bluuebunny/crossref_metadata_2025 huggingface dataset:
Transonic Compressor Influences on Upstream Surface Pressures With Axial Spacing
Authors: Koch Peter J. , Probasco Douglas P. , Wolff J. Mitch , Copenhaver William W. , Chriss Randall M.
Published: December 2014

A set of inlet guide vane (IGV) unsteady surface pressure measurements is presented. The unsteady aerodynamic effects of a highly loaded, high speed downstream compression stage on the upstream inlet guide vane stator surface pressures are characterized through experimental and computational analysis. The axial spacing between the IGV and rotor was varied between 12%, 26%, and 56% of the IGV chord for a 105% speed, peak efficiency operating condition, which is transonic. Unsteady IGV surface pressures were acquired for two spanwise locations on both blade surfaces. The largest unsteady surface pressure magnitudes were obtained at the 12% axial spacing configuration and 95% chord location. In general, spanwise variations were found to be important. The upstream bow shock effect is non-linear in character. Comparisons to a two-dimensional, non-linear unsteady multi-blade row Navier-Stokes analysis at 50% span show a good agreement with the IGV unsteady surface pressure results and higher harmonic content. The results of the study indicate significant variations in the IGV unsteady loading caused by changes in axial spacing.
Application of Foil Bearings to Turbomachinery Including Vertical Operation
Authors: Walton James F. , Heshmat Hooshang
Published: December 2014

A review is made of the function of compliant surface bearings in serving the needs of modern turbomachinery. This service extends over a wide spectrum of severe operational and environmental conditions such as extreme low and high temperatures, speeds over 100,000 rpm and the use of cryogenics as lubricants. The importance of using appropriate simulators that duplicate the actual equipment in evaluating the application of compliant bearings is demonstrated via two specific examples; one, a simulator to evaluate bearings for an air cycle machine and another for an advanced cryogenic device. In view of the known difficulties in using hydrodynamic bearings in vertical machines a new preloaded compliant journal bearing design is offered which performs as well with a vertically mounted shaft as it does in horizontal operation. In terms of the location of the first two rigid body criticals the test data show the compliant bearing’s vertical operation to be at most 15% lower than for the horizontal case whereas the maximum vibrational amplitude stayed the same for both modes of operation. This new class of hydrodynamic compliant surface journal bearings now makes possible development of oil-free machines capable of all attitude operation such as aircraft gas turbine engines undergoing severe pitch maneuvers or machines that must be operated vertically due to space constraints.
Determining the Affordability of Advanced Propulsion Systems
Authors: Mehta Paul P. , Evans Jerry W. , Ludwig Arthur L.
Published: December 2014

The Integrated High Performance Turbine Engine Technology (IHPTET) is a joint Air Force, Navy, Army, DARPA, NASA, and industry initiative focused on developing higher performance turbine engines. The goal of IHPTET is to develop and demonstrate propulsion systems that would, by the turn of the century, double propulsion capability (1987 base year). For this reason, IHPTET engines are now test beds for a high number of advanced composites, intermetallics and single crystal alloys. While satisfying the performance requirements, the program has another salient objective of cost reduction.

This paper will discuss an approach for cost estimating and modeling of components and sub-components, and demonstrate the benefits of employing simulations. Traditional approaches have relied on comparative techniques utilizing complexity factors or Cost Estimating Relationships (CER’s). For advanced materials, these approaches are inadequate, primarily due to non-existence of historic data. A further weakness is their inability to identify cost drivers and quantify cost avoidance potential. Process-oriented cost estimating, albeit cumbersome during build-up and requiring detailed knowledge of manufacturing and process technology, provides a stable foundation for development of a comprehensive cost modeling system. Manufacturing Process Flow Simulation (MPFS) aids in evaluating evolving manufacturing processes (in infancy), studying the impact of alternate manufacturing processes and conducting what-if studies. MPFS can then be incorporated selectively into a cost modeling architecture capable of evaluating production cost for sub-components, components, and complete engines.
Performance Modeling as an Aid in the Preparation of a Test Code for IGCC Plants, PTC 47
Authors: Horazak Dennis A. , Archer David H.
Published: December 2014

An ASME performance test code. PTC 47, for integrated gasification combined cycle, IGCC. plants is currently being written. This code will include definitions of the significant overall plant and plant component performance results — input, output, and effectiveness. It will indicate the measurements and measurement techniques required to calculate these results, and estimate systematic uncertainties associated with each measurement, as well as random uncertainties due to the measuring device or variations in plant conditions during the test. The code writing committee is making use of mathematical models of the performance of various IGCC power plant configurations to aid in the work of code preparation and testing.

The objective of this paper is to describe how computerized system performance models are now being used in the preparation of PTC 47, and to indicate how such models might be used in the conduct of performance tests in the future. The general form of a system performance model is discussed to clarify how it relates to correction factors for system performance parameters — input, output, and effectiveness: but the paper does not include defining or solving the actual equations of a system performance model.
The Role of Fuel Moisture in Gas Turbine Processes
Authors: Raiko Markku O. , Raiko Risto A.
Published: December 2014

Imatran Voima (TVO) is the biggest energy producer in Finland. IVO builds, owns and operates several biomass combustion power plants and carries out active R&D work on further development of small-scale biomass and peat-fired power plants. Both conventional power plants based on fluidized bed boilers and future power plants based on gasification are also developed by IVO.

