bluuebunny/crossref_metadata_2025 huggingface dataset:
Power Turbine Dynamics: An Evaluation of a Shear-Mounted Elastomeric Damper
Authors: Zorzi E. S. , Walton J. , Cunningham R.
Published: April 2015

The safe and reliable operation of high-speed rotating machinery often requires the use of devices that dissipate undesirable rotor vibrations. As an alternative to the more conventional squeeze-film bearing damper designs, a Viton-70 shear-mounted, elastomeric damper was built and tested in a T-55 power turbine high-speed balancing rig. This application demonstrated, for the first time, the feasibility of using elastomers as the primary rotor damping source in production turbine engine hardware. The shear-mounted damper design was selected because of its compatibility with actual gas turbine engine radial space constraints, its accommodation of both the radial and axial thrust loads present in gas turbine engines, and its capability of controlled axial preload. The shear-mounted damper was interchangeable with the production T-55 power turbine roller bearing support so that a direct comparison between the shear damper and the production support structure could be made. Test results showed that the Viton-70 elastomeric damper operated successfully and provided excellent control of both synchronous and nonsynchronous vibrations through all phases of testing to the maximum rotor speed of 1676 rad/s (16,000 rpm). Excellent correlation between the predicted and experienced critical speeds, mode shapes, and log decrements for the power turbine rotor and elastomer damper assembly was also achieved.
Component Synthesis of Multi-Case, Rotating Machinery Trains by the Generalized Receptance Approach
Authors: Palazzolo Alan B. , Wang Bo Ping , Pilkey Walter D.
Published: April 2015

A method is presented for computing the eigenvalues of multicase, coupled, rotating machinery trains. The method is based on a synthesis technique which utilizes generalized receptance formulas, previously derived by the authors. These formulas improve the accuracy of the computed receptances when only an incomplete set of modes is available. A nonsynchronous, gyroscopic, two rotor example is examined to illustrate the synthesis procedure.
On-Line Calibration Technique for Laser Diffraction Droplet Sizing Instruments
Authors: Hirleman E. Dan
Published: April 2015

Laser diffraction (forward scattering) methods for sizing fuel spray droplets in gas turbine applications have been utilized for many years, but a continuing inconvenience with these and all particle sizing techniques is the problem of calibration. This paper discusses the use of photomask reticles to provide a simple, reproducible calibration standard for particle/droplet sizing instruments based on diffraction or imaging methods. Experimental results obtained with prototype standards are presented as well.
Thermodynamic Models for Pipeline Gas Turbine Diagnostics
Authors: Saravanamuttoo H. I. H. , MacIsaac B. D.
Published: April 2015

Thermodynamic models suitable for use as diagnostic tools for pipeline gas turbines have been developed. A basic requirement was the prediction of the performance of gas turbines subject to in-service deterioration, including effects such as compressor fouling, foreign object damage and turbine damage. This was met by creating thermodynamic models capable of operation over the complete running range expected, with a provision for introducing arbitrarily controlled degradations. Models for a variety of types of gas turbines currently in pipeline use have been tested, demonstrating good agreement with user experience. The models are extremely flexible in use and may be used either for investigation of specific problems or to increase user understanding of operating problems.
Measurements of Secondary Flows Within a Cascade of Curved Blades and in the Wake of the Cascade
Authors: Lasser Ronald , Rouleau Wilfred T.
Published: April 2015

A laser-Doppler anemometer was used to measure the three-dimensional velocity field within a typical turbine blade cascade. The blades had a 12.7 cm chord, a turning angle of 104.8°, and a shape conforming to the camber line of a commercial turboexpander. The cascade was operated at a Reynolds number of 1.25×105. Strong secondary velocities, ranging up to 35 percent of the primary flow velocity, were found, resulting from the development of counter-rotating vortices within the blade passages. Large midspan velocity defects in the primary flow were coincident with these high secondary flows. The secondary flow persisted throughout the near wake region.
Testing and Evaluation of a Water-Cooled Gas Turbine Nozzle
Authors: Schilke P. W. , DeGeorge C. L.
Published: April 2015

This paper describes the final phase of testing and evaluation of the second stage monometallic water-cooled nozzles for the Department of Energy-funded High-Temperature Turbine Technology (HTTT) program. Earlier papers described the materials and process development work and the fabrication and initial testing of these nozzles. The additional testing of these nozzles in a static hot-gas path development test stand is described, and the results of this testing are discussed in terms of the component design goals. Evaluation of these nozzles after testing, including nondestructive and destructive examination is described in detail.
STOL Fighter Technology Program
Authors: Selegan David R.
Published: April 2015

In recent years, the Air Force has provided additional funds to investigate the technologies and problems associated with providing fighters a Short Take Off and Landing (STOL) capability without seriously degrading today’s maneuver, load, and cruise performance. Within the Flight Dynamics Laboratory, this technology thrust has been planned and organized under the title of “Runway Independence.”

The thrust is multi-disciplined in that the following technologies are being investigated both singularly and in integrated combinations to quantify their contribution to providing options in solving the STOL design task. These technologies are: aerodynamics, integrated controls, thrust vectoring/reversing exhaust nozzles, landing gear, and cockpit aids and controllers necessary to operate under weather and/or at night.

To help focus these technology efforts and to mature existing technology, the STOL Technology Fighter program was formulated. The objective of the program is to flight validate and mature near-term advanced technologies applicable to providing a STOL capability without sacrificing today’s maneuver, cruise or dash performance. Specific technologies to be addressed in this program are: two-dimensional thrust vectoring/reversing exhaust nozzle; integrated flight/propulsion control; advanced high lift systems; rough/soft field landing gear; and cockpit aids and controllers necessary to locate and land a fighter on the usable portion of the runway at night and in weather.

