bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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.
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

ABSTRACT

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

ABSTRACT

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

ABSTRACT

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

ABSTRACT

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

ABSTRACT

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

ABSTRACTThe 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.
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

MethodsAn 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.ResultsThe 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.
Geochemical modelling of hydrogen gas migration in an unsaturated bentonite buffer
Authors: Sedighi Majid , Thomas Hywel Rhys , Al Masum Shakil , Vardon Philip James , Nicholson Duncan , Chen Qing 
Published: December 2014

Abstract
This paper presents an investigation of the transport and fate of hydrogen gas through compacted bentonite buffer. Various geochemical reactions that may occur in the multiphase and multicomponent system of the unsaturated bentonite buffer are considered. A reactive gas transport model, developed within an established coupled thermal, hydraulic, chemical and mechanical (THCM) framework, is presented. The reactive transport module of the model considers the transport of multicomponent chemicals both in liquid and gas phases, together with an advanced geochemical reaction model. The results of a series of numerical simulations of the reactive transport of hydrogen in unsaturated bentonite are presented in which hydrogen gas, because of the corrosion of a steel canister, has been injected at a realistic rate into a partially saturated bentonite buffer. Gas pressure development and the fate of the hydrogen gas with respect to the geochemical reactions are studied. The results show the high buffering capacity of unsaturated bentonite, when considering a steel canister, over a period of 10 000 years. The presence of accessory minerals is shown to have an important role in mitigating excess hydrogen ions, thus increasing the dissolution capacity of the system to gas. The development of various forms of aqueous complexations between the inorganic components and the hydrogen ions were also found to be important in buffering the excess hydrogen that evolved. Based on the results obtained, it is postulated that the presence of various chemical components in the clay buffer may influence the transport and fate of the hydrogen gas.
In Vivo Radioimaging of Bradykinin Receptor B1, a Widely Overexpressed Molecule in Human Cancer
Authors: Lin Kuo-Shyan , Pan Jinhe , Amouroux Guillaume , Turashvili Gulisa , Mesak Felix , Hundal-Jabal Navjit , Pourghiasian Maral , Lau Joseph , Jenni Silvia , Aparicio Samuel , Bénard François 
Published: December 2014

Abstract
The bradykinin receptor B1R is overexpressed in many human cancers where it might be used as a general target for cancer imaging. In this study, we evaluated the feasibility of using radiolabeled kallidin derivatives to visualize B1R expression in a preclinical model of B1R-positive tumors. Three synthetic derivatives were evaluated in vitro and in vivo for receptor binding and their ability to visualize tumors by PET. Enalaprilat and phosphoramidon were used to evaluate the impact of peptidases on tumor visualization. While we found that radiolabeled peptides based on the native kallidin sequence were ineffective at visualizing B1R-positive tumors, peptidase inhibition with phosphoramidon greatly enhanced B1R visualization in vivo. Two stabilized derivatives incorporating unnatural amino acids (68Ga-SH01078 and 68Ga-P03034) maintained receptor-binding affinities that were effective, allowing excellent tumor visualization, minimal accumulation in normal tissues, and rapid renal clearance. Tumor uptake was blocked in the presence of excess competitor, confirming that the specificity of tumor accumulation was receptor mediated. Our results offer a preclinical proof of concept for noninvasive B1R detection by PET imaging as a general tool to visualize many human cancers. Cancer Res; 75(2); 387–93. ©2014 AACR.