bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic Stress Analysis of Battery Tabs Under Ultrasonic Welding
Authors: Kang Bongsu , Cai Wayne , Tan Chin-An
Published: March 2014

Ultrasonic metal welding is widely used for joining multiple layers of dissimilar metals, such as aluminum/copper battery tabs welding onto copper busbars. It is therefore important to have a robust product/process design using ultrasonic metal welding that ensures consistent welds with desired quality. In this work, the effects of longitudinal and flexural vibrations of the battery tab during ultrasonic welding on the development of axial normal stresses that occasionally cause cracks near the weld area are studied by applying a one-dimensional continuous vibration model for the battery tab. Analysis results indicate that fracture could occur near the weld area, due to low cycle fatigue as a result of large dynamic stresses induced by resonant flexural vibration of the battery tab during welding. This study provides a fundamental understanding of battery tab dynamics during ultrasonic welding and its effects on weld quality, and can be used to develop guidelines for product/process design of ultrasonically welded battery tabs.
Thermal Postbuckling of Imperfect Circular Functionally Graded Material Plates: Examination of Voigt, Mori–Tanaka, and Self-Consistent Schemes
Authors: Kiani Y. , Eslami M. R.
Published: March 2014

Thermal postbuckling of solid circular plates made of a through-the-thickness functionally graded material (FGM) is analyzed in this paper. Initial imperfection of the plate is also taken into account. Each thermomechanical property of the plate is assumed to be a function of the temperature and thickness coordinate. Equivalent properties of the FGM media are obtained based on three different homogenization schemes, namely, Voigt rule, Mori–Tanaka scheme, and self-consistent estimate. Temperature profile is assumed to be through-the-thickness direction only. The solution of the heat conduction equation is obtained using an iterative central finite difference scheme. Various types of thermal loadings, such as uniform temperature rise, temperature specified at surfaces, and heat flux, are considered. Nonlinear equilibrium equations of the plate are obtained by means of the conventional Ritz method. Solution of the resulting nonlinear equilibrium equations and temperature distribution are obtained simultaneously at each step of heating. It is shown that response of a perfect clamped FGM plate is of the bifurcation type of buckling with stable postbuckling equilibrium branch, whereas imperfect clamped and perfect/imperfect simply supported FGM plates do not reveal the bifurcation type of instability through the nonuniform heating process. Furthermore, amplitude of initial imperfection is an important factor on the equilibrium path of FGM circular plates, especially for simply supported ones.
Creating Physiologically Realistic Vertebral Fractures in a Cervine Model
Authors: Corbiere Nicole C. , Lewicki Kathleen A. , Issen Kathleen A. , Kuxhaus Laurel
Published: March 2014

Approximately 50% of women and 25% of men will have an osteoporosis-related fracture after the age of 50, yet the micromechanical origin of these fractures remains unclear. Preventing these fractures requires an understanding of compression fracture formation in vertebral cancellous bone. The immediate research goal was to create clinically relevant (midvertebral body and endplate) fractures in three-vertebrae motion segments subject to physiologically realistic compressional loading conditions. Six three-vertebrae motion segments (five cervine, one cadaver) were potted to ensure physiologic alignment with the compressive load. A 3D microcomputed tomography (microCT) image of each motion segment was generated. The motion segments were then preconditioned and monotonically compressed until failure, as identified by a notable load drop (48–66% of peak load in this study). A second microCT image was then generated. These three-dimensional images of the cancellous bone structure were inspected after loading to qualitatively identify fracture location and type. The microCT images show that the trabeculae in the cervine specimens are oriented similarly to those in the cadaver specimen. In the cervine specimens, the peak load prior to failure is highest for the L4–L6 motion segment, and decreases for each cranially adjacent motion segment. Three motion segments formed endplate fractures and three formed midvertebral body fractures; these two fracture types correspond to clinically observed fracture modes. Examination of normalized-load versus normalized-displacement curves suggests that the size (e.g., cross-sectional area) of a vertebra is not the only factor in the mechanical response in healthy vertebral specimens. Furthermore, these normalized-load versus normalized-displacement data appear to be grouped by the fracture type. Taken together, these results show that (1) the loading protocol creates fractures that appear physiologically realistic in vertebrae, (2) cervine vertebrae fracture similarly to the cadaver specimen under these loading conditions, and (3) that the prefracture load response may predict the impending fracture mode under the loading conditions used in this study.
A Computational Biomechanical Investigation of Posterior Dynamic Instrumentation: Combination of Dynamic Rod and Hinged (Dynamic) Screw
Authors: Erbulut Deniz U. , Kiapour Ali , Oktenoglu Tunc , Ozer Ali F. , Goel Vijay K.
Published: March 2014