The program will either modify an existing fighter like the F-15, F-16 or F-18 or build a hybrid vehicle like the X-29 with these technologies integrated into the vehicle. The contract will be awarded in 1983 with first flight in late 1987. The end objective of the program is to demonstrate take offs and landings under wet runway conditions of under 1500 feet including dispersion. This paper discusses the integration of these technologies into a total flight program.
Development of the Single Crystal Alloys CM SX-2 and CM SX-3 for Advanced Technology Turbine Engines
Authors: Harris K. , Erickson G. L. , Schwer R. E.
Published: April 2015

Two complementary single crystal alloys have been developed from the MAR-M-247 composition, with the objectives of providing high creep-rupture strength, excellent oxidation resistance, good castability, practical solution heat-treatment ranges, high incipient melting points, and stable microstructures. The alloys, CM SX-2 and CM SX-3, are turbine blade and vane alloys, with CM SX-3 showing improved coated oxidation and corrosion resistance. Foundry performance characteristics studied using ten different single crystal casting processes to produce both solid and complex cored, thin-wall turbine blade and vane components were: “freckling” sensitivity, spurious grain formation, microporosity, and alloy/ceramic core reactions. Practical solution heat-treatment ranges (difference between the γ′ solvus and the incipient melting temperatures) have been established and vary from 45–50°F for CM SX-3 and 50–55°F for CM SX-2 measured without prior homogenization treatments. Extensive machined-from-blade (MFB) mechanical property work is reported. Alloy stability investigations were undertaken using prior tested MFB stress-rupture specimens. Environmental evaluations using both bare and coated single crystal specimens, subjected to separate cyclic/dynamic oxidation, and corrosion testing in burner-type rigs are also reviewed. A new γ′ microstructure/heat-treatment technology has been found to be particularly applicable to CM SX-2 and CM SX-3 alloys, because of their low γ/γ′ mismatch and suitable γ′ chemistry. This technology further increases the creep-rupture capability of both alloys by 10–40°F, depending on test temperature.
AFB Technology for Indirect-Fired Gas Turbine/Cogeneration Systems
Authors: Tignac L. L. , Campbell J.
Published: April 2015

The technology involved in coal-fired atmospheric fluidized bed (AFB) air heaters for indirect-fired gas turbine cogeneration systems differs in several respects from that already employed for AFB steam boilers. This paper presents the results to data from on ongoing research program aimed at adopting the AFB boiler firing concept to air heater service. A coal-fired air heater program has been underway since 1980 with an 18- by 18-inch AFB experimental unit. The goal is to resolve those technical issues of special importance to the indirect-fired gas turbine application which are amenable to resolution with short-term testing and small-scale hardware. The issues presently being researched include throttling to loads as low as 20 percent, safety accommodating sudden changes in load (and the interruption in cooling resulting from a turbine trip) and establishing the response characteristics of the AFB combustor/heat exchanger system as they relate to overall control system design. Other issues being evaluated include exploration of the limits of acceptable operation.

The 18- by 18-inch AFB heater test facility is located at the Rockwell Thermodynamics Laboratory in California. A series of coal-burning tests of 12 to 24 hours duration have been conducted to establish the bed operating and heat transfer characteristics at loads between 20 and 135 percent of nominal. Control transient characteristics have been evaluated through simulated load changes and interruption of cooling. Heat exchanger material specimen probes and diagnostic probes for investigation of the corrosion/erosion aspects of heat exchanger materials have been exposed. Results to date indicate that an AFB combustion system will provide a good match to the demands of an indirect-fired gas turbine system.
Ultra-Low NOx Combustor Concept for Methanol Firing
Authors: Smith Kenneth O.
Published: April 2015

An experimental study was conducted to assess the feasibility of achieving ultra-low NOx emissions <10 ppm) from a gas turbine through methanol firing. Baseline tests of a Saturn gas turbine generator set (800 kW) on methanol and natural gas and subscale rig tests of an advanced burner concept were conducted. Methanol fueling of the Saturn gas turbine reduced design point NOx emissions by 63 percent. The advanced combustor tests demonstrated that NOx emissions of 9 ppm (an 86% reduction) could be achieved with methanol at simulated engine design point conditions. The advanced burner was characterized by low CO and hydrocarbon emissions at full load. At part load, NOx levels remained low but CO and unburned hydrocarbons increased.
Low-Solidity Tandem-Cascade Diffusers for Wide-Flow-Range Centrifugal Blowers
Authors: Senoo Yasutoshi , Hayami Hiroshi , Ueki Hironobu
Published: April 2015

The pressure recovery of a low-solidity circular cascade diffuser of a centrifugal blower was predicted by a simple method combining a theory of circular cascade diffusers and that of vaneless diffusers and it was compared with a series of experiments. Furthermore the stall limit of the diffuser was studied. In order to improve the performance further, a series of tandem-cascade diffusers were tested. In these diffusers, the front row of the cascade was designed for a small flow rate while the rear row of the cascade was designed for a large flow rate so that the tandem cascade would accomplish good pressure recovery in a wide range of flow rate. Experimental results showed that the operating range was as wide as that of a vaneless diffuser and the pressure recovery was excellent at a small flow rate while it was somewhat better than that in a vaneless diffuser at a large flow rate.
Film Cooling With Steam Injection Through Three Staggered Rows of Inclined Holes Over a Straight Airfoil
Authors: Conklin G. E. , Han J. C. , Jenkins P. E.
Published: April 2015

