bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermal Predictions of the AGR-3/4 Experiment With Time Varying Gas Gaps
Authors: Hawkes Grant L. , Sterbentz James W. , Maki John T.
Published: March 2016

A thermal analysis was performed for the Advanced Gas Reactor test experiment (AGR-3/4) with time varying gas gaps. The experiment was irradiated at the Advanced Test Reactor (ATR) at the Idaho National Laboratory (INL). Several fuel irradiation experiments are planned for the AGR Fuel Development and Qualification Program which supports the development of the Very-High-Temperature gas-cooled Reactor (VHTR) under the Next-Generation Nuclear Plant (NGNP) project.

AGR-3/4 combines two tests in a series of planned AGR experiments to test tri-structural-isotropic (TRISO)-coated, low-enriched uranium oxy-carbide fuel. The AGR-3/4 test was designed primarily to assess fission product transport through various graphite materials. The AGR-3/4 test irradiation in the ATR started in December 2011 and finished in April 2014. Forty-eight (48) TRISO fueled compacts were inserted into twelve separate capsules for the experiment (four compacts per capsule).

The purpose of this analysis was to calculate the temperatures of each compact and graphite layer to obtain daily average temperatures using time (fast neutron fluence) varying gas gaps and to compare with experimentally measured thermocouple data. Previous experimental data was used for the graphite shrinkage versus fast neutron fluence. Heat rates were input from a detailed physics analysis using the Monte Carlo N-Particle (MCNP) code for each day during the experiment. Individual heat rates for each non-fuel component were input as well. A steady-state thermal analysis was performed for each daily calculation. A finite element model was created for each capsule using the commercial finite element heat transfer and stress analysis package ABAQUS. The fission and neutron gamma heat rates were calculated with the nuclear physics code MCNP. ATR outer shim control cylinders and neck shim rods along with driver fuel power and fuel depletion were incorporated into the daily physics heat rate calculations. Compact and graphite thermal conductivity were input as a function of temperature and neutron fluence with the field variable option in ABAQUS. Surface-to-surface radiation heat transfer along with conduction heat transfer through the gas mixture of helium-neon (used for temperature control) was used in these models. Model results are compared to thermocouple data taken during the experiment.
Stress and Displacement Analysis of a HAWT Under Time-Variable Wind
Authors: Petrova Radostina , Lemu Hirpa G.
Published: March 2016

The article presents a study conducted to analyze the vulnerable zones of horizontal axis wind turbine (HAWT) wings, the nacelle, and the tower during the rotor revolution. The objective of the study is to establish relations between the extreme values of the investigated variables (wind velocity and pressure, von Mises stresses, displacements, etc. vs. angle of rotation or position of the rotor) in order to explore the vulnerable zone. The numerical model, as a computer-aided design (CAD) model geometry of the turbine assembly, was developed using freeform outline of the blade profile according to a previously designed twisted and tapered blade shape and a simplified outline of the nacelle. The tower was assumed to be made of a pipe and unites pipes of increasing diameter; hence its outline is a conic form. All solid bodies, i.e., blades of fiber glass composite and the tower and nacelle of alloy steel, are meshed using parabolic tetrahedral finite elements. The article demonstrates the used simulation technique and the results that are visualized using diverse graphical tools. Though it is hard to precisely point out the location of the vulnerable zone, the results indicate that the highest stresses appear along the trailing edge when the blade is in vertical direction.
Solar Panel Orientation Based on Building Power Consumption
Authors: Cabuk Mesut , Naraghi Mohammad H.
Published: March 2016

In the present work electric energy consumption of a typical building based on its cooling load for summers of five consecutive years were evaluated. The cooling load hourly variations were evaluated based on the eQuest software. It was determined that the peak electric energy consumption of the building occurs around 4:00PM during months of June, July and August. Then the clear sky model was used to determine the solar panel orientation to best match peak energy consumption. The best solar panel orientation to meet building’s peak demand is about 50 degrees tilt angle with azimuth angle of about between fifty and sixty degrees westward. The clearness index model is then used to evaluate the annual energy production of solar panel. It was determined that the annual energy production of the panel based on the present model is approximately 22–23% less than a southward orientation. The present model however, produces twice more electric power during peak demanding hours, when it is needed most.
Numerical Study of Heat Pipes Effects to a 3-Dimensional Room With Natural Driven Ventilation
Authors: Abdullah Z. , Huynh B. P. , Idris A.
Published: March 2016

A Computational Fluid Dynamics (CFD) software package is used to investigate numerically a 3-dimensional rectangular-box room installed with heat pipes heat exchanger (HPHE). Heat pipe heat exchanger utilizing refrigerant by mean of working fluid is installed on top of a room. The air-side heat transfer and the flow pattern of a thermo-siphon heat pipes is studied with a natural driven ventilation of a building. Different opening of the inlet and outlet air where the heat pipe was installed are tested with round edges opening as well as sharp edges. The standard RANS k–ε turbulence model is used. Results with different setting of heat pipe and opening characteristic, air flow rate and flow pattern as well as its temperature effects are examined.
Transient Turbulent Natural Convection in Vertical Tubes for Thermal Energy Storage
Authors: Lakeh Reza Baghaei , Kavehpour H. Pirouz , Wirz Richard E. , Lavine Adrienne S.
Published: March 2016