Currently, rigid fixation systems are the gold standard for degenerative disk disease treatment. Dynamic fixation systems have been proposed as alternatives for the treatment of a variety of spinal disorders. These systems address the main drawbacks of traditional rigid fixation systems, such as adjacent segment degeneration and instrumentation failure. Pedicle-screw-based dynamic stabilization (PDS) is one type of these alternative systems. The aim of this study was to simulate the biomechanical effect of a novel posterior dynamic stabilization system, which is comprised of dynamic (hinged) screws interconnected with a coiled, spring-based dynamic rod (DSDR), and compare it to semirigid (DSRR and RSRR) and rigid stabilization (RSRR) systems. A validated finite element (FE) model of L1-S1 was used to quantify the biomechanical parameters of the spine, such as range of motion, intradiskal pressure, stresses and facet loads after single-level instrumentation with different posterior stabilization systems. The results obtained from in vitro experimental intact and instrumented spines were used to validate the FE model, and the validated model was then used to compare the biomechanical effects of different fixation and stabilization constructs with intact under a hybrid loading protocol. The segmental motion at L4–L5 increased by 9.5% and 16.3% in flexion and left rotation, respectively, in DSDR with respect to the intact spine, whereas it was reduced by 6.4% and 10.9% in extension and left-bending loads, respectively. After instrumentation-induced intradiskal pressure at adjacent segments, L3-L4 and L5-S1 became less than the intact in dynamic rod constructs (DSDR and RSDR) except in the RSDR model in extension where the motion was higher than intact by 9.7% at L3-L4 and 11.3% at L5-S1. The facet loads were insignificant, not exceeding 12N in any of the instrumented cases in flexion. In extension, the facet load in DSDR case was similar to that in intact spine. The dynamic rod constructions (DSDR and RSDR) led to a lesser peak stress at screws compared with rigid rod constructions (DSRR and RSRR) in all loading cases. A dynamic construct consisting of a dynamic rod and a dynamic screw did protect the adjacent level from excessive motion.
A Computational Model to Describe the Regional Interlamellar Shear of the Annulus Fibrosus
Authors: Labus Kevin M. , Han Sang Kuy , Hsieh Adam H. , Puttlitz Christian M.
Published: March 2014

Interlamellar shear may play an important role in the homeostasis and degeneration of the intervertebral disk. Accurately modeling the shear behavior of the interlamellar compartment would enhance the study of its mechanobiology. In this study, physical experiments were utilized to describe interlamellar shear and define a constitutive model, which was implemented into a finite element analysis. Ovine annulus fibrosus (AF) specimens from three locations within the intervertebral disk (lateral, outer anterior, and inner anterior) were subjected to in vitro mechanical shear testing. The local shear stress–stretch relationship was described for the lamellae and across the interlamellar layer of the AF. A hyperelastic constitutive model was defined for interlamellar and lamellar materials at each location tested. The constitutive models were incorporated into a finite element model of a block of AF, which modeled the interlamellar and lamellar layers using a continuum description. The global shear behavior of the AF was compared between the finite element model and physical experiments. The shear moduli at the initial and final regions of the stress–strain curve were greater within the lamellae than across the interlamellar layer. The difference between interlamellar and lamellar shear was greater at the outer anterior AF than at the inner anterior region. The finite element model was shown to accurately predict the global shear behavior or the AF. Future studies incorporating finite element analysis of the interlamellar compartment may be useful for predicting its physiological mechanical behavior to inform the study of its mechanobiology.
An Experimentally Validated Model for Reciprocating Compressor Main Bearings for Applications in Health Monitoring
Authors: Holzenkamp Markus , Kolodziej Jason R. , Boedo Stephen , Delmotte Scott
Published: March 2014

A simple model of compressor main bearings was evaluated using the mobility method. The model allows for the simulation of the three loading conditions of the compressor, as well as accounting for the geometry of the connecting rod and crankshaft. The simulation was then compared against the results from measuring the orbit of the crankshaft. This is a simple and low cost way to monitor the main bearings without installing sensors directly into the bearing sleeve. The results show good qualitative agreement to move forward with developing the model and sensor application with the end goal of application to health monitoring.
Modeling, Identification, and Adaptive Robust Motion Control of Voice-Coil Motor Driven Stages
Authors: Li Chao , Chen Zheng , Yao Bin , Zhu Xiaocong , Liu Hao
Published: March 2014

Voice-coil motors are widely used in precision motion control of industrial applications such as head positioning of hard disk drives, semiconductor fabrication and packaging. In this paper, to achieve high precision movement potential of vertical voice-coil motor driven stages, the accurate modeling of nonlinear rigid body dynamics is developed, and the model parameters are estimated by the identification experiments in time domain. The neglected high-frequency dynamics are also identified through frequency response experiments to verify the validity of the frequency range of the proposed rigid-body dynamical model. To attenuate the serious nonlinear effect of the plant dynamics, Coulomb friction compensation is used when obtaining the frequency response results. Based on the verified nonlinear rigid-body dynamical model, an adaptive robust controller is developed to obtain a guaranteed performance in the presence of both parametric uncertainties and uncertain nonlinearities. Comparative control experimental results obtained show the effectiveness and good tracking performance of the proposed ARC algorithm.
Altitude and Crosswind Motion Control for Optimal Power-Point Tracking in Tethered Wind Energy Systems With Airborne Power Generation
Authors: Vermillion Chris
Published: March 2014

This paper presents a control strategy that combines altitude and crosswind motion control for tethered wind energy systems with airborne turbines and generators. The proposed algorithm adjusts altitude and induces an appropriate level of crosswind motion to present the system with an apparent wind speed that most closely meets, but does not exceed, the rated wind speed of the on-board turbine(s), thereby tracking the turbine’s optimal power point. The adjustment of both altitude and motion control, along with the reduction in crosswind motion and altitude when the rated wind speed is exceeded, differentiates the proposed control architecture from other strategies proposed in the literature. Initial control laws and simulation results are presented for the Altaeros lighter-than-air wind energy system.
Digital Effects and Delays in Connected Vehicles: Linear Stability and Simulations
Authors: Qin Wubing B. , Orosz Gábor
Published: March 2014

