational results from the commercial code CONVERGE are compared to the experimental data obtained from an optically accessible engine. The geometry used in the simulation is a passenger-car sized, four-stroke, spark-ignited engine. The simulation includes the geometry of the combustion chamber as well as the intake and exhaust ports. The hydrogen is supplied at 100 bar from a centrally located injector with a single-hole nozzle.

The comparison between the simulation and experimental data is made on the central vertical plane. The fuel mole concentration and flow field are compared during the compression stroke at different crank angles. The comparison shows good agreement between the numerical and experimental results during the early stage of the compression stroke. The penetration of the jet and the interaction with the cylinder walls are correctly predicted. The fuel spreading is under predicted which results in differences in flow field and fuel mixture during the injection between experimental and numerical results. At the end of the injection, the fuel distribution shows some disagreement which gradually increases during the rest of the simulation.
Methane Leak and Loss Audits of Natural Gas Fueled Compressor
Authors: Johnson Derek , Covington April
Published: December 2014

Natural gas reserves within the United States continue to rise. According to the Energy Information Administration, dry natural gas reserves increased by ten percent from 2010 to 2011, while wet natural gas reserves increased by 38% in 2011. Natural gas consumption also increased from 24.09 trillion cubic feet (TCF) to 24.48 TCF over the same period. As the natural gas supply, demand, and industry continue to grow methane losses across the supply chain will be inevitable. Since methane is a potent greenhouse gas, many studies are currently analyzing the loss of methane from the wells to the end user. As natural gas transmission systems grow there must be an increase in natural gas compressor and storage facilities.

Currently, there is not a detailed inventory describing the emissions associated with natural gas compressor system engines in terms of the emissions resulting from engine unit losses and leaks. Researchers from West Virginia University’s Center for Alternative Fuels, Engines, and Emissions (CAFEE) recently conducted methane leak and loss audits at five compressor stations with a special focus placed on the engine and compressor units. These audits focused on identifying and quantifying the leaks and losses associated with the engines and compressor units of a typically operating site. A micro dilution high volume sampling system was used in conjunction with a portable methane analyzer to quantify leaks and losses. Bag samples of exhaust gas and engine operating parameters were used to calculate the methane flow rate from the reciprocating engines and turbines used to operate compressors at these sites. Leaks are defined as unintended methane releases from components not designed to emit methane. Losses are defined as methane releases that are known to exist or exist by design.
Effects of Injector Nozzle Inclusion Angle on Extending the Lower Load Limit of Gasoline Compression Ignition Using 87 AKI Gasoline
Authors: Kolodziej Christopher P. , Ciatti Stephen A.
Published: December 2014

Gasoline Compression Ignition (GCI) is a promising single-fuel advanced combustion concept for increased efficiency and reduced emissions in comparison with current conventional combustion modes. Gasoline fuels are advantageous in premixed combustion concepts because of their increased volatility and reduced reactivity compared to diesel. These qualities help reduce emissions of particulate matter (PM) and oxides of nitrogen (NOx), while making combustion phasing (and therefore combustion noise reduction) easier to manage. One of the challenges of using a gasoline with an anti-knock index (AKI) of 87 in a premixed combustion concept is being able to achieve stable low load operation. (Note that AKI is equivalent to (RON + MON)/2.) With such small injection quantities of a relatively more volatile and less reactive fuel than diesel, the injection timing of minimum load fueling needs to be early enough to allow the auto-ignition chemistry enough time, but late enough to keep the fuel from over-mixing and losing ignition propensity. The objective of this study was to investigate the advantages and disadvantages of reducing the injector nozzles’ inclusion angle from 148° to 120° on the combustion and emissions performance of GCI at 850 RPM and low load. To assess these effects, minimum fueling injection timing sweeps were performed with a 3% coefficient of variance of indicated mean effective pressure with each injector nozzle angle at 500 and 250 bar injection pressure. The results from these experiments revealed that both reduced injector nozzle angle and reduced injection pressure increased ignition propensity and allowed for reduced fueling and stable low load extension to 1 bar brake mean effective pressure using 87 AKI gasoline without any external boosting or heating. Combustion characteristics (such as noise) and emissions are discussed.
Visual Study of In-Situ EGR Cooler Fouling Layer Evolution
Authors: Li Haochi , Hoard John , Styles Daniel , Salvi Ashwin , Kini Akshay , Bieniek Mitchell , Cao Weiyu , Erickson Nathaniel
Published: December 2014

Exhaust gas recirculation (EGR) is a major technology to reduce NOx from diesel engines for future emission standards. The implementation of EGR coolers has been a common methodology to provide engine in-cylinder NOx reduction. However, EGR cooler fouling is a common problem. The particulate matter in exhaust tends to form a deposit layer on the wall of the heat exchangers. This effect leads to a reduction of thermal effectiveness of the heat exchangers resulting in insufficient EGR cooling and subsequently higher engine NOx emission.