In this study, turbulent natural convection heat transfer during the charge cycle of a Thermal Energy Storage system was studied computationally and analytically. The storage fluids were supercritical CO2 and liquid toluene which are stored in vertical and sealed storage tubes. A computational model was developed and validated to study turbulent natural convection during the charge cycle. The results of this study show that the aspect ratio of the storage tube (L/D) has an important effect on the heat transfer characteristics. A conceptual model was developed that views the thermal storage process as a hot boundary layer that rises along the tube wall and falls in the center to replace the cold fluid in the core. This model shows that dimensionless mean temperature of the storage fluid and average Nusselt number are functions of a Buoyancy-Fourier number.
The Exergy-Based Cost of Crude Oil-Distillation Products: A Novel Perspective
Authors: Gonzalez-Hernandez Jose-Luis , Sciubba Enrico , Hernandez-Guerrero Abel
Published: March 2016

A novel approach to the calculation of the cost of crude oil distillation products is proposed in this paper. The approach is based on the primary exergy “invested” in the entire process, from extraction to final dispatch, in a well-to-final use perspective including all externalities: capital, labor and environmental remediation cost. The method follows the Extended Exergy Accounting (EEA) theory, and results in a quantifier, the specific extended exergy cost eec, expressed in Joules of primary exergy globally used in the process per Joule of final product. This indicator is not meant to substitute the monetary cost currently adopted in all transactions, but rather to complement it by providing designers, industry managers and energy policy planners with a thermodynamically-sound basis for assessing how far a certain productive chain is from being “sustainable” in terms of primary resources.

Several different processes are analyzed, and the quantitative differences in the final eec are calculated and discussed. The conclusions contain some suggestions for a general reassessment of our approach to the exploitation of primary energy resources.
Enhancing Energy and Economic Performances of Combined Cycle Power Plants by Means of Gas-Cycle Regeneration
Authors: Carapellucci Roberto , Giordano Lorena
Published: March 2016

Efficiency improvement in the gas turbine sector has been mainly driven by increasing the turbine inlet temperature and compressor pressure ratio. For a fixed technology level, a further efficiency gain can be achieved through the utilization of waste thermal energy.

Regeneration is an internal recovery technique that allows the reduction of heat input required at combustor, by preheating the air at compressor outlet. Under certain operating conditions, the temperature of exhaust gas leaving the regenerator is still enough high to allow the steam production via an heat recovery steam generator (HRSG).

Regeneration in steam-gas power plants (CCGT) has the potential to enhance thermal efficiency, but reduces the margins for external recovery and then the bottoming steam cycle capacity. Moreover, the reduction of exhausts temperature at gas turbine outlet requires the reconsideration of HRSG operating parameters, in order to limit the increase of waste heat at the stack.

The aim of this study is to explore the potential benefits that regeneration in the gas cycle gives on the whole steam-gas power plant. The extent of energy and economic performances improvement is evaluated, varying the gas turbine specifications and the layout and operating conditions of HRSG. Hence simple and regenerative configurations based on single and multi-pressure HRSG are compared, focusing on efficiency, specific CO2 emissions and unit cost of electricity (COE).
Experimental Investigation of a Packed-Bed Latent Heat Thermal Storage System With Encapsulated Phase Change Material
Authors: Alam Tanvir E. , Dhau Jaspreet , Goswami D. Y. , Rahman M. M. , Stefankos Elias
Published: March 2016

An experimental study on a laboratory scale prototype packed-bed latent heat thermal energy storage (TES) system is presented. Spherical capsules of sodium nitrate melting point of 306°C were used as the PCM and air was used as the heat transfer fluid (HTF). The storage system was operated between 286°C to 326°C and the volumetric flow rate of the HTF was varied from 110 m3/hr to 151 m3/hr. Temperature distribution along the bed and inside the capsules was monitored continuously during charging and discharging of the system. The effect of mass flow rate of the HTF on the charging and discharging time and on the pressure drop across the bed was also evaluated.
Numerical Modeling of Nanostructure-Enhanced Solar Cells
Authors: Li Rongheng , Li Ben Q.
Published: March 2016

This paper presents a computational study of nanostructure-enhanced solar cells. The computer model is developed based on the FDTD solution of the Maxwell equations describing the light propagation in thin film solar cells. With the model, a combination of Ag nanoparticle arrays at the top, Ag nanoparticle embedded into absorption layer and nanograting structures at the bottom of a thin film solar cell is studied. Each nanostructure is known to be capable of enhancing the solar light absorption to a certain degree, with the effect of metal particles coming primarily from the light scattering, the embedded particles from the reflection and that of back reflector from light trapping and reflection. The preliminary data from model simulation illustrate that with an appropriate combination and arrangement of these nanostructures, an increase in both short and long wavelength range can be achieved, thereby overcoming the shorting comings of each of the nanostructures when applied alone.
Experimental Study of a Novel Thermal Storage System Using Sands With High-Conductive Fluids Occupying the Pores
Authors: Han Jingxiao , Xu Ben , Li Peiwen , Kumar Anurag , Yang Yongping
Published: March 2016

