bluuebunny/crossref_metadata_2025 huggingface dataset:
Calcium channels in rat horizontal cells regulate feedback inhibition of photoreceptors through an unconventional GABA‐ and pH‐sensitive mechanism
Authors: Liu Xue , Hirano Arlene A. , Sun Xiaoping , Brecha Nicholas C. , Barnes Steven
Published: April 2013

Key points

Inhibitory feedback from horizontal cells to photoreceptors regulates synaptic gain and contributes to centre–surround receptive field formation via mechanisms that are not fully understood.

We show that horizontal cell calcium channels and ionotropic GABA receptors mediate the inhibitory feedback, and that the results of their actions are blocked by strong pH buffering with Hepes.

GABA appears to act not upon the photoreceptor but instead upon the horizontal cell itself. The horizontal cell GABA receptors are permeable to chloride and bicarbonate, meaning their activation can produce changes in synaptic cleft pH.

These results suggest that activation of calcium channels in a depolarized horizontal cell releases GABA, which acts in an autaptic manner to increase bicarbonate permeability. The resulting influx of bicarbonate contributes to acidification of the synaptic cleft, inhibiting photoreceptor calcium channels, the hallmark of inhibitory feedback at this synapse.

Abstract  Horizontal cells send inhibitory feedback to photoreceptors, helping form antagonistic receptive fields in the retina, but the neurotransmitter and the mechanisms underlying this signalling are not known. Since the proteins responsible for conventional Ca2+‐dependent release of GABAergic synaptic vesicles are present in mammalian horizontal cells, we investigated this conventional mechanism as the means by which horizontal cells inhibit photoreceptors. Using Ca2+ imaging in rat retinal slices, we confirm that horizontal cell depolarization with kainate inhibits and horizontal cell hyperpolarization with NBQX disinhibits the Ca2+ signals produced by pH‐sensitive activation of voltage‐gated calcium channels (Ca channels) in photoreceptors. We show that while 100 μm Co2+ reduces photoreceptor Ca2+ signals, it disinhibits them at 10 μm, an effect reminiscent of earlier studies where low [Co2+] eliminated feedback. The low [Co2+] disinhibition is pH sensitive. We localized L‐, N‐ and P/Q‐type Ca channels in rat horizontal cells, and showed that both the N‐type Ca channel blocker ω‐conotoxin GVIA and the P/Q‐type Ca channel blocker ω‐agatoxin IVA increased Ca2+ signals in photoreceptors in a pH‐sensitive manner. Pronounced actions of GABAergic agents on feedback signals to photoreceptors were observed, and are pH sensitive, but are inconsistent with direct inhibition by GABA of photoreceptor [Ca2+]. Patch‐clamp studies revealed that GABA activates a conductance having high bicarbonate permeability in isolated horizontal cells, suggesting that the commonality of pH sensitivity throughout the results could arise from a GABA autofeedback action in horizontal cells. This could change cleft pH with concomitant inhibitory influences on photoreceptor Ca channels.
The kinetic properties of the α3 rat glycine receptor make it suitable for mediating fast synaptic inhibition
Authors: Marabelli Alessandro , Moroni Mirko , Lape Remigijus , Sivilotti Lucia G.
Published: April 2013

Key points

In the adult, most inhibitory transmission mediated by glycine uses channels containing α1 subunits, but both α1 and the related α3 subunit are present in spinal areas that process pain.

We recorded the effect of a range of fixed glycine concentrations on the activity of individual glycine channels expressed in vitro to contain only α3 subunits.

Glycine is very effective in opening α3 channels. At full activation, both α1 and α3 channels are open nearly 100% of the time, but α3 channels need all, or almost all, of the five glycine binding sites to be occupied, whereas α1 channels need only three.

When channels were activated in synaptic‐like conditions (fast, 1 ms, 10 mm glycine pulses), α3 responses decayed more slowly than α1 responses.

This difference is likely to be too small to allow α1‐ and α3‐mediated synaptic responses to be distinguishable on the basis of time course alone.

Abstract  Glycine receptors mediate fast synaptic inhibition in spinal cord and brainstem. Two α subunits are present in adult neurones, α1, which forms most of the synaptic glycine receptors, and α3. The physiological role of α3 is not known, despite the fact that α3 expression is concentrated in areas involved in nociceptive processing, such as the superficial dorsal horn. In the present study, we characterized the kinetic properties of rat homomeric α3 glycine receptors heterologously expressed in HEK293 cells. We analysed steady state single channel activity at a range of different glycine concentrations by fitting kinetic schemes and found that α3 channels resemble α1 receptors in their high maximum open probability (99.1% cf. 98% for α1), but differ in that maximum open probability is reached when all five binding sites are occupied by glycine (cf. three out of five sites for α1). α3 activation was best described by kinetic schemes that allow the channel to open also when partially liganded and that contain more than the minimum number of shut states, either as desensitized distal states (Jones and Westbrook scheme) or as pre‐open gating intermediates (flip scheme). We recorded also synaptic‐like α3 currents elicited by the rapid application of 1 ms pulses of high concentration glycine to outside‐out patches. These currents had fast deactivation, with a time constant of decay of 9 ms. Thus, if native synaptic currents can be mediated by α3 glycine receptors, they are likely to be very close in their kinetics to α1‐mediated synaptic events.
Interference Between Two Stationary or Elastically Supported Rigid Circular Cylinders of Unequal Diameters in Tandem and Staggered Arrangements
Authors: Huang Shan , Sworn Andy
Published: April 2013