Typically, biomass fuels have high moisture content. High moisture content of fuel has, however, a negative effect on power generation cycles because of higher combustion losses.

IVO has researched and developed a steam drying system for small-scale gasification power plants for the sole domestic fuels peat and biomass. This is described and the experience gained in testing it is briefly reviewed.

The main focus of this paper is the thermal analysis of pressurized steam drying for biomass gasification power plants. Special emphasis is given to the thermal analysis of fuel moisture in alternative power plant processes. Fuel moisture removal is analyzed as a separate process.
A New Technique for Identifying Synchronous Resonances Using Tip-Timing
Authors: Heath S.
Published: December 2014

Non-contact measurement of vibration at turbomachinery rotor blade tips using blade tip-timing has become an industry-standard procedure. Current research focuses on analysis methods for interpretation of the measured vibration data from a limited number of probes. The methods are classified by the form of the vibration they can identify. Identification of asynchronous response amplitude and frequency is well documented. Whilst a method for identifying maximum synchronous resonance amplitude has existed since the early 1970s, there is no published evidence of a method for directly identifying frequency or engine order using a small number of probes. This paper presents a new analysis method for identifying synchronous resonance engine order using two tip-timing vibration measurements. The measurements are made at different locations on the turbomachinery casing using a minimum of two probes. A detailed description of the method and results from its practical application are given. The potential of the method to identify the amplitude and frequency of close modes, not possible with current methods, is demonstrated. The effect of blade mistuning on the accuracy of the method is investigated. Existing synchronous response analysis methods and the new method presented here give the response amplitude and frequency after the resonance has been traversed. Real-time identification of synchronous response amplitude and frequency would allow tip-timing to be used as a safety monitor of all blades. Real-time methods, their limitations and practical application are discussed. The future use of tip-timing as the dominant vibration measurement system is discussed with reference to experience on measurements made solely with tip-timing on assemblies with undefined vibration characteristics.
Active Control of Discrete-Frequency Turbomachinery Noise Using a Rotary-Valve Actuator
Authors: Sawyer Scott D. , Fleeter Sanford
Published: December 2014

Turbomachine discrete-frequency tones, a significant environmental concern, are generated by rotor-stator interactions. Specific spatial modes are generated, but not all generated modes propagate to the far field. It is the propagating spatial modes generated by rotor-stator that represent the community-disturbing far field discrete-frequency noise. Fundamental active airfoil source discrete-frequency noise control experiments are performed, with the active airfoil source control optimized to generate propagating spatial modes to cancel the propagating spatial modes generated by the rotor-stator interaction. These experiments demonstrate the viability and effectiveness of rotary-valve discrete-frequency noise control. Specifically, the active noise control system combines the active airfoil source control with in-duct spatial mode measurement. In this unique design, the active airfoils of the stator vane row are driven by a remote centerbody-mounted rotary-valve system. Propagating spatial mode reductions of 5 dB and 9 dB upstream and downstream with negligible modal spillover are demonstrated.
Forced Vibrations of Frictionally Damped Stator Segments
Authors: Berruti T. , Goglio L. , Filippi S. , Gola M. M.
Published: December 2014

The paper deals with the use of friction among bladed segments to reduce vibrations in turbomachinery. The non-linearity of the phenomenon is included in the analysis after that the detailed finite element model of the segment has been condensed. In the solution search, both numerical integration and harmonic balance method are used. The latter is here extended to the case of slip among parts in relative motion. By means of a sample case it is shown that the simplified harmonic solution can lead to the same results given by time-consuming numerical integration. Some insight on the slipping phenomenon between segments is obtained.
Computation of the Optimal Normal Load of a Friction Damper Under Different Types of Excitation
Authors: Cha D. , Sinha A.
Published: December 2014

In this paper, forced responses of a frictionally damped turbine blade are investigated for three different types of excitation: white noise excitation, narrow band random excitation and deterministic sinusoidal excitation. To determine the steady state nonlinear response, the harmonic balance method is used for sinusoidal excitation, and the equivalent linearization method is used for white noise and narrow band random excitations. Using a new set of nondimensionalized variables, the optimal value of normal load of a friction damper is found to be almost independent of the nature of excitation. The effectiveness of the damper in reducing the vibration level is also examined for the aforementioned three different types of excitation.
Advantages of the LV100 as a Power Producer in a Hybrid Propulsion System for Future Fighting Vehicles
Authors: Koschier Angelo V. , Mauch Hagen R.
Published: December 2014

The core of any hybrid propulsion system is a high power density, low weight, and fuel efficient electric energy producer. The LV100 recuperated turbine engine is such a system. This engine is well suited to provide electric power efficiently at a volume and weight significantly lower than current systems. Originally designed for vehicular use and environment to drive a Hydrokinetic transmission, the turbine’s high output speed lends itself to incorporate into the engine design an advanced generating device.

This LV100 engine-based electric energy producer will provide in excess of 1MW of electric power in a volume of under one cubic meter at a weight of about 2500 pounds at fuel efficiencies comparable to advanced vehicular diesel engines.