To improve the ride quality in connected vehicle platoons, information about the motion of the leader can be transmitted using vehicle-to-vehicle (V2V) communication and such information can be incorporated in the controllers of the following vehicle. However, according to the current V2V standards, dedicated short range communication (DSRC) devices transmit information every 100 ms which introduces time delays into the control loops. In this paper we study the effects of these time delays on the dynamics of vehicle platoons subject to digital control and derive conditions for plant stability and string stability. It is shown that when the time delay exceeds a critical value, no gain combination can stabilize the system. Our results have important implications on connected vehicle design.
Network Control of Vehicle Lateral Dynamics With Control Allocation and Dynamic Message Priority Assignment
Authors: Shuai Zhibin , Zhang Hui , Wang Junmin , Li Jianqiu , Ouyang Minggao
Published: March 2014

In this paper we study the lateral motion control and torque allocation for four-wheel-independent-drive electric vehicles (4WID-EVs) with combined active front steering (AFS) and direct yaw moment control (DYC) through in-vehicle networks. It is well known that the in-vehicle networks and x-by-wire technologies have considerable advantages over the traditional point-to-point communications, and bring great strengths to 4WID-EVs. However, there are also bandwidth limitations which would lead to message time delays in network communication. We propose a method on effectively utilizing the limited bandwidth resources and attenuating the adverse influence of in-vehicle network-induced time delays, based on the idea of dynamic message priority assignment according to the vehicle states and control signals. Simulation results from a high-fidelity vehicle model in CarSim® show that the proposed vehicle lateral control and torque allocation algorithm can improve the 4WID-EV lateral motion control performance, and the proposed message priority dynamic assignment algorithm can significantly reduce the adverse influence of the in-vehicle network-induced time delays.
Flatness-Based Control of Mode Transitions Between Conventional and Premixed Charge Compression Ignition on a Modern Diesel Engine With Variable Valve Actuation
Authors: Hall Carrie M. , Van Alstine Dan , Shaver Gregory M.
Published: March 2014

Energy needs in the transportation sector and strict emissions regulations have caused a growing focus on increasing engine efficiency while simultaneously minimizing engine out emissions. One method for accomplishing this is to leverage advanced combustion strategies which are efficient yet very clean. One such combustion mode is premixed charge compression ignition (PCCI). PCCI can lead to drastically lower emissions than conventional diesel combustion while still maintaining engine efficiencies; however, the engine operation region over which it can be utilized is limited. In order to take advantage of this advanced combustion mode, engines must be designed to move between conventional diesel combustion and PCCI. To achieve transitions between different combustion modes, a control strategy was developed which utilizes a extensively validated gas exchange model and flatness-based methods for trajectory planning and trajectory tracking to enable smooth transitions between different combustion modes on a modern diesel engine with variable valve actuation. Since the engine considered here has the ability to alter valve timings, the control method exploits both capabilities to control the gas exchange process as well as the effective compression ratio of the engine. Simulation results indicate that this flatness-based approach is effective in enabling mode transitions.
Smoothly Transitioning Between Ballistic and Corrective Control to Produce Human-Like Movement
Authors: Shelton Jeffrey N. , Mynderse James A. , Chiu George T.-C.
Published: March 2014

Human reaching movement appears to consist of an initial ballistic segment that drives the hand toward the target, then a corrective segment that brings the hand into the target region. This article discusses how the motions produced by two different controllers, one guiding the ballistic portion and one directing the corrective potion, can be merged into a single smooth movement that is reminiscent of human reaching. Simulated movements based on the proposed methodology are shown to be consistent with human kinematic trajectories.
An Iterative Learning Controller for High Precision Calibration of an Inertial Measurement Unit Using a Piezoelectric Platform
Authors: Edamana Biju , Oldham Kenn
Published: March 2014

A novel threshold sensing strategy for improving accuracy of a tracking controller used in calibration of an Inertial Measurement Unit (IMU) with a piezoelectric micro-actuator is presented in this paper. An asynchronous threshold sensor is hypothesized as a way to improve state estimates obtained from analog sensor measurements of micro-actuator motion. In order to produce accurate periodic signals using the proposed piezoelectric actuator and sensing arrangement, an Iterative Learning Control (ILC) is employed for control system design. Three sensing strategies: (i) an analog sensor alone with a Kalman filter, (ii) an analog sensor and threshold sensor with a Kalman filter and (iii) an analog sensor and threshold sensor with a Kalman smoother are compared in simulation. Results show that incorporating threshold sensors into the piezoelectric micro-actuation system should allow at least certain angular positions or rates to be known with much higher accuracy than from analog sensing alone, which can be useful for identifying calibration curves from the linear region of IMU operation.
Structural Dynamic Imaging Through Interfaces Using Piezoelectric Actuation and Laser Vibrometry for Diagnosing the Mechanical Properties of Composite Materials
Authors: Watson Christopher C. , Rhoads Jeffrey F. , Adams Douglas E.
Published: March 2014

