bluuebunny/crossref_metadata_2025 huggingface dataset:
One Dimensional Transient Pneumatic System Simulation
Authors: Kratschun Filipp , van Bebber David , Murrenhoff Hubertus
Published: December 2017

The increase of system dynamic within the area of pneumatics requires sophisticated numerical methods to determine the systems’ performance. Cycle durations in the range of just a few milliseconds and below violate the assumption of a stationary process. State of the art pneumatic calculations are built upon this assumption and, therefore, gas dynamic solvers have to be used to predict the systems’ behavior accurately.

In general it is possible to calculate several flow parameters for transient gaseous flows using computational fluid dynamics (CFD) software, but despite increasing processing power of modern computers, solving particular problems is yet time-consuming. A simulation of a few milliseconds results in a computational time of several hours which makes the design of a highly dynamic pneumatic system lengthy.

This paper presents a one dimensional transient numerical model which is capable of computing a transient pneumatic system’s performance time-efficiently yet retaining the accuracy of a CFD simulation. It allows to determine flow parameters, e.g., density, pressure and velocity, within transient gaseous flows including discontinuities.

In particular the proposed model depicts an approach to calculate transient flows with discontinuous flow curvature. Such jumps naturally occur in pneumatic systems within hose connectors or valves. Numerical results are compared to a CFD parameter study to verify the one dimensional simulation.
Cavitation Erosion in the Portion of an Oil Passage Through Which Bubbles Pass
Authors: Kumagai Kento , Kazama Toshiharu
Published: December 2017

Cavitation erosion is a serious problem in the hydraulic system of construction machinery. In particular, the erosion which occurs even when cavitation bubbles only pass through oil passages, occurs at a connecting portion between the hydraulic components and piping, and the erosion causes oil leakage, which is a serious problem for hydraulic systems. However, it is difficult to predict the eroded area and to prevent the erosion because of a lack of research findings. The present study investigated erosion in the portion through which cavitation bubbles passes using a basic experimental apparatus that simulates an oil passage of hydraulic components, and by conducting a computational fluid dynamics simulation. The following results were obtained. Erosion occurs near the outlet of the oil passage, cavitation bubbles frequently disappear rapidly near the area of erosion, and the cause of bubble disappearance is the pressure distribution and amplification of the pressure wave of cavitation jets at the outlet of the oil passage. These results help explain the erosion generation mechanism and the characteristics of erosion in oil passages of hydraulic components, and can be used to design methods of reducing erosion.
Pressure Control for a Hot Gas Bulge Test Using Parallel On-Off Valves
Authors: Matthiesen Gunnar , Murrenhoff Hubertus , Storz Johannes , Braun Alexander
Published: December 2017

Weight reduction is an ongoing trend in multiple industries. Especially in the mobility sectors, hot forming of sheet metal parts has become an alternative production process for high strength components. New material concepts, e.g., boron-manganese steels, enable the design of lighter parts at equivalent or even higher strength. During the preliminary process development phase detailed knowledge of the thermo-mechanical material properties of these sheet metals is required at elevated temperatures and high strain rates. Since hot tensile tests can only be evaluated up to comparably low strains, new test designs are needed to supply material parameters at elevated temperatures and higher strain rates. Therefore, the hot gas bulge test has been developed, that allows for such test conditions. In this paper, first the concept of the hot gas bulge test and the developed test bench are described. Opposed to standardized bulge tests, which use hydraulic oil as forming medium, the newly designed test uses gas as medium to account for the hot stamping conditions, i.e., temperatures of up to 950°C. As the forming speed has an increasing influence on the material behaviour at increasing temperatures, a closed loop control of the forming speed was developed. Since there are no proportional pneumatic valves available for the required pressure range, a parallel valve concept was chosen. By combining different valves, the characteristics of a larger proportional valve are imitated. A control algorithm was developed, that maps the required valves conductance into a valve combination to control the mass flow into the pressure chamber. The developed control system is presented and experimental results from the material test procedure are shown. These results reveal that the developed system is capable to track the required mass flow rate for low as well as high forming speeds up to a certain deformation when the deformation of the sheet becomes uncontrollable.
Mathematical Modelling and Multi-Objective Optimization Design of a Large Flow Water Hydraulic Proportional Cartridge Valve
Authors: Han Mingxing , Liu Yinshui , Tan Huaijiang , Wu Defa
Published: December 2017