This paper utilized a unique test rig offering visible and infrared optical access to the deposit layer in a simulated diesel EGR cooler to study the evolution of the layer from fresh to heavy deposit. A 460μm thick deposit layer was built during a 37 hour exposure. Time lapse videos were taken provide visual in-situ evidence for the investigation of the layer thickness development and morphology change during the deposition. The layer growth tended to stabilize from about 22 hours of deposition. The shear force exerted by the gas flow moves surface particles of 20μm in diameter or larger. This could contribute to the stabilization phenomenon.
Understanding the Effect of Wall Conditions and Engine Geometry on Thermal Stratification and HCCI Combustion
Authors: Lawler Benjamin , Joshi Satyum , Lacey Joshua , Guralp Orgun , Najt Paul , Filipi Zoran
Published: December 2014

Thermal stratification of the unburned charge in the cylinder has a profound effect on the burn characteristics of a Homogeneous Charge Compression Ignition (HCCI) engine. Experimental data was collected in a single cylinder, gasoline-fueled, HCCI engine in order to determine the effects of combustion chamber geometry and wall conditions on thermal stratification and HCCI combustion. The study includes a wall temperature sweep and variations of piston top surface material, piston top geometry, and compression ratio. The data is processed with a traditional heat release routine, as well as a post-processing tool termed the Thermal Stratification Analysis, which calculates an unburned temperature distribution from heat release. For all of the sweeps, the 50% burned point was kept constant by varying the intake temperature. Keeping the combustion phasing constant ensures the separation of the effects of combustion phasing from the effects of wall conditions alone on HCCI and thermal stratification.

The results for the wall temperature sweep show no changes to the burn characteristics once the combustion phasing has been matched with intake temperature. This result suggests that the effects of wall temperature on HCCI are mostly during the gas-exchange portion of the cycle. The ceramic coatings were able to very slightly decrease the thermal width, increase the burn rate, increase the combustion efficiency, and decrease the cumulative heat loss. The combustion efficiency increased with the lower surface area to volume ratio piston and the lower compression ratio. Lastly, the compression ratio comparison showed a noticeable effect on the temperature distribution due to the effect of pressure on ignition delay, and the variation of TDC temperature required to match combustion phasing.
The kinase Itk and the adaptor TSAd change the specificity of the kinase Lck in T cells by promoting the phosphorylation of Tyr
192
Authors: Granum Stine , Sundvold-Gjerstad Vibeke , Gopalakrishnan Ramakrishna Prabhu , Berge Tone , Koll Lise , Abrahamsen Greger , Sørlie Morten , Spurkland Anne
Published: December 2014

Phosphorylation of a tyrosine residue in the SH2 domain of the kinase Lck alters its substrate specificity in T cells.
Neuregulin 1–activated ERBB4 interacts with YAP to induce Hippo pathway target genes and promote cell migration
Authors: Haskins Jonathan W. , Nguyen Don X. , Stern David F.
Published: December 2014

Two pathways regulating tissue growth and oncogenic signaling are functionally linked.
A Two-Cell Collaboration for Inflammation
Authors: Mueller Kristen L.
Published: December 2014

Blood neutrophil cells sample platelets in the bloodstream before infiltrating surrounding tissue.
Identification and Deconvolution of Cross-Resistance Signals from Antimalarial Compounds Using Multidrug-Resistant Plasmodium falciparum Strains
Authors: Chugh Monika , Scheurer Christian , Sax Sibylle , Bilsland Elizabeth , van Schalkwyk Donelly A. , Wicht Kathryn J. , Hofmann Natalie , Sharma Anil , Bashyam Sridevi , Singh Shivendra , Oliver Stephen G. , Egan Timothy J. , Malhotra Pawan , Sutherland Colin J. , Beck Hans-Peter , Wittlin Sergio , Spangenberg Thomas , Ding Xavier C.
Published: December 2014