Analysis of model test results was carried out to investigate the hydrodynamic interaction between pairs of fixed or elastically supported rigid cylinders of dissimilar diameters in a water flume. The two cylinders are placed with one situated in the wake of the other. The spacing between the cylinders ranges from 1 to 15 times the larger cylinder diameter. The Reynolds numbers are within the subcritical range. For the vibrating cylinders which are free to oscillate in both the in-line and the cross-flow directions, the reduced velocity ranges from 1 to 13 and the low damping ratio of the test setup at 0.006 gives a combined mass-damping parameter of 0.02. For the fixed cylinders, the downstream cylinder experiences a drag reduction and it was found that this drag reduction also depends upon the diameter ratio. The lift on the fixed downstream cylinder has the frequency components derived from the upstream cylinder's vortex shedding as well as from its own vortex shedding, and the relative importance of the two sources is influenced by the spacing between the two cylinders. This is reflected in the downstream cylinder's vortex induced vibration (VIV) response which appears to be dependent upon the actual reduced velocities of both the cylinders.
An Efficient Three-Dimensional FNPF Numerical Wave Tank for Large-Scale Wave Basin Experiment Simulation
Authors: Nimmala Seshu B. , Yim Solomon C. , Grilli Stephan T.
Published: April 2013

This paper presents a parallel implementation and validation of an accurate and efficient three-dimensional computational model (3D numerical wave tank), based on fully nonlinear potential flow (FNPF) theory, and its extension to incorporate the motion of a laboratory snake piston wavemaker, as well as an absorbing beach, to simulate experiments in a large-scale 3D wave basin. This work is part of a long-term effort to develop a “virtual” computational wave basin to facilitate and complement large-scale physical wave-basin experiments. The code is based on a higher-order boundary-element method combined with a fast multipole algorithm (FMA). Particular efforts were devoted to making the code efficient for large-scale simulations using high-performance computing platforms. The numerical simulation capability can be tailored to serve as an optimization tool at the planning and detailed design stages of large-scale experiments at a specific basin by duplicating its exact physical and algorithmic features. To date, waves that can be generated in the numerical wave tank (NWT) include solitary, cnoidal, and airy waves. In this paper we detail the wave-basin model, mathematical formulation, wave generation, and analyze the performance of the parallelized FNPF-BEM-FMA code as a function of numerical parameters. Experimental or analytical comparisons with NWT results are provided for several cases to assess the accuracy and applicability of the numerical model to practical engineering problems.
Reduced Order Modeling of a Bladed Rotor With Geometric Mistuning Via Estimated Deviations in Mass and Stiffness Matrices
Authors: Bhartiya Yasharth , Sinha Alok
Published: April 2013

This paper deals with further development of modified modal domain analysis (MMDA), which is a breakthrough method in the reduced order modeling of a bladed rotor with geometric mistuning. The main focus of this paper is to show that deviations in mass and stiffness matrices due to mistuning, estimated by Taylor series expansions in terms of independent proper orthogonal decomposition variables representing geometric variations of blades, can be used for MMDA. This result has rendered Monte Carlo simulation of the response of a bladed rotor with geometric mistuning to be easy and computationally efficient.
Crackle Noise in Heated Supersonic Jets
Authors: Nichols Joseph W. , Lele Sanjiva K. , Ham Frank E. , Martens Steve , Spyropoulos John T.
Published: April 2013

Crackle noise from heated supersonic jets is characterized by the presence of strong positive pressure impulses resulting in a strongly skewed far-field pressure signal. These strong positive pressure impulses are associated with N-shaped waveforms involving a shocklike compression and, thus, is very annoying to observers when it occurs. Unlike broadband shock-associated noise which dominates at upstream angles, crackle reaches a maximum at downstream angles associated with the peak jet noise directivity. Recent experiments (Martens et al., 2011, “The Effect of Chevrons on Crackle—Engine and Scale Model Results,” Proceedings of the ASME Turbo Expo, Paper No. GT2011-46417) have shown that the addition of chevrons to the nozzle lip can significantly reduce crackle, especially in full-scale high-power tests. Because of these observations, it was conjectured that crackle is associated with coherent large scale flow structures produced by the baseline nozzle and that the formation of these structures are interrupted by the presence of the chevrons, which leads to noise reduction. In particular, shocklets attached to large eddies are postulated as a possible aerodynamic mechanism for the formation of crackle. In this paper, we test this hypothesis through a high-fidelity large-eddy simulation (LES) of a hot supersonic jet of Mach number 1.56 and a total temperature ratio of 3.65. We use the LES solver CHARLES developed by Cascade Technologies, Inc., to capture the turbulent jet plume on fully-unstructured meshes.
A Methodology to Improve the Robustness of Gas Turbine Engine Performance Monitoring Against Sensor Faults
Authors: Dewallef Pierre , Borguet Sébastien
Published: April 2013