The large flow water hydraulic proportional cartridge valve is one of the most important components and also the technical difficulties in the high performance large-tonnage engineering machinery, such as the die casting machine. The structure and principle of the large flow water hydraulic proportional cartridge valve are presented in this paper. The valve utilizes a two-stage structure with the high performance proportional valves as the pilot stage and the cartridge poppet valve as the main stage to overcome the fundamental tradeoff between the flow capacity and dynamic characteristics. A detailed and precise nonlinear mathematical model of the cartridge valve considering both structural parameters and nonlinear factors (compressibility of water, leakage, friction, flow force, etc.) is established. And then MATLAB/Simulink software is employed to build the simulation model and the dynamic simulation is carried out. Compared with the simulation results of the valve with different design parameters, the static and dynamic characteristics of the proportional cartridge throttle valve have been analyzed. The impacts of the parameters on the performance of step-response have been studied. Finally, based on multi-objective optimization method, the optimal parameters of the cartridge valve have been obtained. The simulation results show that the performances have been significantly improved.
Model-Based Estimation of Gas Leakage for Fluid Power Accumulators in Wind Turbines
Authors: Liniger Jesper , Pedersen Henrik C. , Soltani Mohsen
Published: December 2017

The fluid power accumulator is a high-risk component in the safety shutdown system of most modern wind turbines. Recent studies of failures in wind turbines have shown a high failure rate of such accumulators. This paper proposes an estimation method for detecting one of the most common faults for accumulators, namely gas leakage. The method utilizes an Extended Kalman Filter for joint state and parameter estimation with special attention to limiting the use of sensors to those commonly used in wind turbines. The precision of the method is investigated on an experimental setup which allows for operation of the accumulator similar to the conditions in a turbine. The results show that gas leakage is indeed detectable during start-up of the turbine and robust behavior is achieved in a multi-fault environment where both gas and external fluid leakage occur simultaneously. The estimation precision is shown to be sensitive to initial conditions for the gas temperature and volume.
An Investigation of Hydraulic Fluid Composition and Aeration in an Axial Piston Pump
Authors: Gullapalli Sravani , Michael Paul , Kensler Jennifer , Cheekolu Mercy , Taylor Robert Ian , Lizarraga-Garcia Enrique
Published: December 2017

Manufacturers of fluid power equipment have decreased the size of hydraulic fluid reservoirs in response to economic, environmental and performance requirements. Residence times as brief as 30 seconds in mobile equipment are not unusual. Shorter fluid residence times dictate use of hydraulic fluids with improved air release characteristics. In this investigation, hydraulic fluids of the same ISO viscosity grade but varying base oil and additive composition were evaluated in a dynamometer fitted with a reservoir that incorporated an aerator at the inlet, and a mass flow meter at the outlet. The effects of aeration on piston pump efficiency and air borne noise generation were evaluated. Fluids of the same ISO viscosity grade exhibited significantly different air release rates and as a result sustained different volume fractions of entrained air. Hydraulic oils that entrained a greater volume of air demonstrated lower volumetric efficiencies and higher sound levels. Aerated fluids of the identical viscosity grade differed in volumetric efficiency by as much as 8% and perceived sound level by as much as 50%. Models for the effect of aeration on pump performance are presented.
Stability-Guaranteed Nonlinear Model-Based Control of Hydraulically Actuated Lightweight Structures
Authors: Koivumäki Janne , Mattila Jouni , Semini Claudio , Caldwell Darwin G.
Published: December 2017

Hydraulic actuators benefit robotic systems as they can produce significant force/torque for their size and are robust. However, their dynamic behavior is highly nonlinear, making high-performance closed-loop control a challenging task. With articulated robotic systems, the associated nonlinear multibody dynamics make the control design task even more challenging.