Plasmodium falciparum
, the most deadly agent of malaria, displays a wide variety of resistance mechanisms in the field. The ability of antimalarial compounds in development to overcome these must therefore be carefully evaluated to ensure uncompromised activity against real-life parasites. We report here on the selection and phenotypic as well as genotypic characterization of a panel of sensitive and multidrug-resistant
P. falciparum
strains that can be used to optimally identify and deconvolute the cross-resistance signals from an extended panel of investigational antimalarials. As a case study, the effectiveness of the selected panel of strains was demonstrated using the 1,2,4-oxadiazole series, a newly identified antimalarial series of compounds with
in vitro
activity against
P. falciparum
at nanomolar concentrations. This series of compounds was to be found inactive against several multidrug-resistant strains, and the deconvolution of this signal implicated
pfcrt
, the genetic determinant of chloroquine resistance. Targeted mode-of-action studies further suggested that this new chemical series might act as falcipain 2 inhibitors, substantiating the suggestion that these compounds have a site of action similar to that of chloroquine but a distinct mode of action. New antimalarials must overcome existing resistance and, ideally, prevent its
de novo
appearance. The panel of strains reported here, which includes recently collected as well as standard laboratory-adapted field isolates, is able to efficiently detect and precisely characterize cross-resistance and, as such, can contribute to the faster development of new, effective antimalarial drugs.
Novel Dengue Virus NS2B/NS3 Protease Inhibitors
Authors: Wu Hongmei , Bock Stefanie , Snitko Mariya , Berger Thilo , Weidner Thomas , Holloway Steven , Kanitz Manuel , Diederich Wibke E. , Steuber Holger , Walter Christof , Hofmann Daniela , Weißbrich Benedikt , Spannaus Ralf , Acosta Eliana G. , Bartenschlager Ralf , Engels Bernd , Schirmeister Tanja , Bodem Jochen
Published: December 2014

Dengue fever is a severe, widespread, and neglected disease with more than 2 million diagnosed infections per year. The dengue virus NS2B/NS3 protease (PR) represents a prime target for rational drug design. At the moment, there are no clinical PR inhibitors (PIs) available. We have identified diaryl (thio)ethers as candidates for a novel class of PIs. Here, we report the selective and noncompetitive inhibition of the serotype 2 and 3 dengue virus PR
in vitro
and in cells by benzothiazole derivatives exhibiting 50% inhibitory concentrations (IC
50
s) in the low-micromolar range. Inhibition of replication of DENV serotypes 1 to 3 was specific, since all substances influenced neither hepatitis C virus (HCV) nor HIV-1 replication. Molecular docking suggests binding at a specific allosteric binding site. In addition to the
in vitro
assays, a cell-based PR assay was developed to test these substances in a replication-independent way. The new compounds inhibited the DENV PR with IC
50
s in the low-micromolar or submicromolar range in cells. Furthermore, these novel PIs inhibit viral replication at submicromolar concentrations.
Antiviral Potential of ERK/MAPK and PI3K/AKT/mTOR Signaling Modulation for Middle East Respiratory Syndrome Coronavirus Infection as Identified by Temporal Kinome Analysis
Authors: Kindrachuk Jason , Ork Britini , Hart Brit J. , Mazur Steven , Holbrook Michael R. , Frieman Matthew B. , Traynor Dawn , Johnson Reed F. , Dyall Julie , Kuhn Jens H. , Olinger Gene G. , Hensley Lisa E. , Jahrling Peter B.
Published: December 2014

Middle East respiratory syndrome coronavirus (MERS-CoV) is a lineage C betacoronavirus, and infections with this virus can result in acute respiratory syndrome with renal failure. Globally, MERS-CoV has been responsible for 877 laboratory-confirmed infections, including 317 deaths, since September 2012. As there is a paucity of information regarding the molecular pathogenesis associated with this virus or the identities of novel antiviral drug targets, we performed temporal kinome analysis on human hepatocytes infected with the Erasmus isolate of MERS-CoV with peptide kinome arrays. bioinformatics analysis of our kinome data, including pathway overrepresentation analysis (ORA) and functional network analysis, suggested that extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phosphoinositol 3-kinase (PI3K)/serine-threonine kinase (AKT)/mammalian target of rapamycin (mTOR) signaling responses were specifically modulated in response to MERS-CoV infection
in vitro
throughout the course of infection. The overrepresentation of specific intermediates within these pathways determined by pathway and functional network analysis of our kinome data correlated with similar patterns of phosphorylation determined through Western blot array analysis. In addition, analysis of the effects of specific kinase inhibitors on MERS-CoV infection in tissue culture models confirmed these cellular response observations. Further, we have demonstrated that a subset of licensed kinase inhibitors targeting the ERK/MAPK and PI3K/AKT/mTOR pathways significantly inhibited MERS-CoV replication
in vitro
whether they were added before or after viral infection. Taken together, our data suggest that ERK/MAPK and PI3K/AKT/mTOR signaling responses play important roles in MERS-CoV infection and may represent novel drug targets for therapeutic intervention strategies.
Lactate as a Novel Quantitative Measure of Viability in Schistosoma mansoni Drug Sensitivity Assays
Authors: Howe Stephanie , Zöphel Dorina , Subbaraman Harini , Unger Clemens , Held Jana , Engleitner Thomas , Hoffmann Wolfgang H. , Kreidenweiss Andrea
Published: December 2014