Experiments have been performed to investigate the film cooling characteristics of steam injection through three staggered rows of 60 degree inclined holes over a straight aluminum airfoil with a circular leading edge. The axial distance between cooling hole rows is five hole diameters. The lateral distance is four hole diameters. Data have been taken for the local film cooling effectiveness of steam and air with blowing rates varying from 0.3 to 1.8. It shows that at small blowing rates, steam has an effectiveness up to 2.5 times greater than air; but, as the blowing rates are increased, the difference between the steam and air effectiveness is gradually decreased. It also shows that the steam effectiveness is less dependent upon the blowing rates than is the air effectiveness. The results generally support the previous analytical prediction.
Pressure Recovery of Collectors With Annular Curved Diffusers
Authors: Senoo Yasutoshi , Kawaguchi Nobumasa
Published: April 2015

Pressure recovery is examined for axisymmetric annular curved diffusers with various values of inlet/exit area ratio. The conditions of inlet flow include three swirl angles and two values of boundary layer blockage. Then, one of the diffuser is connected to two types of collectors with different size. The discharge pressure is decreased by the collector. The cause is not deterioration of diffuser performance due to asymmetric pressure distribution but formation of a cork screw type vortex flow inside the collector. An attempt to retard the vortex motion was successful by inserting obstructions in the collector. If a large size collector is used together with proper obstructions inside the collector, pressure-rise is possible in the collector rather than pressure drop.
A Small Engine High Temperature Core Research Programme
Authors: Burgess A. W.
Published: April 2015

A general description of a small engine high temperature research vehicle is presented along with other aspects of the associated programme directed primarily towards the investigation of an air cooled turbine system. The general philosophy and style of the programme is discussed and comparisons made with alternative approaches. The instrumentation used is detailed along with a brief review of the test facility and data retrieval system. The presentation of engine design features and results is limited due to the classified nature of the work. The project is reviewed in the light of the 5 years test experience gained.
Techniques for Obtaining Detailed Heat Transfer Coefficient Measurements Within Gas Turbine Blade and Vane Cooling Passages
Authors: Clifford R. J. , Jones T. V. , Dunne S. T.
Published: April 2015

This paper reviews the techniques developed jointly by Rolls-Royce Bristol and Oxford University for determining detailed heat transfer coefficient distributions inside turbine blade and vane cooling passages.

These techniques make use of a low temperature phase change paint to map the heat flux distributions within models of the cooling passages. The paints change from an opaque coating to a clear liquid at a well defined melting point.

Thus, the surface temperature history of a model subjected to transient convective heating is recorded. From this history the heat transfer coefficient distribution is deduced using a transient conduction analysis within the model. The general method may be applied to a range of model thicknesses and geometries. The Rolls-Royce data are usually obtained from the inner surface of thick walled models whereas the Oxford measurements are performed on the outside of thin walls.

Results are presented for the detailed heat transfer coefficient distributions within a variety of cooling passages. Firstly, smooth ducts of circular cross section are considered and serve the purpose of validating the experimental techniques. Secondly, results for complex passages with varying cross-sectional area are presented, and the effect of introducing discrete roughness elements and film cooling exhausts into these ducts assessed. Finally, data obtained from a comprehensive examination of a typical engine multi-pass cooling geometry are presented.
Retrofitting a 100,000 HP Simple Cycle Gas Turbine Compressor Station With Regenerators
Authors: Klyn Arjo , Wylens Hans
Published: April 2015

In its gas transport system N.V. Nederlandse Gasunie found a shift from peak load to base load at stations which were not originally designed for that duty. A study was made of the application of recuperators on GE frame 5 gas turbines, based on experience with a prototype installation four years ago. The paper describes the Breda-regenerator in general and the experience of one of the two prototypes which was installed on a Gasunie frame 5 two shaft 24 mW gas turbine compressor unit in 1978. In June 1981 Gasunie decided to equip two more identical gas turbine compressor units at their 100,000 HP compressor station at Zweekhorst with Breda-regenerators. The paper covers all aspects of retrofitting the simple cycle gas turbine installations with regenerators at the Zweekhorst station.
Numerical simulation of an atmospheric pressure RF-driven plasma needle and heat transfer to adjacent human skin using COMSOL
Authors: Schröder Maximilian , Ochoa Angel , Breitkopf Cornelia
Published: April 2015

Plasma medicine is an emerging field where plasma physics is used for therapeutical applications. Temperature is an important factor to take into account with respect to the applications of plasma to biological systems. During the treatment, the tissue temperature could increase to critical values. In this work, a model is presented, which is capable of predicting the skin temperature during a treatment with a radio frequency driven plasma needle. The main gas was helium. To achieve this, a discharge model was coupled to a heat transfer and fluid flow model. The results provide maximum application times for different power depositions in order to avoid reaching critical skin temperatures.
Sarcomere Disruptions of Slow Fiber Resulting From Mountain Ultramarathon
Authors: Carmona Gerard , Roca Emma , Guerrero Mario , Cussó Roser , Irurtia Alfredo , Nescolarde Lexa , Brotons Daniel , Bedini Josep L. , Cadefau Joan A.
Published: April 2015

Objective:

To investigate changes after a mountain ultramarathon (MUM) in the serum concentration of fast (FM) and slow (SM) myosin isoforms, which are fiber-type-specific sarcomere proteins. The changes were compared against creatine kinase (CK), a widely used fiber-sarcolemma-damage biomarker, and cardiac troponin I (cTnI), a widely used cardiac biomarker.

Methods:

Observational comparison of response in a single group of 8 endurance-trained amateur athletes. Time-related changes in serum levels of CK, cTnI, SM, and FM from competitors were analyzed before, 1 h after the MUM, and 24 and 48 h after the start of the MUM by 1-way ANOVA for repeated measures or Friedman and Wilcoxon tests. Pearson correlation coefficient was employed to examine associations between variables.

