bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal sequence of activation of cells involved in purinergic neurotransmission in the colon
Authors: Baker Salah A. , Hennig Grant W. , Ward Sean M. , Sanders Kenton M.
Published: January 2015

Key points

Platelet derived growth factor receptor α (PDGFRα+) cells in colonic muscles are innervated by enteric inhibitory motor neurons.

PDGFRα+ cells generate Ca2+ transients in response to exogenous purines and these responses were blocked by MRS‐2500.

Stimulation of enteric neurons, with cholinergic and nitrergic components blocked, evoked Ca2+ transients in PDGFRα+ and smooth muscle cells (SMCs).

Responses to nerve stimulation were abolished by MRS‐2500 and not observed in muscles with genetic deactivation of P2Y1 receptors.

Ca2+ transients evoked by nerve stimulation in PDGFRα+ cells showed the same temporal characteristics as electrophysiological responses.

PDGFRα+ cells express gap junction genes, and drugs that inhibit gap junctions blocked neural responses in SMCs, but not in nerve processes or PDGFRα+ cells.

PDGFRα+ cells are directly innervated by inhibitory motor neurons and purinergic responses are conducted to SMCs via gap junctions.

Interstitial cells, known as platelet derived growth factor receptor α (PDGFRα+) cells, are closely associated with varicosities of enteric motor neurons and suggested to mediate purinergic hyperpolarization responses in smooth muscles of the gastrointestinal tract (GI), but this concept has not been demonstrated directly in intact muscles. We used confocal microscopy to monitor Ca2+ transients in neurons and post‐junctional cells of the murine colon evoked by exogenous purines or electrical field stimulation (EFS) of enteric neurons. EFS (1–20 Hz) caused Ca2+ transients in enteric motor nerve processes and then in PDGFRα+ cells shortly after the onset of stimulation (latency from EFS was 280 ms at 10 Hz). Responses in smooth muscle cells (SMCs) were typically a small decrease in Ca2+ fluorescence just after the initiation of Ca2+ transients in PDGFRα+ cells. Upon cessation of EFS, several fast Ca2+ transients were noted in SMCs (rebound excitation). Strong correlation was noted in the temporal characteristics of Ca2+ transients evoked in PDGFRα+ cells by EFS and inhibitory junction potentials (IJPs) recorded with intracellular microelectrodes. Ca2+ transients and IJPs elicited by EFS were blocked by MRS‐2500, a P2Y1 antagonist, and absent in P2ry1(−/−) mice. PDGFRα+ cells expressed gap junction genes, and gap junction uncouplers, 18β‐glycyrrhetinic acid (18β‐GA) and octanol blocked Ca2+ transients in SMCs but not in neurons or PDGFRα+ cells. IJPs recorded from SMCs were also blocked. These findings demonstrate direct innervation of PDGFRα+ cells by motor neurons. PDGFRα+ cells are primary targets for purinergic neurotransmitter(s) in enteric inhibitory neurotransmission. Hyperpolarization responses are conducted to SMCs via gap junctions.
Toward a Probabilistic Approach to Determine Nominal Values of Tank Sloshing Loads in Structural Design of Liquefied Natural Gas FPSOs
Authors: Paik Jeom Kee , Lee Sang Eui , Kim Bong Ju , Seo Jung Kwan , Ha Yeon Chul , Matsumoto Toshiyuki , Byeon Su Hwan
Published: January 2015

The aim of this study is to develop a new probabilistic approach to determine nominal values for tank sloshing loads in structural design of LNG FPSO (liquefied natural gas, floating production, storage, and offloading units). Details of the proposed procedure are presented in a flow chart showing the key subtasks. The applicability of the method is demonstrated using an example of a hypothetical LNG FPSO operating in a natural gas site off a hypothetical oceanic region. It is noted that the proposed method is still under development for determining reliable estimates of extreme sloshing induced impact loads. It is concluded that the developed method is useful for determining the sloshing design loads in ship-shaped offshore LNG installations in combination with virtual metocean data and operational conditions.
One to One Nonlinear Internal Resonance of Sensor Diaphragm Under Initial Tension
Authors: Long Xinhua , Yu Miao
Published: January 2015

In this paper, investigations into the nonlinear asymmetric vibrations of a pressure sensor diaphragm under initial tension are presented. A comprehensive mechanics model based on a plate with in-plane tension is presented and the effect of cubic nonlinearity is studied. Specifically, the nonlinear asymmetric response is investigated when the excitation frequency is close to the natural frequency of an asymmetric mode of the plate. The obtained results show that in the presence of an internal resonance, depending on the initial tension, the response can have not only the form of a standing wave but also the form of a traveling wave. In addition, damping can be used to reduce the nonlinear effect and avoid the nonlinear interactions. The results of this work will benefit the design of diaphragm-type structures used in microscale sensors including pressure sensors.
Efficient Prediction of SAGD Productions Using Static Factor Clustering
Authors: Lee Haeseon , Jin Jeongwoo , Shin Hyundon , Choe Jonggeun
Published: January 2015