Because of the capability of large capacity thermal storage, concentrated solar power (CSP) technology is getting more attentions in the recent years. The energy storage allows power generation using solar energy during the late afternoon and evening time. For a large capacity of thermal energy storage, a dual-media system is typically adopted for reducing the use of the heat transfer fluid (HTF), which is usually expensive. In a dual-media system, the solid material must have large heat capacity and be inexpensive. One type of configuration for a dual-media system is that HTF flowing in pipes which are imbedded into the solid material. The present study considers sands, a major component of concrete, as low-cost solid thermal storage materials. The novel approach is that the sand is saturated with high thermal conductive fluid. Compared to using concrete for thermal storage, this method avoids issues of heat transfer degradation associated with the mismatch of thermal expansion of pipes and concrete. Since only sands are porous materials and the heat transfer performance is low, a high conductive fluid (XCELTHERM® 600 hot oil) was used to saturate sands, which then forms a new thermal storage material that can have better heat transfer. Results of thermal storage process with sands only and with the oil-saturated sands are presented and discussed.
Thermal Performance of a Parabolic Trough Receiver With Perforated Conical Inserts for Heat Transfer Enhancement
Authors: Mwesigye Aggrey , Bello-Ochende Tunde , Meyer Josua P.
Published: March 2016

Heat transfer enhancement in receivers of parabolic trough collectors offers several benefits including reduction in absorber tube circumferential temperature differences, reduced emissivity of the absorber tube selective coating, thus improved thermal and thermodynamic performance of the receiver. In this work, heat transfer enhancement in a parabolic trough receiver using perforated conical inserts was numerically investigated. The analysis was carried out for dimensionless insert’s cone angles in the range 0.40–0.90, dimensionless insert spacing in the range 0.06–0.18 and dimensionless insert size in the range 0.45–0.91. The flow was considered fully developed turbulent with Reynolds numbers in the range 1.02 × 104 ≤ Re ≤ 7.38 × 105 depending on the temperature of the heat transfer fluid. The heat transfer fluid temperatures used were 400 K, 500 K, 600 K and 650 K. The numerical solution was obtained using the finite volume method together with the realizable k-ε model for turbulence modeling. From the study, there is a range of Reynolds numbers and geometrical parameters for which the gain in performance is more than the increase in pumping power due to heat transfer enhancement. The use of perforated conical inserts in the receiver’s absorber tube increases the thermal efficiency in the range 3–8% for some range of geometrical parameters.
Development of Conservative Form of RELAP5 Thermal Hydraulic Equations: Part II — Numerical Approach and Code Results
Authors: Fu Zheng , Aydogan Fatih , Wagner Richard J.
Published: March 2016

One of the principle features of RELAP5-based system thermal hydraulic codes is the use of a two-fluid, non-equilibrium, non-homogeneous, hydrodynamic model for the transient simulation of the two-phase system behavior. This model includes six governing equations to describe the mass, energy, and momentum of the two fluids. The current version of RELAP-5 uses non-conservative numerical approximation form of conservation equations. The current version of RELAP5 versions have mass and energy errors during time advancements, either resulting in (a) automatic reduction of time steps used in the advancement of the equations and increased run times or (b) the growth of unacceptably large errors in the transient results. Therefore, conservative conservation equations and closure equations were developed to address this problem in the first part of the paper series This part of the series demonstrates the numerical approach to implement the developed conservative conservation equations into RELAP5 and the results of RELAP5 including developed conservative form of conservation equations. RELAP5 versions including conservative and non-conservative conservation equations are compared for various tests from a single pipe to a whole Pressurized Water Reactor (PWR) model.
Numerical and Experimental Analysis of a PCM Thermal Storage System
Authors: Sciacovelli Adriano , Verda Vittorio
Published: March 2016

Phase-change materials (PCM) are particularly promising for thermal storage in energy systems where the working fluid is either characterized by small specific heat or small temperature difference. In these cases, sensible heat storage would involve small energy densities (i.e. energy per unit volume). Latent heat storage would allow one to reduce the volume of storage tanks, but also reduce problems related with thermal stratification. On the other hand, heat transfer in PCMs needs to be enhanced in order to complete the charging and discharging processes in reasonable time.

This paper reports the numerical and experimental activity performed by the authors related with the design of latent heat storage systems for district heating applications. Among the various enhancement methods, fins present some technical advantages related with manufacturing and management, which make them suitable for the application in district heating systems. The following aspects are considered in this paper: 1) melting and solidification; 2) modeling approaches and validation; 3) thermal enhancement with circular, radial or Y-shaped fins.
Formation of VO2 by rapid thermal annealing and cooling of sputtered vanadium thin films
Authors: Ba Cheikhou O. F. , Fortin Vincent , Bah Souleymane T. , Vallée Réal , Pandurang Ashrit
Published: March 2016

Sputtered vanadium-rich films were subjected to rapid thermal annealing-cooling (RTAC) in air to produce vanadium dioxide (VO2) thin films with thermochromic switching behavior. High heating and cooling rates in the thermal oxidation process provided an increased ability to control the film's microstructure. X-ray diffraction patterns of the films revealed less intense VO2 peaks compared to traditional polycrystalline samples fabricated with a standard (slower) cooling time. Such films also exhibit a high optical switching reflectance contrast, unlike the traditional polycrystalline VO2 thin films, which show a more pronounced transmittance switching. The authors find that the RTAC process stabilizes the VO2 (M2) metastable phase, enabling a rutile-semiconductor phase transition (R-M2), followed by a semiconductor–semiconductor phase transition (M2-M1).
Quantification of the effects of audible rattle and source type on the human response to environmental vibration
Authors: Woodcock J. , Sica G. , Peris E. , Sharp C. , Moorhouse A. T. , Waddington D. C.
Published: March 2016