Results:

While SM was significantly (P = .009) increased in serum 24 h after the beginning of the MUM, FM and cTnI did not change significantly. Serum CK activity peak was observed 1 h after the MUM (P = .002). Moreover, serum peaks of CK and SM were highly correlated (r = .884, P = .004).

Conclusions:

Since there is evidence of muscle damage after prolonged mountain running, the increase in SM serum concentration after a MUM could be indirect evidence of slow- (type I) fiber-specific sarcomere disruptions.
Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy
Authors: So Jonathan , Pasculescu Adrian , Dai Anna Y. , Williton Kelly , James Andrew , Nguyen Vivian , Creixell Pau , Schoof Erwin M. , Sinclair John , Barrios-Rodiles Miriam , Gu Jun , Krizus Aldis , Williams Ryan , Olhovsky Marina , Dennis James W. , Wrana Jeffrey L. , Linding Rune , Jorgensen Claus , Pawson Tony , Colwill Karen
Published: April 2015

Analysis of kinase signaling involved in TRAIL-induced cell death highlights potential targets for combination cancer therapy.
Deacylated Wnt forms inactive oligomers
Authors: VanHook Annalisa M.
Published: April 2015

Notum antagonizes Wnt signaling by depalmitoleoylating Wnt.
Switched on by metal
Authors: Gough Nancy R.
Published: April 2015

Riboswitches for Ni
2+
and Co
2+
and for Mn
2+
control production of proteins that prevent metal toxicity in bacteria.
Donor monocytes suppress graft-versus-host disease
Authors: Gough Nancy R.
Published: April 2015

G-SCF–mobilized CD34
+
monocytes inhibit graft-versus-host disease by producing nitric oxide and inducing regulatory T cells.
Imatinib holds adenomas in check
Authors: Smith Orla
Published: April 2015

Imatinib, an inhibitor of the kinase cAbl, reduces intestinal tumor initiation and growth.
Impact of Combination Antimicrobial Therapy on Mortality Risk for Critically Ill Patients with Carbapenem-Resistant Bacteremia
Authors: Bass Stephanie N. , Bauer Seth R. , Neuner Elizabeth A. , Lam Simon W.
Published: April 2015

There are limited treatment options for carbapenem-resistant Gram-negative infections. Currently, there are suggestions in the literature that combination therapy should be used, which frequently includes antibiotics to which the causative pathogen demonstrates
in vitro
resistance. This case-control study evaluated risk factors associated with all-cause mortality rates for critically ill patients with carbapenem-resistant Gram-negative bacteremia. Adult patients who were admitted to an intensive care unit with sepsis and a blood culture positive for Gram-negative bacteria resistant to a carbapenem were included. Patients with polymicrobial, recurrent, or breakthrough infections were excluded. Included patients were classified as survivors (controls) or nonsurvivors (cases) at 30 days after the positive blood culture. Of 302 patients screened, 168 patients were included, of whom 90 patients died (53.6% [cases]) and 78 survived (46.4% [controls]) at 30 days. More survivors received appropriate antibiotics (antibiotics with
in vitro
activity) than did nonsurvivors (93.6% versus 53.3%;
P
< 0.01). Combination therapy, defined as multiple appropriate agents given for 48 h or more, was more common among survivors than nonsurvivors (32.1% versus 7.8%;
P
< 0.01); however, there was no difference in multiple-agent use when
in vitro
activity was not considered (including combinations with carbapenems) (87.2% versus 80%;
P
= 0.21). After adjustment for baseline factors with multivariable logistic regression, combination therapy was independently associated with decreased risk of death (odds ratio, 0.19 [95% confidence interval, 0.06 to 0.56];
P
< 0.01). These data suggest that combination therapy with multiple agents with
in vitro
activity is associated with improved survival rates for critically ill patients with carbapenem-resistant Gram-negative bacteremia. However, that association is lost if
in vitro
activity is not considered.
Open-Label, Single-Dose, Parallel-Group Study in Healthy Volunteers To Determine the Drug-Drug Interaction Potential between KAE609 (Cipargamin) and Piperaquine
Authors: Stein Daniel S. , Jain Jay Prakash , Kangas Michael , Lefèvre Gilbert , Machineni Surendra , Griffin Paul , Lickliter Jason
Published: April 2015