Nonlinear model-based (NMB) control methods can be used to address the system nonlinearities. Among NMB control methods, a number of state-of-the-art control performance improvements have been demonstrated for hydraulic manipulators using the virtual decomposition control (VDC) approach. However, all studies on hydraulic systems with VDC have focused on high-inertia and heavy-duty manipulators. In hydraulic cylinder actuated low-inertia and light-weight systems, highly uncertain and hard-to-model nonlinearities, such as actuator friction, can become very dominant in the system’s dynamic behaviour.

This paper details the design of a VDC-based controller for a hydraulically actuated light-weight robotic leg. An adaptive friction compensation is incorporated in the control design. The stability of the designed controller is rigorously guaranteed. The experiments with the controller demonstrate a comparable free-space control performance in relation to the state-of-the-art controller for heavy-duty hydraulic manipulators.
Stability-Guaranteed Anti-Sway Controller Design for a Redundant Articulated Hydraulic Manipulator in the Vertical Plane
Authors: Mustalahti Pauli , Koivumäki Janne , Mattila Jouni
Published: December 2017

Articulated hydraulic manipulators are widely used for moving heavy loads. Commercial manipulators are most often equipped with a rotating load-grasping tool connected at the end of the manipulator via a pair of passive (unactuated) revolute joints. In free-space motion, these passive joints are subject to swaying motions due to the manipulator tip accelerations. Because these passive joints are not directly controllable due to their passive nature, a skilled driver is needed to compensate for the load swaying. In this paper, we extend the nonlinear model-based Virtual Decomposition Control (VDC) theory to cover anti-sway control of underactuated multiple degrees-of-freedom (DOF) hydraulic redundant manipulators. The proposed nonlinear controller performs the control design and stability analysis of the hydraulic robotic manipulator at the subsystem level. Experiments are conducted in a full-scale loader manipulator to verify that the proposed controller can efficiently damp the load swaying in a case study of redundant vertical plane motion.
Finite Element-Based Control of a Single-Link Flexible Hydraulic Manipulator
Authors: Mäkinen Petri , Mattila Jouni
Published: December 2017

In this study, a stability-guaranteed, nonlinear, finite element-based control is presented for a single-link flexible manipulator with hydraulic actuation, subject to experimental validation. The strong, inherent nonlinearities of the hydraulic cylinder and fluid dynamics, coupled with flexible link dynamics, cause remarkable challenges in controlling the system effectively. In an attempt to cope with these challenges, a controller based on the Virtual Decomposition Control (VDC) approach is introduced. The VDC approach takes advantage of subsystem-dynamics-based control, enabling the handling of the dynamics and control of the hydraulic actuator and the flexible link separately, thus keeping the controller design relatively simple. The rigorous stability theory of the VDC approach guarantees the stability of the entire system. The experiments demonstrate the VDC controller’s performance in end-point control with built-in vibration dampening.
A Comparison of Hydraulic and Electrical Switch-Mode Converters
Authors: Wiens Travis , Das Debdatta
Published: December 2017

Electrical switched-mode DC-DC converters have become ubiquitous in the last decade, primarily driven by their high energy efficiency. Although considerable academic research has been performed on the analogous hydraulic switched-inertance converters, widespread adoption has lagged. This paper presents a comparison of the two technologies, comparing theoretical and practical limits to their performance. First we develop a simple model for the efficiency and specific power capacities of buck and boost converters in the ideal case, so that critical parameters can be identified as well as their physical limitations. We then expand our analysis to include practical effects such as wave propagation, switching losses and operating limits, in an attempt to identify if there are any reasons to continue or discontinue development of the hydraulic switched-inertance converter.
A Fuzzy Logic Controller for a Hydrostatic Transmission for an Electric Hybrid Bus in Bogotá, Colombia
Authors: Leon Quiroga Jorge A. , Gonzalez Mancera Andres L. , Garcia Bravo Jose M.
Published: December 2017