Oil sands have great amount of reserves in the world with increasing commercial productions. Prediction of reservoir performances of oil sands is challenging mainly due to long simulation time for modeling heat and fluids flows in steam assisted gravity drainage (SAGD) operations. Because of accurate modeling difficulties and limited geophysical data, it requires many simulation cases of geostatistically generated fields to cover uncertainty in reservoir modeling. Therefore, it is imperative to develop a new technique to analyze production performances efficiently and economically. This paper presents a new ranking method using a static factor that can be used for efficient prediction of oil sands production. The features vector proposed can reflect shale barrier effects in terms of shale length and relative distance from the injection well. It preprocesses area that steam chamber bypasses, and then counts steam chamber expanding an area cumulatively. K-means clustering selects a few fields for full simulation run and they will cover cumulative probability distribution function (CDF) of all the fields examined. Accuracy of the prediction is high when cluster number is more than 10 based on cases of cluster number 5, 10, and 15. This technique is applied to fields with 3%, 5%, 10%, and 15% shale fraction and all the cases allow efficient and economical predictions of oil sands productions.
Fault Detection for Gas Turbine Sensors Using I/O Dynamic Linear Models: Methodology of Fault Code Generation
Authors: Bettocchi R. , Spina P. R. , Azzoni P. M.
Published: January 2015

This paper presents a methodology of sensor diagnosis which appears to be particularly suitable also for application in the field of small/medium power size industrial gas turbines.

The methodology is based on the Analytical Redundancy technique and uses ARX (Auto Regressive with eXternal input) MISO (Multi-Input/Single-Output) linear dynamic models obtained from time series data of the gas turbine operating condition. The linear models allow the on-line calculation of some measurable parameter starting from the values of other measured parameters. The comparison between computed and measured values of the same parameters allows setting-up a vector of residuals which, if compared with the columns of the fault matrix, permits the identification of a possible sensor fault.

The initial applications of the methodology to a single-shaft industrial gas turbine show an unambiguous and certain detection and isolation of fault in sensors used both in the measurement only and in feedback by the machine control system.
Specifics of Damping Evaluation in Rotating Machines
Authors: Muszynska Agnes
Published: January 2015

Focused on rotor lateral modes, the paper discusses specifics of damping evaluation in rotating machines. Rotors force the fluid trapped in small rotor-to-stator radial clearances to rotate in circumferential fashion. The fluid in circumferential motion generates a tangential force acting in feedback on the rotor. This force direction is opposite to that of damping force. The “effective damping” is, therefore, reduced or even nullified by the fluid interaction effects. The classical measures of damping in mechanical structures, such as Logarithmic Decrement and Amplification Factor, which are used to evaluate machine susceptibility to instability based on documented vibration data, have to be adjusted to include the fluid interaction effects. These measures now represent the measures of Quadrature Dynamic Stiffness (QDS). It is shown that they contain the expression defined as Stability Margin (or Nondimensional Stability Margin), derived from the stability condition of the rotor system. A simple model of isotropic rotor lateral vibrations is used to obtain the QDS measures.
Heat Transfer Computations for Turbine Blade Airfoils
Authors: Slimani Jamel , Kulisa Pascale
Published: January 2015

The design and optimization of turbine blades subjected to high temperature flows require the prediction of aerodynamic and thermal flow characteristics. A computation of aerothermal viscous flow model has been developed suitable for the turbine blade design process. The computational time must be reduced to allow intensive use in an industrial framework. The physical model is based on a compressible boundary layer approach, and the turbulence is a one-equation model. Special attention has been paid to the influence of wall curvature on the turbulence modelling. Tests were performed on convex wall flows to validate the turbulence model. Turbine blade configurations were then computed. These tests include most difficulties that can be encountered in practice : laminar-turbulent transition, separation bubble, strong accelerations, shock wave. Satisfactory predictions of the wall heat transfer are observed.
Testing the Model V84.3A Gas Turbine: Experimental Techniques and Results
Authors: Boehm W. , Raake D. , Regnery D. , Seume J. , Terjung K.
Published: January 2015

Like its predecessors, Siemens’ first Hybrid Burner Ring® machine (Becker et al., 1995) underwent an extensive experimental development and test programm prior to its introduction to the market.

The present paper describes the philosophy of prototype testing, some of the challenges encountered in instrumenting the machine and the methodology and experimental techniques used to solve the problems. In particular, it describes some of the advanced implementations of blade vibration measurements, optical pyrometry and other temperature measurements, and techniques to determine efficiency.

The experimental results confirm the design of the model V84.3A gas turbine and show some potential for further improvements.
Numerical Calculation of Three-Dimensional Turbulent Flow in a Turbine-Stator Passage
Authors: Song B. , Amano R. S.
Published: January 2015

A numerical study on three-dimensional turbulent flow in a turbine-stator passage is presented in this paper. The standard κ–ε model with the one equation, near-wall model (SKE) and the Launder-Sharma model (L-S) are used for turbulence computations. The computational results obtained using these models were compared in order to investigate the turbulence effect in the near-wall region. The governing equations in a generalized curvilinear coordinate system are discretized by using the SIMPLEC method with non-staggered grids. The oscillation of pressure and velocity due to non-staggered grids is eliminated by using the interpolation method suggested by Rhie and Chow (1983). The predicted midspan pressure coefficients using SKE and L-S models are compared with experimental data. It was shown that the present results obtained by using both models are satisfactory. Computations were then extended to cover the entire blade-to-blade flow passage, and the three-dimensional effects on pressure and turbulence kinetic energy were evaluated. It was observed that two turbulence models predict similar results for the pressure and velocity but these predict different results in the turbulence kinetic energy.
A New Experimental Method of Combined Fatigue of Actual Turbine Disk Mortise Teeth at Elevated Temperature
Authors: Wang Rongqiao , Nie Jingxu
Published: January 2015