KAE609 represents a new class of potent, fast-acting, schizonticidal antimalarials. This study investigated the safety and pharmacokinetics of KAE609 in combination with the long-acting antimalarial piperaquine (PPQ) in healthy volunteers. A two-way pharmacokinetic interaction was hypothesized for KAE609 and PPQ, as both drugs are CYP3A4 substrates and inhibitors. The potential for both agents to affect the QT interval was also assessed. This was an open-label, parallel-group, single-dose study with healthy volunteers. Subjects were randomized to four parallel dosing arms with five cohorts (2:2:2:2:1), receiving 75 mg KAE609 plus 320 mg PPQ, 25 mg KAE609 plus 1,280 mg PPQ, 25 mg KAE609 alone, 320 mg PPQ alone, or 1,280 mg PPQ alone. Triplicate electrocardiograms were performed over the first 24 h after dosing, with single electrocardiograms at other time points. Routine safety (up to 89 days) and pharmacokinetic (up to 61 days) assessments were performed. Of the 110 subjects recruited, 99 completed the study. Coadministration of PPQ had no overall effect on exposure to KAE609, although 1,280 mg PPQ decreased the KAE609 maximum concentration (
C
max
) by 17%. The group that received 25 mg KAE609 plus 1,280 mg PPQ showed a 32% increase in the PPQ area under the concentration-time curve from 0 to infinity (AUC
inf
), while the group that received 75 mg KAE609 plus 320 mg PPQ showed a 14% reduction. Mean changes from baseline in the QT interval corrected by Fridericia's method (QTcF) and the QT interval corrected by Bazett's method (QTcB) with PPQ were consistent with its known effects. PPQ but not KAE609 exposure correlated with corrected QT interval (QTc) increases, and KAE609 did not affect the PPQ exposure-QTc relationship. The QTcF effect for PPQ (least-squares estimate of the difference in mean maximal changes from baseline of 7.47 ms [90% confidence interval, 3.55 to 11.4 ms]) was consistent with the criteria for a positive thorough QT study. No subject had QTcF or QTcB values of >500 ms. Both drugs given alone or in combination were well tolerated, with no deaths, serious adverse events (AEs), or severe AEs reported. Most AEs were mild; upper respiratory tract infections, headache, diarrhea, and oropharyngeal pain were most common. PPQ and KAE609 coadministration had no relevant effect on exposure to either agent, and KAE609 did not affect or potentiate the known effects of PPQ on cardiac conduction.
Characterization of Multiple NDM-1-Producing Enterobacteriaceae Isolates from the Same Patient
Authors: Tijet Nathalie , Richardson David , MacMullin Gregory , Patel Samir N. , Melano Roberto G.
Published: April 2015

A male patient was admitted to a community hospital in Ontario, Canada, with an infected sacral ulcer after returning from India, where he was hospitalized. Carbapenem-resistant
Escherichia coli
(isolated from blood cultures),
Enterobacter cloacae
, and
Providencia stuartii
(from urine samples), all positive for
bla
NDM-1
, were recovered. Comparative NDM-1 plasmid analysis suggests both lateral plasmid transfer and independent acquisition of the
bla
NDM-1
gene in these clinical isolates.
The Sheep as a Model of Preclinical Safety and Pharmacokinetic Evaluations of Candidate Microbicides
Authors: Holt Jonathon D. S. , Cameron David , Dias Nicola , Holding Jeremy , Muntendam Alex , Oostebring Freddy , Dreier Peter , Rohan Lisa , Nuttall Jeremy
Published: April 2015

When developing novel microbicide products for the prevention of HIV infection, the preclinical safety program must evaluate not only the active pharmaceutical ingredient but also the product itself. To that end, we applied several relatively standard toxicology study methodologies to female sheep, incorporating an assessment of the pharmacokinetics, safety, tolerability, and local toxicity of a dapivirine-containing human vaginal ring formulation (Dapivirine Vaginal Ring-004). We performed a 3-month general toxicology study, a preliminary pharmacokinetic study using drug-loaded vaginal gel, and a detailed assessment of the kinetics of dapivirine delivery to plasma, vaginal, and rectal fluid and rectal, vaginal, and cervical tissue over 28 days of exposure and 3 and 7 days after removal of the ring. The findings of the general toxicology study supported the existing data from both preclinical and clinical studies in that there were no signs of toxicity related to dapivirine. In addition, the presence of the physical dapivirine ring did not alter local or systemic toxicity or the pharmacokinetics of dapivirine. Pharmacokinetic studies indicated that the dapivirine ring produced significant vaginal tissue levels of dapivirine. However, no dapivirine was detected in cervical tissue samples using the methods described here. Plasma and vaginal fluid levels were lower than those in previous clinical studies, while there were detectable dapivirine levels in the rectal tissue and fluid. All tissue and fluid levels tailed off rapidly to undetectable levels following removal of the ring. The sheep represents a very useful model for the assessment of the safety and pharmacokinetics of microbicide drug delivery devices, such as the vaginal ring.
A Pantetheinase-Resistant Pantothenamide with Potent, On-Target, and Selective Antiplasmodial Activity
Authors: Macuamule Cristiano J. , Tjhin Erick T. , Jana Collins E. , Barnard Leanne , Koekemoer Lizbé , de Villiers Marianne , Saliba Kevin J. , Strauss Erick
Published: April 2015

Pantothenamides inhibit blood-stage
Plasmodium falciparum
with potencies (50% inhibitory concentration [IC
50
], ∼20 nM) similar to that of chloroquine. They target processes dependent on pantothenate, a precursor of the essential metabolic cofactor coenzyme A. However, their antiplasmodial activity is reduced due to degradation by serum pantetheinase. Minor modification of the pantothenamide structure led to the identification of α-methyl-
N
-phenethyl-pantothenamide, a pantothenamide resistant to degradation, with excellent antiplasmodial activity (IC
50
, 52 ± 6 nM), target specificity, and low toxicity.
Profiling of β-Lactam Selectivity for Penicillin-Binding Proteins in Streptococcus pneumoniae D39
Authors: Kocaoglu Ozden , Tsui Ho-Ching T. , Winkler Malcolm E. , Carlson Erin E.
Published: April 2015