In many engineering applications, diagnostic techniques are needed to characterize the mechanical properties of internal components that are not readily visible at the surface of an object, as in the use of nondestructive testing to detect sub-surface damage in composite materials. Understanding the role of structural interfaces between two bodies is a key factor in developing these diagnostic techniques because the mechanical and geometric properties of the interface determine the degree to which measurements on the surface can be used to interrogate sub-surface components. In this paper, vibration measurements on a polycarbonate material, henceforth referred to as the buffer, are used to characterize the mechanical properties of a polymer particulate composite, henceforth referred to as the target, which is located beneath the buffer. To this end, a three-dimensional laser Doppler vibrometer and piezoelectric inertial actuator are used to measure the broadband response of the two-body structural dynamic system. Because of the importance of the actuator dynamics to the diagnostic measurements, a descriptive model is developed to better understand these dynamics and interpret the results. The longitudinal dynamics of the two-body system are shown to involve stronger coupling between the target and buffer materials as compared to the transverse dynamics. A Complex Mode Indicator Function is then used to extract the modal deflection shapes, and it is shown that the interface between the bodies introduces complexity in the dynamic response. Changes in the surface velocity of the buffer material are also studied as a function of a key mechanical property — the volume fraction of crystals in the target composite material. It is demonstrated that both the linear and nonlinear vibration characteristics of the buffer material change as a function of the composition of the target material, suggesting that a compositional diagnostic procedure is possible using surface vibration measurements.
Reliable Sensing of Leaks in Pipelines
Authors: Chatzigeorgiou Dimitris M. , Wu You , Youcef-Toumi Kamal , Ben-Mansour Rached
Published: March 2014

Leakage is the major factor for unaccounted losses in every pipe network around the world (oil, gas or water). In most cases the deleterious effects associated with the occurrence of leaks may present serious economical and health problems. Therefore, leaks must be quickly detected, located and repaired. Unfortunately, most state of the art leak detection systems have limited applicability, are neither reliable nor robust, while others depend on user experience.

In this work we present a new in-pipe leak detection system, PipeGuard. PipeGuard performs autonomous leak detection in pipes and, thus, eliminates the need for user experience. This paper focuses on the detection module and its main characteristics. Detection in based on the presence of a pressure gradient in the neighborhood of the leak. Moreover, the proposed detector can sense leaks at any angle around the circumference of the pipe with only two sensors. We have validated the concepts by building a prototype and evaluated its performance under real conditions in an experimental laboratory setup.
Kinematic Synthesis of Minimally Actuated Multi-Loop Planar Linkages With Second Order Motion Constraints for Object Grasping
Authors: Soh Gim Song , Robson Nina
Published: March 2014

In this paper, we consider the dimensional synthesis of one degree-of-freedom multi-loop planar linkages such that they do not violate normal direction and second order curvature constraints imposed by contact with objects. Our goal is in developing minimally actuated multi-loop mechanical devices for human-robot interaction, that is, devices whose tasks will happen in a human environment.

Currently no systematic method exists for the kinematic synthesis of robotic fingers that incorporate multi-loop kinematic structure with second order task constraints, related to curvature. We show how to use these contact and curvature effects to formulate the synthesis equations for the design of a planar one-degree-of-freedom six-bar linkage. An example for the design of a finger that maintains a specified contact with an object, for an anthropomorphic task, is presented at the end of the paper.

It is important to note, that the theoretical foundation presented in this paper, assists in solving some of the open problems of this field, providing preliminary results on the synthesis of kinematic chains with multi-loop topology and the use of novel task specifications that incorporate curvature constraints with future applications in grasping and object manipulation.
Hybrid Electric Vehicle Energy Management With Battery Thermal Considerations Using Multi-Rate Dynamic Programming
Authors: Johri Rajit , Liang Wei , McGee Ryan
Published: March 2014

Battery capacity and battery thermal management control have a significant impact on the Hybrid Electric Vehicle (HEV) fuel economy. Additionally, battery temperature has a key influence on the battery health in an HEV. In the past, battery temperature and cooling capacity has not been included while performing optimization studies for power management or optimal battery sizing. This paper presents an application of Dynamic Programming (DP) to HEV optimization with battery thermal constraints. The optimization problem is formulated with 3 state variables, namely, the battery State Of Charge (SOC), the engine speed and the battery bulk temperature. This optimization is critical for determining appropriate battery size and battery thermal management design. The proposed problem has a major challenge in computation time due to the large state space. The paper describes a novel multi-rate DP algorithm to reduce the computational challenges associated with the particular class of large-scale problem where states evolve at very different rates. In HEV applications, the battery thermal dynamics is orders of magnitude slower than powertrain dynamics. The proposed DP algorithm provides a novel way of tackling this problem with multiple time rates for DP with each time rate associated with the fast and slow states separately. Additionally, the paper gives possible numerical techniques to reduce the DP computational time and the time reduction for each technique is shown.
Optimized Control of Different Actuation Strategies for FES and Orthosis Aided Gait
Authors: Kirsch Nicholas , Alibeji Naji A. , Sharma Nitin
Published: March 2014