For studying the L-HCCF of an actual turbine disk mortise teeth at elevated temperature, this paper presents a new experimental system, using actual disk as experimental component, ingeniously achieving the combined loading (simulating low cycle radial centrifugal force and high cycle crosswise vibration of blade), the high-frequency induction local heating (550 °C constant temperature), the control of high cycle vibrating frequency and amplitude, and the crack real-time detection. The experimental result is identical with the practical flight failure. This method can be easily popularized for the L-HCCF studying of many components.
The Gas Turbine Family GT13E and GT13E2 Provides Reliable Power for Asia
Authors: Gnädig Gregor
Published: January 2015

Many Asian countries are experiencing economic growth which averages 5–10% per year. This environment has led to a privatization process in the power generation industry from typically state-run utilities to a system in which a federal agency oversees a market divided by private utilities and independent power producers (IPP) with the need for high efficiency, reliable power generation running on natural gas and diesel oil. In the 50 Hz market, modem, high efficient gas turbines of the type GT13E and GT13E2 have been chosen as prime movers in many combined cycle power plants in Asian countries. This paper includes a product description, and a general overview of GT13E and GT13E2 operating experience, well as an economic evaluation of a typical 500 MW combined cycle power plant.
Fate of Ash Forming Elements in Gas Turbine Combustion of Pulverized Wood: Chemical Equilibrium Model Calculations
Authors: Kallner Per , Nordin Anders , Backman Rainer
Published: January 2015

A new concept for direct combustion of wood in a gas turbine is presently developed and tested in Sweden. The process is based on a fuel rich cyclone gasifier/separator and a direct coupled modified standard gas turbine combustor. A main concern is the behaviour of ash forming elements in the turbine. A picture of this can be obtained with chemical equilibrium calculations.

The objective of the present work was to determine the equilibrium speciation of the ash forming elements from wood passing through the turbine of a gas turbine engine for varying feed characteristics and operating conditions. In addition, the differences between using only stoichiometric and using non-ideal solution models as thermodynamic input data were illustrated.

The equilibrium relationships at the turbine stage were evaluated in a parametric study, utilizing statistical experimental designs to systematically perform the model calculations. A wide range of operating conditions, wood compositions and cyclone elemental retention efficiencies were thereby covered.

The results show considerable variation in the alkali speciation as well as in devolitalization and condensation temperatures, depending on the elemental composition. Plots of the effects of the most influential variables are presented and results not directly displayed in this work are illustrated with model equations provided.
Protective Coatings and Degradation Experiences for First Stage Buckets on GE MS-5002B/C Gas Turbines
Authors: Boestaman Refrizal , Swaminathan V. P. , Bernstein H. L.
Published: January 2015

PT Arun operates 21 GE Model MS-5002 B/C gas turbines as mechanical drive with a total power of 514 MW, and a total of 2.7 million hours of accumulated operation. The first generations of simple cycle gas turbines were designed at 1700 F (927 C) firing temperature using first stage buckets design cast from IN-738LC and coated with a conventional 2-phase platinum aluminide coating (Pt-Al). Since 1989, the output power was increased by raising gas turbine firing temperature to 1770 F (965 C). This uprate was implemented by using first stage buckets cast from GTD-111 DS and coated with GT-29 Plus.

Metallurgical examination of these coatings at various operating hours have been performed to check their performance and the cause of coating degradation. These results are considered for future coating selection.

In the last two years PT Arun has explored a new single phase NiCoCrAlY coating and a single phase Pt-Al diffusion coating using chemical vapor disposition process as an alternate to GT-29 plus coating replacement. Both of these coatings are used at PT Arun and have accumulated 32,400 hours for NiCoCrAlY or GT-33 and 2880 hours for single phase Pt-Al or MDC-150L coating as of June 1996. The information regarding qualification of these alternate coatings (zero running hours) will be discussed in this paper.
Combustion Instability Investigations on the BR710 Jet Engine
Authors: Konrad Wolfgang , Brehm Norbert , Kameler Frank , Freeman Chris , Day Ivor J.
Published: January 2015

During the development of the BR710 jet engine audible combustor instabilities (termed ‘rumble’) occurred. Amplitudes measured with test cell microphones were up to 130 dB at around 100 Hz. Disturbances of this amplitude are clearly undesirable, even if only present during start-up, and a research program was initiated to eliminate the problem.

Presented here is the methodical and structured approach used to identify, understand, and remove the instability. Some reference is made to theory, which was used for guidance, but the focus of the work is on the research done to find the cause of the problem and to correct it. The investigation followed two separate, but parallel, paths — one looking in detail at individual ‘components of the engine to identify possible involvement in the instability and the other looking at the pressure signals from various parts of a complete engine to help pin-point the source of the disturbance.

The main cause of the BR710 combustor rumble was found to be a self-excited aerodynamic instability arising from the design of the fuel injector head. In the end, minor modifications lead to spray pattern changes which greatly reduced the combustor noise. As a result of this work, new recommendations are made for reducing the risk of combustion instabilities in jet engines.
Neural Networks for the Diagnostics of Gas Turbine Engines
Authors: Torella G. , Lombardo G.
Published: January 2015

The paper describes the activities carried out for developing and testing Back Propagation Neural Networks (BPNN) for the gas turbine engine diagnostics.