Selective fluorescent β-lactam chemical probes enable the visualization of the transpeptidase activity of penicillin-binding proteins (PBPs) at different stages of bacterial cell division. To facilitate the development of new fluorescent probes for PBP imaging, we evaluated 20 commercially available β-lactams for selective PBP inhibition in an unencapsulated derivative of the D39 strain of
Streptococcus pneumoniae
. Live cells were treated with β-lactam antibiotics at different concentrations and subsequently incubated with Bocillin FL (Boc-FL; fluorescent penicillin) to saturate uninhibited PBPs. Fluorophore-labeled PBPs were visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and fluorescence scanning. Among 20 compounds tested, carbapenems (doripenem and meropenem) were coselective for PBP1a, PBP2x, and PBP3, while six of the nine penicillin compounds were coselective for PBP2x and PBP3. In contrast, the seven cephalosporin compounds tested display variability in their PBP-binding profiles. Three cephalosporin compounds (cefoxitin, cephalexin, and cefsulodin) and the monobactam aztreonam exhibited selectivity for PBP3, while only cefuroxime (a cephalosporin) was selective for PBP2x. Treatment of
S. pneumoniae
cultures with a sublethal concentration of cefuroxime that inhibited 60% of PBP2x activity and less than 20% of the activity of other PBPs resulted in formation of elongated cells. In contrast, treatment of
S. pneumoniae
cultures with concentrations of aztreonam and cefoxitin that inhibited up to 70% of PBP3 activity and less than 30% of other PBPs resulted in no discernible morphological changes. Additionally, correlation of the MIC and IC
50
s for each PBP, with the exception of faropenem, amdinocillin (mecillinam), and 6-APA, suggests that pneumococcal growth inhibition is primarily due to the inhibition of PBP2x.
Complete Genome Sequence of Lactobacillus plantarum Strain B21, a Bacteriocin-Producing Strain Isolated from Vietnamese Fermented Sausage Nem Chua
Authors: Golneshin Aida , Adetutu Eric , Ball Andrew S. , May Bee K. , Van Thi Thu Hao , Smith Andrew T.
Published: April 2015

Lactobacillus plantarum
strain B21 was isolated from Vietnamese sausage (nem chua) and demonstrated broad antimicrobial activity due to the production of bacteriocins. Here, we report the complete genome sequence of this strain (3,284,260 bp).
Genome Sequence of Fungal Species No.11243, Which Produces the Antifungal Antibiotic FR901469
Authors: Matsui Makoto , Yokoyama Tatsuya , Nemoto Kaoru , Kumagai Toshitaka , Terai Goro , Arita Masanori , Machida Masayuki , Shibata Takashi
Published: April 2015

Fungal species No.11243 was originally isolated from a decayed leaf sample collected in Kyoto, Japan. It produces FR901469, a 1,3-beta-glucan synthase inhibitor. The genome sequence of No.11243 was determined and annotated to obtain useful information for improving productivity of the effective antifungal agent FR901469.
A Distinct Group II Alphabaculovirus Isolated from a Peridroma Species
Authors: Rohrmann George F. , Erlandson Martin A. , Theilmann David A.
Published: April 2015

The genome sequence of an alphabaculovirus isolated from a Peridroma species indicated that it is a novel member of a group II lineage most closely related to alphabaculoviruses from
Spodoptera exigua
and Agrotis segetum. It contains a genome of 151,110 nucleotides (nt), with a G+C content of 53.3%.
Genome Sequence of the Butyrate
-
Producing Anaerobic Bacterium Anaerostipes hadrus PEL 85
Authors: Kant Ravi , Rasinkangas Pia , Satokari Reetta , Pietilä Taija E. , Palva Airi
Published: April 2015

Anaerostipes hadrus
PEL 85, which was isolated from human feces, is a Gram-positive rod-shaped bacterium. The species may play an important role in gut health, as it was previously reported to produce butyric acid. Here, we present the genome assembly of PEL 85, a novel strain of A. hadrus.
Deciphering the Genome Sequences of the Hydrophobic Cyanobacterium Scytonema tolypothrichoides VB-61278
Authors: Das Abhishek , Panda Arijit , Singh Deeksha , Chandrababunaidu Mathu Malar , Mishra Gyan Prakash , Bhan Sushma , Adhikary Siba Prasad , Tripathy Sucheta
Published: April 2015

Scytonema tolypothrichoides VB-61278, a terrestrial cyanobacterium, can be exploited to produce commercially important products. Here, we report for the first time a 10-Mb draft genome assembly of S. tolypothrichoides VB-61278, with 214 scaffolds and 7,148 putative protein-coding genes.
Draft Genome Sequence of Aneurinibacillus migulanus NCTC 7096
Authors: Alenezi Faizah N. , Weitz Hedda J. , Belbahri Lassaad , Nidhal Jedidi , Luptakova Lenka , Jaspars Marcel , Woodward Stephen
Published: April 2015

Aneurinibacillus migulanus
has biocontrol activities against fungal, fungus-like, and bacterial plant pathogens with different levels of efficacy depending on the target pathogens. Here, we report the high-quality draft genome sequence of A. migulanus NCTC 7096.
Draft Genome Sequence of Empedobacter (Formerly Wautersiella) falsenii comb. nov. Wf282, a Strain Isolated from a Cervical Neck Abscess
Authors: Traglia German Matías , Dixon Chelsea , Chiem Kevin , Almuzara Marisa , Barberis Claudia , Montaña Sabrina , Merino Cindy , Mussi María Alejandra , Tolmasky Marcelo E. , Iriarte Andres , Vay Carlos , Ramírez María Soledad
Published: April 2015

Empedobacter (formerly Wautersiella) falsenii comb. nov. strain Wf282 was isolated from a cervical neck abscess sample from an 18-year-old female patient. The isolate was resistant to many antibiotics, including meropenem and colistin. The total DNA from the multidrug-resistant E. falsenii comb. nov. Wf282 clinical isolate was sequenced.
Draft Genome Sequence of Pseudomonas sp. nov. H2
Authors: Loftie-Eaton Wesley , Suzuki Haruo , Bashford Kelsie , Heuer Holger , Stragier Pieter , De Vos Paul , Settles Matthew L. , Top Eva M.
Published: April 2015