The present research quantifies the influence of source type and the presence of audible vibration-induced rattle on annoyance caused by vibration in residential environments. The sources of vibration considered are railway and the construction of a light rail system. Data were measured in the United Kingdom using a socio-vibration survey (N = 1281). These data are analyzed using ordinal logit models to produce exposure-response relationships describing community annoyance as a function of vibration exposure. The influence of source type and the presence of audible vibration-induced rattle on annoyance are investigated using dummy variable analysis, and quantified using odds–ratios and community tolerance levels. It is concluded that the sample population is more likely to express higher levels of annoyance if the vibration source is construction compared to railway, and if vibration-induced rattle is audible.
The import of within-listener variability to understanding the precedence effect
Authors: Pastore M. Torben , Trahiotis Constantine , Braasch Jonas
Published: March 2016

The purpose of this study was to gather behavioral data concerning the precedence effect as manifested by the localization-dominance of the leading elements of compound stimuli. This investigation was motivated by recent findings of Shackleton and Palmer [(2006). J. Assoc. Res. Otolaryngol. 7, 425–442], who measured the electro-physiological responses of single units in the inferior colliculus of the guinea pig. The neural data from Shackleton and Palmer indicated that processing of binaural cues like those relevant to understanding localization dominance is greatly affected by internal, neural noise. In order to evaluate the generality of their physiological results to human perception, the present study measured localization dominance so that behavioral responses within and across sets of samples (i.e., tokens) of frozen noises could be compared. Conceptually consistent with Shackleton and Palmer's neural data, the variability of perceived intracranial lateral positions produced by repeated presentations of the same tokens of noise was greater than the variability of intracranial lateral positions measured across different tokens of noise. This was true for each of the four individual listeners and for each of the 72 stimulus conditions studied. Thus, measured either neuro-physiologically (Shackleton and Palmer, 2006) or behaviorally (this study), the import of within-listener variability appears to be a general, intrinsic aspect of binaural information processing.
Three-Minute All-Out Test in Swimming
Authors: Tsai Ming-Chang , Thomas Scott G.
Published: March 2016

Purpose:

To validate the 3-minute all-out exercise test (3MT) protocol against the traditional critical-speed (CS) model (CSM) in front-crawl swimming.

Methods:

Ten healthy swimmers or triathletes (mean ± SD age 35.2 ± 10.5 y, height 176.5 ± 5.4 cm, body mass 69.6 ± 8.2 kg) completed 5 tests (3MT, 100m, 200m, 400m, 800m) over 2 wk on separate days. Traditional CS and anaerobic distance capacity (D′) were determined for each of the 3 traditional CSMs (linear distance-time, LIN; linear speed/time, INV; nonlinear time-speed, NLIN) from the 4 set-distance time trials. For the 3MT, CS was determined as the mean speed during the final 30 s of the test and D′ was estimated as the power-time integral above the CS.

Results:

Our results indicated no significant difference between the CS estimates determined from the traditional CSM and 3MT except for the INV model (P = .0311). Correlations between traditional CSMs and 3MT were high (r = .95, P < .01) However, D′ differed and post hoc analysis indicated that D′ estimated from 3MT was significantly lower than LIN (P = .0052) and NLIN (P < .0001). Correlations were weak (r < .55, P > .1). In addition, Bland-Altman plots between the traditional CSMs and 3MT CS estimates showed scattered points above and below the zero line, suggesting there is no consistent bias of one approach versus the other.

Conclusions:

The 3MT is a valid protocol for swimming to estimate CS. The demonstrated concurrent validity of the 3MT may allow more widespread use of CSMs to evaluate participants and responses to training.
The Decremental Protocol as an Alternative Protocol to Measure Maximal Oxygen Consumption in Athletes
Authors: Taylor Katrina , Seegmiller Jeffrey , Vella Chantal A.
Published: March 2016

Purpose:

To determine whether a decremental protocol could elicit a higher maximal oxygen consumption (VO2max) than an incremental protocol in trained participants. A secondary aim was to examine whether cardiac-output (Q) and stroke-volume (SV) responses differed between decremental and incremental protocols in this sample.

Methods:

Nineteen runners/triathletes were randomized to either the decremental or incremental group. All participants completed an initial incremental VO2max test on a treadmill, followed by a verification phase. The incremental group completed 2 further incremental tests. The decremental group completed a second VO2max test using the decremental protocol, based on their verification phase. The decremental group then completed a final incremental test. During each test, VO2, ventilation, and heart rate were measured, and cardiac variables were estimated with thoracic bioimpedance. Repeated-measures analysis of variance was conducted with an alpha level set at .05.

Results:

There were no significant main effects for group (P = .37) or interaction (P = .10) over time (P = .45). VO2max was similar between the incremental (57.29 ± 8.94 mL · kg–1 · min–1) and decremental (60.82 ± 8.49 mL · kg–1 · min–1) groups over time. Furthermore, Q and SV were similar between the incremental (Q 22.72 ± 5.85 L/min, SV 119.64 ± 33.02 mL/beat) and decremental groups (Q 20.36 ± 4.59 L/min, SV 109.03 ± 24.27 mL/beat) across all 3 trials.

Conclusions:

The findings suggest that the decremental protocol does not elicit higher VO2max than an incremental protocol but may be used as an alternative protocol to measure VO2max in runners and triathletes.
Dependence of the Nature of the Pedaling Activity on Maximal Aerobic Power in Cycling
Authors: Bouillod Anthony , Pinot Julien , Soenen Flavien , Ouvrard Theo , Grappe Frederic
Published: March 2016

Purpose:

To analyze the effect of the pedaling activity in different 4-min time trials (TT4s) (laboratory and field conditions) and compare TT4 and maximal aerobic power (MAP) determined from the classical incremental exercise test in laboratory. It was hypothesized that the exercises performed on the field would determine higher physical (power output [PO]) and mental involvements due to different environmental conditions.

