bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydraulic Efficiency Conversion From a Model to Prototype Pump Based on Effects of Reynolds Number and Surface Roughness
Authors: Yoda Hiroaki , Uranishi Kazuo , Oshima Masao , Sakurai Takaki , Torii Daichi , Miyabe Masahiro , Kobayashi Kazuta , Ikezawa Masashi
Published: December 2016

New equations for hydraulic efficiency conversion from a model to a prototype centrifugal pump including mixed and axial flow types have been developed and proposed in this paper. In order to establish a set of conversion equations applicable for all type numbers of pumps, the following factors related to the conversion equations were examined.

1) The ratio of scalable loss to total hydraulic loss was examined by using CFD (Computational Fluid Dynamics) analysis. The ratio is related with the effect of actual complex velocity distributions in the flow passages in the impeller and diffuser/volute casing.

2) The conversion equation was constructed by two terms dealing with flow passages in two major hydrodynamic components, impeller and diffuse/volute separately, where contributions of each component to the efficiency step-up was expressed explicitly.

3) The friction coefficient ratio between a model and prototype pump was expressed in a simplified equation, applicable for both hydraulically-smooth and transitional surfaces. This expression was found to be useful to determine the relationship between equivalent machined surface roughness and uniform sand roughness, as the friction coefficient diagram expressed for uniform sand roughness is used for conversion of hydraulic losses between the model and prototype pumps.

4) The difference between the friction coefficients for decelerating flow and for a flat plate with uniform flow was examined by CFD analysis, and it was found that the friction coefficient for a flat plate can be used for the conversion without causing any substantial deviation.
Near Term Ship Motion Forecasting From Prior Motion
Authors: Vorwald John , Schwartz Alan , Kent Christopher
Published: December 2016

Ship-motion forecasting can be useful for naval operations such as aircraft landing, cargo transfer, off-loading of small boats, and ship “mating” between a large transport ship and smaller ships. The forecasted ship motion is particularly useful in sea states above SS3 when unanticipated large motions can suddenly occur. A 5- to 10-second forecast of future ship motion provides the operator time to compensate for the motion to avoid serious collisions. Ship motion forecasting can enable autonomous landing during higher sea states and can also provide an alternative ship location estimate during emergency procedures such as loss of communication link. This paper summarizes the evaluation of four categories of forecasting methodologies: subspace algorithms, autoregressive algorithms, nonlinear autoregressive using a wavelet network, and perturbation error methods. Simulated Model 5415 ship motion was evaluated in 24 conditions including sea states 4–6, ship speeds of 5, 10, 20, and 30 kts, and wave headings 150 and 180 deg (bow and head seas). For each condition, the simulation motion data was divided into twenty 7.5-minute segments consisting of 0.5 to 5 minutes of training data and 2.5 minutes of testing data. Two types of forecasting accuracy metrics were developed. One metric was based on forecasting simulated ship motion and the other metric involved forecasting periods when the motion exceeds threshold limits within a 4-second window, representing a quiescent period. The results indicate that for simulation forecast accuracy, the correlation coefficient between forecasted and actual motion was greater than 80% for 5-sec forecast horizons, and greater than 60% for 10-sec forecast horizons. For motion threshold forecasting, the forecasting accuracy was greater than 90% for 5-sec horizons and greater than 60% for 10-sec horizons. A qualitative assessment of both simulation and threshold metrics indicated that 80% accuracy produces a good forecast and 60% accuracy produces an acceptable forecast. Threshold forecasting can forecast the presence and duration of near-future quiescent periods, enabling safer, more efficient operations and reduced cost of ship-based aviation operations such as launch, recovery, and movement of aircraft.
Characteristics of High Concentration Pulses in Turbulent Mass Diffusion
Authors: Endo Mayasa , Shao Qianqian , Tsukahara Takahiro , Kawaguchi Yasuo
Published: December 2016

When a material spreads in turbulent flow, areas with high concentration are formed by the local turbulence. These high concentration islands can lead to heavy damage. In this study, the high concentration areas are extracted as pulses by a conditional sampling technique, and statistical analysis were performed in order to investigate the difference between the pulses and concentration plume.

Assuming homogeneous flow, a series of images by Planar Laser Induced Fluorescence and Particle Image Velocimetry techniques are acquired at several downstream positions. For PLIF images, a conditional sampling technique is used to extract the high concentration areas. For simultaneous PIV and PLIF images, wavelet analysis is performed to probe into the relationship between high concentration pulses and velocity fluctuation.

Turbulent diffusion coefficient of the high concentration areas is found to increase with the downstream distance whereas that of the concentration plume is constant, which implies that the diffusion process of the pulses differs from that of the plume. Besides by wavelet analysis result, it is indicated that concentration fluctuation in the pulses is negatively correlated with streamwise velocity fluctuation. It is concluded that high concentration pulses and plume have different generative mechanisms.
Analysis of Turbulence Generation and Energy Transfer Mechanisms in Boundary Layer Transition Using Direct Numerical Simulation
Authors: Bhushan Shanti , Borse Manish , Walters D. Keith , Pasiliao Crystal L.
Published: December 2016