One of the aims of this study was to analyze the problems encountered during training using large number of patterns.

Each pattern contains information about the engine thermodynamic behaviour when there is a fault in progress.

Moreover the research studied different architectures of BPNN for testing their capability to recognize patterns even when information is noised.

The results showed that it is possible to set-up and optimize suitable and robust Neural Networks useful for gas turbine diagnostics. The methods of Gas Path Analysis furnish the necessary data and information about engine behaviour.

The best architecture, among the ones studied, is formed by 13, 26 and 47 neurons in the input, hidden and output layer respectively. The investigated Nets have shown that the best encoding of faults is the one using a unitary diagonal matrix.

Moreover the calculation have identified suitable laws of learning rate factor (LRF) for improving the learning rate.

Finally the authors used two different computers. The first one has a classical architecture (sequential, vectorial and parallel). The second one is the Neural Computer, SYNAPSE-1, developed by Siemens.
Integrated Coal Gasification Combined Cycle: Current Experience — Future Promise
Authors: Kaupang Bjorn , Todd Douglas M.
Published: January 2015

Significant progress has been made in the installation and initial operation of several IGCC power plants. At least six IGCC projects are scheduled to enter commercial operation in the USA and in Europe during 1996. Several additional IGCC projects are under construction or under development using many different gasification systems. Gas turbine manufacturers introduced advanced gas turbine technology in 1995, resulting in IGCC efficiency for coal and heavy oil-fired plants of up to 50% (LHV) with plant costs consistent with conventional steam plants. Gas turbine developments specifically aimed at IGCC applications allow the use of environmentally low quality fuels without added impact on the environment.

This paper discusses the current operating experience of several of the initial IGCC plants and illustrates the very attractive fuels flexibility with the combined-cycle plants burning naphtha or distillate oils initially with later conversions to IGCC burning lignite, heavy oil or orimulsion. This paper also discusses the heat rate and output performance capabilities of the IGCC with H level gas turbine technology and the resulting impacts on the cost of electricity from IGCC plants.
Experimental Refinement of Technologies for Environmental Update of Gas Turbine Units Applied to Electrogenerator Driving
Authors: Soudarev A. V. , Vinogradov E. D. , Zakharov Ju. I.
Published: January 2015

The results of experimental elaboration of engineering approaches relating to environmental update of combustors for the GTK-10 10 MW, GTG-1500 1.5 MW and GT-100 100 MW gas turbine engines are presented. The combustor update was carried out by a technique of directed dosed air blow into the maximum temperature zone with in the fire space.

The advantages of the technique are as follows:

• feasibility of reduction of Nox concentration in waste gases to 50 ppm;

• simplicity and adaptability to manufacture of the structure;

• no need in changing the design of the engine components and systems;

• short-time outage of the unit at update.
Industrial Power Company Cogeneration at Eastern Industrial Estate, Map Ta Phut, Thailand: First Single Shaft Combined Cycle Application of 50 MW GT8C
Authors: van der Linden Septimus , Baerfuss Paul A. , Vonau Karl-Heinz
Published: January 2015

Smaller CC plants below 80 MW offer economic solutions in cogeneration to industrial parks in the South East Asian power market which is typically dominated by large gas turbines and power plants. For the Industrial Power CO-GEN project, the single shaft power train arrangement for combined cycle/cogeneration is the first GT8C application of reference plant concepts.

Commercial operation will commence in September 1997 with first components to be shipped in October 1996. This paper describes the GT8C single shaft combined cycle arrangement applied to industrial power cogeneration as well as some specifics of the Industrial Power Co. Ltd. project (IP CO-GEN project) at Eastern Industrial Estate, Map Ta Phut, Thailand related to plant layout, operating and control philosophy.
Reduction of Secondary Flow Effects in a Linear Cascade by Use of an Air Suction From the Endwall
Authors: Funazaki K. , Endo T. , Tanuma T.
Published: January 2015

The objective of this study is to reduce secondary flow effects in a linear cascade by sucking the working fluid from the endwall. It is widely known that the secondary flow developed in a cascade has a significant impact on the cascade loss or blade erosion in steam turbines. Therefore, a number of studies have been made on the physics of the secondary flow and several devices to control the secondary flow, such as a fence, have been examined. In this study, considering the application to nozzles in gas turbines or steam turbines, the air suction approach is investigated for reducing the secondary flow effects. A suction slit is provided on the lower endwall of the cascade and a flow rate of the sucked air is controlled by adjusting the exit pressure of the slit. The effects of the suction upon the flow nearby the endwall and the secondary flow are observed through several flow visualizing techniques, for example an oil flow method or a tuft method. Furthermore, velocity and stagnation pressure measurement are conducted by a five-hole pressure tube. This clearly demonstrates the vorticity and loss profiles downstream of the cascade with and without the endwall suction.
Development in Industrial Scale Gas Turbine Systems
Authors: Anson Donald , Duffy Thomas E. , White David , Waslo S.
Published: January 2015

The variety of applications in which small industrial gas turbines are used requires that they be readily capable of integration into cogeneration schemes and combined gas/steam cycles as well as providing reliable and efficient stand-alone performance. Several gas turbine based power systems are reviewed briefly. Simple cycle and recuperative engines, and possibly intercooled/recuperative engines, appear to be the most likely primary arrangements for developing more efficient industrial gas turbine based systems. These systems include high pressure, high temperature steam turbines recently developed. When coupled with high pressure, high temperature steam generators, industrial scale simple cycle gas turbines can offer high electrical generation efficiencies with excellent turndown and overall heat utilization in cogeneration mode.