Methods:

Sixteen male cyclists underwent an incremental test to exhaustion and 3 TT4s under different conditions: cycle ergometer (CE), level ground (LG), and uphill (UP).

Results:

Correlation was observed for PO with a trivial effect size and narrow limits of agreement between MAP and CE TT4 (r = .96, P < .001). The comparison between the CE, LG, and UP tests indicates that PO was significantly higher in UP than in CE (+8.0%, P < .001) and LG (+11.0%, P < .001).

Conclusions:

The results suggest that PO depends on the nature of the pedaling activity. Moreover, PO under CE TT4 is a relevant predictor of MAP. It seems important to measure MAP by taking into account the cycling conditions, considering that coaches and scientists use this parameter to assess the aerobic potential of athletes and determine the exercise intensities useful for monitoring adaptation to training.
Low-Frequency Drug Resistance in HIV-Infected Ugandans on Antiretroviral Treatment Is Associated with Regimen Failure
Authors: Kyeyune Fred , Gibson Richard M. , Nankya Immaculate , Venner Colin , Metha Samar , Akao Juliet , Ndashimye Emmanuel , Kityo Cissy M. , Salata Robert A. , Mugyenyi Peter , Arts Eric J. , Quiñones-Mateu Miguel E.
Published: March 2016

Most patients failing antiretroviral treatment in Uganda continue to fail their treatment regimen even if a dominant drug-resistant HIV-1 genotype is not detected. In a recent retrospective study, we observed that approximately 30% of HIV-infected individuals in the Joint Clinical Research Centre (Kampala, Uganda) experienced virologic failure with a susceptible HIV-1 genotype based on standard Sanger sequencing. Selection of minority drug-resistant HIV-1 variants (not detectable by Sanger sequencing) under antiretroviral therapy pressure can lead to a shift in the viral quasispecies distribution, becoming dominant members of the virus population and eventually causing treatment failure. Here, we used a novel HIV-1 genotyping assay based on deep sequencing (DeepGen) to quantify low-level drug-resistant HIV-1 variants in 33 patients failing a first-line antiretroviral treatment regimen in the absence of drug-resistant mutations, as screened by standard population-based Sanger sequencing. Using this sensitive assay, we observed that 64% (21/33) of these individuals had low-frequency (or minority) drug-resistant variants in the intrapatient HIV-1 population, which correlated with treatment failure. Moreover, the presence of these minority HIV-1 variants was associated with higher intrapatient HIV-1 diversity, suggesting a dynamic selection or fading of drug-resistant HIV-1 variants from the viral quasispecies in the presence or absence of drug pressure, respectively. This study identified low-frequency HIV drug resistance mutations by deep sequencing in Ugandan patients failing antiretroviral treatment but lacking dominant drug resistance mutations as determined by Sanger sequencing methods. We showed that these low-abundance drug-resistant viruses could have significant consequences for clinical outcomes, especially if treatment is not modified based on a susceptible HIV-1 genotype by Sanger sequencing. Therefore, we propose to make clinical decisions using more sensitive methods to detect minority HIV-1 variants.
Drug-Drug Interaction Associated with Mold-Active Triazoles among Hospitalized Patients
Authors: Andes David , Azie Nkechi , Yang Hongbo , Harrington Rachel , Kelley Caroline , Tan Ruo-Ding , Wu Eric Q. , Franks Billy , Kristy Rita , Lee Edward , Khandelwal Nikhil , Spalding James
Published: March 2016

The majority of hospitalized patients receiving mold-active triazoles are at risk of drug-drug interactions (DDIs). Efforts are needed to increase awareness of DDIs that pose a serious risk of adverse events. Triazoles remain the most commonly utilized antifungals. Recent developments have included the mold-active triazoles (MATs) itraconazole, voriconazole, and posaconazole, which are first-line agents for the treatment of filamentous fungal infections but have the potential for DDIs. This objective of this study was to evaluate the prevalence of triazole DDIs. Hospitalized U.S. adults with MAT use were identified in the Cerner HealthFacts database, which contained data from over 150 hospitals (2005 to 2013). The severities of DDIs with MATs were categorized, using drug labels and the drug information from the Drugdex system (Thompson Micromedex), into four groups (contraindicated, major, moderate, and minor severity). DDIs of minor severity were not counted. A DDI event was considered to have occurred if the following two conditions were met: (i) the patient used at least one drug with a classification of at least a moderate interaction with the MAT during the hospitalization and (ii) there was a period of overlap between the administration of the MAT and that of the interacting drug of at least 1 day. A total of 6,962 hospitalizations with MAT use were identified. Among them, 88% of hospitalizations with voriconazole use, 86% of hospitalizations with itraconazole use, and 93% of hospitalizations with posaconazole use included the use of a concomitant interacting drug. A total of 68% of hospitalizations with posaconazole use, 34% of hospitalizations with itraconazole use, and 20% of hospitalizations with voriconazole use included the use of at least one drug with a DDI of contraindicated severity. A total of 83% of hospitalizations with posaconazole use, 61% of hospitalizations with itraconazole use, and 82% of hospitalizations with voriconazole use included the use of at least one drug that resulted in a severe DDI. The findings of this study demonstrate that a majority of hospitalized patients receiving MAT are at risk for severe drug-drug interactions and highlight the need for antifungal stewardship.
Curcumin Enhances the Anti-Trypanosoma cruzi Activity of Benznidazole-Based Chemotherapy in Acute Experimental Chagas Disease
Authors: Novaes Rômulo Dias , Sartini Marcus Vinicius Pessoa , Rodrigues João Paulo Ferreira , Gonçalves Reggiani Vilela , Santos Eliziária Cardoso , Souza Raquel Lopes Martins , Caldas Ivo Santana
Published: March 2016