Temporally developing DNS for channel flow at Reτ = 180 and 590 are performed to understand the turbulence generation mechanism for wall bound flow transition. Simulations for Reτ = 180 were performed for initial turbulence intensities TI = 0.1%, 1%, 2.5% and 5% and for Reτ = 590 with TI = 1% and 5%. The results in the fully developed turbulent region were compared with Moser et al. (1999) DNS data to validate the predictions. The near-wall vortical structures, mean and turbulent stresses and energy spectra, and turbulent kinetic energy (TKE) and stress budget in the pre-transition, transition and turbulent regions are analyzed to understand the turbulence onset, growth and decay mechanism. Finally, molecular diffusion and pressure strain time scales in the pre-transition to turbulent regions are analyzed to evaluate the turbulence onset criteria.
On the Improvement of CFD-DEM Coarse Graining Predictions
Authors: Elghannay Husam , Yu Kuahai , Tafti Danesh
Published: December 2016

Discrete Element Method (DEM) coupled to Computational Fluid Mechanics (CFD) is a powerful tool for simulating complex multiphase flows. The cost of this Eulerian-Lagrangian description, however, increases with the increase of the number of particles ∼O(Np) which limit its use in natural and industrial scale systems. Efforts to reduce the cost of CFD-DEM capability include reducing the total number of simulated particles by lumping them in larger size representative particles (RP Model). The scaled Representative Particle simulations are less compute intensive compared to the more expensive high fidelity un-scaled/resolved simulations. The prediction accuracy of the RP model, however, decreases as larger scaling factors are used. In the current work, we study the possibility of getting improved results from RP model by using two different techniques. First attempts will be made to identify reasons for reduction in RP model prediction accuracy, then different techniques for improvement of RP model are suggested and tested. In the second part, the ability of the co-kriging surrogate model to improve CFD-DEM predictions by combining many reduced-order RP model simulations with a few high-fidelity unscaled calculations is tested. Appropriate systems are selected to evaluate each method.
Optimization of High Pressure Pump Flow Passages Based on Adjoint and CFD
Authors: Sekino Yumiko , Watanabe Hiroyoshi , Christakopoulos Faidon , Zangeneh Mehrdad
Published: December 2016

In order to improve overall performance of a turbomachinery, it is important to reduce losses of stationary flow passages, such as diffusers and return channels, as well as impellers. For multi-stage pumps, to achieve high uniformity of the inlet flow of the latter impeller can prevent degradation of subsequent performance.

A two stages high pressure pump which was developed by the authors applied vaned diffuser sections located downstream of the first stage impeller and second stage impeller. The vaned diffusers can be replaced to fit the required specification of operating condition. This design is able to help pumps share the casings so that customers can purchase our products at a low cost.

However, the loss of the first stage diffuser section and crossover downstream of the first stage diffuser to the second impeller is large, so that it has a negative impact on overall performance of the pump. It was difficult to reduce loss of the both sections by conventional way such as trial and error approach by modifying geometrical parameters. If we try to reduce the loss of the diffuser section, loss of the crossover passage increases.

We therefore applied a technology called Adjoint method to the design optimization of the diffuser and crossover sections of the pump. The adjoint method has recently been put to practical use. By using this method it is possible to obtain a complex three-dimensional shape for realizing an optimum flow field in a very short time while maintaining a high degree of freedom.

In this study two objectives were specified in the design optimization of the stationery sections; one is to increase the uniformity of the flow field at the inlet of the second stage impeller and the other is to minimize the loss of the first stage diffuser and crossover passage. In the optimization process, the change of sensitivity of the geometry deformation to the weights of objective functions was analyzed by sensitivity maps. The sensitivity maps show directions of the geometry modification depending on the objectives. The geometry in this design was optimized with 50% - 50% weighting ratio between flow uniformity and pressure loss. The loss of the vaned diffuser and crossover passage, velocity uniformity at the outlet of the crossover passage were verified with Computational Fluid Dynamics (CFD). The improvement of pump stage performance was expected by the optimization.

This optimization design procedure applying Adjoint method is effective to improve overall performance of a two stages high pressure pump which has complex three-dimensional flow passages.
Effects of Parallel Processing on Large Eddy Simulations in ANSYS Fluent
Authors: Li Puxuan , Eckels Steve J. , Zhang Ning , Mann Garrett W.
Published: December 2016

Parallel processing is an effective computation in which many calculations are carried out simultaneously. In this paper, effects of shared-memory parallel processing on Large Eddy Simulations (LES) in ANSYS Fluent are presented. Fluent provides parallel processing to improve the speed of running programs. LES is one of the most popular viscosity models for turbulence used in computational fluid dynamics (CFD). Three kinds of LES with different sub-grid turbulence models were evaluated: Smagorinsky-Lilly Model (Lilly model), Wall-Adapting Local Eddy-viscosity Model (WALE model) and Wall Modeled Large Eddy Simulation (WMLES model). The running speed of the different models simulating a square duct on a single computer are compared. The relationship between wall-clock time and number of processors reveals the performances of different LES models. The part of the time that is not parallelizable such as file IO and data transfer is also considered based on Amdahl’s law.
Aerodynamic Drag Reduction Investigation for a Simplified Road Vehicle Using Plasma Flow Control
Authors: Khalighi Bahram , Ho Joanna , Cooney John , Neiswander Brian , Corke Thomas C. , Han Taeyoung
Published: December 2016