For turbine engine performance monitoring purposes, system identification techniques are often used to adapt a turbine engine simulation model to some measurements performed while the engine is in service. Doing so, the simulation model is adapted through a set of so-called health parameters whose values are intended to represent a faithful image of the actual health condition of the engine. For the sake of low computational burden, the problem of random errors contaminating the measurements is often considered to be zero mean, white, and Gaussian random variables. However, when a sensor fault occurs, the measurement errors no longer satisfy the Gaussian assumption and the results given by the system identification rapidly become unreliable. The present contribution is dedicated to the development of a diagnosis tool based on a Kalman filter whose structure is slightly modified in order to accommodate sensor malfunctions. The benefit in terms of the diagnostic reliability of the resulting tool is illustrated on several sensor faults that may be encountered on a current turbofan layout.
Advanced Combustor Concepts for Low Emissions Supersonic Propulsion
Authors: Smith Lance L. , Dai Zhongtao , Lee Jeremiah C. , Fotache Catalin G. , Cohen Jeffrey M. , Hautman Donald J.
Published: April 2013

Novel lean-burn combustor concepts were designed and evaluated for supersonic aircraft propulsion, with a focus on cruise NOx emissions. Premixing to lean conditions is especially challenging at supersonic cruise because combustor inlet temperatures are high and autoignition times are short. However, combustor pressure is significantly lower than at takeoff, so at cruise this allows heated jet fuel to be vaporized before injection as an aid to mixing. Two concepts—differentiated by swirler aerodynamics, swirler size, and staging method—were evaluated in the work reported here, both using injection of vaporized jet fuel. Computational fluid dynamics (CFD) calculations of mixing and combustion were used to design hardware for each concept. Injectors for each were fabricated using stereolithography (SLA) for cold-flow mixing tests, and using metal fabrication for subsequent combustion tests. Combustion test results show that emissions index for NOx (EINOx) < 5 was achieved for both concepts in single-sector tests at supersonic cruise combustor conditions.
Modeling and Validation of Rotational Vibration Responses for Accessory Drive System—Part II: Simulations and Analyses
Authors: Shangguan Wen-Bin , Zeng Xiang-Kun
Published: April 2013

This is the second part of the paper for modeling and validation of the rotational vibration responses for an accessory drive system. The unified formulas for modeling the rotational vibration of an accessory drive system are presented. In the modeling of an accessory drive system, the damping and stiffness of a belt are regarded as the function of the excitation frequency of an engine and the amplitude of belt stretching. Additionally, the creeping effect of a belt on the pulley wrap arc is included in the model. A general purpose software for calculating the rotational vibration of an accessory drive system is developed, based on the presented unified formulas. One accessory drive system with seven pulleys, a tensioner, and a serpentine belt is used as a studying example to demonstrate the unified formulas and the procedure for obtaining the rotational vibration. In the simulation of the accessory drive system, the stiffness and damping of the belt, the friction coefficient between the belt and pulley, and the excitation torques with multifrequency components from the crankshaft torsional vibration are obtained from the experiment in the first part of this paper. The static tension and steady-state tension of each belt span, along with the natural frequency of the accessory drive system, rotational vibrations of the driven pulley and tensioner arm, and the dynamic tension of the belt span are calculated and compared well with the experimental data, which validate the presented unified formulas and the developed general purpose software. The modeling method and the procedure described in this paper are instructive for designing an accessory drive system.
Boundary Layer Stagnation-Point Flow Toward a Stretching/Shrinking Sheet in a Nanofluid
Authors: Bachok Norfifah , Ishak Anuar , Pop Ioan
Published: April 2013

An analysis is carried out to study the steady two-dimensional stagnation-point flow of a nanofluid over a stretching/shrinking sheet in its own plane. The stretching/shrinking velocity and the ambient fluid velocity are assumed to vary linearly with the distance from the stagnation point. The model used for the nanofluid incorporates the effects of Brownian motion and thermophoresis. A similarity solution is presented which depends on the Prandtl number Pr, Lewis number Le, Brownian motion parameter Nb and thermophoresis parameter Nt. It is found that the local Nusselt number is a decreasing function, while the local Sherwood number is an increasing function of each parameters Pr, Le, Nb, and Nt. Different from a stretching sheet, the solutions for a shrinking sheet are nonunique.
Influence of Boiler Load Swing Rates on Response of Drum Water Level
Authors: Habib M. A. , Alzaharnah I. , El-Shafei M. , Al-Anizi S. , Al-Awwad M. Y. , Hajji M.
Published: April 2013