Recent state-of-the-art improvements in materials and component technology will permit further reductions in volume/weight and increase the system fuel efficiency.

The technologies required to reach a volume of under one cubic meter, the system performance projections obtainable by technology upgrades and the program achievements to date are discussed.
Impact of Film–Cooling Jets on Turbine Aerodynamic Losses
Authors: Walters Dibbon K. , Leylek James H.
Published: December 2014

This paper documents a computational investigation of the aerodynamic impact of film cooling on a linear turbine airfoil cascade. The simulations were for single row injection on both the pressure and suction surfaces, downstream of the leading edge region. The cases match experimental efforts previously documented in the open literature. Results were obtained for density ratio equal to 1.0 and 2.0, and a blowing ratio range from 0.91 to 6.6. The domain included the passage flow as well as the film-hole and blade interior. The simulation used a dense, high-quality, unstructured hybrid–topology grid, comprised of hexahedra, tetrahedra, prisms and pyramids. The processing was performed with a pressure-correction solution procedure and a second–order discretization scheme. Turbulence closure was obtained using standard, RNG, and “realizable” k-ε models, as well as a Reynolds stress model. Results were compared to experimental data in terms of total pressure loss downstream of the blade row. Flow mechanisms responsible for the variation of aerodynamic losses due to suction and pressure surface coolant injection are documented. The results demonstrate that computational methods can be used to accurately predict losses on film–cooled airfoils.
Second Vane Endwall Heat Transfer Reduction by Iceform Contouring
Authors: LaFleur Ronald S. , Whitten Timothy S. , Araujo Juan A.
Published: December 2014

Endwall heat transfer within high pressure turbines is important in the quest for higher gas turbine combustion temperatures, improved cycle performance and longer part life. In this paper, the iceformation design method was used to reduce endwall heat transfer by contouring the endwall, altering the secondary flows that produce elevated endwall heat transfer load and obtaining an isothermal endwall geometry. Iceformation is analogous to metal melting regions where a hot fluid alters the isothermal surface shape of a part being maintained by a cooling fluid. The passage flow, heat transfer and geometry evolve together under the constraints of flow and thermal boundary conditions.

The iceformation concept is not media dependent and can be used in analogous flows and materials to evolve novel boundary shapes. In the past, this method has been shown to reduce aerodynamic drag and total pressure loss in flows such as diffusers and cylinder/endwall junctures. This paper adds to the iceformation design record by investigating endwall surface heat transfer reduction in an air flow. The second vane endwall heat transfer problem is important as combustion temperatures rise with the demand for higher thrust or work output and with the limited amount of cooling air devoted to components beyond the first stage. A Reynolds number matched geometry reduced the averaged endwall Stanton number by 24% compared to the rotationally symmetric geometry of an Energy Efficiency Engine (E3) second vane endwall. The iceformation method has applications in experimentally or computationally shaping an isothermal endwall geometry prior to detailed design of internal convection and film cooling circuits.
Detailed Mass Transfer Distribution in Rotating, Two-Pass Ribbed Coolant Channels With Vortex Generators
Authors: Eliades V. , Nikitopoulos D. E. , Acharya S.
Published: December 2014

Local and global effects of cylindrical vortex generators on the mass transfer distributions over the four active walls of a square, rib-roughened rotating duct with a sharp 180° bend are investigated. Cylindrical vortex generators (rods) are placed above, and parallel to, every other rib on the leading and trailing walls of the duct so that their wake can interact with the shear layer and recirculation region formed behind the ribs, as well as the rotation-generated secondary flows. Local increases in near-wall turbulence intensity resulting from these interactions give rise to local enhancement of mass (heat) transfer. Measurements are presented for duct Reynolds numbers (Re) in the range 5000–30,000, and for rotation numbers in the range 0 to 0.3. The rib height-to-hydraulic diameter ratio (e/Dh) is fixed at 0.1, while the rib pitch-to-rib height ratio (P/e) is 10.5. The vortex generator rods have a diameter-to-rib height ratio (d/e) of 0.78, and the distance separating them from the ribs relative to the rib height (s/e) is 0.55. Mass transfer measurements of naphthalene sublimation have been carried out using an automated acquisition system and are correlated with heat transfer using the heat/mass transfer analogy. The results indicate that the vortex generators tend to enhance overall mass transfer in the duct, compared to the case where only ribs are present, both before and after the bend at high Reynolds and Rotation numbers. Local enhancements of up to 30% are observed on all four walls of the duct. At low Reynolds numbers (e.g. 5,000) the insertion of the rods often leads to degradation. At high Reynolds numbers (e.g. 30,000) the enhancement due to the rods occurs on the surfaces stabilized by rotation (trailing edge on the inlet pass and leading edge on the outlet pass) and the side walls.. The enhancement is more pronounced as the Rotation number is increased. The detailed measurements in a ribbed duct with vortex-generator rods clearly show localized regions of enhanced mass (heat) transfer at Reynolds and Rotation numbers within the envelope of practical interest for gas-turbine blade cooling applications.
Recovery of Microstructure and Mechanical Properties of Service Run GTD-111 DS Buckets
Authors: Cheruvu N. S. , Swaminathan V. P. , Kinney C. D.
Published: December 2014