The effect of plasma flow control on reducing aerodynamic drag for ground vehicles is investigated. The experiments were carried out for a simplified ground vehicle using single dielectric barrier discharge (SDBD) plasma actuators. The plasma actuators were designed to alter the flow structure in the wake region behind the vehicle. The Ahmed body was modified to allow eight different vehicle geometries (with backlight or slant angles of 0° and 35°). Each of these were further modified by rounding the edges with different radii. Flow visualizations such as particle streams and surface oil were used to quantify features of the local flow field. The drag on the models was measured using a force balance as well as by integrating the mean velocity profiles in the model wakes. The results indicated that flow modifications needed to be applied symmetrically (upper to lower and/or side to side). This was demonstrated with the 0° backlight angle (square-back) that had all four side-corners rounded. Plasma actuators were applied to all four of the rounded edges to enhance the ability to direct the flow into the wake. Wake measurements showed that steady actuation at a fixed actuator voltage reduced the drag by an average of 20% at the lower velocities (below 15 m/s) and by 3% at the highest velocity tested (20 m/s). Model constraints prevented increasing the plasma actuator voltage that was needed to maintain the higher drag reduction observed at the lower speeds.
Re-Thinking of Data Acquisition Rates in the Era of Expensive Data
Authors: Smith Barton L. , Neal Douglas R.
Published: December 2016

It is well known that the mean of a sample converges at a rate of 1/N, where N is the number of samples, assuming that are samples are statistically independent. This paper will show the impact of non-independent samples using real data as well as investigating the efficacy of methods to determine the effective number of samples with non-independent samples are acquired.
Use of the Adjoint Method to Assess the Error in Simulations
Authors: Carrier A. , Nicolle J. , Deschênes C.
Published: December 2016

In this work, a sensitivity calculation approach called the adjoint method is explored to estimate and control the discretization error in computational fluid dynamic (CFD). This paper describes how the adjoint is applied to incompressible RANS simulations to approach the continuous solution which is unknown. While the adjoint method is already widespread in aerodynamics to optimize designs, here it is used as an error estimator. The error is thus calculated from the scalar product of sensitivities to an objective function selected by the user (efficiency, power, losses, etc.) with respect to residuals of governing equations. The key point is that adjoint method pinpoints the sensitive areas of the simulation. By adapting the mesh accordingly, it is possible to improve the numerical accuracy while keeping the mesh size manageable.
Numerical Investigation on the Aerodynamic Performance of an Airfoil With Leading-Edge Protuberances
Authors: Cai Chang , Zuo Zhigang , Liu Shuhong
Published: December 2016

Leading edge protuberance modifications on airfoils or wings have attracted extensive attentions as a new passive technique for separation control. In this paper, the hydrodynamic performance of a NACA 634-021 foil and a modified foil with leading-edge protuberances were numerically investigated using Spalart-Allmaras turbulence model. Compared to the sharp decline of baseline lift coefficient, the stall angle of the modified foils was advanced and the decline of lift coefficient became mild, and the post-stall performance was improved. A special bi-periodic flow pattern may occur and stay extremely steady at a wide range of attack angles, accompanied with a relatively steady lift. The transformation from single-periodicity to bi-periodicity occurred within a small range of range of attack angle. A couple of counter-rotating streamwise vortex was formed on the shoulder of each protuberance, altering the vorticity line to share a similar shape as the leading-edge profile. At larger angles of attack, the development of streamwise vortex would be accompanied with transformation to lateral vortex, where strong interaction may happen and give rise to the occurrence of bi-periodic condition. The formation mechanism and control method of the special phenomenon should be investigated more deeply in the future.
Improvement of Wind Turbine Efficiency by Using Synthetic Jets
Authors: Zeynali Khameneh Nooshin , Tadjfar Mehran
Published: December 2016

In this paper we investigated the applicability of using synthetic jets to improve the efficiency of wind turbines. We used the NREL Phase VI rotor which is a stall regulated two bladed wind turbine with linear taper and nonlinear twist distribution over the blades and uses the S809 airfoil from root to tip. We validated our base flow (uncontrolled) results with the experimental tests that were performed in the NASA/AMES 80 ft. × 120 ft. wind tunnel. Synthetic jet is an active flow control device and was applied along the blade from root to tip at 0.1 chord location. The non-dimensionalized jet frequencies of Fjet+ = 1 and 0.5 and the blowing ratio of Vj/U∞ = 1 and 2 are used during the control cycle.
Elimination of diazinon insecticide from cucumber surface by atmospheric pressure air-dielectric barrier discharge plasma
Authors: Dorraki Naghme , Mahdavi Vahideh , Ghomi Hamid , Ghasempour Alireza
Published: December 2016

The food industry is in a constant search for new technologies to improve the commercial sterilization process of agricultural commodities. Plasma treatment may offer a novel and efficient method for pesticide removal from agricultural product surfaces. To study the proposed technique of plasma food treatment, the degradation behavior of diazinon insecticide by air-dielectric barrier discharge (DBD) plasma was investigated. The authors studied the effect of different plasma powers and treatment times on pesticide concentration in liquid form and coated on the surface of cucumbers, where the diazinon residue was analyzed with mass spectroscopy gas chromatography. Our results suggest that atmospheric pressure air-DBD plasma is potentially effective for the degradation of diazinon insecticide, and mainly depends on related operating parameters, including plasma treatment time, discharge power, and pesticide concentrations. Based on the interaction between reactive oxygen species and electrons in the plasma with the diazinon molecule, two degradation pathway of diazinon during plasma treatment are proposed. It was also found that produced organophosphate pesticides are harmless and less hazardous compounds than diazinon.
Effects of age and hearing loss on concurrent vowel identification
Authors: Chintanpalli Ananthakrishna , Ahlstrom Jayne B. , Dubno Judy R.
Published: December 2016