In this study, swing rates of drum boilers are investigated in regard to maintaining proper drum level limits. The nonlinear boiler model employed in study investigations was validated by comparing simulated results against literature data. Experimental field data was recorded for variations in firing, steam, and feedwater flow rates in addition to drum pressure and water level were obtained from a Saudi Aramco power plant. The experimental results were used also for tuning the water level control loop and finding the proportional and integral gains of the boiler model that was simulated using matlab. Influence of steam demand perturbations on water drum levels was tested using four different perturbation schemes and in all cases the levels were found to be within the allowable limits. The time variation of drum water level in response to 40% ramp increase in steam demand occurring at the four different input perturbations was obtained. The considered values of swing rates of steam flow were eight steps of 5% per minute, four steps of 10% per minute, two steps of 20% per minute, or one step of 40% per minute. Although the maximum transient water level overshoot is attained due to the one step of 40% per minute perturbation, still remains within the allowable limits of either the low or high levels according to the boiler manufacturer specifications. The present results indicate that the allowable swing rates are much lower in the case of drop in steam demand in comparison to the case of rise in steam demand.
Proof-of-Concept of the Shape Memory Alloy ReseTtable Dual Chamber Lift Device for Pedestrian Protection With Tailorable Performance
Authors: Otten James , Luntz Jonathan , Brei Diann , Strom Kenneth A. , Browne Alan L. , Johnson Nancy L.
Published: April 2013

As automobile use expands in population-dense cities across the world, there is a growing need for new approaches to mitigate the consequences to pedestrians of pedestrian/automotive collisions. This is especially challenging for passive approaches since there is an increasing internal space demand that reduces the crush zone between the relatively compliant hood and rigid underhood components. One unique approach is an active hood lift which raises the hood upon detection of a collision with a pedestrian to increase the crush zone. This approach is technically challenging due to the fast and accurate timing which is sensitive to extrinsic factors (including pedestrian height and weight and the need for reusable/automatically resettable functionality. This paper presents a novel hood lift concept: the shape memory alloy ReseTtable (SMArt) dual chamber lift device which is reusable, automatically resettable, and has tunable performance both off-line, and on-line to adjust to extrinsic factors. This device is situated under the rear corners of the hood and stores energy in the form of compressed air in opposing sides of a dual chamber pneumatic cylinder and a high-speed shape memory alloy exhaust valve (SEV) vents the upper chamber within milliseconds to allow the lower chamber to deploy the hood. A general multistage sequential design process is outlined that enables lift timing performance to be tailored by parametric design off-line and by varying operating parameters on-line. A proof-of-concept prototype was built and experimentally characterized for a midsize sedan case study confirming the timing, load capability and stroke of the device on the benchtop and the complete operational cycle in a full-scale automobile hood bay. The impact of additional mass on the lift timing was measured and two on-line adjustable operating parameters (pressure and valve timing) were investigated for their ability to compensate for the mass and other extrinsic effects. While this was a limited study of this new active technological approach to pedestrian safety, it does indicate promise to meet the strict demands of an active lift and a tailorable, resettable/reusable device.
Research on Wave Mode Conversion of Curved Beam Structures by the Wave Approach
Authors: Xiuchang Huang , Hongxing Hua , Yu Wang , Zhipeng Du
Published: April 2013

A general wave approach for the vibration analysis of curved beam structures is presented. The analysis is based on wave propagation, transmission, and reflection, including the effects of both propagating and decaying near-field wave components. A matrix formulation is used that offers a systematic and concise method for tackling free and forced vibrations of complex curved beam structures. To illustrate the effectiveness of the approach, several numerical examples are presented. The predictions made using the wave approach are shown to be in excellent agreement with a conventional finite element analysis, with the advantage of reduced computational costs and good conditioning number of the characteristic equation. The developed wave approach is applied to investigate the free vibration, vibration transmission, and power flow of built-up structures consisting of curved beams, straight beams, and masses, with the aim for designing vibration isolation structure with high attenuation ability. Wave reflection and transmission in the infinite curved beam structure, as well as vibration and energy transmission in coupled finite curved beam structure are investigated. Numerical results show that wave mode conversion takes place for the reflected and transmitted wave propagating through a curved beam, and the power flow in the coupled curved beam structure shows energy attenuation and conversion by curved beam and the discontinuities. The investigation will shed some light on the designing of curved beam structures.
Analytical Solutions for Stable and Unstable Period-1 Motions in a Periodically Forced Oscillator With Quadratic Nonlinearity
Authors: Luo Albert C. J. , Yu Bo
Published: April 2013

In this note, a closed-form solution of periodic motions in a periodically forced oscillator with quadratic nonlinearity is presented without any small parameters. The perturbation method is based on one harmonic term plus perturbation modification, and the traditional harmonic balance is to arbitrarily select harmonic terms with constant coefficients. If harmonic terms are not enough included in the approximate solution, such a solution is not an appropriate, analytical solution for periodic motions, and some analytical solutions cannot be caught.
Coherent Streamwise Vortex Structures in the Near-Field of the Three-Dimensional Wall Jet
Authors: Namgyal Lhendup , Hall Joseph W.
Published: April 2013