The control strategy in a hydraulic hybrid vehicle is very important for taking advantage of its full potential. In a hydraulic hybrid vehicle, the hydrostatic transmission can be controlled to optimize the entire system. A hydrostatic transmission is composed basically of a hydraulic motor and a hydraulic pump. For an electric hybrid vehicle, an electric motor is the prime mover. In this study, the control variables are the displacements of the hydraulic devices and the objective is to optimize the system efficiency. All possible combinations of displacements were tested through simulation and the most efficient combination was recorded. Compared with a fixed displacement hydrostatic transmission, around 4.5% of the energy can be saved using the most efficient configuration of the hydrostatic transmission. Fuzzy logic theory was used to simulate the driver input and it was used as a control strategy for the hydrostatic transmission.
Stability and Energy Efficiency Improvement of Hydraulic Excavator Arm Control System With a Novel Asymmetric Pump
Authors: Quan Long , Ge Lei , Yang Jing , Zhao Bin , Lu Zhen , Li Bin
Published: December 2017

Pump controlled hydraulic circuit is an energy efficient alternative to valve controlled system, as they eliminate the throttling loss and require less cooling power. In all pump controlled systems, the internal and external leakages of the pump and actuator, especially the unequal flow rates of the single rod cylinder must be compensated. In presently existing solutions, an additional pump or some valves are used to compensate the unequal flow rates, leakages and to pressurize the system. However, these approaches increase the system complexity and complex control strategies are required to improve the overall system dynamic performances. Also, some of them suffer from undesired and uncontrolled pressure and velocity oscillations when the load force is small or its direction changes. This paper addresses the unequal flow rates compensation problem and stability problem of pump controlled single rod cylinder system, and proposes a novel solution for it. The system under consideration utilizes a new designed asymmetric pump which can match the unequal flow rates of the single rod cylinder basically. The feasibility of the new circuit is validated by both mathematics and multi-body simulation model. The results show that the undesired velocity oscillations can be removed up. Furthermore, the operating characteristics and energy efficiency of the arm cylinder with the new scheme based on the designed open-loop and closed-loop strategies are studied on a real excavator. The results show that there is no obvious velocity fluctuation with the asymmetric pump and the position controlled precision is satisfied. Compared with the independent metering circuit, the energy-saving ratio reaches to 57% during a working cycle.
Stability Study of a Pump-Controlled Circuit for Single Rod Cylinders via the Concept of Lyapunov Exponents
Authors: Sun Yuming , Imam Ahmed , Wu Christine , Sepehri Nariman
Published: December 2017

Pump-controlled hydraulic actuators of single rod cylinders, while efficient, often exhibit undesirable performances during pump mode of operation switching. Although the oscillatory performances have been found in both simulations and experiments, a rigorous proof of such undesirable dynamics has rarely been reported due to lack of proper theoretical tools. In many previous works, traditional stability analysis of pump-controlled single rod hydraulic actuator systems was carried out by studying eigenvalues of the linearized models in each of various regions, separately. This may lead to a conservative conclusion. In this paper, such mode switching instability is analyzed using the concept of Lyapunov exponents. More specifically, the impact of the cracking pressures of the pilot operated check valves on system dynamics of a commonly used pump-controlled circuit is investigated. The numerical results are in agreement with the experimental findings, indicating the efficacy of the proposed method. The paper thus contributes to the systematic stability analysis for non-smooth hydraulic actuator systems, which can subsequently facilitate the controller design.
Experimental Studies of a Novel Alternating Flow (AF) Hydraulic Pump
Authors: Foss Ryan J. , Li Mengtang , Barth Eric J. , Stelson Kim A. , Van de Ven James D.
Published: December 2017