Basically, high efficiency depends on firing temperature (TRIT). Firing temperature will continue to increase using advanced metal casting and cooling techniques developed in the aircraft engine sector, and possibly ceramics, which are more applicable in industrial engines than elsewhere. Electrical efficiencies for rated outputs of 5–20 MW will be 32–35 percent for simple cycle gas turbines, up to 42 percent in recuperative engines and cogeneration systems, and 45 percent in combined cycles.

The paper lists references describing in detail many of the developments that have contributed to state-of-the-art industrial turbine design.
Lubricant Analysis for Gas Turbine Condition Monitoring
Authors: Lukas M. , Anderson D. P.
Published: January 2015

Analysis of used lubricating oil is a fast evolving technique for predictive maintenance with any closed loop lubricating system such as those in gas and steam turbines, diesel and gasoline engines, transmissions, gearboxes, compressors, pumps, bearings and hydraulic systems.
Slurry Coating Systems for Low and High Temperature Turbine Protection: New Developments
Authors: Thoma M. , Morant M.
Published: January 2015

Inorganic slurry coatings based on a ceramic binder which contains aluminum or aluminum and silicon are very effective coatings in engines and gas turbines.

All these coatings contain much chromic acid, causing health problems when applied by the usual spraying technique. A new generation of slurry coatings with minimized Cr6+ (<0.5% weight) content has been developed.

- Ceral 114 systems as Al ceramic overlay coatings for corrosion protection of steel compressor parts. The excellent properties are presented.

- Ceral 10 aluminide silicon doped for hot corrosion protection of turbine components made of superalloys. Coating structures and properties are discussed.
Sensitivity to interaural envelope correlation changes in bilateral cochlear-implant users
Authors: Goupell Matthew J. , Litovsky Ruth Y.
Published: January 2015

Provision of bilateral cochlear implants (CIs) to people who are deaf is partially justified by improved abilities to understand speech in noise when comparing bilateral vs unilateral listening conditions. However, bilateral CI listeners generally show only monaural head shadow with little improvement in speech understanding due to binaural unmasking. Sensitivity to change in interaural envelope correlation, which is related to binaural speech unmasking, was investigated. Bilateral CI users were tested with bilaterally synchronized processors at single, pitch-matched electrode pairs. First, binaural masking level differences (BMLDs) were measured using 1000 pulse-per-second (pps) carriers, yielding BMLDs of 11.1 ± 6.5 and 8.5 ± 4.2 dB for 10- and 50-Hz bandwidth masking noises, respectively. Second, envelope correlation change just-noticeable differences (JNDs) were measured. Stimuli presented at 1000 pps yielded lower JNDs than those presented at 100 pps. Furthermore, perfectly correlated reference stimuli produced lower JNDs than uncorrelated references, and uncorrelated references generally produced immeasurable JNDs. About 25% of JNDs measured in the CI listeners were in the range of JNDs observed in normal-hearing listeners presented CI simulations. In conclusion, CI listeners can perceive changes in interaural envelope correlation, but the poor performance may be a major limiting factor in binaural unmasking tested to date in realistic listening environments.
Perceptual thresholds for realistic double-slope decay reverberation in large coupled spaces
Authors: Luizard Paul , Katz Brian F. G. , Guastavino Catherine
Published: January 2015

Reverberation highly influences sound perception in enclosed spaces. The reverberation time (RT) metric, used to quantify reverberation in single volumes, is inappropriate for coupled spaces characterized by non-exponential double-slope energy decays. Previous research on reverberation perception of double-slope decays has been predominantly based on varying basic impulse response characteristics such as decay times corresponding to reverberation times of individual volumes presented as independent variables. Alternatively, several studies have employed geometrical room acoustic software simulations to generate collections of responses while varying architectural parameters such as coupling area and room volumes. To avoid issues related to geometrical acoustics simulations, such as position dependence and limitations of some software to properly simulate coupled volume behavior, this study examines perception of the variability of reverberation typical of a physical coupled volume system. Employing an established statistical model, the control parameter of coupling area aperture which acoustically connects the volumes serves as the independent variable. Two listening tests were conducted to determine perceptual thresholds using an ABX discrimination task. The range of tested values corresponded to physically realizable variations. Just noticeable differences (JNDs) were derived with an average JND of ≈ 10% variation of the coupling aperture. No significant differences were found between different musical excerpts.
Fewer lesions, more baby mice
Authors: Gough Nancy R.
Published: January 2015

The estrogen-dependent inflammatory and neuroangiogenic activities that drive endometriosis can be suppressed by estrogen receptor ligands in mice.
A Novel CDK7 Inhibitor of the Pyrazolotriazine Class Exerts Broad-Spectrum Antiviral Activity at Nanomolar Concentrations
Authors: Hutterer Corina , Eickhoff Jan , Milbradt Jens , Korn Klaus , Zeitträger Isabel , Bahsi Hanife , Wagner Sabrina , Zischinsky Gunther , Wolf Alexander , Degenhart Carsten , Unger Anke , Baumann Matthias , Klebl Bert , Marschall Manfred
Published: January 2015