Differences in formant frequencies and fundamental frequencies (F0) are important cues for segregating and identifying two simultaneous vowels. This study assessed age- and hearing-loss-related changes in the use of these cues for recognition of one or both vowels in a pair and determined differences related to vowel identity and specific vowel pairings. Younger adults with normal hearing, older adults with normal hearing, and older adults with hearing loss listened to different-vowel and identical-vowel pairs that varied in F0 differences. Identification of both vowels as a function of F0 difference revealed that increased age affects the use of F0 and formant difference cues for different-vowel pairs. Hearing loss further reduced the use of these cues, which was not attributable to lower vowel sensation levels. High scores for one vowel in the pair and no effect of F0 differences suggested that F0 cues are important only for identifying both vowels. In contrast to mean scores, widely varying differences in effects of F0 cues, age, and hearing loss were observed for particular vowels and vowel pairings. These variations in identification of vowel pairs were not explained by acoustical models based on the location and level of formants within the two vowels.
Late-phase synthesis of IκBα insulates the TLR4-activated canonical NF-κB pathway from noncanonical NF-κB signaling in macrophages
Authors: Chatterjee Budhaditya , Banoth Balaji , Mukherjee Tapas , Taye Nandaraj , Vijayaragavan Bharath , Chattopadhyay Samit , Gomes James , Basak Soumen
Published: December 2016

Macrophage-specific insulation of canonical NF-κB signaling from the noncanonical pathway prevents excessive inflammation.
Widespread control of calcium signaling by a family of SERCA-inhibiting micropeptides
Authors: Anderson Douglas M. , Makarewich Catherine A. , Anderson Kelly M. , Shelton John M. , Bezprozvannaya Svetlana , Bassel-Duby Rhonda , Olson Eric N.
Published: December 2016

A family of micropeptides inhibits calcium reuptake by the endoplasmic reticulum in diverse cell types.
Papers of note in
Science Translational Medicine
Authors: Ferrarelli Leslie K.
Published: December 2016

This week’s articles describe new avenues to improve immunotherapy and treat Parkinson’s disease and a way to monitor androgen receptor status while treating prostate cancer.
Papers of note in
Science
Authors: VanHook Annalisa M.
Published: December 2016

This week’s papers highlight a role for glial cells in the spread of pain hypersensitivity, the importance of amino acid availability and metabolism in hematopoiesis, the epigenetics of T cell exhaustion, and similarities between plant and animal innate immunity.
Carbapenemase-Producing Enterobacteriaceae Recovered from the Environment of a Swine Farrow-to-Finish Operation in the United States
Authors: Mollenkopf Dixie F. , Stull Jason W. , Mathys Dimitria A. , Bowman Andrew S. , Feicht Sydnee M. , Grooters Susan V. , Daniels Joshua B. , Wittum Thomas E.
Published: December 2016

Carbapenem-resistant
Enterobacteriaceae
(CRE) present an urgent threat to public health. While use of carbapenem antimicrobials is restricted for food-producing animals, other β-lactams, such as ceftiofur, are used in livestock. This use may provide selection pressure favoring the amplification of carbapenem resistance, but this relationship has not been established. Previously unreported among U.S. livestock, plasmid-mediated CRE have been reported from livestock in Europe and Asia. In this study, environmental and fecal samples were collected from a 1,500-sow, U.S. farrow-to-finish operation during 4 visits over a 5-month period in 2015. Samples were screened using selective media for the presence of CRE, and the resulting carbapenemase-producing isolates were further characterized. Of 30 environmental samples collected from a nursery room on our initial visit, 2 (7%) samples yielded 3 isolates, 2 sequence type 218 (ST 218)
Escherichia coli
and 1
Proteus mirabilis
, carrying the metallo-β-lactamase gene
bla
IMP-27
on IncQ1 plasmids. We recovered on our third visit 15 IMP-27-bearing isolates of multiple
Enterobacteriaceae
species from 11 of 24 (46%) environmental samples from 2 farrowing rooms. These isolates each also carried
bla
IMP-27
on IncQ1 plasmids. No CRE isolates were recovered from fecal swabs or samples in this study. As is common in U.S. swine production, piglets on this farm receive ceftiofur at birth, with males receiving a second dose at castration (≈day 6). This selection pressure may favor the dissemination of
bla
IMP-27
-bearing
Enterobacteriaceae
in this farrowing barn. The absence of this selection pressure in the nursery and finisher barns likely resulted in the loss of the ecological niche needed for maintenance of this carbapenem resistance gene.
A Prolonged Outbreak of KPC-3-Producing Enterobacter cloacae and Klebsiella pneumoniae Driven by Multiple Mechanisms of Resistance Transmission at a Large Academic Burn Center
Authors: Kanamori Hajime , Parobek Christian M. , Juliano Jonathan J. , van Duin David , Cairns Bruce A. , Weber David J. , Rutala William A.
Published: December 2016