A combination of functional electrical stimulation (FES) and an orthosis can be used to restore lower limb function in persons with paraplegia. This artificial intervention may allow them to regain the ability to walk again, however, only for short time durations. To improve the time duration of hybrid (FES and orthosis) gait, the muscle fatigue due to FES and the fatigue in arms, caused by a user’s supported weight on a walker, needs to be minimized. In this paper, we show that dynamic optimization can be used to compute stimulation/torque profiles and their corresponding joint angle trajectories which minimize electrical stimulation and walker push or pull forces. Importantly, the computation of these optimal stimulation or torque profiles did not require a predefined or a nominal gait trajectory (i.e., a tracking control problem was not solved). Rather the trajectories were computed based only on pre-defined end-points. For optimization we utilized the recently developed three-link dynamic walking model, which includes both single and double support phases and muscle dynamics. Moreover, different optimal actuation strategies for FES and orthosis aided gait under various scenarios (e.g., use of a powered or an unpowered orthosis combined with stimulation of all or few selected lower-limb muscles) were calculated. The qualitative comparison of these results depict the advantages and disadvantages of each actuation strategy. The computed optimal FES/orthosis aided gait were also compared with able-bodied trajectories to illustrate how they differed from able-bodied walking.
Modeling and incorporating cardiac‐induced lung tissue motion in a breathing motion model
Authors: White Benjamin M. , Santhanam Anand , Thomas David , Min Yugang , Lamb James M. , Neylon Jack , Jani Shyam , Gaudio Sergio , Srinivasan Subashini , Ennis Daniel , Low Daniel A.
Published: March 2014

Purpose:

The purpose of this work is to develop a cardiac‐induced lung motion model to be integrated into an existing breathing motion model.

Methods:

The authors’ proposed cardiac‐induced lung motion model represents the lung tissueˈs specific response to the subjectˈs cardiac cycle. The model is mathematically defined as a product of a converging polynomial functionh of the cardiac phase (c) and the maximum displacement of each voxel () among all the cardiac phases. The function h(c) was estimated from cardiac‐gated MR imaging of ten healthy volunteers using an Akaike Information Criteria optimization algorithm. For each volunteer, a total of 24 short‐axis and 18 radial planar views were acquired on a 1.5 T MR scanner during a series of 12–15 s breath‐hold maneuvers. Each view contained 30 temporal frames of equal time‐duration beginning with the end‐diastolic cardiac phase. The frames in each of the planar views were resampled to create a set of three‐dimensional (3D) anatomical volumes representing thoracic anatomy at different cardiac phases. A 3D multiresolution optical flow deformable image registration algorithm was used to quantify the difference in tissue position between the end‐diastolic cardiac phase and the remaining cardiac phases. To account for image noise, voxel displacements whose maximum values were less than 0.3 mm, were excluded. In addition, the blood vessels were segmented and excluded in order to eliminate registration artifacts caused by blood‐flow.

Results:

The average cardiac‐induced lung motions for displacements greater than 0.3 mm were found to be 0.86 ± 0.74 and 0.97 ± 0.93 mm in the left and right lungs, respectively. The average model residual error for the ten healthy volunteers was found to be 0.29 ± 0.08 mm in the left lung and 0.38 ± 0.14 mm in the right lung for tissue displacements greater than 0.3 mm. The relative error decreased with increasing cardiac‐induced lung tissue motion. While the relative error was > 60% for submillimeter cardiac‐induced lung tissue motion, the relative error decreased to < 5% for cardiac‐induced lung tissue motion that exceeded 10 mm in displacement.

Conclusions:

The authors’ studies implied that modeling and including cardiac‐induced lung motion would improve breathing motion model accuracy for tissues with cardiac‐induced motion greater than 0.3 mm.
Risk for Exercise Addiction: A Comparison of Triathletes Training for Sprint-, Olympic-, Half-Ironman-, and Ironman-Distance Triathlons
Authors: Youngman Jason , Simpson Duncan
Published: March 2014

Researchers have noted that when taken to an excessive level, exercise may become addictive. This study investigated the risk of exercise addiction for triathletes using the Exercise Addiction Inventory (EAI; Terry, Szabo, & Griffths, 2004). The sample consisted of 1,285 male and female triathletes, ranging in age from 18–70 years old. Results indicated that approximately 20% of triathletes are at risk for exercise addiction, and that training for longer distance races (i.e., Olympic, Half-Ironman, and Ironman) puts triathletes at greater risk for exercise addiction than training for shorter races (i.e., Sprint). No significant association was found between the risk for exercise addiction and the number of years of participating. However, as the number of weekly training hours increased, so did a triathlete’s risk for exercise addiction. At-risk triathletes need greater clinical attention, and further research should be conducted to help clinicians develop awareness and appropriate interventions.
Immune Responses to Vi Capsular Polysaccharide Typhoid Vaccine in Children 2 to 16 Years Old in Karachi, Pakistan, and Kolkata, India
Authors: Ochiai R. Leon , Khan M. Imran , Soofi Sajid B. , Sur Dipika , Kanungo Suman , You Young Ae , Habib M. Atif , Sahito Shah Muhammad , Manna Byomkesh , Dutta Shanta , Acosta Camilo J. , Ali Mohammad , Bhattacharya Sujit K. , Bhutta Zulfiqar A. , Clemens John D.
Published: March 2014