Degradation of microstructure and mechanical properties of a service run GTD-111 DS blade was evaluated. The blade was coated with a CoCrAlY coating (GT-29) and had operated on a GE Model MS 5002 engine for 54,850 hours. To recover the microstructure of the degraded blade, the effect of solution treatment temperature on the microstructure and properties was evaluated. The blanks removed from the airfoil tip section were given a commonly used partial solution treatment 2050°F (1120°C) for GTD-111 and a high temperature solution treatment 2175°F (1190°C) prior to the partial solution and aging treatments. Microstructure and creep test results of these heat treated specimens revealed that the high temperature solution treatment was necessary to recover the microstructure and properties of in-service degraded GTD-111 DS buckets.
Non Equilibrium Effects in NO Formation Modeled With PDF Method Using Adaptive Look-Up Tables
Authors: Risalvato V. , Biagioli F.
Published: December 2014

The objective of this work is to investigate the finite rate kinetics effect on NO formation in turbulent non-premixed flames by using the presumed pdf method with two scalars where one scalar accounts for finite-rate chemistry. To overcome the increase of computational time demanded by the above method, an adaptive non-structured table look-up procedure has been implemented to interpolate thermochemical properties. These quantities are obtained from the look-up table during the integration of the turbulent reacting flow thus replacing a very computationally onerous integration with a less expensive interpolation. To study the non-equilibrium effects in non-premixed combustion and to assess the capabilities of the adaptive table, the numerical simulation of a turbulent syngas-air flame (experimentally studied by Drake et al.[4]) has been performed under equilibrium and non-equilibrium conditions.
CFD Analysis of a Centrifugal Compressor Impeller and Volute
Authors: Pitkänen Harri , Esa Hannu , Sallinen Petri , Larjola Jaakko
Published: December 2014

In this study, centrifugal compressor performance was predicted using CFD. Three-dimensional time-averaged impeller and volute simulations were performed using a Navier–Stokes code. The presented performance prediction method has been divided into three phases. Firstly, the impeller was calculated with a vaneless diffuser. That gives inlet boundary conditions for the volute analysis and the pressure ratio at the diffuser exit. Next, the volute analysis was performed and a static pressure recovery coefficient obtained. Finally, that result was combined with the pressure ratio prediction from the impeller analysis, and the overall compressor performance thus obtained.
Active Stabilization of Surge in an Axi-Centrifugal Turboshaft Engine
Authors: Nelson E. B. , Paduano J. D. , Epstein A. H.
Published: December 2014

Active stabilization of surge was implemented on an Allied Signal LTS-101 axi-centrifugal gas producer, reducing the surging mass flow by 1%, for an operating range increase of 11%. Control was achieved using high response sensors in the inlet and diffuser throat, coupled to actuators that injected air near the diffuser throat. System identification and modeling indicate that a classical surge-type eigenmode and an eigenmode associated with engine duct acoustics dominate the engine’s input-output properties. The surge eigenmode’s stability determines the open-loop surge mass flow. A robust linear controller with three inputs and one output stabilized this eigenmode without destabilizing the acoustic mode. The controller facilitated a 1% reduction in surging mass flow at 95% N1 corrected; this increases the engine’s choke to surge stable operating range by 11%. This paper elucidates the measured unsteady pre-surge behavior of the engine, and outlines a systematic procedure for surge control law development.
Influence of Compressor Deterioration on Engine Dynamic Behavior and Transient Stall-Margin
Authors: Spakovszky Z. S. , Gertz J. B. , Sharma O. P. , Paduano J. D. , Epstein A. H. , Greitzer E. M.
Published: December 2014

This paper presents an experimental and analytical investigation of compressor stability assessment during engine transient operation. A 2-dimensional, linear, compressible, state-space analysis of stall-inception (Feulner et al. (1996)) was modified to account for engine transients and deterioration, with the latter modeled as increased tip-clearance and flow blockage.

Experiments were performed on large commercial aircraft engines in both undeteriorated and deteriorated states. Unsteady measurements of pressure in these test engines during rapid accelerations revealed the growth of pre-stall disturbances, which rotate at rotor speed and at approximately half rotor speed. These disturbances are stronger in deteriorated engines.

The model showed that the signal at shaft speed was the first compressible system mode, whose frequency is near shaft speed, excited by geometric nonuniformities. The computed behavior of this mode during throttle transients closely matched engine data. The signal increased in strength as stall was approached and as the engine deteriorated. This work firmly establishes the connection between observed signals in the these engines and first principles stability models.
Reconditioning of Gas Turbine Components by Heat Treatment
Authors: Brown Julie A. , Freer Robert , Rowley Andrew T.
Published: December 2014