Klebsiella pneumoniae
carbapenemase (KPC)-producing
Enterobacter cloacae
has been recently recognized in the United States. Whole-genome sequencing (WGS) has become a useful tool for analysis of outbreaks and for determining transmission networks of multidrug-resistant organisms in health care settings, including carbapenem-resistant
Enterobacteriaceae
(CRE). We experienced a prolonged outbreak of CRE
E. cloacae
and
K. pneumoniae
over a 3-year period at a large academic burn center despite rigorous infection control measures. To understand the molecular mechanisms that sustained this outbreak, we investigated the CRE outbreak isolates by using WGS. Twenty-two clinical isolates of CRE, including
E. cloacae
(
n
= 15) and
K. pneumoniae
(
n
= 7), were sequenced and analyzed genetically. WGS revealed that this outbreak, which seemed epidemiologically unlinked, was in fact genetically linked over a prolonged period. Multiple mechanisms were found to account for the ongoing outbreak of KPC-3-producing
E. cloacae
and
K. pneumoniae
. This outbreak was primarily maintained by a clonal expansion of
E. cloacae
sequence type 114 (ST114) with distribution of multiple resistance determinants. Plasmid and transposon analyses suggested that the majority of
bla
KPC-3
was transmitted via an identical Tn
4401
b element on part of a common plasmid. WGS analysis demonstrated complex transmission dynamics within the burn center at levels of the strain and/or plasmid in association with a transposon, highlighting the versatility of KPC-producing
Enterobacteriaceae
in their ability to utilize multiple modes to resistance gene propagation.
High-Throughput Screening and Prediction Model Building for Novel Hemozoin Inhibitors Using Physicochemical Properties
Authors: Huy Nguyen Tien , Chi Pham Lan , Nagai Jun , Dang Tran Ngoc , Mbanefo Evaristus Chibunna , Ahmed Ali Mahmoud , Long Nguyen Phuoc , Thoa Le Thi Bich , Hung Le Phi , Titouna Afaf , Kamei Kaeko , Ueda Hiroshi , Hirayama Kenji
Published: December 2016

It is essential to continue the search for novel antimalarial drugs due to the current spread of resistance against artemisinin by
Plasmodium falciparum
parasites. In this study, we developed
in silico
models to predict hemozoin inhibitors as a potential first-step screening for novel antimalarials. An
in vitro
colorimetric high-throughput screening assay of hemozoin formation was used to identify hemozoin inhibitors from 9,600 structurally diverse compounds. The physicochemical properties of positive hits and randomly selected compounds were extracted from the ChemSpider database; they were used for developing prediction models to predict hemozoin inhibitors using two different approaches, i.e., traditional multivariate logistic regression and Bayesian model averaging. Our results showed that a total of 224 positive-hit compounds exhibited the ability to inhibit hemozoin formation, with 50% inhibitory concentrations (IC
50
s) ranging from 3.1 μM to 199.5 μM. The best model according to traditional multivariate logistic regression included the three variables octanol-water partition coefficient, number of hydrogen bond donors, and number of atoms of hydrogen, while the best model according to Bayesian model averaging included the three variables octanol-water partition coefficient, number of hydrogen bond donors, and index of refraction. Both models had a good discriminatory power, with area under the curve values of 0.736 and 0.781 for the traditional multivariate model and Bayesian model averaging, respectively. In conclusion, the prediction models can be a new, useful, and cost-effective approach for the first screen of hemozoin inhibition-based antimalarial drug discovery.
Safety and Pharmacokinetics of CD101 IV, a Novel Echinocandin, in Healthy Adults
Authors: Sandison Taylor , Ong Voon , Lee Jonathan , Thye Dirk
Published: December 2016

CD101 IV is a novel echinocandin with distinctive pharmacokinetic properties that is being developed as a once-weekly treatment for candidemia and invasive candidiasis. CD101 has potent
in vitro
activity and
in vivo
efficacy against a broad range of
Candida
and
Aspergillus
species. The primary objective of two randomized, double-blind, placebo-controlled, dose-escalation studies in healthy adults was to determine the safety and tolerability of CD101 IV. Sequential cohorts of 8 subjects (
n
= 6, active;
n
= 2, placebo) were administered single (50, 100, 200, 400 mg) or multiple once-weekly (100 mg given once weekly for two weeks [×2], 200 mg ×2, 400 mg ×3) doses of CD101 IV infused over 1 h. There were no deaths, serious adverse events (SAEs), severe adverse events (AEs), or withdrawals from the study due to an AE. The majority of AEs were mild, and all completely resolved. There was a higher incidence of total AEs and mild transient infusion reactions in the 400-mg ×3 dose group. There were no clinically meaningful trends in postbaseline laboratory abnormalities and no safety issues related to electrocardiograms, vital signs, or physical exams. CD101 showed dose-proportional plasma exposures, minor accumulation (30% to 55%), low apparent clearance (<0.28 liter/h), long half-life (
t
1/2
) (>80 h), and minimal urine excretion. CD101 IV was safe and well tolerated at single and multiple doses of up to 400 mg given once weekly for 3 weeks and exhibited a long
t
1/2
, minimal accumulation over several weeks, negligible renal excretion, and high plasma exposures enabling once-weekly dosing.
Pharmacokinetic Evaluation of Darunavir Administered Once or Twice Daily in Combination with Ritonavir or the Three-Direct-Acting Antiviral Regimen of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir in Adults Coinfected with Hepatitis C and Human Immunodeficiency Viruses
Authors: King Jennifer R. , Khatri Amit , Trinh Roger , Viani Rolando M. , Ding Bifeng , Zha Jiuhong , Menon Rajeev
Published: December 2016