A turbulent three-dimensional wall jet with an exit Reynolds number of 250,000 was investigated using stereoscopic particle image velocimetry (PIV) in the near-field region (x/D = 5). The proper orthogonal decomposition (POD) was applied to all three components of the velocity field to investigate the underlying coherent structures in the flow. A low-dimensional reconstruction of the turbulent velocity field using the first five POD modes showed the presence of coherent streamwise vortex structures formed in the outer shear-layers of the wall jet, not unlike those found in the near-field of free jets. The instantaneous streamwise vorticity reconstructed from the low-dimensional reconstructed velocity field indicates the presence of a persistent vortex pair close to the wall and on either side of the jet centerline that appear similar to the mean streamwise vorticity. These regions do not appear to be directly related to the positioning of the streamwise vortex structures in the outer shear-layer.
A Study on Module Clustering and Evaluation of Large Gantry Machining Centers
Authors: Chen Weifang , Cao Lijie , Ye Wenhua
Published: April 2013

Due to the various requirements of users and large volume of machine tools, most machine tool manufacturers are adopting the small-lot production mode, which largely prolongs the product development cycle. To raise the design efficiency and reduce the complexity, modular design is becoming widely used in serial production of machine tools, especially large gantry machining centers. In this paper, we introduced a function and structure decomposition method to construct the function and structure correlations between components and employed a clustering method based on atomic theory to solve the module clustering problems. The clustering algorithm is modified by integrating the function and structure matrices in order that it applies to modularization of large machine tools. Furthermore, an evaluation method based on the concept of entropy is proposed here to evaluate and optimal select module partition schemes. Finally, we took the large gantry machining center QLMT6300 as an example and compiled the program with Microsoft Visual C++ 6.0 to illustrate the validity of the methods proposed. The presented clustering and evaluation method can be easily applied to different machine tools for modular design, reducing the work amount of designers.
On the Correctness and Strictness of the Position and Orientation Characteristic Equation for Topological Structure Design of Robot Mechanisms
Authors: Yang Ting-Li , Liu An-Xin , Shen Hui-Ping , Luo Yu-Feng , Hang Lu-Bin , Shi Zhi-Xin
Published: April 2013

Position and orientation characteristic (POC) equations for topological structure synthesis of serial and parallel mechanisms were proposed in a published paper by the authors. This paper will further prove the correctness and strictness of the theoretical foundation for POC equations and also be a reply to the reviewers of our follow-up papers. The main contents of this paper include: symbolic representation of mechanism topological structure and its invariance, velocity characteristic (VC) set and POC set of link and its invariance, one-to-one correspondence between elements of the VC set and POC set, POC equations for the serial mechanism and 10 corresponding “union” operation rules, and POC equations for the parallel mechanism and 14 corresponding “intersection” operation rules. In addition, the interrelations and differences among three methods (POC set based method, screw theory based method, and displacement subgroup based method) for mechanism topological structure design are concluded.
Objective-Oriented Sequential Sampling for Simulation Based Robust Design Considering Multiple Sources of Uncertainty
Authors: Arendt Paul D. , Apley Daniel W. , Chen Wei
Published: April 2013

Sequential sampling strategies have been developed for managing complexity when using computationally expensive computer simulations in engineering design. However, much of the literature has focused on objective-oriented sequential sampling methods for deterministic optimization. These methods cannot be directly applied to robust design, which must account for uncontrollable variations in certain input variables (i.e., noise variables). Obtaining a robust design that is insensitive to variations in the noise variables is more challenging. Even though methods exist for sequential sampling in design under uncertainty, the majority of the existing literature does not systematically take into account the interpolation uncertainty that results from limitations on the number of simulation runs, the effect of which is inherently more severe than in deterministic design. In this paper, we develop a systematic objective-oriented sequential sampling approach to robust design with consideration of both noise variable uncertainty and interpolation uncertainty. The method uses Gaussian processes to model the costly simulator and quantify the interpolation uncertainty within a robust design objective. We examine several criteria, including our own proposed criteria, for sampling the design and noise variables and provide insight into their performance behaviors. We show that for both of the examples considered in this paper the proposed sequential algorithm is more efficient in finding the robust design solution than a one-shot space filling design.
Passive Dynamic Biped Walking—Part I: Development and Validation of an Advanced Model
Authors: Koop Derek , Wu Christine Q.
Published: April 2013

Passive dynamic walking is a manner of walking developed, partially or in whole, by the energy provided by gravity. Studying passive dynamic walking provides insight into human walking and is an invaluable tool for designing energy-efficient biped robots. The objective of this research was to develop a continuous mathematical model of passive dynamic walking, in which the Hunt–Crossley contact model, and the LuGre friction model were used to represent the normal and tangential ground reactions continuously. A physical passive walker was built to validate the proposed mathematical model. A traditional impact-based passive walking model was also used as a reference to demonstrate the advancement of the proposed passive dynamic walking model. The simulated gait of the proposed model matched the gait of the physical passive walker exceptionally well, both in trend and magnitude.
Pinion Assembly Strategies for Planetary Gear Sets
Authors: Feng Pei-en , Qi Yuxuan , Qiu Qingying
Published: April 2013