Whole-organism compound sensitivity assays are a valuable strategy in infectious diseases to identify active molecules. In schistosomiasis drug discovery, larval-stage
Schistosoma
allows the use of a certain degree of automation in the screening of compounds. Unfortunately, the throughput is limited, as drug activity is determined by manual assessment of
Schistosoma
viability by microscopy. To develop a simple and quantifiable surrogate marker for viability, we targeted glucose metabolism, which is central to
Schistosoma
survival. Lactate is the end product of glycolysis in human
Schistosoma
stages and can be detected in the supernatant. We assessed lactate as a surrogate marker for viability in
Schistosoma
drug screening assays. We thoroughly investigated parameters of lactate measurement and performed drug sensitivity assays by applying schistosomula and adult worms to establish a proof of concept. Lactate levels clearly reflected the viability of schistosomula and correlated with schistosomulum numbers. Compounds with reported potencies were tested, and activities were determined by lactate assay and by microscopy. We conclude that lactate is a sensitive and simple surrogate marker to be measured to determine
Schistosoma
viability in compound screening assays. Low numbers of schistosomula and the commercial availability of lactate assay reagents make the assay particularly attractive to throughput approaches. Furthermore, standardization of procedures and quantitative evaluation of compound activities facilitate interassay comparisons of potencies and, thus, concerted drug discovery approaches.
Evolution of Carbapenem-Resistant Acinetobacter baumannii Revealed through Whole-Genome Sequencing and Comparative Genomic Analysis
Authors: Li Henan , Liu Fei , Zhang Yawei , Wang Xiaojuan , Zhao Chunjiang , Chen Hongbin , Zhang Feifei , Zhu Baoli , Hu Yongfei , Wang Hui
Published: December 2014

Acinetobacter baumannii
is a globally important nosocomial pathogen characterized by an evolving multidrug resistance. A total of 35 representative clinical
A. baumannii
strains isolated from 13 hospitals in nine cities in China from 1999 to 2011, including 32 carbapenem-resistant and 3 carbapenem-susceptible
A. baumannii
strains, were selected for whole-genome sequencing and comparative genomic analysis. Phylogenetic analysis revealed that the earliest strain, strain 1999BJAB11, and two strains isolated in Zhejiang Province in 2004 were the founder strains of carbapenem-resistant
A. baumannii
. Ten types of AbaR resistance islands were identified, and a previously unreported AbaR island, which comprised a two-component response regulator, resistance-related proteins, and RND efflux system proteins, was identified in two strains isolated in Zhejiang in 2004. Multiple transposons or insertion sequences (ISs) existed in each strain, and these gradually tended to diversify with evolution. Some of these IS elements or transposons were the first to be reported, and most of them were mainly found in strains from two provinces. Genome feature analysis illustrated diversified resistance genes, surface polysaccharides, and a restriction-modification system, even in strains that were phylogenetically and epidemiologically very closely related. IS-mediated deletions were identified in the type VI secretion system region, the
csuE
region, and core lipooligosaccharide (LOS) loci. Recombination occurred in the heme utilization region, and intrinsic resistance genes (
bla
ADC
and
bla
OXA-51-like
variants) and three novel
bla
OXA-51-like
variants (
bla
OXA-424
,
bla
OXA-425
, and
bla
OXA-426
) were identified. Our results could improve the understanding of the evolutionary processes that contribute to the emergence of carbapenem-resistant
A. baumannii
strains and help elucidate the molecular evolutionary mechanism in
A. baumannii
.
Correlation between Nasal Microbiome Composition and Remote Purulent Skin and Soft Tissue Infections
Authors: Johnson Ryan C. , Ellis Michael W. , Lanier Jeffrey B. , Schlett Carey D. , Cui Tianyuan , Merrell D. Scott
Published: December 2014