The three-direct-acting antiviral (3D) regimen containing ombitasvir, paritaprevir, ritonavir, and dasabuvir with or without ribavirin (RBV) is approved for treatment of hepatitis C virus (HCV) genotype 1 (GT1)/human immunodeficiency virus type 1 (HIV-1) coinfection. Results of a pharmacokinetic substudy of 3D and darunavir are presented. HCV/HIV-1-coinfected subjects were randomized to maintain an antiretroviral regimen with darunavir at 800 mg once daily (QD) or switched to a regimen with darunavir at 600 mg twice daily (BID). On study day 1, subjects received 3D and RBV plus darunavir for 12 weeks. Pharmacokinetic parameters were compared for darunavir and ritonavir with and without 3D (week 4 and day −1). Pharmacokinetic parameters of 3D were compared to historical data. Ten subjects received darunavir QD, and 12 subjects received darunavir BID. The central value ratios (90% confidence interval [CI]) for maximum concentrations (
C
max
), area under the plasma concentration-time curve between 0 and 24 h postdose (AUC
24
), and trough plasma concentration at 24 h postdose (
C
24
) of darunavir administered QD with 3D versus administration of darunavir alone were 0.92 (0.72, 1.18), 0.83 (0.71, 0.98), and 0.64 (0.44, 0.93), respectively. The ratios (90% CI) for darunavir
C
max
, AUC
12
, and
C
12
administered BID with 3D were 0.92 (0.76, 1.12), 0.88 (0.73, 1.05), and 0.73 (0.58, 0.92), respectively. Exposures of 3D were similar to or slightly lower than those in historical data. All darunavir trough concentrations (
C
trough
) associated with an HIV-1 RNA level of >40 copies/ml were above the darunavir 50% effective concentration (EC
50
) of 550 ng/ml for resistant virus. In conclusion, the 3D regimen with darunavir QD or BID did not affect darunavir
C
max
and AUC, whereas the darunavir
C
trough
decreased. Changes in pharmacokinetic parameters of 3D were not considered clinically significant. Episodes of intermittent HIV-1 viremia were infrequent and were not associated with darunavir
C
trough
values below 550 ng/ml. (This study has been registered at ClinicalTrials.gov under identifier NCT01939197.)
Genotyping and Prevalence of Pyrazinamide- and Moxifloxacin-Resistant Tuberculosis in China, 2000 to 2010
Authors: Pang Yu , Zhang Zhijian , Wang Yufeng , Wang Shengfen , Song Yuanyuan , Zhao Bing , Zhou Yang , Ou Xichao , Li Qiang , Xia Hui , Zheng Yang , Fang Xiangqun , Zhao Yanlin
Published: December 2016

We investigated the prevalence, trends, and risk factors for pyrazinamide (PZA) and moxifloxacin (MOX) resistance among tuberculosis (TB) cases in China and also analyzed the population structure of
Mycobacterium tuberculosis
strains. All the
M. tuberculosis
strains enrolled in this study were collected from the national TB prevalence surveys. Each strain was genotyped by analyzing the regions of RD105 and IS
6110
in the NTF region. The Bactec MGIT 960 system was used to detect the drug susceptibility of
M. tuberculosis
isolates to PZA and MOX. Based on the genotyping results, 241 (66.4%) strains were classified as Beijing genotype in 2000, which was significantly lower than in 2010 (76.2%,
P
< 0.01). The proportion of the modern Beijing genotype increased significantly from 49.6% in 2000 to 68.1% in 2010 (
P
< 0.01), while no significant difference was observed in the rate of ancient Beijing genotype between 2000 and 2010 (
P
= 0.676). In addition, we found that the proportion of PZA resistance in 2010 (15.0%) was significantly higher than that in 2000 (9.6%,
P
= 0.04). For MOX, there were more MOX-resistant isolates detected in 2010 (7.7%) than in 2000 (3.0%). In conclusion, our data demonstrate that the Beijing genotype was the predominant
M. tuberculosis
lineage during the past decade. The proportion of Beijing genotype isolates significantly increased from 2000 to 2010, largely due to an increase in the modern Beijing sublineage. In addition, resistance to PZA and MOX increased significantly in China between 2000 and 2010.
Inhibition of Antigen-Specific and Nonspecific Stimulation of Bovine T and B Cells by Lymphostatin from Attaching and Effacing Escherichia coli
Authors: Cassady-Cain Robin L. , Blackburn Elizabeth A. , Bell Charlotte R. , Elshina Elizaveta , Hope Jayne C. , Stevens Mark P.
Published: December 2016

EnterohemorrhagicEscherichia coli(EHEC) and enteropathogenicE. coli(EPEC) are enteric bacterial pathogens of worldwide importance. Most EPEC and non-O157 EHEC strains express lymphostatin (also known as LifA), a chromosomally encoded 365-kDa protein. We previously demonstrated that lymphostatin is a putative glycosyltransferase that is important in intestinal colonization of cattle by EHEC serogroup O5, O111, and O26 strains. However, the nature and consequences of the interaction between lymphostatin and immune cells from the bovine host are ill defined. Using purified recombinant protein, we demonstrated that lymphostatin inhibits mitogen-activated proliferation of bovine T cells and, to a lesser extent, proliferation of cytokine-stimulated B cells, but not NK cells. It broadly affected the T cell compartment, inhibiting all cell subsets (CD4, CD8, WC-1, and γδ T cell receptor [γδ-TCR]) and cytokines examined (interleukin 2 [IL-2], IL-4, IL-10, IL-17A, and gamma interferon [IFN-γ]) and rendered T cells refractory to mitogen for a least 18 h after transient exposure. Lymphostatin was also able to inhibit proliferation of T cells stimulated by IL-2 and by antigen presentation using aTheileria-transformed cell line and autologous T cells fromTheileria-infected cattle. We conclude that lymphostatin is likely to act early in T cell activation, as stimulation of T cells with concanavalin A, but not phorbol 12-myristate 13-acetate combined with ionomycin, was inhibited. Finally, a homologue of lymphostatin fromE. coliO157:H7 (ToxB; L7095) was also found to possess comparable inhibitory activity against T cells, indicating a potentially conserved strategy for interference in adaptive responses by attaching and effacingE. coli.
A Sulfur Oxygenase from the Haloalkaliphilic Bacterium Thioalkalivibrio paradoxus with Atypically Low Reductase Activity
Authors: Rühl Patrick , Pöll Uwe , Braun Johannes , Klingl Andreas , Kletzin Arnulf
Published: December 2016