We report the draft genome sequence of Pseudomonas sp. nov. H2, isolated from creek sediment in Moscow, ID, USA. The strain is most closely related to
Pseudomonas putida
. However, it has a slightly smaller genome that appears to have been impacted by horizontal gene transfer and poorly maintains IncP-1 plasmids.
Genome of Pseudomonas sp. FeS53a, a Putative Plant Growth-Promoting Bacterium Associated with Rice Grown in Iron-Stressed Soils
Authors: de Souza Rocheli , Sant’Anna Fernando Hayashi , Ambrosini Adriana , Tadra-Sfeir Michele , Faoro Helisson , Pedrosa Fabio Oliveira , Souza Emanuel Maltempi , Passaglia Luciane M. P.
Published: April 2015

Pseudomonas sp. FeS53a was isolated from the roots of rice plants cultivated in one area with a well-established history of iron toxicity. The FeS53a genome sequence provides the genetic basis for understanding its lifestyle and survival in association with rice in conditions of iron toxicity.
Draft Genome Sequence of Streptomyces sp. Strain 150FB, a Mushroom Mycoparasite Antagonist
Authors: Tarkka M. T. , Feldhahn L. , Krüger D. , Arnold N. , Buscot F. , Wubet T.
Published: April 2015

Streptomyces sp. strain 150FB, isolated from the cap surface of a bolete mushroom, inhibits the growth of the mycoparasitic
Sepedonium
species. Functional annotation of the strain 150FB draft genome identified 22 putative secondary metabolite biosynthetic gene clusters and genes encoding secreted proteins, which may contribute to the inhibition of the mycoparasite.
Selective Requirement of the Shikimate Pathway of Legionella pneumophila for Intravacuolar Growth within Human Macrophages but Not within Acanthamoeba
Authors: Jones Snake C. , Price Christopher T. D. , Santic Marina , Abu Kwaik Yousef
Published: April 2015

Legionella pneumophila
utilizes the Dot/Icm type IV translocation system to proliferate within a vacuole in a wide variety of natural amoebal hosts and in alveolar macrophages of the human accidental host. Although
L. pneumophila
utilizes host amino acids as the main sources of carbon and energy, it is not known whether
de novo
synthesis of amino acids by intravacuolar
L. pneumophila
contributes to its nutrition. The
aroB
and
aroE
genes encode enzymes for the shikimate pathway that generates the aromatic amino acids Phe, Trp, and Tyr. Here we show the
aroB
and
aroE
mutants of
L. pneumophila
to be defective in growth in human monocyte-derived macrophages (hMDMs) but not in
Acanthamoeba
spp. The
aroB
and
aroE
mutants are severely attenuated in intrapulmonary proliferation in the A/J mouse model of Legionnaires' disease, and the defect is fully complemented by the respective wild-type alleles. The two mutants grow normally in rich media but do not grow in defined media lacking aromatic amino acids, and the growth defect is rescued by inclusion of the aromatic amino acids, which are essential for production of the pyomelanin pigment. Interestingly, supplementation of infected hMDMs with the three aromatic amino acids or with Trp alone rescues the intramacrophage defect of the
aroE
but not the
aroB
mutant. Therefore, the shikimate pathway of
L. pneumophila
is differentially required for optimal growth within human macrophages, which are auxotrophic for Trp and Phe, but is dispensable for growth within the
Acanthamoeba
spp. that synthesize the aromatic amino acids.
Mechanisms of Inflammasome Activation by Vibrio cholerae Secreted Toxins Vary with Strain Biotype
Authors: Queen Jessica , Agarwal Shivani , Dolores Jazel S. , Stehlik Christian , Satchell Karla J. F.
Published: April 2015

Activation of inflammasomes is an important aspect of innate immune responses to bacterial infection. Recent studies have linked
Vibrio cholerae
secreted toxins to inflammasome activation by using murine macrophages. To increase relevance to human infection, studies of inflammasome-dependent cytokine secretion were conducted with the human THP-1 monocytic cell line and corroborated in primary human peripheral blood mononuclear cells (PBMCs). Both El Tor and classical strains of
V. cholerae
activated ASC (apoptosis-associated speck-like protein-containing a CARD domain)-dependent release of interleukin-1β (IL-1β) when cultured with human THP-1 cells, but the pattern of induction was distinct, depending on the repertoire of toxins the strains produced. El Tor biotype strains induced release of IL-1β dependent on NOD-like receptor family pyrin domain-containing 3 (NLRP3) and ASC due to the secreted pore-forming toxin hemolysin. Unlike in studies with mouse macrophages, the MARTX toxin did not contribute to IL-1β release from human monocytic cells. Classical biotype strains, which do not produce either hemolysin or the MARTX toxin, activated low-level IL-1β release that was induced by cholera toxin (CT) and dependent on ASC but independent of NLRP3 and pyroptosis. El Tor strains likewise showed increased IL-1β production dependent on CT when the hemolysin gene was deleted. In contrast to studies with murine macrophages, this phenotype was dependent on a catalytically active CT A subunit capable of inducing production of cyclic AMP and not on the B subunit. These studies demonstrate that the induction of the inflammasome in human THP-1 monocytes and in PBMCs by
V. cholerae
varies with the biotype and is mediated by both NLRP3-dependent and -independent pathways.
AMA1-Deficient Toxoplasma gondii Parasites Transiently Colonize Mice and Trigger an Innate Immune Response That Leads to Long-Lasting Protective Immunity
Authors: Lagal Vanessa , Dinis Márcia , Cannella Dominique , Bargieri Daniel , Gonzalez Virginie , Andenmatten Nicole , Meissner Markus , Tardieux Isabelle
Published: April 2015