Previous works illustrate that the orientation of pinion run-out errors has strong effect on the load sharing behavior of floating planetary gear sets. To minimize the inequality of load sharing, an in-phase rule for assembling pinions is recommended by other researchers, while a theoretical proof is still lacking. In this paper, not only the orientation but also the assembly sequence of the pinions is under scrutiny. A generalized mathematical model is developed in order to study the best load sharing conditions and floating gear sets with 4-6 pinions are specially treated. Through statistical calculation, several pinion sequence rules and orientation rules are extracted. By numerical simulation, four different pinion assembly strategies, which originate from the combinations of the existing rules and methods, are compared with each other. The most effective assembly strategies for systems with 4-6 pinions are proposed. The statistical analysis indicates that the proposed strategies significantly improve the load sharing behavior if only pinion run-out errors are considered and retain their effectiveness when pinhole position errors and tooth thickness errors are introduced as interference factors.
An Experimental and Modeling Study of the Viscoelastic Behavior of Collagen Gel
Authors: Xu Bin , Li Haiyue , Zhang Yanhang
Published: April 2013

The macroscopic viscoelastic behavior of collagen gel was studied through relaxation time distribution spectrum obtained from stress relaxation tests and viscoelastic constitutive modeling. Biaxial stress relaxation tests were performed to characterize the viscoelastic behavior of collagen gel crosslinked with Genipin solution. Relaxation time distribution spectrum was obtained from the stress relaxation data by inverse Laplace transform. Peaks at the short (0.3 s–1 s), medium (3 s–90 s), and long relaxation time (>200 s) were observed in the continuous spectrum, which likely correspond to relaxation mechanisms involve fiber, inter-fibril, and fibril sliding. The intensity of the long-term peaks increases with higher initial stress levels indicating the engagement of collagen fibrils at higher levels of tissue strain. We have shown that the stress relaxation behavior can be well simulated using a viscoelastic model with viscous material parameters obtained directly from the relaxation time spectrum. Results from the current study suggest that the relaxation time distribution spectrum is useful in connecting the macro-level viscoelastic behavior of collagen matrices with micro-level structure changes.
Clinical Uncertainty of Prostate Cancer Genetic Risk Panels
Authors: Pomerantz Mark , Freedman Matthew L.
Published: April 2013

Scores of genetic markers associated with prostate-cancer risk have been discovered to date, but their clinical utility remains unclear.
T2 Magnetic Resonance Enables Nanoparticle-Mediated Rapid Detection of Candidemia in Whole Blood
Authors: Neely Lori A. , Audeh Mark , Phung Nu Ai , Min Michael , Suchocki Adam , Plourde Daniella , Blanco Matthew , Demas Vasiliki , Skewis Lynell R. , Anagnostou Theodora , Coleman Jeffrey J. , Wellman Parris , Mylonakis Eleftherios , Lowery Thomas J.
Published: April 2013

Nanoparticles and T2 magnetic resonance allow for DNA amplification and detection of
Candida
species in clinical whole-blood specimens.
Is Pulmonary Arterial Hypertension a Cancer?
Authors: Tonelli Adriano R.
Published: April 2013

Nutlin-3A, a selective molecule that stabilizes p53, can induce pulmonary artery smooth-muscle cell-growth arrest, preventing or reversing pulmonary hypertension in mouse models.
Partial Disruption of Translational and Posttranslational Machinery Reshapes Growth Rates of Bartonella birtlesii
Authors: Rolain Jean Marc , Vayssier-Taussat Muriel , Saisongkorh Watcharee , Merhej Vicky , Gimenez Gregory , Robert Catherine , Le Rhun Danielle , Dehio Christoph , Raoult Didier
Published: April 2013

Specialization of bacteria in a new niche is associated with genome repertoire changes, and speciation in bacterial specialists is associated with genome reduction. Here, we tested a signature-tagged mutant library of 3,456
Bartonella birtlesii
clones to detect mutants that could grow rapidly
in vitro
. Overall, we found 124 mutants that grew faster than the parental wild-type strain
in vitro
. We sequenced the genomes of the four mutants with the most rapid growth (formed visible colonies in only 1 to 2 days compared with 5 days for the wild type) and compared them to the parental isolate genome. We found that the number of disrupted genes associated with translation in the 124 rapid-growth clones was significantly higher than the number of genes involved in translation in the full genome (
P
< 10
−6
). Analysis of transposon integration in the genome of the four most rapidly growing clones revealed that one clone lacked one of the two wild-type RNA ribosomal operons. Finally, one of the four clones did not induce bacteremia in our mouse model, whereas infection with the other three resulted in a significantly lower bacterial count in blood than that with the wild-type strain.