The geometric mean concentration (GMC) and the proportion maintaining a protective level (150 enzyme-linked immunosorbent assay (ELISA) units [ELU]/ml) 2 years following a single dose of 25 μg of injectable Vi capsular polysaccharide typhoid vaccine was measured against that of the control hepatitis A vaccine in children 2 to 16 years old in cluster randomized trials in Karachi and Kolkata. The GMC for the Vi group (1,428 ELU/ml) was statistically significantly different from the GMC of the control hepatitis A vaccine group (86 ELU/ml) after 6 weeks. A total of 117 children (95.1%) in the Vi group and 9 (7.5%) in the hepatitis A group showed a 4-fold rise in Vi IgG antibody concentrations at 6 weeks (P< 0.01). Protective antibody levels remained significantly different between the two groups at 2 years (38% in the Vi vaccine groups and 6% in the hepatitis A group [P< 0.01]). A very small proportion of younger children (2 to 5 years old) maintained protective Vi IgG antibody levels at 2 years, a result that was not statistically significantly different compared to that for the hepatitis A group (38.1% versus 10.5%). The GMCs of the Vi IgG antibody after 2 years were 133 ELU/ml for children 2 to <5 years old and 349 ELU/ml for children 5 to 16 years old. In conclusion, Vi capsular polysaccharide typhoid vaccine is immunogenic in children in settings of South Asia where typhoid is highly endemic. The antibody levels in children who received this vaccine remained higher than those in children who received the control vaccine but were significantly reduced at 2 years of follow-up.
Major Variation in MICs of Tigecycline in Gram-Negative Bacilli as a Function of Testing Method
Authors: Marchaim Dror , Pogue Jason M. , Tzuman Oran , Hayakawa Kayoko , Lephart Paul R. , Salimnia Hossein , Painter Theresa , Zervos Marcus J. , Johnson Laura E. , Perri Mary Beth , Hartman Pamela , Thyagarajan Rama V. , Major Sharon , Goodell Melanie , Fakih Mohamad G. , Washer Laraine L. , Newton Duane W. , Malani Anurag N. , Wholehan Jason M. , Mody Lona , Kaye Keith S.
Published: March 2014

Tigecycline is one of the few remaining therapeutic options for extensively drug-resistant (XDR) Gram-negative bacilli (GNB). MICs of tigecycline to
Acinetobacter baumannii
have been reported to be elevated when determined by the Etest compared to determinations by the broth microdilution (BMD) method. The study aim was to compare the susceptibility of GNB to tigecycline by four different testing methods. GNB were collected from six health care systems (25 hospitals) in southeast Michigan from January 2010 to September 2011. Tigecycline MICs among
A. baumannii
, carbapenem-resistant
Enterobacteriaceae
(CRE), extended-spectrum β-lactamase (ESBL)-producing
Enterobacteriaceae
, and susceptible
Enterobacteriaceae
isolates were determined by Etest, BMD, Vitek-2, and MicroScan. Nonsusceptibility was categorized as a tigecycline MIC of ≥4 μg/ml for both
A. baumannii
and
Enterobacteriaceae
. The study included 4,427 isolates: 2,065 ESBL-producing
Enterobacteriaceae
, 1,105
A. baumannii
, 888 susceptible
Enterobacteriaceae
, and 369 CRE isolates. Tigecycline nonsusceptibility among
A. baumannii
isolates was significantly more common as determined by Etest compared to that determined by BMD (odds ratio [OR], 10.3;
P
< 0.001), MicroScan (OR, 12.4;
P
< 0.001), or Vitek-2 (OR, 9.4;
P
< 0.001). These differences were not evident with the other pathogens. Tigecycline MICs varied greatly according to the
in vitro
testing methods among
A. baumannii
isolates. Etest should probably not be used by laboratories for tigecycline MIC testing of
A. baumannii
isolates, since MICs are significantly elevated with Etest compared to those determined by the three other methods.
Travel-Related Carbapenemase-Producing Gram-Negative Bacteria in Alberta, Canada: the First 3 Years
Authors: Peirano Gisele , Ahmed-Bentley Jasmine , Fuller Jeff , Rubin Joseph E. , Pitout Johann D. D.
Published: March 2014

We describe here the characteristics of Alberta, Canada, patients with infections or colonizations with carbapenemase-producing Gram-negative bacteria during 2010 to 2013 that were linked to recent travel outside Canada. Antimicrobial susceptibility was determined by broth microdilution, and isolates were characterized using PCR, sequencing, and multilocus sequencing typing. A broth mating study was used to assess the transferability of resistance plasmids, which were subsequently characterized. All the patients (
n
= 12) included in our study had contact with a health care system while abroad. Most of the patients presented with urinary tract infections (UTIs) and were admitted to hospitals within weeks after their return to Alberta. Secondary spread occurred in 1 case, resulting in the death of another patient. The carbapenemase-producing bacteria (
n
= 17) consisted of
Escherichia coli
(sequence type 101 [ST101], ST365, ST405, and ST410) with NDM-1,
Klebsiella pneumoniae
(ST15, ST16, ST147, ST258, ST340, ST512, and ST972) with NDM-1, OXA-181, KPC-2, and KPC-3,
Acinetobacter baumannii
with OXA-23,
Providencia rettgeri
with NDM-1,
Enterobacter cloacae
with KPC-2, and
Citrobacter freundii
with NDM-1. The
bla
NDM-1
gene was associated with various narrow- (i.e., IncF) and broad- (i.e., IncA/C and IncL/M) host-range plasmids with different addiction factors. Our results show that NDM-producing
K. pneumoniae
, belonging to a variety of sequence types with different plasmid scaffolds, are regularly imported from India into Alberta. Clinical microbiology laboratories should remain vigilant in detecting bacteria with carbapenemases.
Evidence for Subclinical Influenza A(H1N1)pdm09 Virus Infection among Dogs in Guangdong Province, China
Authors: Su Shuo , Chen Jidang , Jia Kun , Khan Salah Uddin , He Shuyi , Fu Xinliang , Hong Malin , Sun Lingshuang , Qi Wenbao , Gray Gregory C. , Li Shoujun
Published: March 2014