The apical membrane antigen 1 (AMA1) protein was believed to be essential for the perpetuation of two Apicomplexa parasite genera,
Plasmodium
and
Toxoplasma
, until we genetically engineered viable parasites lacking
AMA1
. The reduction in invasiveness of the
Toxoplasma gondii
RH-AMA1 knockout (RH-AMA1
KO
) tachyzoite population,
in vitro
, raised key questions about the outcome associated with these tachyzoites once inoculated in the peritoneal cavity of mice. In this study, we used AMNIS technology to simultaneously quantify and image the parasitic process driven by AMA1
KO
tachyzoites. We report their ability to colonize and multiply in mesothelial cells and in both resident and recruited leukocytes. While the RH-AMA1
KO
population amplification is rapidly lethal in immunocompromised mice, it is controlled in immunocompetent hosts, where immune cells in combination sense parasites and secrete proinflammatory cytokines. This innate response further leads to a long-lasting status immunoprotective against a secondary challenge by high inocula of the homologous type I or a distinct type II
T. gondii
genotypes. While AMA1 is definitively not an essential protein for tachyzoite entry and multiplication in host cells, it clearly assists the expansion of parasite population
in vivo
.
Air Pollution Particulate Matter Alters Antimycobacterial Respiratory Epithelium Innate Immunity
Authors: Rivas-Santiago César E. , Sarkar Srijata , Cantarella Pasquale , Osornio-Vargas Álvaro , Quintana-Belmares Raúl , Meng Qingyu , Kirn Thomas J. , Ohman Strickland Pamela , Chow Judith C. , Watson John G. , Torres Martha , Schwander Stephan
Published: April 2015

Inhalation exposure to indoor air pollutants and cigarette smoke increases the risk of developing tuberculosis (TB). Whether exposure to ambient air pollution particulate matter (PM) alters protective human host immune responses againstMycobacterium tuberculosishas been little studied. Here, we examined the effect of PM from Iztapalapa, a municipality of Mexico City, with aerodynamic diameters below 2.5 μm (PM2.5) and 10 μm (PM10) on innate antimycobacterial immune responses in human alveolar type II epithelial cells of the A549 cell line. Exposure to PM2.5or PM10deregulated the ability of the A549 cells to express the antimicrobial peptides human β-defensin 2 (HBD-2) and HBD-3 upon infection withM. tuberculosisand increased intracellularM. tuberculosisgrowth (as measured by CFU count). The observed modulation of antibacterial responsiveness by PM exposure was associated with the induction of senescence in PM-exposed A549 cells and was unrelated to PM-mediated loss of cell viability. Thus, the induction of senescence and downregulation of HBD-2 and HBD-3 expression in respiratory PM-exposed epithelial cells leading to enhancedM. tuberculosisgrowth represent mechanisms by which exposure to air pollution PM may increase the risk ofM. tuberculosisinfection and the development of TB.
Distinct Paths for Basic Amino Acid Export in Escherichia coli: YbjE (LysO) Mediates Export of
l
-Lysine
Authors: Pathania Amit , Sardesai Abhijit A.
Published: April 2015

In
Escherichia coli
,
argO
encodes an exporter for
l
-arginine (Arg) and its toxic analogue canavanine (CAN), and its transcriptional activation and repression, by Arg and
l
-lysine (Lys), respectively, are mediated by the regulator ArgP. Accordingly
argO
and
argP
mutants are CAN supersensitive (CAN
ss
). We report the identification of
ybjE
as a gene encoding a predicted inner membrane protein that mediates export of Lys, and our results confirm the previous identification with a different approach of YbjE as a Lys exporter, reported by Ueda and coworkers (T. Ueda, Y. Nakai, Y. Gunji, R. Takikawa, and Y. Joe, U.S. patents 7,629,142 B2 [December 2009] and 8,383,363 B1 [February 2013] and European patent 1,664,318 B1 [September 2009]).
ybjE
was isolated as a multicopy suppressor of the CAN
ss
phenotype of a strain lacking ArgO. The absence of YbjE did not confer a CAN
ss
phenotype but instead conferred hypersensitivity to the lysine antimetabolite thialysine and led to growth inhibition by the dipeptide lysylalanine, which is associated with elevated cellular Lys content. YbjE overproduction resulted in Lys excretion and syntrophic cross-feeding of a Lys auxotroph. Constitutive overexpression of
argO
promoted Lys cross-feeding that is indicative of a latent Lys export potential of ArgO. Arg modestly repressed
ybjE
transcription in an ArgR-dependent manner, and ArgR displayed Arg-sensitive binding to the
ybjE
promoter region
in vitro
. Our studies suggest that the reciprocal repression of
argO
and
ybjE
, respectively, by Lys and Arg confers the specificity for basic amino acid export by distinct paths and that such cross-repression contributes to maintenance of cytoplasmic Arg/Lys balance. We propose that YbjE be redesignated LysO.

IMPORTANCE
This work ascribes a lysine export function to the product of the
ybjE
gene of
Escherichia coli
, leading to a physiological scenario wherein two proteins, ArgO and YbjE, perform the task of separately exporting arginine and lysine, respectively, which is distinct from that seen for
Corynebacterium glutamicum
, where the ortholog of ArgO, LysE, mediates export of both arginine and lysine. Repression of
argO
transcription by lysine is thought to effect this separation. Accordingly, ArgO mediates lysine export when repression of its transcription by lysine is bypassed. Repression of
ybjE
transcription by arginine via the ArgR repressor, together with the lysine repression of
argO
effected by ArgP, is indicative of a mechanism of maintenance of arginine/lysine balance in
E. coli
.