The incidence of skin and soft tissue infections (SSTIs) has increased dramatically over the past decade, resulting in significant morbidity in millions of otherwise healthy individuals worldwide. Certain groups, like military personnel, are at increased risk for SSTI development. Although nasal colonization withStaphylococcus aureusis an important risk factor for the development of SSTIs, it is not clear why some colonized individuals develop disease while others do not. Recent studies have revealed the importance of microbial diversity in human health. Therefore, we hypothesized that the nasal microbiome may provide valuable insight into SSTI development. To examine this hypothesis, we obtained anterior-naris samples from military trainees with cutaneous abscesses and from asymptomatic (non-SSTI) participants. We also obtained samples from within abscess cavities. Specimens were analyzed by culture, and the microbial community within each sample was characterized using a 16S sequencing-based approach. We collected specimens from 46 non-SSTI participants and from 40 participants with abscesses. We observed a significantly higher abundance ofProteobacteriain the anterior nares in non-SSTI participants (P< 0.0001) than in participants with abscesses. Additionally, we noted a significant inverse correlation betweenCorynebacteriumspp. andS. aureus(P= 0.0001). The sensitivity of standard microbiological culture for abscesses was 71.4%. These data expand our knowledge of the complexity of the nasal and abscess microbiomes and potentially pave the way for novel therapeutic and prophylactic countermeasures against SSTI.
Updated UK Recommendations for HER2 assessment in breast cancer
Authors: Rakha Emad A , Pinder Sarah E , Bartlett John M S , Ibrahim Merdol , Starczynski Jane , Carder Pauline J , Provenzano Elena , Hanby Andrew , Hales Sally , Lee Andrew H S , Ellis Ian O
Published: December 2014

Human epidermal growth factor receptor 2 (HER2) overexpression is present in approximately 15% of early invasive breast cancers, and is an important predictive and prognostic marker. The substantial benefits achieved with anti-HER2 targeted therapies in patients with HER2-positive breast cancer have emphasised the need for accurate assessment of HER2 status. Current data indicate that HER2 test accuracy improved following previous publication of guidelines and the implementation of an external quality assessment scheme with a decline in false-positive and false-negative rates. This paper provides an update of the guidelines for HER2 testing in the UK. The aim is to further improve the analytical validity and clinical utility of HER2 testing by providing guidelines of test performance parameters, and recommendations on the postanalytical interpretation of test results. HER2 status should be determined in all newly diagnosed and recurrent breast cancers. Testing involves immunohistochemistry with >10% complete strong membrane staining defining a positive status.In situhybridisation, either fluorescent or bright field chromogenic, is used either upfront or in immunohistochemistry borderline cases to detect the presence ofHER2 gene amplification. Situations where repeat HER2 testing is advised are outlined and the impact of genetic heterogeneity is discussed. Strict quality control and external quality assurance of validated assays are essential. Testing laboratories should perform ongoing competency assessment and proficiency tests and ensure the reliability and accuracy of the assay. Pathologists, oncologists and surgeons involved in test interpretation and clinical use should adhere to published guidelines and maintain accurate performance and consistent interpretation of test results.
Evaluation of spinosad for the oral treatment and control of flea infestations on cats in Europe
Authors: Franc M. , Bouhsira E. , Böhm C. , Wolken S. , Wolf O. , Löhlein W. , Wiseman S. , Hayes B. , Schnitzler B. , Fisher M.
Published: December 2014

Methods

An ectoparasiticide containing spinosad was evaluated as an oral formulation for cats. Two European laboratory studies and a European multicentre field efficacy and safety study assessed the use of a chewable tablet formulation of spinosad at a dose range of 50–75 mg/kg for treatment and control of flea infestations on cats.

Results

The studies with experimentally infested cats consistently demonstrated persistent activity against Ctenocephalides felis with >98 per cent efficacy at four weeks post‐treatment. In the field study with naturally infested client‐owned cats from 18 clinics across Germany and Italy, two monthly doses of spinosad were administered; selamectin was the comparator product. Safety was evaluated in 226 cats, each receiving at least one dose of spinosad or selamectin; both products were well tolerated. 113 spinosad‐treated cats and 71 selamectin‐treated cats showed >97 per cent reductions in geometric mean flea counts within 14 days post‐treatment and at 60 days post‐treatment efficacy was >98 per cent in both groups. Analysis of success rates showed 96 per cent in spinosad‐treated cats compared with 90.9 per cent in selamectin‐treated cats at day 60. The spinosad tablets were successfully administered to over 98 percent of cats. These studies indicate that this formulation of spinosad is safe and efficacious for treatment and prevention of flea infestations in cats.
Vitamin E and vitamin C do not reduce insulin sensitivity but inhibit mitochondrial protein expression in exercising obese rats
Authors: Picklo Matthew J. , Thyfault John P.
Published: December 2014