At the high operating temperatures experienced within a gas turbine, creep damage is a major life-limiting factor. This is especially true for components which are highly stressed and closest to the hot gas inlet end of the machine, such as the rotating blades in this area. The ability to recover the creep properties of used gas turbine components might enable their service lives to be increased considerably. Thereby, maintenance costs could be reduced. Previous research into the feasibility of reconditioning crept superalloys by heat treatment will be reviewed and perceived limitations identified. The current work will add to knowledge on the effects of conventional recovery techniques and will explore potential new heat treatment regimes. The experimental and analytical methods to be used will be both described and supported by preliminary results.
Investigations on the Deposition and the Efficiency of a Multilayer High Temperature Coating System for Gas Turbine Blades
Authors: Lugscheider Erich , Eritt Ulrich , von Hayn Gunter , Neuschuetz Dieter , Mueller Juergen
Published: December 2014

The content of this work is the development and investigation of a high temperature coating system for gas turbine blades. On a single crystal CMSX4 substrate a thin CVD layer of alpha-alumina was deposited as a diffusion barrier coating. As a protection against high-temperature corrosion it was covered with a PVD NiCoCrAlY layer, which also performs as a bond-coat for the following thermal barrier coating deposited by Atmospheric Plasma Spraying. The surface preparation techniques and coating parameters for the multilayer coating were optimized with respect to the bonding mechanisms of the different deposition techniques. The samples were annealed at 1100°C for 100 h under a neutral atmosphere. Furthermore thermocycle experiments were carried out to investigate thermocycle behaviour. The coating system proved its efficiency: no cracks were observed except vertical segmentation cracks in the TBC, all layers showed good adhesion and the diffusion barrier remained intact suppressing any noticeable diffusion of Al, Cr, Ta, Re, W and Ti.
The ANACONDA algorithm for deformable image registration in radiotherapy
Authors: Weistrand Ola , Svensson Stina
Published: December 2014

Purpose:

The purpose of this work was to describe a versatile algorithm for deformable image registration with applications in radiotherapy and to validate it on thoracic 4DCT data as well as CT/cone beam CT (CBCT) data.

Methods:

ANAtomically CONstrained Deformation Algorithm (ANACONDA) combines image information (i.e., intensities) with anatomical information as provided by contoured image sets. The registration problem is formulated as a nonlinear optimization problem and solved with an in‐house developed solver, tailored to this problem. The objective function, which is minimized during optimization, is a linear combination of four nonlinear terms: 1. image similarity term; 2. grid regularization term, which aims at keeping the deformed image grid smooth and invertible; 3. a shape based regularization term which works to keep the deformation anatomically reasonable when regions of interest are present in the reference image; and 4. a penalty term which is added to the optimization problem when controlling structures are used, aimed at deforming the selected structure in the reference image to the corresponding structure in the target image.

Results:

To validate ANACONDA, the authors have used 16 publically available thoracic 4DCT data sets for which target registration errors from several algorithms have been reported in the literature. On average for the 16 data sets, the target registration error is 1.17 ± 0.87 mm, Dice similarity coefficient is 0.98 for the two lungs, and image similarity, measured by the correlation coefficient, is 0.95. The authors have also validated ANACONDA using two pelvic cases and one head and neck case with planning CT and daily acquired CBCT. Each image has been contoured by a physician (radiation oncologist) or experienced radiation therapist. The results are an improvement with respect to rigid registration. However, for the head and neck case, the sample set is too small to show statistical significance.

Conclusions:

ANACONDA performs well in comparison with other algorithms. By including CT/CBCT data in the validation, the various aspects of the algorithm such as its ability to handle different modalities, large deformations, and air pockets are shown.
Npr2 inhibits TORC1 to prevent inappropriate utilization of glutamine for biosynthesis of nitrogen-containing metabolites
Authors: Laxman Sunil , Sutter Benjamin M. , Shi Lei , Tu Benjamin P.
Published: December 2014

Analysis of the metabolome of yeast grown in nutrient-poor conditions reveals a key role for Npr2 and TORC1 signaling complexes in regulating the use of glutamine as a nitrogen source.
Microbes Thwart Malaria
Authors: Berndt Jason D.
Published: December 2014

Exposure to bacteria produces circulating antibodies that inhibit transmission of malarial parasites.
Dynamic Signals Enhance Information Transfer
Authors: Ray L. Bryan
Published: December 2014

Signaling dynamics increase the information transmission capacity of biochemical signaling pathways.
Biochemical Characterization of the POM-1 Metallo-β-Lactamase from Pseudomonas otitidis
Authors: Borgianni Luisa , De Luca Filomena , Thaller Maria Cristina , Chong Yunsop , Rossolini Gian Maria , Docquier Jean-Denis
Published: December 2014

The POM-1 metallo-β-lactamase is a subclass B3 resident enzyme produced by
Pseudomonas otitidis
, a pathogen causing otic infections. The enzyme was overproduced in
Escherichia coli
BL21(DE3), purified by chromatography, and subjected to structural and functional analysis. The purified POM-1 is a tetrameric enzyme of broad substrate specificity with higher catalytic activities with penicillins and carbapenems than with cephalosporins.
Enantiospecific Reassessment of the Pharmacokinetics and Pharmacodynamics of Oral Eflornithine against Late-Stage Trypanosoma brucei gambiense Sleeping Sickness
Authors: Jansson-Löfmark R. , Na-Bangchang K. , Björkman S. , Doua F. , Ashton M.
Published: December 2014