Sequence comparisons showed that the sulfur oxygenase reductase (SOR) of the haloalkaliphilic bacterium
Thioalkalivibrio paradoxus
Arh 1 (
Tp
SOR) is branching deeply within dendrograms of these proteins (29 to 34% identity). A synthetic gene encoding
Tp
SOR expressed in
Escherichia coli
resulted in a protein 14.7 ± 0.9 nm in diameter and an apparent molecular mass of 556 kDa. Sulfite and thiosulfate were formed from elemental sulfur in a temperature range of 10 to 98°C (optimum temperature ≈ 80°C) and a pH range of 6 to 11.5 (optimum pH ≈ 9; 308 ± 78 U/mg of protein). Sulfide formation had a maximum specific activity of 0.03 U/mg, or <1% of the corresponding activity of other SORs. Hence, reductase activity seems not to be an integral part of the reaction mechanism.
Tp
SOR was most active at NaCl or glycine betaine concentrations of 0 to 1 M, although 0.2% of the maximal activity was detected even at 5 M NaCl and 4 M betaine. The melting point of
Tp
SOR was close to 80°C, when monitored by circular dichroism spectroscopy or differential scanning fluorimetry; however, the denaturation kinetics were slow: 55% of the residual activity remained after 25 min of incubation at 80°C. Site-directed mutagenesis showed that the active-site residue Cys
44
is essential for activity, whereas alanine mutants of the two other conserved cysteines retained about 0.5% residual activity. A model of the sulfur metabolism in
T. paradoxus
is discussed.
IMPORTANCE
Sulfur oxygenase reductases (SORs) are the only enzymes catalyzing an oxygen-dependent disproportionation of elemental sulfur and/or polysulfides to sulfite, thiosulfate, and hydrogen sulfide. SORs are known from mesophilic and extremophilic archaea and bacteria. All SORs seem to form highly thermostable 24-subunit hollow spheres. They carry a low-potential mononuclear nonheme iron in the active site and an indispensable cysteine; however, their exact reaction mechanisms are unknown. Typically, the reductase activity of SORs is in the range of 5 to 50% of the oxygenase activity, but mutagenesis studies had so far failed to identify residues crucial for the reductase reaction. We describe here the first SOR, which is almost devoid of the reductase reaction and which comes from a haloalkaliphilic bacterium.
An urban collection of modern-day large micrometeorites: Evidence for variations in the extraterrestrial dust flux through the Quaternary
Authors: Genge M.J. , Larsen J. , Van Ginneken M. , Suttle M.D.
Published: December 2016

We report the discovery of significant numbers (500) of large micrometeorites (>100 μm) from rooftops in urban areas. The identification of particles as micrometeorites is achieved on the basis of their compositions, mineralogies, and textures. All particles are silicate-dominated (S type) cosmic spherules with subspherical shapes that form by melting during atmospheric entry and consist of quench crystals of magnesian olivine, relict crystals of forsterite, and iron-bearing olivine within glass. Four particles also contain Ni-rich metal-sulfide beads. Bulk compositions are chondritic apart from depletions in the volatile, moderately volatile, and siderophile elements, as observed in micrometeorites from other sources. The reported particles are likely to have fallen on Earth in the past 6 yr and thus represent the youngest large micrometeorites collected to date. The relative abundance ratio of barred olivine to cryptocrystalline spherule types in the urban particles of 1.45 is shown to be higher than a Quaternary average of ∼0.9, suggesting variations in the extraterrestrial dust flux over the past 800 k.y. Changes in the entry velocities of dust caused by quasi-periodic gravitational perturbation during transport to Earth are suggested to be responsible. Variations in cosmic spherule abundance within the geologic column are thus unavoidable and can be a consequence of dust transport as well as major dust production events.
Overbank sedimentation from the historic A.D. 2011 flood along the Lower Mississippi River, USA
Authors: Heitmuller Franklin T. , Hudson Paul F. , Kesel Richard H.
Published: December 2016

In this study, we document sedimentary characteristics of overbank flood deposits associated with the epic A.D. 2011 flood along the Lower Mississippi River (southern USA) and directly compare the findings to sedimentation from a comparable flood event in 1973, with the general purpose of understanding how extreme floods contribute to floodplain depositional patterns and accretion rates of embanked fluvial systems. The thicknesses of the 2011 flood deposits averaged 138 mm along natural levee crests, 9 mm on meander scrolls, and 3 mm in backswamps. These thicknesses are considerably less than those documented for the 1973 flood, sampled at the same locations. We contend that less sedimentation in 2011 occurred because the flood was not supplied with much upstream sediment from the Missouri River. Further, the 2011 sediments are coarser than in 1973, indicating that the higher 2011 flood levels were associated with more energetic overbank flows that flushed fine-grained sediments downstream within the narrow embanked floodplain corridor. The largest recorded flood in North American history is only marginally preserved in the embanked floodplain stratigraphy of the alluvial valley of Earth’s third largest fluvial system.
Nocturnal antihypertensive treatment in patients with type 1 diabetes with autonomic neuropathy and non-dipping: a randomised, placebo-controlled, double-blind cross-over trial
Authors: Hjortkjær Henrik Øder , Jensen Tonny , Kofoed Klaus F , Mogensen Ulrik M , Sigvardsen Per Ejlstrup , Køber Lars , Hilsted Karen Lisa , Corinth Helle , Theilade Simone , Hilsted Jannik
Published: December 2016