Controversy exists as to whether supplementation with the antioxidants vitamin E and vitamin C blocks adaptation to exercise. Exercise is a first-line means to treat obesity and its complications. While diet-induced obesity alters mitochondrial function and induces insulin resistance (IR), no data exist as to whether supplementation with vitamin E and vitamin C modify responses to exercise in pre-existing obesity. We tested the hypothesis that dietary supplementation with vitamin E (0.4 g α-tocopherol acetate/kg) and vitamin C (0.5 g/kg) blocks exercise-induced improvements on IR and mitochondrial content in obese rats maintained on a high-fat (45% fat energy (en)) diet. Diet-induced obese, sedentary rats had a 2-fold higher homeostasis model assessment of insulin resistance and larger insulin area under the curve following glucose tolerances test than rats fed a low-fat (10% fat en) diet. Exercising (12 weeks at 5 times per week in a motorized wheel) of obese rats normalized IR indices, an effect not modified by vitamin E and vitamin C. Vitamin E and vitamin C supplementation with exercise elevated mtDNA content in adipose and skeletal muscle to a greater extent (20%) than exercise alone in a depot-specific manner. On the other hand, vitamin C and vitamin E decreased exercise-induced increases in mitochondrial protein content for complex I (40%) and nicotinamide nucleotide transhydrogenase (35%) in a muscle-dependent manner. These data indicate that vitamin E and vitamin C supplementation in obese rodents does not modify exercise-induced improvements in insulin sensitivity but that changes in mitochondrial biogenesis and mitochondrial protein expression may be modified by antioxidant supplementation.
A mixed integer programming approach for asset protection during escaped wildfires
Authors: van der Merwe Martijn , Minas James P. , Ozlen Melih , Hearne John W.
Published: December 2014

Incident management teams (IMTs) are responsible for managing the response to wildfires. One of the objectives of IMTs is the protection of assets and infrastructure. In this paper, we develop a mathematical model to assist IMTs in assigning resources to asset protection activities during wildfires. We present a mixed integer programming model for resource allocation with the aim of protecting the maximum possible total value of assets. The model allows for mixed vehicle types with interchangeable capabilities and with travel times determined by vehicle-specific speed and road network information. We define location-specific protection requirements in terms of vehicle capabilities. The formulated model extends classic variants of the team orienteering problem with time windows. The model capabilities are demonstrated using a hypothetical fire scenario impacting South Hobart, Tasmania, Australia. Computational testing shows that realistically sized problems can be solved within a reasonable time.
Perinatal oxygen in the developing lung
Authors: Vogel Elizabeth R. , Britt Rodney D. , Trinidad Mari Charisse , Faksh Arij , Martin Richard J. , MacFarlane Peter M. , Pabelick Christina M. , Prakash Y.S.
Published: December 2014

Lung diseases, such as bronchopulmonary dysplasia (BPD), wheezing, and asthma, remain significant causes of morbidity and mortality in the pediatric population, particularly in the setting of premature birth. Pulmonary outcomes in these infants are highly influenced by perinatal exposures including prenatal inflammation, postnatal intensive care unit interventions, and environmental agents. Here, there is strong evidence that perinatal supplemental oxygen administration has significant effects on pulmonary development and health. This is of particular importance in the preterm lung, where premature exposure to room air represents a hyperoxic insult that may cause harm to a lung primed to develop in a hypoxic environment. Preterm infants are also subject to increased episodes of hypoxia, which may also result in pulmonary damage and disease. Here, we summarize the current understanding of the effects of oxygen on the developing lung and how low vs. high oxygen may predispose to pulmonary disease that may extend even into adulthood. Better understanding of the underlying mechanisms will help lead to improved care and outcomes in this vulnerable population.
Two-body strong decay of light mesons with Gaussian expansion method
Authors: Chen Xiaoyun , Yan Zhaozhao , Ping Jialun
Published: December 2014

In this paper, we survey the radial and orbital excitations of I = 0 and [Formula: see text] systems anticipated up to 2.0 GeV in the framework of the chiral quark model. The Schrödinger equation is solved by using Gaussian expansion method. And using the wave functions obtained, instead of the simple harmonic oscillator wave functions, we study systematically the two-body strong decay (limited to S + S modes) of the systems. By comparing with the experimental data, we try to identify the normal states and exotic states.
An ICA/HHT Hybrid Approach for Automatic Ocular Artifact Correction
Authors: Gao Chang , Ma Lin , Li Haifeng
Published: December 2014