This study aimed to characterize the stereoselective pharmacokinetics of oral eflornithine in 25 patients with late-stage
Trypanosoma brucei
gambiense
sleeping sickness. A secondary aim was to determine the concentrations of
l
- and
d
-eflornithine required in plasma or cerebrospinal fluid (CSF) for an efficient eradication of the
T. brucei gambiense
parasites. Patients were randomly allocated to receive either 100 (group I,
n
= 12) or 125 (group II,
n
= 13) mg/kg of body weight of drug every 6 h for 14 days. The concentrations of
l
- and
d
-eflornithine in the plasma and CSF samples were measured using a stereospecific liquid chromatographic method. Nonlinear mixed-effects modeling was used to characterize the plasma pharmacokinetics. The plasma concentrations of
l
-eflornithine were on average 52% (95% confidence interval [CI], 51, 54%;
n
= 321) of the
d
-enantiomer concentrations. The typical oral clearances of
l
- and
d
-eflornithine were 17.4 (95% CI, 15.5, 19.3) and 8.23 (95% CI, 7.36, 9.10) liters/h, respectively. These differences were likely due to stereoselective intestinal absorption. The distributions of eflornithine enantiomers to the CSF were not stereoselective. A correlation was found between the probability of cure and plasma drug exposure, although it was not more pronounced for the
l
-enantiomer than for that of total eflornithine. This study may explain why oral treatment for late-stage human African trypanosomiasis (HAT) patients with racemic eflornithine has previously failed; the more potent
l
-enantiomer is present at much lower concentrations in both plasma and CSF than those of the
d
-enantiomer. Eflornithine stereoselective pharmacokinetics needs to be considered if an oral dosage regimen is to be explored further.
Evaluation of the Pharmacokinetic Interaction between Repeated Doses of Rifapentine or Rifampin and a Single Dose of Bedaquiline in Healthy Adult Subjects
Authors: Winter Helen , Egizi Erica , Murray Stephen , Erondu Ngozi , Ginsberg Ann , Rouse Doris J. , Severynse-Stevens Diana , Pauli Elliott
Published: December 2014

This study assessed the effects of rifapentine or rifampin on the pharmacokinetics of a single dose of bedaquiline and its M2 metabolite in healthy subjects using a two-period single-sequence design. In period 1, subjects received a single dose of bedaquiline (400 mg), followed by a 28-day washout. In period 2, subjects received either rifapentine (600 mg) or rifampin (600 mg) from day 20 to day 41, as well as a single bedaquiline dose (400 mg) on day 29. The pharmacokinetic profiles of bedaquiline and M2 were compared over 336 h after the administration of bedaquiline alone and in combination with steady-state rifapentine or rifampin. Coadministration of bedaquiline with rifapentine or rifampin resulted in lower bedaquiline exposures. The geometric mean ratios (GMRs) and 90% confidence intervals (CIs) for the maximum observed concentration (
C
max
), area under the concentration-time curve to the last available concentration time point (AUC

0–
t

), and AUC extrapolated to infinity (AUC
0–inf
) of bedaquiline were 62.19% (53.37 to 72.47), 42.79% (37.77 to 48.49), and 44.52% (40.12 to 49.39), respectively, when coadministered with rifapentine. Similarly, the GMRs and 90% CIs for the
C
max
, AUC

0–
t

, and AUC
0–inf
of bedaquiline were 60.24% (51.96 to 69.84), 41.36% (37.70 to 45.36), and 47.32% (41.49 to 53.97), respectively, when coadministered with rifampin. The
C
max
, AUC

0–
t

, and AUC
0–inf
of M2 were also altered when bedaquiline was coadministered with rifapentine or rifampin. Single doses of bedaquiline, administered alone or with multiple doses of rifapentine or rifampin, were well tolerated, with no safety concerns related to coadministration. Daily administration of rifapentine to patients with tuberculosis presents the same drug interaction challenges as rifampin and other rifamycins. Strong inducers of the cytochrome P450 isoenzyme CYP3A4 should be avoided when considering the use of bedaquiline. (This study is registered at clinicaltrials.gov under identifier NCT02216331.)
Pharmacodynamic Target Evaluation of a Novel Oral Glucan Synthase Inhibitor, SCY-078 (MK-3118), Using an
In Vivo
Murine Invasive Candidiasis Model
Authors: Lepak Alexander J. , Marchillo Karen , Andes David R.
Published: December 2014