Although curcumin can increase the effectiveness of drugs against malaria, combination therapies using the molecule have never been investigated in Chagas disease (ChD). Therefore, we evaluated the efficacy of curcumin as a complementary strategy to benznidazole (Bz)-based chemotherapy in mice acutely infected with
Trypanosoma cruzi
. Eighty-four 12-week-old Swiss mice were equally randomized into seven groups: uninfected (NI),
T. cruzi
infected and untreated (INF), infected and treated with 100 mg/kg of body weight Bz (B100), 50 mg/kg Bz (B50), 100 mg/kg curcumin (C100), 100 mg/kg Bz plus 100 mg/kg curcumin (B100 plus C100), and 50 mg/kg Bz plus 100 mg/kg curcumin (B50 plus C100). After microscopic identification of blood trypomastigotes (4 days after inoculation), both drugs were administered by gavage once a day for 20 days. Curcumin showed limited antiparasitic, anti-inflammatory, and antioxidant effects when administered alone. When curcumin and Bz were combined, there was a drastic reduction in parasitemia, parasite load, mortality, anti-
T. cruzi
IgG reactivity, circulating levels of cytokines (gamma interferon [IFN-γ], interleukin 4 [IL-4], and MIP1-α), myocardial inflammation, and morphological and oxidative cardiac injury; these results exceeded the isolated effects of Bz. The combination of Bz and curcumin was also effective at mitigating liver toxicity triggered by Bz, increasing the parasitological cure rate, and preventing infection recrudescence in noncured animals, even when the animals were treated with 50% of the recommended therapeutic dose of Bz. By limiting the toxic effects of Bz and enhancing its antiparasitic efficiency, the combination of the drug with curcumin may be a relevant therapeutic strategy that is possibly better tolerated in ChD treatment than Bz-based monotherapy.
Emergence and Diversity of Salmonella enterica Serovar Indiana Isolates with Concurrent Resistance to Ciprofloxacin and Cefotaxime from Patients and Food-Producing Animals in China
Authors: Bai Li , Zhao Jiayong , Gan Xin , Wang Juan , Zhang Xiuli , Cui Shenghui , Xia Shengli , Hu Yujie , Yan Shaofei , Wang Jiahui , Li Fengqin , Fanning Séamus , Xu Jin
Published: March 2016

Salmonellosis is a major global foodborne infection, and strains that are resistant to a great variety of antibiotics have become a major public health concern. The aim of this study was to identify genes conferring resistance to fluoroquinolones and extended-spectrum β-lactams in nontyphoidal
Salmonella
(NTS) from patients and food-producing animals in China. In total, 133 and 21 NTS isolates from animals and humans, respectively, exhibiting concurrent resistance to ciprofloxacin and cefotaxime were cultured independently from 2009 to ∼2013. All of the isolates were identified, serotyped, and subjected to antimicrobial susceptibility testing. Importantly, the isolates with concurrent resistance to ciprofloxacin and cefotaxime all were confirmed as
S. enterica
serovar Indiana. The presence of fluoroquinolone resistance genes and extended-spectrum β-lactamases (ESBLs) was established by PCR and DNA sequencing. The occurrence and diversity of different genes conferring fluoroquinolone resistance [
qepA
,
oqxAB
, and
aac
(
6
′)-
Ib-cr
] with mutations in topoisomerase-encoding genes (
gyrA
and
parC
) and several ESBLs (including CTX-M-65, CTX-M-27, CTX-M-15, CTX-M-14, and CTX-M-14/CTX-M-15) were noteworthy. Genes located on mobile genetic elements were identified by conjugation and transformation. Pulsed-field gel electrophoresis, used to determine the genetic relationships between these isolates, generated 91 pulsotypes from 133 chicken isolates and 17 pulsotypes from the 21 clinical isolates that showed considerable diversity. Analysis of the pulsotypes obtained with the isolates showed some clones appeared to have existed for several years and had been disseminating between humans and food-producing animals. This study highlights the emergence of ciprofloxacin- and cefotaxime-resistant
S. enterica
serovar Indiana, posing a threat to public health.
Pharmacokinetics-Pharmacodynamics of a Novel β-Lactamase Inhibitor, CB-618, in Combination with Meropenem in an
In Vitro
Infection Model
Authors: VanScoy Brian D. , Trang Michael , McCauley Jennifer , Conde Haley , Bhavnani Sujata M. , Friedrich Lawrence V. , Alexander Dylan C. , Ambrose Paul G.
Published: March 2016