Protein kinases represent central and multifunctional regulators of a balanced virus-host interaction. Cyclin-dependent protein kinase 7 (CDK7) plays crucial regulatory roles in cell cycle and transcription, both connected with the replication of many viruses. Previously, we developed a CDK7 inhibitor, LDC4297, that inhibits CDK7
in vitro
in the nano-picomolar range. Novel data from a kinome-wide evaluation (>330 kinases profiled
in vitro
) demonstrate a kinase selectivity. Importantly, we provide first evidence for the antiviral potential of the CDK7 inhibitor LDC4297, i.e., in exerting a block of the replication of human cytomegalovirus (HCMV) in primary human fibroblasts at nanomolar concentrations (50% effective concentration, 24.5 ± 1.3 nM). As a unique feature compared to approved antiherpesviral drugs, inhibition occurred already at the immediate-early level of HCMV gene expression. The mode of antiviral action was considered multifaceted since CDK7-regulated cellular factors that are supportive of HCMV replication were substantially affected by the inhibitors. An effect of LDC4297 was identified in the interference with HCMV-driven inactivation of retinoblastoma protein (Rb), a regulatory step generally considered a hallmark of herpesviral replication. In line with this finding, a broad inhibitory activity of the drug could be demonstrated against a selection of human and animal herpesviruses and adenoviruses, whereas other viruses only showed intermediate drug sensitivity. Summarized, the CDK7 inhibitor LDC4297 is a promising candidate for further antiviral drug development, possibly offering new options for a comprehensive approach to antiviral therapy.
Depot Medroxyprogesterone Acetate in Combination with a Twice-Daily Lopinavir-Ritonavir-Based Regimen in HIV-Infected Women Showed Effective Contraception and a Lack of Clinically Significant Interactions, with Good Safety and Tolerability: Results of the ACTG 5283 Study
Authors: Luque Amneris E. , Cohn Susan E. , Park Jeong-Gun , Cramer Yoninah , Weinberg Adriana , Livingston Elizabeth , Klingman Karin L. , Aweeka Francesca , Watts D. Heather
Published: January 2015

We conducted an open-label, steady-state pharmacokinetic (PK) study of drug-drug interactions between depot medroxyprogesterone acetate (DMPA) and twice-daily lopinavir (LPV) plus low-dose ritonavir (RTV) (LPV/r) among 24 HIV-infected women and compared the results to those for HIV-infected women receiving DMPA while on no antiretroviral therapy or on nucleosides only (
n
= 14 subjects from the control arm of AIDS Clinical Trials Group [ACTG] study 5093). The objectives of the study were to address the effect of LPV/r on DMPA and to address the effect of DMPA on LPV/r therapy. PK parameters were estimated using noncompartmental analysis with between-group comparisons of medroxyprogesterone acetate (MPA) PKs and within-subject comparisons of LPV and RTV PKs before and 4 weeks after DMPA dosing. Plasma progesterone concentrations were measured every 2 weeks after DMPA dosing through week 12. Although the MPA area under the concentration-time curve and maximum concentration of drug in plasma were statistically significantly increased in the study women on LPV/r compared to those in the historical controls, these increases were not considered clinically significant. There were no changes in LPV or RTV exposure after DMPA. DMPA was well tolerated, and suppression of ovulation was maintained. (This study has been registered at ClinicalTrials.gov under registration no. NCT01296152.)
Major Pathways of Polymyxin-Induced Apoptosis in Rat Kidney Proximal Tubular Cells
Authors: Azad Mohammad A. K. , Akter Jesmin , Rogers Kelly L. , Nation Roger L. , Velkov Tony , Li Jian
Published: January 2015

Identifying the pathways involved in the apoptotic cell death that is associated with polymyxin-induced nephrotoxicity is crucial for the development of strategies to ameliorate this dose-limiting side effect and for the development of novel safer polymyxins. The primary aim of this study was to identify the major pathways which lead to polymyxin-induced apoptosis in cultured rat kidney proximal tubular cells (NRK-52E). Caspase-3, -8, and -9 were activated by polymyxin B treatment in a concentration-dependent manner. Concentration- and time-dependent expression of FasL and deformation of mitochondrial morphology were revealed following polymyxin B treatment. The proportion of cells with filamentous mitochondria (regular morphology) following an 8-h treatment with 1.0 mM polymyxin B was 56.2% ± 9.7% (
n
= 3). This was decreased to 30.7% ± 7.5% when the polymyxin B concentration was increased to 2.0 mM. The mitochondrial membrane potential (Δψ
m
) decreased to 14.1% ± 2.9% in the cells treated with 1.0 mM polymyxin B for 24 h (
n
= 3) compared to that in the untreated control group. Concomitantly, concentration- and time-dependent production of mitochondrial superoxide was also observed. This study is the first to have demonstrated that polymyxin-induced apoptosis is mediated through both the death receptor and mitochondrial pathways in cultured renal tubular cells. It provides key information not only for the amelioration of polymyxin-induced nephrotoxicity but also for the discovery of novel safer polymyxin-like antibiotics against Gram-negative “superbugs.”
The C-Terminal Heavy-Chain Domain of Botulinum Neurotoxin A Is Not the Only Site That Binds Neurons, as the N-Terminal Heavy-Chain Domain Also Plays a Very Active Role in Toxin-Cell Binding and Interactions
Authors: Ayyar B. Vijayalakshmi , Aoki K. Roger , Atassi M. Zouhair
Published: January 2015