Echinocandins inhibit the synthesis of β-1,3-
d
-glucan in
Candida
and are the first-line therapy in numerous clinical settings. Their use is limited by poor oral bioavailability, and they are available only as intravenous therapies. Derivatives of enfumafungin are novel orally bioavailable glucan synthase inhibitors. We performed an
in vivo
pharmacodynamic (PD) evaluation with a novel enfumafungin derivative, SCY-078 (formerly MK-3118), in a well-established neutropenic murine model of invasive candidiasis against
C. albicans
,
C. glabrata
, and
C. parapsilosis
. The SCY-078 MICs varied 8-fold. Oral doses of 3.125 to 200 mg/kg SCY-078 salt in sterile water produced peak levels of 0.04 to 2.66 μg/ml, elimination half-lives of 5.8 to 8.5 h, areas under the concentration-time curve from 0 to 24 h (AUC
0–24 h
) of 0.61 to 41.10 μg · h/ml, and AUC from 0 to infinity (AUC
0—∞
) values of 0.68 to 40.31 μg · h/ml. The pharmacokinetics (PK) were approximately linear over the dose range studied. Maximum response (
E
max
) and PK/PD target identification studies were performed with 4
C. albicans
, 4
C. glabrata
, and 3
C. parapsilosis
isolates. The PD index AUC/MIC was explored by using total (
t
AUC) and free (
f
AUC) drug concentrations. The maximum responses were 4.0, 4.0, and 4.3 log
10
CFU/kidney reductions for
C. albicans
,
C. glabrata
, and
C. parapsilosis
, respectively. The AUC/MIC was a robust predictor of efficacy (
R
2
, 0.53 to 0.91). The 24-h PD targets were a static dose of 63.5 mg/kg, a
t
AUC/MIC of 500, and an
f
AUC/MIC of 1.0 for
C. albicans
; a static dose of 58.4 mg/kg, a
t
AUC/MIC of 315, and an
f
AUC/MIC of 0.63 for
C. glabrata
; and a static dose of 84.4 mg/kg, a
t
AUC/MIC of 198, and an
f
AUC/MIC of 0.40 for
C. parapsilosis
. The mean
f
AUC/MIC values associated with a 1-log kill endpoint against these species were 1.42, 1.26, and 0.91 for
C. albicans
,
C. glabrata
, and
C. parapsilosis
, respectively. The static and 1-log kill endpoints were measured relative to the burden at the start of therapy. The static and 1-log kill doses, as well as the total and free drug AUC/MIC PD targets, were not statistically different between species but were numerically lower than those observed for echinocandins. SCY-078 is a promising novel oral glucan synthase inhibitor against
Candida
species, and further investigation is warranted.
Detailed Mutational Analysis of Vga(A) Interdomain Linker: Implication for Antibiotic Resistance Specificity and Mechanism
Authors: Lenart Jakub , Vimberg Vladimir , Vesela Ludmila , Janata Jiri , Balikova Novotna Gabriela
Published: December 2014

Detailed mutational analysis examines the roles of individual residues of the Vga(A) linker in determining the antibiotic resistance phenotype. It defines a narrowed region of residues 212 to 220 whose composition determines the resistance specificity to lincosamides, pleuromutilins, and/or streptogramins A. From the analogy with the recently described function of the homologous ABC-F protein EttA as a translational factor, we infer that the Vga(A) linker interacts with the ribosome and directly or indirectly affects the binding of the respective antibiotic.
“Pick-up Lines”: A Fun Way to Facilitate Learning Microbiological Concepts
Authors: dela Cruz Thomas Edison E.
Published: December 2014

Learning microbiology can be made fun by writing funny lines related to microbiology. Students were tasked to create their own pick-up lines and explain these based on their understanding of the basic concepts in microbiology.
Using Facebook to Engage Microbiology Students Outside of Class Time
Authors: Legaree Blaine A.
Published: December 2014

Learning microbiology can be made fun by writing funny lines related to microbiology. Students were tasked to create their own pick-up lines and explain these basNumerous usage studies show that a high percentage of college age students are subscribers of the social media service Facebook. Modern teaching methods have a high emphasis on student engagement in the classroom, however, not all students participate equally and therefore it is important to find alternate methods for student engagement. The popularity of social media services and the wealth of online biology resources therefore seem like an obvious way to additionally engage students, particularly non-traditional students who may be less likely to participate in class discussions. In order to investigate how to engage students using this tool, I set up a Facebook group for my medical microbiology class over two semesters. Afterwards I surveyed students on its usefulness. The feedback was mostly positive, and of the resources shared with students, they were most likely to view online videos. Students also found it helpful to have an alternate means of interacting with the instructor and their peers.
Active Learning for Basic Metabolic Pathways
Authors: Yung Sonja B. , Primm Todd P.
Published: December 2014

Understanding the basic cellular function of metabolic pathways and how those pathways interact in cellular metabolism is a foundational concept in microbiology and general biology. A cooperative learning activity has been designed where students first generate cards to represent basic facts about each pathway, and then they connect these pathways given certain specific environmental scenarios. This should enhance their working knowledge of how pathways allow cells to adapt to the environment.
Pseudomonas Isolation and Identification: An Introduction to the Challenges of Polyphasic Taxonomy
Authors: Sandman Kathleen , Ecker Christopher
Published: December 2014

The ability to isolate an organism in pure culture from the environment is a manageable task for undergraduate students; the identification of that organism requires integration of both genotypic and phenotypic data and illustrates the challenges inherent in contemporary bacterial taxonomy. In this ten-laboratory period series of exercises, students isolate a strain ofPseudomonasfrom soil and characterize its biochemical and physiological properties, as well as determine the DNA sequence of its 16S rRNA genes. Integrating these data positions students to defend their classification of the isolate as a new species or as a member of a validly described species. Assessment data demonstrate that both knowledge of and confidence in understanding of the principles of laboratory handling ofPseudomonasand bacterial taxonomy increased following the exercises.
Inquiry-Based Laboratory Activity to Investigate Physical Growth Requirements of Microorganisms
Authors: Furlong Michelle , McFarlane Renee
Published: December 2014