In the field of electroencephalogram (EEG) signal processing, the ocular artifact (OA), especially the blink is the most commonly observed, gives the largest disturbance, and can hardly be automatically corrected due to its sudden appearance and wide frequency band influence. In this paper, we focus on a 2-stage independent component analysis/Hilbert Huang transformation (ICA/HHT) hybrid OA correction method which realizes an automatic OA correction as well as a better information conservation to the OA distorted EEG data. In the 1st stage, the ICA is introduced to convert the raw EEG signals into a set of independent signal sources, i.e. a number of independent components (ICs). In the 2nd stage, the HHT is then applied to analyze the ICs in order to emphasize the differences between the OA related ICs and the normal EEG related ICs. On the intrinsic mode functions (IMFs) of each IC extracted by the empirical mode decomposition (EMD), the Hilbert spectrums can clearly indicate where an OA exists and make an automatic OA correction possible. EEG signal samples randomly picked from a variety of neuropsychology tasks were used to evaluate the proposed automatic OA correction method, and the outcomes approved an excellent OA correction performance as well as a better information conservation ability comparing to the well applied methods nowadays.
A theorem about Cremona maps and symbolic Rees algebras
Authors: Costa Barbara , Simis Aron , Ramos Zaqueu
Published: December 2014

This work is about the structure of the symbolic Rees algebra of the base ideal of a Cremona map. We give sufficient conditions under which this algebra has the "expected form" in some sense. The main theorem in this regard seemingly covers all previous results on the subject so far. The proof relies heavily on a criterion of birationality and the use of the so-called inversion factor of a Cremona map. A pretty long selection of examples of plane and space Cremona maps has been given to test against the conditions of the theorem, with special emphasis on Cohen–Macaulay base ideals.
The affine index polynomial invariant of flat virtual knots
Authors: Kim Joonoh
Published: December 2014

We define the affine index polynomial of a flat virtual knot in a similar way as the case of a virtual knot, and show that it is described by the affine index polynomial of any overlying virtual knot. Let K be a virtual knot, and F the underlying flat virtual knot of K. Then we have necessary conditions for the invariant of F about invertibility and amphicheirality of K and F. As applications of the invariant, we raise examples such as (1) F is non-invertible, and (2) K is non-amphicheiral. We also give an alternative proof of a fact that Hrencecin and Kauffman's flat virtual knots are mutually distinct, which is originally proved by Im, Lee and Son.
Mixed Solution Strategy for MCGDM Problems Using Entropy/Cross Entropy in Interval-Valued Intuitionistic Fuzzy Environment
Authors: Gupta Anjana , Mehra Aparna , Appadoo S. S.
Published: December 2014

Although several weight determining methods have been studied for multiple criteria group decision making (MCGDM) problems under intuitionistic fuzzy environment, in the present study, besides the criteria values provided by the decision makers (DMs), we propose to also use the historical data of alternatives-criteria to compute the criteria weights. This is a reasonable thought as the past information may influence the decision makers' choice of entries in their respective alternatives-criteria decision matrices. To this aim, we introduce a novel mixed solution strategy to derive the criteria final weight vector. Initially, the alternatives-criteria decision matrices provided by the DMs are taken to involve interval-valued intuitionistic fuzzy numbers (IVIFNs). The entropy measure for IVIFNs, studied by Ye [2010a], is used to aggregate these decision matrices. We also introduce a new definition of cross entropy for IVIFNs and used it to rank the alternatives. Finally, an example is presented to illustrate the proposed approach.
Finite Time Ruin Probability of the Compound Renewal Model with Constant Interest Rate and Weakly Negatively Dependent Claims with Heavy Tails
Authors: Thampi K. K.
Published: December 2014

This paper establishes a simple asymptotic formula for the finite time ruin probability of a compound renewal risk model with constant interest force. We assume that the claim sizes are Weakly Negatively Dependent (WND) and identically distributed random variables belonging to the class of regularly varying tails. The results obtained have extended and improved some corresponding results of related papers.
Evolutionary Games and Local Dynamics
Authors: Uyttendaele Philippe , Thuijsman Frank
Published: December 2014

In this paper, we examine several options for modeling local interactions within the framework of evolutionary game theory. Several examples show that there is a major difference between population dynamics using local dynamics versus global dynamics. Moreover, different modeling choices may lead to very diverse results.
Quasi-3D Stability and Vibration Analyses of Sandwich Piezoelectric Plates with an Embedded CNT-Reinforced Composite Core
Authors: Wu Chih-Ping , Li Wei-Chen
Published: December 2014