During 2012, we identified sampled dogs with elevated levels of antibodies (≥1:40) against A(H1N1)pdm09 virus by using a hemagglutination inhibition (HI) assay (seroprevalence, 24.7%) and a microneutralization (MN) assay (seroprevalence, 10.8%). These high seroprevalences of A(H1N1)pdm09 among dogs without clinical signs of influenza support the premise that dogs may play a role in the human influenza ecology in China.
Performance of the EUCAST Disk Diffusion Method, the CLSI Agar Screen Method, and the Vitek 2 Automated Antimicrobial Susceptibility Testing System for Detection of Clinical Isolates of Enterococci with Low- and Medium-Level VanB-Type Vancomycin Resistance: a Multicenter Study
Authors: Hegstad Kristin , Giske Christian G. , Haldorsen Bjørg , Matuschek Erika , Schønning Kristian , Leegaard Truls M. , Kahlmeter Gunnar , Sundsfjord Arnfinn
Published: March 2014

Different antimicrobial susceptibility testing methods to detect low-level vancomycin resistance in enterococci were evaluated in a Scandinavian multicenter study (
n
= 28). A phenotypically and genotypically well-characterized diverse collection of
Enterococcus faecalis
(
n
= 12) and
Enterococcus faecium
(
n
= 18) strains with and without nonsusceptibility to vancomycin was examined blindly in Danish (
n
= 5), Norwegian (
n
= 13), and Swedish (
n
= 10) laboratories using the EUCAST disk diffusion method (
n
= 28) and the CLSI agar screen (
n
= 18) or the Vitek 2 system (bioMérieux) (
n
= 5). The EUCAST disk diffusion method (very major error [VME] rate, 7.0%; sensitivity, 0.93; major error [ME] rate, 2.4%; specificity, 0.98) and CLSI agar screen (VME rate, 6.6%; sensitivity, 0.93; ME rate, 5.6%; specificity, 0.94) performed significantly better (
P
= 0.02) than the Vitek 2 system (VME rate, 13%; sensitivity, 0.87; ME rate, 0%; specificity, 1). The performance of the EUCAST disk diffusion method was challenged by differences in vancomycin inhibition zone sizes as well as the experience of the personnel in interpreting fuzzy zone edges as an indication of vancomycin resistance. Laboratories using Oxoid agar (
P
< 0.0001) or Merck Mueller-Hinton (MH) agar (
P
= 0.027) for the disk diffusion assay performed significantly better than did laboratories using BBL MH II medium. Laboratories using Difco brain heart infusion (BHI) agar for the CLSI agar screen performed significantly better (
P
= 0.017) than did those using Oxoid BHI agar. In conclusion, both the EUCAST disk diffusion and CLSI agar screening methods performed acceptably (sensitivity, 0.93; specificity, 0.94 to 0.98) in the detection of VanB-type vancomycin-resistant enterococci with low-level resistance. Importantly, use of the CLSI agar screen requires careful monitoring of the vancomycin concentration in the plates. Moreover, disk diffusion methodology requires that personnel be trained in interpreting zone edges.
Crystal Structure of the Herpesvirus Inner Tegument Protein UL37 Supports Its Essential Role in Control of Viral Trafficking
Authors: Pitts Jared D. , Klabis Jenifer , Richards Alexsia L. , Smith Gregory A. , Heldwein Ekaterina E.
Published: March 2014

In cells infected with herpesviruses, two capsid-associated, or inner tegument, proteins, UL37 and UL36, control cytosolic trafficking of capsids by as yet poorly understood mechanisms. Here, we report the crystal structure of the N-terminal half of UL37 from pseudorabies virus, an alphaherpesvirus closely related to herpes simplex viruses and varicella-zoster virus. The structure—the first for any alphaherpesvirus inner tegument protein—reveals an elongated molecule of a complex architecture rich in helical bundles. To explore the function of the UL37 N terminus, we used the three-dimensional framework provided by the structure in combination with evolutionary trace analysis to pinpoint several surface-exposed regions of potential functional importance and test their importance using mutagenesis. This approach identified a novel functional region important for cell-cell spread. These results suggest a novel role for UL37 in intracellular virus trafficking that promotes spread of viral infection, a finding that expands the repertoire of UL37 functions. Supporting this, the N terminus of UL37 shares structural similarity with cellular multisubunit tethering complexes (MTCs), which control vesicular trafficking in eukaryotic cells by tethering transport vesicles to their destination membranes. Our results suggest that UL37 could be the first viral MTC mimic and provide a structural rationale for the importance of UL37 for viral trafficking. We propose that herpesviruses may have co-opted the MTC functionality of UL37 to bring capsids to cytoplasmic budding destinations and further on to cell junctions for spread to nearby cells.