Standard "cookbook" laboratory activities that are used to teach students the optimal physical growth conditions of microorganisms should be modified so that they more effectively foster student's higher order cognitive skills and attract student interest. This paper describes a laboratory activity that engages students in an inquiry-based approach to studying the physical growth requirements of microorganisms. In this activity, students design and implement an experiment to obtain pure cultures of specific microorganisms, with distinct growth properties, that are provided to them in a mixed culture.
Ethical Challenges in Teaching Genetics for Medical Students
Authors: Nagle Erika , Kažoka Dzintra
Published: December 2014

Although inclusion of ethics as a study course in medical students’ curricula is a common practice, special approaches in teaching ethics in the context of genetics should be considered. In the realm of genomics, there are several ethically sensitive topics such as diagnosis of genetic diseases,
in vitro
fertilization, and identification of genetic susceptibility to common diseases. In addition, in communication with the general public, genetic terms should be used with caution. Demonstration of the phenotypes of affected individuals should be regarded as a particular aspect of teaching genetics. In a description of a patient’s phenotype, not only is it necessary to provide scientifically precise characteristics of a patient; voice timbre, facial expression, and body language should also be carefully controlled. Furthermore, in medicine, the theory–practice gap is a problematic aspect, and students often find it difficult to apply knowledge on ethical issues to real situations in clinics. For this purpose, clinical cases are presented during classes and their analysis requires a very respectful attitude on the part of both students and lecturers. For many genetic diseases, evaluation of minor anomalies such as a curved fifth finger, low situated ears, or missing of some teeth is required. Some minor anomalies are found in healthy individuals too, and interpretation of such features must therefore be considered carefully. This article describes our experiences in teaching genetics at Riga Stradinš University, ethical problems faced while teaching genetics, and their solutions.
The Tuskegee Experiment: An Introduction in Ethics for Pre-Healthcare Professional Students
Authors: Miranda Daniel , Sanchez David Jesse
Published: December 2014

Over the past years, professional students have had extensive exposure to clinical cases during basic science classes. With this in mind, we have taken this clinical case exposure moment to be an opportune time to introduce the ethics of working with patients during biomedical research. Our goal is to present a straightforward assignment that allows for active student research into the facts of the Tuskegee Experiment of the 1900s. The assignment provides the necessary background to allow for a student-centered discussion on the ethical issues of the events and ramifications of what happened. Thus, in educating a class on the event’s happenings, one concomitantly creates a platform for meaningful discussion on the principles and ethics of patient care. We have found that an ethics-infused event such as the Tuskegee Experiment is an excellent way to introduce students to these topics.
Infusing Bioethics into Biology and Microbiology Courses and Curricula: A Vertical Approach
Authors: Jagger Kathleen S. , Furlong Jack
Published: December 2014

With the rise of biomedicine and biotechnology, there has been a corresponding growth in the need for better understanding of consequent ethical questions. Increasingly, biologists are being asked not only to offer technical clarifications but also to venture ethical opinions, for which most feel poorly equipped. This expectation puts pressure on biology instructors at the university level to provide biology majors the skills and experience to discuss with some confidence and competence bioethical issues which may arise in either the workplace or through public discourse in everyday contexts. Many fine curricular resources about bioethics are available for varied pedagogical purposes, but few target undergraduate biology or microbiology student audiences. When it occurs in the context of a course, bioethics instruction often is taught by non-biologists outside standard biology curricula. We propose that biologists should strive to “infuse” bioethical thinking into their courses and major curricula but not in such a way as merely to point at ethical problems, treating them at a surface level. We suggest what we call “vertical infusion”: taking one bioethical issue per course and integrating this issue within the context of a relevant biological topic, challenging students to push their thinking beyond their initial intuitions toward underlying scientific and ethical principles. While the vertical approach lacks widespread coverage of ethical issues throughout a single course, it has the advantage of taking the bioethical dimension seriously and in intimate relation to contemporary discoveries in biology and to the biological principles, processes, or procedures that occasioned the ethical quandaries in the first place.
A Multi-Unit Project for Building Scientific Confidence via Authentic Research in Identification of Environmental Bacterial Isolates
Authors: Chatfield Christa
Published: December 2014

This authentic research project is designed to identify environmental isolates by metabolic phenotypes and 16s sequence analysis and with an investigation of biofilm growth is presented as implemented in an upper-level microbiology lab course. Three units were used in the lab: one for basic metabolic identification, one for the 16s rDNA sequencing and a third for biofilm growth analysis. Assessment was by weekly notebook entries detailing the outcomes of each day in lab, providing relatively on-time feedback on student understanding and learning to both the student and the instructor. The intent for these units was for each to increase the uncertainty of the project outcomes and to challenge students to design projects with open-ended results. All student groups have been able to obtain DNA sequence data in the limited 6-7 weeks of the lab project. Students report increased confidence in their abilities and a general excitement about the project methods and results. The data produced by the students can be incorporated into larger research questions posed by the faculty running the course as determined by the source of the unknown bacterial isolates.