The usefulness of β-lactam antimicrobial agents is threatened as never before by β-lactamase-producing bacteria. For this reason, there has been renewed interest in the development of broad-spectrum β-lactamase inhibitors. Herein we describe the results of dose fractionation and dose-ranging studies carried out using a one-compartment
in vitro
infection model to determine the exposure measure for CB-618, a novel β-lactamase inhibitor, most predictive of the efficacy when given in combination with meropenem. The challenge panel included
Enterobacteriaceae
clinical isolates, which collectively produced a wide range of β-lactamase enzymes (KPC-2, KPC-3, FOX-5, OXA-48, SHV-11, SHV-27, and TEM-1). Human concentration-time profiles were simulated for each drug, and samples were collected for drug concentration and bacterial density determinations. Using data from dose fractionation studies and a challenge
Klebsiella pneumoniae
isolate (CB-618-potentiated meropenem MIC = 1 mg/liter), relationships between change from baseline in log
10
CFU/ml at 24 h and each of CB-618 area under the concentration-time curve over 24 h (AUC
0–24
), maximum concentration (
C
max
), and percentage of the dosing interval that CB-618 concentrations remained above a given threshold were evaluated in combination with meropenem at 2 g every 8 h (q8h). The exposure measures most closely associated with CB-618 efficacy in combination with meropenem were the CB-618 AUC
0–24
(
r
2
= 0.835) and
C
max
(
r
2
= 0.826). Using the CB-618 AUC
0–24
indexed to the CB-618-potentiated meropenem MIC value, the relationship between change from baseline in log
10
CFU/ml at 24 h and CB-618 AUC
0–24
/MIC ratio in combination with meropenem was evaluated using the pooled data from five challenge isolates; the CB-618 AUC
0–24
/MIC ratio associated with net bacterial stasis and the 1- and 2-log
10
CFU/ml reductions from baseline at 24 h were 27.3, 86.1, and 444.8, respectively. These data provide a pharmacokinetics-pharmacodynamics (PK-PD) basis for evaluating potential CB-618 dosing regimens in combination with meropenem in future studies.
Excreted Cytoplasmic Proteins Contribute to Pathogenicity in Staphylococcus aureus
Authors: Ebner Patrick , Rinker Janina , Nguyen Minh Thu , Popella Peter , Nega Mulugeta , Luqman Arif , Schittek Birgit , Di Marco Moreno , Stevanovic Stefan , Götz Friedrich
Published: March 2016

Excretion of cytoplasmic proteins in pro- and eukaryotes, also referred to as “nonclassical protein export,” is a well-known phenomenon. However, comparatively little is known about the role of the excreted proteins in relation to pathogenicity. Here, the impact of two excreted glycolytic enzymes, aldolase (FbaA) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), on pathogenicity was investigated in
Staphylococcus aureus
. Both enzymes bound to certain host matrix proteins and enhanced adherence of the bacterial cells to host cells but caused a decrease in host cell invasion. FbaA and GAPDH also bound to the cell surfaces of staphylococcal cells by interaction with the major autolysin, Atl, that is involved in host cell internalization. Surprisingly, FbaA showed high cytotoxicity to both MonoMac 6 (MM6) and HaCaT cells, while GAPDH was cytotoxic only for MM6 cells. Finally, the contribution of external FbaA and GAPDH to
S. aureus
pathogenicity was confirmed in an insect infection model.
Staphylococcus aureus Phenol-Soluble Modulins Impair Interleukin Expression in Bovine Mammary Epithelial Cells
Authors: Deplanche Martine , Alekseeva Ludmila , Semenovskaya Ksenia , Fu Chih-Lung , Dessauge Frederic , Finot Laurence , Petzl Wolfram , Zerbe Holm , Le Loir Yves , Rainard Pascal , Smith David G. E. , Germon Pierre , Otto Michael , Berkova Nadia
Published: March 2016

The role of the recently described interleukin-32 (IL-32) inStaphylococcus aureus-induced mastitis, an inflammation of the mammary gland, is unclear. We determined expression of IL-32, IL-6, and IL-8 inS. aureus- andEscherichia coli-infected bovine mammary gland epithelial cells. Using live bacteria, we found that inS. aureus-infected cells, induction of IL-6 and IL-8 expression was less pronounced than inE. coli-infected cells. Notably, IL-32 expression was decreased inS. aureus-infected cells, while it was increased inE. coli-infected cells. We identified the staphylococcal phenol-soluble modulin (PSM) peptides as key contributors to these effects, as IL-32, IL-6, and IL-8 expression by epithelial cells exposed topsmmutant strains was significantly increased compared to that in cells exposed to the isogenicS. aureuswild-type strain, indicating that PSMs inhibit the production of these interleukins. The use of genetically complemented strains confirmed this observation. Inasmuch as the decreased expression of IL-32, which is involved in dendritic cell maturation, impairs immune responses, our results support a PSM-dependent mechanism that allows for the development of chronicS. aureus-related mastitis.
Novel Strategy To Protect against Influenza Virus-Induced Pneumococcal Disease without Interfering with Commensal Colonization
Authors: Greene Christopher J. , Marks Laura R. , Hu John C. , Reddinger Ryan , Mandell Lorrie , Roche-Hakansson Hazeline , King-Lyons Natalie D. , Connell Terry D. , Hakansson Anders P.
Published: March 2016