Botulinum neurotoxins (BoNTs) possess unique specificity for nerve terminals. They bind to the presynaptic membrane and then translocate intracellularly, where the light-chain endopeptidase cleaves the SNARE complex proteins, subverting the synaptic exocytosis responsible for acetylcholine release to the synaptic cleft. This inhibits acetylcholine binding to its receptor, causing paralysis. Binding, an obligate event for cell intoxication, is believed to occur through the heavy-chain C-terminal (H
C
) domain. It is followed by toxin translocation and entry into the cell cytoplasm, which is thought to be mediated by the heavy-chain N-terminal (H
N
) domain. Submolecular mapping analysis by using synthetic peptides spanning BoNT serotype A (BoNT/A) and mouse brain synaptosomes (SNPs) and protective antibodies against toxin from mice and cervical dystonia patients undergoing BoNT/A treatment revealed that not only regions of the H
C
domain but also regions of the H
N
domain are involved in the toxin binding process. Based on these findings, we expressed a peptide corresponding to the BoNT/A region comprising H
N
domain residues 729 to 845 (H
N
729–845). H
N
729–845 bound directly to mouse brain SNPs and substantially inhibited BoNT/A binding to SNPs. The binding involved gangliosides GT1b and GD1a and a few membrane lipids. The peptide bound to human or mouse neuroblastoma cells within 1 min. Peptide H
N
729–845 protected mice completely against a lethal BoNT/A dose (1.05 times the 100% lethal dose). This protective activity was obtained at a dose comparable to that of the peptide from positions 967 to 1296 in the H
C
domain. These findings strongly indicate that H
N
729–845 and, by extension, the H
N
domain are fully programmed and equipped to bind to neuronal cells and in the free state can even inhibit the binding of the toxin.
Blocking Yersiniabactin Import Attenuates Extraintestinal Pathogenic Escherichia coli in Cystitis and Pyelonephritis and Represents a Novel Target To Prevent Urinary Tract Infection
Authors: Brumbaugh Ariel R. , Smith Sara N. , Subashchandrabose Sargurunathan , Himpsl Stephanie D. , Hazen Tracy H. , Rasko David A. , Mobley Harry L. T.
Published: January 2015

The emergence and spread of extended-spectrum beta-lactamases and carbapenemases among common bacterial pathogens are threatening our ability to treat routine hospital- and community-acquired infections. With the pipeline for new antibiotics virtually empty, there is an urgent need to develop novel therapeutics. Bacteria require iron to establish infection, and specialized pathogen-associated iron acquisition systems like yersiniabactin, common among pathogenic species in the familyEnterobacteriaceae, including multidrug-resistantKlebsiella pneumoniaeand pathogenicEscherichia coli, represent potentially novel therapeutic targets. Although the yersiniabactin system was recently identified as a vaccine target for uropathogenicE. coli(UPEC)-mediated urinary tract infection (UTI), its contribution to UPEC pathogenesis is unknown. Using anE. colimutant (strain 536ΔfyuA) unable to acquire yersiniabactin during infection, we established the yersiniabactin receptor as a UPEC virulence factor during cystitis and pyelonephritis, a fitness factor during bacteremia, and a surface-accessible target of the experimental FyuA vaccine. In addition, we determined through transcriptome sequencing (RNA-seq) analyses of RNA fromE. colicausing cystitis in women that iron acquisition systems, including the yersiniabactin system, are highly expressed by bacteria during natural uncomplicated UTI. Given that yersiniabactin contributes to the virulence of several pathogenic species in the familyEnterobacteriaceae, including UPEC, and is frequently associated with multidrug-resistant strains, it represents a promising novel target to combat antibiotic-resistant infections.
Structure-Function Analysis of VapB4 Antitoxin Identifies Critical Features of a Minimal VapC4 Toxin-Binding Module
Authors: Jin Guangze , Pavelka Martin S. , Butler J. Scott
Published: January 2015

Bacterial toxin-antitoxin systems play a critical role in the regulation of gene expression, leading to developmental changes, reversible dormancy, and cell death. Type II toxin-antitoxin pairs, composed of protein toxins and antitoxins, exist in nearly all bacteria and are classified into six groups on the basis of the structure of the toxins. The VapBC group comprises the most common type II system and, like other toxin-antitoxin systems, functions to elicit dormancy by inhibiting protein synthesis. Activation of toxin function requires protease degradation of the VapB antitoxin, which frees the VapC toxin from the VapBC complex, allowing it to hydrolyze the RNAs required for translation. Generally, type II antitoxins bind with high specificity to their cognate toxins via a toxin-binding domain and endow the complex with DNA-binding specificity via a DNA-binding domain. Despite the ubiquity of VapBC systems and their critical role in the regulation of gene expression, few functional studies have addressed the details of VapB-VapC interactions. Here we report on the results of experiments designed to identify molecular determinants of the specificity of theMycobacterium tuberculosisVapB4 antitoxin for its cognate VapC4 toxin. The results identify the minimal domain of VapB4 required for this interaction as well as the amino acid side chains required for binding to VapC4. These findings have important implications for the evolution of VapBC toxin-antitoxin systems and their potential as targets of small-molecule protein-protein interaction inhibitors.