IMPORTANCE
Here, we show that specialization in a specific niche could be caused by the disruption of critical genes. Most of these genes were involved in translation, and we show that evolution of obligate parasitism bacteria was specifically associated with disruption of translation system-encoding genes.
Divergent Protein Motifs Direct Elongation Factor P-Mediated Translational Regulation in Salmonella enterica and Escherichia coli
Authors: Hersch Steven J. , Wang Mengchi , Zou S. Betty , Moon Kyung-Mee , Foster Leonard J. , Ibba Michael , Navarre William Wiley
Published: April 2013

Elongation factor P (EF-P) is a universally conserved bacterial translation factor homologous to eukaryotic/archaeal initiation factor 5A. In
Salmonella
, deletion of the
efp
gene results in pleiotropic phenotypes, including increased susceptibility to numerous cellular stressors. Only a limited number of proteins are affected by the loss of EF-P, and it has recently been determined that EF-P plays a critical role in rescuing ribosomes stalled at PPP and PPG peptide sequences. Here we present an unbiased
in vivo
investigation of the specific targets of EF-P by employing stable isotope labeling of amino acids in cell culture (SILAC) to compare the proteomes of wild-type and
efp
mutant
Salmonella
. We found that metabolic and motility genes are prominent among the subset of proteins with decreased production in the
Δefp
mutant. Furthermore, particular tripeptide motifs are statistically overrepresented among the proteins downregulated in
efp
mutant strains. These include both PPP and PPG but also additional motifs, such as APP and YIRYIR, which were confirmed to induce EF-P dependence by a translational fusion assay. Notably, we found that many proteins containing polyproline motifs are not misregulated in an EF-P-deficient background, suggesting that the factors that govern EF-P-mediated regulation are complex. Finally, we analyzed the specific region of the PoxB protein that is modulated by EF-P and found that mutation of any residue within a specific GSCGPG sequence eliminates the requirement for EF-P. This work expands the known repertoire of EF-P target motifs and implicates factors beyond polyproline motifs that are required for EF-P-mediated regulation.

IMPORTANCE
Bacterial cells regulate gene expression at several points during and after transcription. During protein synthesis, for example, factors can interact with the ribosome to influence the production of specific proteins. Bacterial elongation factor P (EF-P) is a protein that facilitates the synthesis of proteins that contain polyproline motifs by preventing the ribosome from stalling. Bacterial cells that lack EF-P are viable but are sensitive to a large number of stress conditions. In this study, a global analysis of protein synthesis revealed that EF-P regulates many more proteins in the cell than predicted based solely on the prevalence of polyproline motifs. Several new EF-P-regulated motifs were uncovered, thereby providing a more complete picture of how this critical factor influences the cell’s response to stress at the level of protein synthesis.
Pulmonary sarcoid-like granulomatous disease in an 11-month-old girl
Authors: Nathan Nadia , Pautrat Jade , Coulomb l'Hermine Aurore , Corvol Harriet
Published: April 2013

Sarcoidosis is a chronic granulomatous disease of unknown aetiology. It is extremely rare in children, especially the early onset form, presenting with eye, skin and joint symptoms but no lung involvement. We report an 11-month-old girl with granulomatous disease restricted to the lungs consistent with sarcoidosis. This unusual presentation has never been described in the paediatric literature so far.
Low bilirubin kernicterus with sepsis and hypoalbuminaemia
Authors: Odutolu Yetunde , Emmerson Anthony J
Published: April 2013

A near-term female neonate with total serum bilirubin levels not exceeding the exchange transfusion level with hypoalbuminaemia developed abnormal movements while recovering from sepsis. Investigations showed an evidence of kernicterus on brain imaging and bilateral auditory neuropathic changes.
Lead shot incarceration in appendix: an unusual cause of appendicular foreign body
Authors: Munipalle P C , Little M , Garud T
Published: April 2013

A previously fit man was investigated for right-sided abdominal pain and an appendicular foreign body (FB) caused by ingested lead shot was found. He had associated urinary tract infection causing his symptoms and hence was treated conservatively. We present this rare case, followed by discussion of the causes, investigations, clinical significance and management of appendicular FBs.
Which patients with chronic obstructive pulmonary disease benefit from the addition of an inhaled corticosteroid to their bronchodilator? A cluster analysis
Authors: DiSantostefano Rachael L , Li Hao , Rubin David B , Stempel David A
Published: April 2013

Objective

To identify subsets of chronic obstructive pulmonary disease (COPD) patients who are more protected from exacerbations with the use of an inhaled corticosteroid/long-acting β2agonist (ICS/LABA) combination, compared with the use of LABA monotherapy.

Design

Post hoc cluster analysis of patients from two randomised clinical trials of salmeterol/fluticasone propionate (SFC) and salmeterol (SAL) that had primary endpoints of moderate/severe exacerbation rates.

Setting

Centres in North America.

Participants

1543 COPD patients were studied.

Interventions

SFC 50/250 µg or SAL 50 µg, twice daily.

Primary and secondary outcome measures

The analysis identified clusters of COPD patients more responsive to SFC versus SAL with respect to the annual rate of moderate/severe exacerbations and compared their baseline clinical characteristics.

Results

Overall, SFC significantly reduced the annual rate of moderate/severe exacerbations as compared with SAL alone (rate ratio (RR)=0.701, p<0.001). Three-patient clusters were identified: COPD patients receiving diuretics (RR=0.56, p<0.001); patients not receiving diuretics but with forced expiratory volume in 1 s (FEV1) reversibility ≥12% (RR=0.67, p<0.001) exhibited a substantial reduction in the annual rate of moderate/severe exacerbations relative to SAL. A third cluster, consisting of patients not receiving diuretics and without FEV1reversibility, demonstrated no difference for SFC versus SAL. Patients receiving diuretics had a significantly higher prevalence of comorbid cardiovascular disease.