Streptococcus pneumoniae
commonly inhabits the nasopharynx as a member of the commensal biofilm. Infection with respiratory viruses, such as influenza A virus, induces commensal
S. pneumoniae
to disseminate beyond the nasopharynx and to elicit severe infections of the middle ears, lungs, and blood that are associated with high rates of morbidity and mortality. Current preventive strategies, including the polysaccharide conjugate vaccines, aim to eliminate asymptomatic carriage with vaccine-type pneumococci. However, this has resulted in serotype replacement with, so far, less fit pneumococcal strains, which has changed the nasopharyngeal flora, opening the niche for entry of other virulent pathogens (e.g.,
Streptococcus pyogenes
,
Staphylococcus aureus
, and potentially
Haemophilus influenzae
). The long-term effects of these changes are unknown. Here, we present an attractive, alternative preventive approach where we subvert virus-induced pneumococcal disease without interfering with commensal colonization, thus specifically targeting disease-causing organisms. In that regard, pneumococcal surface protein A (PspA), a major surface protein of pneumococci, is a promising vaccine target. Intradermal (i.d.) immunization of mice with recombinant PspA in combination with LT-IIb(T13I), a novel i.d. adjuvant of the type II heat-labile enterotoxin family, elicited strong systemic PspA-specific IgG responses without inducing mucosal anti-PspA IgA responses. This response protected mice from otitis media, pneumonia, and septicemia and averted the cytokine storm associated with septic infection but had no effect on asymptomatic colonization. Our results firmly demonstrated that this immunization strategy against virally induced pneumococcal disease can be conferred without disturbing the desirable preexisting commensal colonization of the nasopharynx.
The Helicobacter pylori CZB Cytoplasmic Chemoreceptor TlpD Forms an Autonomous Polar Chemotaxis Signaling Complex That Mediates a Tactic Response to Oxidative Stress
Authors: Collins Kieran D. , Andermann Tessa M. , Draper Jenny , Sanders Lisa , Williams Susan M. , Araghi Cameron , Ottemann Karen M.
Published: March 2016

Cytoplasmic chemoreceptors are widespread among prokaryotes but are far less understood than transmembrane chemoreceptors, despite being implicated in many processes. One such cytoplasmic chemoreceptor isHelicobacter pyloriTlpD, which is required for stomach colonization and drives a chemotaxis response to cellular energy levels. Neither the signals sensed by TlpD nor its molecular mechanisms of action are known. We report here that TlpD functions independently of the other chemoreceptors. When TlpD is the sole chemoreceptor, it is able to localize to the pole and recruits CheW, CheA, and at least two CheV proteins to this location. It loses the normal membrane association that appears to be driven by interactions with other chemoreceptors and with CheW, CheV1, and CheA. These results suggest that TlpD can form an autonomous signaling unit. We further determined that TlpD mediates a repellent chemotaxis response to conditions that promote oxidative stress, including being in the presence of iron, hydrogen peroxide, paraquat, and metronidazole. Last, we found that all testedH. pyloristrains express TlpD, whereas other chemoreceptors were present to various degrees. Our data suggest a model in which TlpD coordinates a signaling complex that responds to oxidative stress and may allowH. pylorito avoid areas of the stomach with high concentrations of reactive oxygen species.

IMPORTANCEHelicobacter pylorisenses its environment with proteins called chemoreceptors. Chemoreceptors integrate this sensory information to affect flagellum-based motility in a process called chemotaxis. Chemotaxis is employed during infection and presumably aidsH. pyloriin encountering and colonizing preferred niches. A cytoplasmic chemoreceptor named TlpD is particularly important in this process, and we report here that this chemoreceptor is able to operate independently of other chemoreceptors to organize a chemotaxis signaling complex and mediate a repellent response to oxidative stress conditions.H. pyloriencounters and must cope with oxidative stress during infection due to oxygen and reactive oxygen species produced by host cells. TlpD's repellent response may allow the bacteria to escape niches experiencing inflammation and elevated reactive oxygen species (ROS) production.
Transcriptome Analysis of Escherichia coli during dGTP Starvation
Authors: Itsko Mark , Schaaper Roel M.
Published: March 2016

Our laboratory recently discovered that
Escherichia coli
cells starved for the DNA precursor dGTP are killed efficiently (dGTP starvation) in a manner similar to that described for thymineless death (TLD). Conditions for specific dGTP starvation can be achieved by depriving an
E. coli
optA1 gpt
strain of the purine nucleotide precursor hypoxanthine (Hx). To gain insight into the mechanisms underlying dGTP starvation, we conducted genome-wide gene expression analyses of actively growing
optA1 gpt
cells subjected to hypoxanthine deprivation for increasing periods. The data show that upon Hx withdrawal, the
optA1 gpt
strain displays a diminished ability to derepress the
de novo
purine biosynthesis genes, likely due to internal guanine accumulation. The impairment in fully inducing the
purR
regulon may be a contributing factor to the lethality of dGTP starvation. At later time points, and coinciding with cell lethality, strong induction of the SOS response was observed, supporting the concept of replication stress as a final cause of death. No evidence was observed in the starved cells for the participation of other stress responses, including the
rpoS
-mediated global stress response, reinforcing the lack of feedback of replication stress to the global metabolism of the cell. The genome-wide expression data also provide direct evidence for increased genome complexity during dGTP starvation, as a markedly increased gradient was observed for expression of genes located near the replication origin relative to those located toward the replication terminus.

IMPORTANCE
Control of the supply of the building blocks (deoxynucleoside triphosphates [dNTPs]) for DNA replication is important for ensuring genome integrity and cell viability. When cells are starved specifically for one of the four dNTPs, dGTP, the process of DNA replication is disturbed in a manner that can lead to eventual death. In the present study, we investigated the transcriptional changes in the bacterium
E. coli
during dGTP starvation. The results show increasing DNA replication stress with an increased time of starvation, as evidenced by induction of the bacterial SOS system, as well as a notable lack of induction of other stress responses that could have saved the cells from cell death by slowing down cell growth.