Objectives

Cardiovascular autonomic neuropathy (CAN) and abnormal circadian blood pressure (BP) rhythm are independent cardiovascular risk factors in patients with diabetes and associations between CAN, non-dipping of nocturnal BP and coronary artery disease have been demonstrated. We aimed to test if bedtime dosing (BD) versus morning dosing (MD) of the ACE inhibitor enalapril would affect the 24-hour BP profile in patients with type 1 diabetes (T1D), CAN and non-dipping.

Setting

Secondary healthcare unit in Copenhagen, Denmark.

Participants

24 normoalbuminuric patients with T1D with CAN and non-dipping were included, consisting of mixed gender and Caucasian origin. Mean±SD age, glycosylated haemoglobin and diabetes duration were 60±7 years, 7.9±0.7% (62±7 mmol/mol) and 36±11 years.

Interventions

In this randomised, placebo-controlled, double-blind cross-over study, the patients were treated for 12 weeks with either MD (20 mg enalapril in the morning and placebo at bedtime) or BD (placebo in the morning and 20 mg enalapril at bedtime), followed by 12 weeks of switched treatment regimen.

Primary and secondary outcome measures

Primary outcome was altered dipping of nocturnal BP. Secondary outcomes included a measurable effect on other cardiovascular risk factors than BP, including left ventricular function (LVF).

Results

Systolic BP dipping increased 2.4% (0.03–4.9%; p=0.048) with BD compared to MD of enalapril. There was no increase in mean arterial pressure dipping (2.2% (−0.1% to 4.5%; p=0.07)). No difference was found on measures of LVF (p≥0.15). No adverse events were registered during the study.

Conclusions

We demonstrated that patients with T1D with CAN and non-dipping can be treated with an ACE inhibitor at night as BD as opposed to MD increased BP dipping, thereby diminishing the abnormal BP profile. The potentially beneficial effect on long-term cardiovascular risk remains to be determined.

Trial registration number

EudraCT2012-002136-90; Post-results.
Distinguishing between those dying suddenly or not suddenly from coronary heart disease: long-term prospective results from the Northwick Park Heart Study
Authors: Meade Tom , Clayton Tim , Chamberlain Douglas
Published: December 2016

Aim

To establish whether ECG findings are associated with subsequent risk of sudden death from coronary heart disease (CHD).

Methods and results

Potential risk factors for CHD were measured at entry to the first Northwick Park Heart Study of 2167 men. ECG findings were coded as high or low risk for CHD according to definitions in the Minnesota code. Sudden or non-sudden deaths were defined as occurring in less than or more than 24 hours, respectively. The only factor independently associated with sudden death among the 262 men dying of CHD was high-risk ECG. Of 184 sudden CHD deaths, 34 men (18.5%) had had high-risk ECGs at entry to the study compared with 5 (6.4%) of 78 men who experienced non-sudden deaths (adjusted OR 3.94 (95% CI 1.33 to 11.67)) (p=0.006). Findings were also compared among all 2167 men, where high-risk ECGs were again associated with sudden death. T-wave changes were the main abnormalities associated with a high risk of sudden death.

Conclusions

In a group of men who had not previously experienced major episodes of CHD but who subsequently died from it, there was strong evidence that high-risk ECG changes, mainly T-wave abnormalities, differentiated between those who later died sudden deaths and those who survived for >24 hours.
Large pi-systems containing W–N=N–W groups
Authors: Vilarrubias Pere
Published: December 2016

The compound Cl–W(Mes)3–N=N–W(Mes)3–Cl can polymerize, giving large inorganic pi systems containing N2 and W(Mes)3, where Mes = mesityl. Some of these compounds have been studied in the present paper using B3LYP functional. A description of the molecular orbitals from the pi system is given, explaining the role of the mesityl groups, the terminal chlorines, and the d atomic orbitals from W in the whole conjugated system. Other data such as bond order, atomic partial charges, or geometry are studied. These compounds are also compared with some hypothetical derivatives.
Minimum age for clear-cutting native species with energetic potential in the Brazilian semi-arid region
Authors: Santana Otacilio Antunes
Published: December 2016

What is the minimum age for clear-cutting native species with energetic potential in the Brazilian semi-arid region? This was the central question of this study, which aimed at estimating the minimum cutting cycle for native woody species from an area covered by a sustainable forest management plan. Individuals (n = 240) of 12 species native to the semi-arid region were measured, and wood discs were taken from them to collect data relative to (i) volume, by an industrial 3D scanner, (ii) density, using a high-frequency densitometer, (iii) age, by a growth ring measuring device, and (iv) the lower heating value, by an oxygen bomb calorimeter and an elemental analyzer. Data were fitted to mathematical models by regression analysis to determine the relationship and significance between the variables analyzed. The estimated minimum age for the harvesting of native woody species was 47 years, determined by the age at which there was stabilization of volume growth curves over time and an increase in density and heating power (wood retraction).