IMPORTANCE
To move within an infected cell, viruses encode genes for proteins that interact with host trafficking machinery. In cells infected with herpesviruses, two capsid-associated proteins control the cytosolic movement of capsids by as yet poorly understood mechanisms. Here, we report the crystal structure for the N-terminal half of one of these proteins, UL37. Structure-based mutagenesis revealed a novel function for UL37 in virus trafficking to cell junctions for cell-cell spread. The unexpected structural similarity to components of cellular multisubunit tethering complexes, which control vesicular traffic, suggests that UL37 could be the first viral MTC mimic and provides a structural basis for the importance of UL37 for virus trafficking.
Herpes Simplex Virus 1 Protein UL37 Interacts with Viral Glycoprotein gK and Membrane Protein UL20 and Functions in Cytoplasmic Virion Envelopment
Authors: Jambunathan Nithya , Chouljenko Dmitry , Desai Prashant , Charles Anu-Susan , Subramanian Ramesh , Chouljenko Vladimir N. , Kousoulas Konstantin G.
Published: March 2014

We have shown that glycoprotein K (gK) and its interacting partner, the UL20 protein, play crucial roles in virion envelopment. Specifically, virions lacking either gK or UL20 fail to acquire an envelope, thus causing accumulation of capsids in the cytoplasm of infected cells. The herpes simplex virus 1 (HSV-1) UL37 protein has also been implicated in cytoplasmic virion envelopment. To further investigate the role of UL37 in virion envelopment, the recombinant virus DC480 was constructed by insertion of a 12-amino-acid protein C (protC) epitope tag within the UL37 amino acid sequence immediately after amino acid 480. The DC480 mutant virus expressed full-size UL37 as detected by the anti-protC antibody in Western immunoblots, accumulated unenveloped capsids in the cytoplasm of infected cells, and produced very small plaques on African green monkey kidney (Vero) cells that were similar in size to those produced by the UL20-null and UL37-null viruses. The DC480 virus replicated nearly 4 log less efficiently than the parental wild-type virus when grown on Vero cells. However, DC480 mutant virus titers increased nearly 20-fold when the virus was grown on FRT cells engineered to express the UL20 gene in comparison to the titers on Vero cells, while the UL37-null virus replicated approximately 20-fold less efficiently than the DC480 virus on FRT cells. Coimmunoprecipitation experiments and proximity ligation assays showed that gK and UL20 interact with the UL37 protein in infected cells. Collectively, these results indicate that UL37 interacts with the gK-UL20 protein complex to facilitate cytoplasmic virion envelopment.

IMPORTANCE
Herpes simplex viruses acquire their final envelopes by budding into cytoplasmic membranes derived from the
trans
-Golgi network (TGN). The tegument proteins UL36 and UL37 are known to be transported to the TGN sites of virus envelopment and to function in virion envelopment, since mutants lacking UL37 accumulate capsids in the cytoplasm that are unable to bud into TGN membranes. Viral glycoprotein K (gK) also functions in cytoplasmic envelopment, in a protein complex with the membrane-associated protein UL20 (UL20mp). This work shows for the first time that the UL37 protein functionally interacts with gK and UL20 to facilitate cytoplasmic virion envelopment. This work may lead to the design of specific drugs that can interrupt UL37 interactions with the gK-UL20 protein complex, providing new ways to combat herpesviral infections.
Inhibition of Dengue Virus Replication by a Class of Small-Molecule Compounds That Antagonize Dopamine Receptor D4 and Downstream Mitogen-Activated Protein Kinase Signaling
Authors: Smith Jessica L. , Stein David A. , Shum David , Fischer Matthew A. , Radu Constantin , Bhinder Bhavneet , Djaballah Hakim , Nelson Jay A. , Früh Klaus , Hirsch Alec J.
Published: March 2014

Dengue viruses (DENV) are endemic pathogens of tropical and subtropical regions that cause significant morbidity and mortality worldwide. To date, no vaccines or antiviral therapeutics have been approved for combating DENV-associated disease. In this paper, we describe a class of tricyclic small-molecule compounds—dihydrodibenzothiepines (DHBTs), identified through high-throughput screening—with potent inhibitory activity against DENV serotype 2. SKI-417616, a highly active representative of this class, displayed activity against all four serotypes of DENV, as well as against a related flavivirus, West Nile virus (WNV), and an alphavirus, Sindbis virus (SINV). This compound was characterized to determine its mechanism of antiviral activity. Investigation of the stage of the viral life cycle affected revealed that an early event in the life cycle is inhibited. Due to the structural similarity of the DHBTs to known antagonists of the dopamine and serotonin receptors, we explored the roles of two of these receptors, serotonin receptor 2A (5HTR2A) and the D4 dopamine receptor (DRD4), in DENV infection. Antagonism of DRD4 and subsequent downstream phosphorylation of epidermal growth factor receptor (EGFR)-related kinase (ERK) were found to impact DENV infection negatively, and blockade of signaling through this network was confirmed as the mechanism of anti-DENV activity for this class of compounds.

IMPORTANCE
The dengue viruses are mosquito-borne, reemerging human pathogens that are the etiological agents of a spectrum of febrile diseases. Currently, there are no approved therapeutic treatments for dengue-associated disease, nor is there a vaccine. This study identifies a small molecule, SKI-417616, with potent anti-dengue virus activity. Further analysis revealed that SKI-417616 acts through antagonism of the host cell dopamine D4 receptor and subsequent repression of the ERK phosphorylation pathway. These results suggest that SKI-417616, or other compounds targeting the same cellular pathways, may have therapeutic potential for the treatment of dengue virus infections.