Conclusions

COPD patients receiving diuretics and those not receiving diuretics but with FEV1reversibility >12% at baseline were significantly more likely to experience a reduction in COPD-associated exacerbations with SFC versus SAL alone.

Trial registration

NCT00115492,NCT00144911
Centor criteria in children in a paediatric emergency department: for what it is worth
Authors: Roggen Inge , van Berlaer Gerlant , Gordts Frans , Pierard Denis , Hubloue Ives
Published: April 2013

Introduction

Centor criteria (fever >38.5°C, swollen, tender anterior cervical lymph nodes, tonsillar exudate and absence of cough) are an algorithm to assess the probability of group A β haemolyticStreptococcus(GABHS) as the origin of sore throat, developed for adults. We wanted to evaluate the correlation between Centor criteria and presence of GABHS in children with sore throat admitted to our paediatric emergency department (PED).

Design

Retrospective cohort study.

Setting

The emergency department of a large tertiary university hospital in Brussels, with over 20 000 yearly visits for children below age 16.

Participants

All medical records (from 2008 to 2010) of children between ages 2 and 16, who were diagnosed with pharyngitis, tonsillitis or sore throat and having a throat swab culture for GABHS. Children with underlying chronic respiratory, cardiac, haematological or immunological diseases and children who had already received antibiotics (AB) prior to the PED consult were excluded. Only records with a full disease history were selected. Out of a total 2118 visits for sore throats, 441 met our criteria. The children were divided into two age groups, 2–5 and 5–16 years.

Results

The prevalence of GABHS was higher in the older children compared to the preschoolers (38.7 vs 27.6; p=0.01), and the overall prevalence was 32%. There was no significant difference in the prevalence of GABHS for all different Centor scores within an age group. Likelihood ratios (LR) demonstrate that none of the individual symptoms or a Centor score of ≥3 seems to be effective in ruling in or ruling out GABHS. Pooled LR (CI) for Centor ≥3 was 0.67 (CI 0.50 to 0.90) for the preschoolers and 1.37 (CI 1.04 to 1.79) for the older children.

Conclusions

Our results confirm the ineffectiveness of Centor criteria as a predicting factor for finding GABHS in a throat swab culture in children.
Dysregulation of CDX1, CDX2 and SOX2 in patients with gastric cancer also affects the non-malignant mucosa
Authors: Bornschein Jan , Tóth Kinga , Selgrad Michael , Kuester Doerthe , Wex Thomas , Molnár Béla , Tulassay Zsolt , Malfertheiner Peter
Published: April 2013

The interplay between gastric and intestinal transcription factors has an important impact on gastric carcinogenesis. We compared the gene expression of CDX1, CDX2, SOX2 and related downstream genes in tumour and tumour surrounding gastric tissue of 48 gastric cancer patients with 30 healthy controls. There was no difference of gene expression of CDX1 and CDX2 between tumour or tumour-adjacent and tumour-distant mucosa, but both factors were significantly higher expressed in cancer patients compared with controls (p<0.01). SOX2 was downregulated in tumour tissue compared to controls, whereas tumour-adjacent and tumour-distant mucosa showed intermediate SOX2 expression. Laurén type andHelicobacter pyloriinfection had no significant impact on expression of the transcription factors. Expression of CDX1 and CDX2 was higher in the presence of intestinal metaplasia. The differential regulation of the gene expression of CDX1, CDX2 and SOX2 in patients with gastric cancer affects not only the tumour but also the non-neoplastic tumour-distant mucosa.
Prevalence and incidence ofTrichomonas vaginalisinfections in women participating in a clinical trial in Durban, South Africa
Authors: Naidoo Sarita , Wand Handan
Published: April 2013

Background and objectives

Trichomonas vaginalisis known to be the most common, curable, sexually transmitted infection among sexually active women and may be associated with the acquisition and transmission of HIV. The purpose of this analysis is to determine the prevalence and incidence ofT vaginalisand assess risk factors associated withT vaginalisinfection in a cohort of women participating in a clinical trial.

Methods

We analysed data from women participating in a phase III vaginal diaphragm trial conducted in two communities in Durban, South Africa from 2003 to 2006. A total of 3492 women were screened and 1485 women meeting the respective study eligibility criteria were enrolled.T vaginalisinfection was determined at the initial screening visit and at quarterly visits among the enrolled women. Sexual behaviour and sociodemographic data were collected as per the study protocol. Combined data were analysed using STATA V.10.0.

Results

At baseline, prevalence of infection was 6.5%. The overall incident rate was estimated to be 8.6/100 women-years. PrevalentT vaginalisinfection was associated with having a concurrent chlamydial infection and incident infections were associated with increased number of sex partners.

Conclusions

T vaginalisinfection was found to be relatively high among this cohort of women. Given the association of this infection with HIV, there is an evident need forT vaginalisscreening and treatment in populations at risk for both infections.