Quasi-three-dimensional (3D) stability and free vibration analyses of bi-axially loaded, simply-supported, sandwich piezoelectric plates with an embedded either a functionally graded (FG) carbon nanotube-reinforced composite (CNTRC) core or a multilayered fiber-reinforced composite (FRC) one are presented. Three different distributions of carbon nanotubes (CNTs) through the thickness of the CNTRC core, i.e. uniformly distributed and FG V-, rhombus- and X-type variations, are considered, and the effective material properties of the CNTRC core are estimated using the rule of mixtures. The Pagano method, which is conventionally used for the analysis of multilayered FRC plates, is modified to be feasible for the study of sandwich hybrid CNTRC and piezoelectric ones, in which Reissner mixed variational theorem, the successive approximation and transfer matrix methods, and the transformed real-valued solutions of the system equations are used. The modified Pagano solutions for the stability and free vibration of multilayered hybrid FRC and piezoelectric plates are in excellent agreement with the exact 3D ones available in the literature, and those for sandwich hybrid CNTRC and piezoelectric plates may be used as the benchmark solutions to assess the ones obtained by using various 2D theories and numerical models.
Identifying adverse drug reactions and drug-induced diseases using network-based drug mapping
Authors: Shoshi Alban , Ogultarhan Venus , Hoppe Tobias , Kormeier Benjamin , Müller Ulrich , Hofestädt Ralf
Published: December 2014

Drugs are essential for the prevention and treatment of diseases. However, co-administration of multiple drugs may cause serious adverse drug reactions, which are usually known but sometimes unknown. Package inserts of prescription drugs are supposed to contain risks and side effects, but such information is not necessarily complete. At the core of efforts to improve prescription quality, there is reliance on the extent and quality of information used for decision of a medical doctor. To address this on-going need, GraphSAW provides users a comprehensive view on drug-related pharmacological and molecular information. The features of GraphSAW allow users to analyze drug cocktails for adverse drug reactions and drug-induced diseases. Network visualization by drug mapping enables exploring associative networks of drugs, pathways, and diseases to fully understand effects of drugs in an intuitive way. GraphSAW is meant to be a platform and starting point for health professionals and researchers for educational and scientific research in order to achieve substantial improvements in patient safety.
Hunting the "impossible atoms" Pauli exclusion principle violation and spontaneous collapse of the wave function at test
Authors: Curceanu Catalina , Bartalucci Sergio , Bassi Angelo , Bertolucci Sergio , Berucci Carolina , Bragadireanu Alexandru Mario , Cargnelli Michael , Clozza Alberto , Di Matteo Sergio , Donadi S. , D'uffizi Alessandro , Egger J.-P. , Guaraldo Carlo , Iliescu Mihail , Ishiwatari Tomoichi , Laubenstein Matthias , Marton Johann , Milotti Edoardo , Pietreanu Dorel , Piscicchia Kristian , Ponta Titus , Sbardella Emanuele , Scordo Alessandro , Shi Hexi , Sirghi Diana , Sirghi Florin , Sperandio Laura , Doce Oton Vazquez , Zmeskal Johann
Published: December 2014

The Pauli exclusion principle (PEP) and, more generally, the spin-statistics connection, are at the very basis of our understanding of matter, life and Universe. The PEP spurs, presently, a lively debate on its possible limits, deeply rooted in the very foundations of Quantum Mechanics. It is, therefore, extremely important to test the limits of its validity. The Violation of the PEP (VIP) experiment established the best limit on the probability that PEP is violated by electrons, using the method of searching for PEP forbidden atomic transitions in copper. We describe the experimental method, the obtained results, and plans to go beyond the actual limit by upgrading the experimental apparatus. We discuss the possibility of using a similar experimental technique to search for X-rays as a signature of the spontaneous collapse of the wave function predicted by continuous spontaneous localization (CSL) theories.
Method for Organizing Grover's Quantum Oracle
Authors: Ito Hideaki , Iida Saburou
Published: December 2014

In a quantum computation, some algorithms use oracles (black boxes) for abstract computational objects. This paper presents an example for organizing Grover's quantum oracle by synthesizing several unitary gates such as CNOT gates, Toffoli gates, and Hadamard gates. As an example, we show a concrete quantum circuit for the knapsack problem, which belongs to the class of NP-complete problems. The time complexity of an oracle for the knapsack problem is estimated to be O(n2), where n is the number of variables. And the same order is obtained for space complexity.
Total graph of the ring ℤn × ℤm
Authors: Dhorajia Alpesh M.
Published: December 2014

Let R be a commutative ring and Z(R) be the set of all zero-divisors of R. The total graph of R, denoted by T Γ(R), is the (undirected) graph with vertices set R. For any two distinct elements x, y ∈ R, the vertices x and y are adjacent if and only if x + y ∈ Z(R). In this paper, we obtain certain fundamental properties of the total graph of ℤn × ℤm, where n and m are positive integers. We determine the clique number and independent number of the total graph T Γ(ℤn × ℤm).