IMPORTANCEVapBC toxin-antitoxin pairs are the most widespread type II toxin-antitoxin systems in bacteria, where they are thought to play key roles in stress-induced dormancy and the formation of persisters. The VapB antitoxins are critical to these processes because they inhibit the activity of the toxins and provide the DNA-binding specificity that controls the synthesis of both proteins. Despite the importance of VapB antitoxins and the existence of several VapBC crystal structures, little is known about their functional featuresin vivo. Here we report the findings of the first comprehensive structure-function analysis of a VapB toxin. The results identify the minimal toxin-binding domain, its modular antitoxin function, and the specific amino acid side chains required for its activity.
Successfully treated symptomatic fusiform basilar artery aneurysm in a patient with hindbrain malformation via inverted Y-stenting
Authors: Purakal Alixandra S , Ginat Daniel Thomas , Lee Seon-Kyu
Published: January 2015

A double overlapping reverse Y-stent approach to creating flow diversion using traditional open-cell stent technology was evaluated as a treatment option symptomatic fusiform basilar aneurysms. A 36-year-old man with a complex hindbrain malformation presented with acute ocular dysmotility due to a rapidly enlarging fusiform basilar artery aneurysm. The aneurysm was treated by insertion of two stents into the vertebrobasilar system in an inverted Y-configuration from the basilar tip to the V4 segments of the bilateral vertebral arteries, essentially creating flow diversion without using a dedicated flow diversion device. This resulted in immediate symptomatic improvement. The stents remained patent and the aneurysm was obliterated at 6 months follow-up. Furthermore, the patient remained free of associated symptoms at 10 months follow-up. Thus, the double stenting technique can be used instead of a flow diversion device to effectively create flow diversion, promote aneurysm sac thrombosis, and lead to resolution of symptoms in large fusiform basilar artery aneurysms.
Congenital atresia of the inferior vena cava and antithrombin III deficiency in a young adult: compounding risk factors for deep vein thrombosis
Authors: Muscianese Laura , Seese Ronald R , Graham William , Williams James H
Published: January 2015

Atresia, or absence, of the inferior vena cava (AIVC) is a rare, usually fortuitous finding on advanced imaging that predisposes patients to deep venous thrombosis (DVT). In young adults who lack predisposing risk factors but nonetheless develop extensive or bilateral DVTs, AIVC should be considered. We describe a case of a previously healthy 17-year-old male patient who developed an extensive renal vein thrombus due to the absence of the superior portion of his IVC compounded with previously undiagnosed antithrombin III deficiency. We discuss the diagnosis and management of this complicated condition.
Cardiac asystoles misdiagnosed as epileptic seizures
Authors: Chiesa Valentina , Vignoli Aglaia , Canevini Maria Paola
Published: January 2015

We report a case of a 78-year-old man who presented several episodes of transient loss of consciousness preceded by sensation of ascending heat from the feet, with increasing frequency and duration within a few weeks. One month later he was admitted because he started to fall during the episodes, which became daily. Brain MRI detected a gliotic right frontal area, and EEG showed slow activity in the same region. Carbamazepine was started without clinical response despite high plasmatic level. Video-EEG polygraphic monitoring was performed and the patient showed an episode of left hemifacial clonic jerks followed by loss of consciousness, starting 17 s after the beginning of asystole. Synus rhythm reappeared 32 s later and the patient regained consciousness in few seconds. A pacemaker was implanted and carbamazepine was withdrawn. No further episodes occurred.
Extension of pancreatic pseudocyst into psoas muscle in a setting of acute pancreatitis
Authors: Aswani Yashant , Anandpara Karan Manoj , Hira Priya
Published: January 2015

Pancreatic pseudocysts are known to extend beyond the confines of the pancreatic bed due to the digestive nature of enzyme rich pancreatic fluid. Extension of a pseudocyst beyond the retroperitoneum, along the retrofascial plane within the psoas muscle is, however, unusual, with only a handful of cases described in the literature. We report a case of a 28-year-old man who presented with right lumbar pain and painful ipsilateral hip extension. Imaging findings revealed extension of the pseudocyst into psoas along with features of acute pancreatitis. The pseudocyst was drained percutaneously under image guidance, which led to resolution of symptoms.
Adenosine-induced tachycardia acceleration: an unusual proarrhythmia
Authors: Singh Vini , Salehi Negar , Thakur Ranjan Kumar
Published: January 2015

Adenosine is an effective agent for termination of most re-entrant supraventricular arrhythmias involving the atrioventricular node and often also used as a diagnostic agent for wide QRS tachycardias. Adenosine terminates 90–99% of re-entrant supraventricular tachycardias but it may rarely accelerate tachycardias. Adenosine-induced tachycardia acceleration is a rare phenomenon, as only a handful of cases have been described in the literature. We present a case of a 36-year-old man with a narrow complex, short RP tachycardia at a rate of 165 bpm and an initial blood pressure of 110/78 mm Hg. A bolus of 12 mg of adenosine resulted in slowing of the tachycardia to 150 bpm for 2–3 s, followed by acceleration of the tachycardia to 185 bpm that lasted for approximately 20 s and returned to baseline at 165 bpm. The main mechanism of adenosine-induced acceleration may be the secondary sympathetic stimulation, which may be preceded by transient bradycardia and/or hypotension.