The ideal variable displacement pump for a displacement control circuit is efficient across a wide operating range and readily mounted on a common shaft with multiple pumps. This paper presents a novel variable displacement pump architecture for displacement control circuits that uses the concept of alternating flow (AF) between piston pairs that share a common cylinder. The displacement is adjusted by varying the phase angle between the piston pairs. When the pistons are in phase, the pump displacement is at a maximum and when the pairs of pistons are out of phase, fluid is shuttled between the pistons and the pump produces no net flow. A prototype of the AF pump was constructed from two inline triplex pumps that were modified so that three piston pairs were created. The crankshafts of the two pumps were connected via a sprocket-and-chain transmission. The sprockets allow for accurate measurement of the phase angle, which is adjusted, in this early phase prototype, by disassembling the chain and shifting the sprockets. The prototype AF pump was then mounted to the test stand and experiments were conducted to map the AF pump efficiency and cylinder pressure dynamics across a range of operating pressure, speed, and displacement. The AF pump’s efficiency was measured for 8 diferent phase angles with an efficiency of near 90% at full flow and 65% at 36% displacement. The experimental results were compared to simulation results, presented in a companion paper at this conference.
A Model-Based Comparative Investigation on the Noise Source of Hydraulic Gear Pumps
Authors: Woo Sangbeom , Zhao Xinran , Vacca Andrea , Rigosi Manuel
Published: December 2017

The reduction of the noise emission level of hydraulic pumps has been a primary research goal in the fluid power field for decades. To pursue this goal, a significant effort has been put in identifying the sources of noise generation, and formulating proper methods to reduce them. Most common methods include the analysis of the kinematic features of the displacing action realized by the unit, and/or the pressure fluctuation at the pump ports. However, the physical complexity associated with the noise transmission into the pump structure and the surrounding environment has not permitted so far to achieve clear correlations between fluid-borne noise sources and actual emitted noise. Recently, the advancement in numerical acoustic modelling techniques has permitted to explore these features, so that in future, quieter units could be designed with the help from simulation.

This paper contributes in this topic, considering as a particular reference unit, the case of external gear pumps. An acoustic model developed by the authors’ research group permits to perform analysis of both structure- and air-borne noise, by combining a modal analysis performed in ANSYS and an acoustic simulation in LMS.Virtual.Lab. As pressure and force loading inputs, the model utilizes the results of the authors’ HYGESim tool.

To show the model’s potentials, the paper takes into considerations two alternative gear designs suitable for the same pump casing: one single flank and one dual flank (zero-backlash). The dual-flank design is commonly considered as a quieter solution for spur gear pumps. These designs are properly selected to show differences in fluid-borne noise source, and describes the features of the noise transmission as predicted by the model. By showing the simulated level of airborne noise for the two considered designs, the results of this paper confirm the advantages of the dual-flank solution, and point out how the proposed model can be used in future for virtual design purposes.
Improving Efficiency of Micro Excavator With Decentralized Hydraulics
Authors: Zhang Shuzhong , Minav Tatiana , Pietola Matti
Published: December 2017

Government regulations incentivize investigation of the potential for hybridization of non-road mobile machinery (NRMM). Many approaches to energy saving in hydraulic systems have been established. One of the methods first introduced in the aerospace industry is “decentralized” or “zonal” hydraulics. The decentralized system is realized with pump-controlled actuators, which are distributed throughout the system. In this research, decentralized hydraulics are realized with a direct-driven hydraulics (DDH) drive and implemented on a 1-ton class JCB micro excavator. The original valve-controlled system for boom, stick, and bucket is replaced with three DDH units. In a DDH unit, a double fixed displacement pump/motors with a speed-controlled electric servomotor directly controls the amount of hydraulic oil pumped into and out of the system. The hydraulic pump/motors create flows dependant on the rotating speed of the servomotor. A hydraulic accumulator is used as a conventional tank replacement. The aim of this paper is to investigate the efficiency improvement of the excavator with decentralized hydraulics compared to an electrified conventional load sensing system, from an energy consumption point of view under a typical digging cycle. In order to acquire the energy consumption distributions of the DDH and load sensing (LS) system, a model of the micro excavator which comprises mechanics, hydraulics, electronics, and control systems is developed in Matlab/Simulink. Simulation results demonstrate that the total efficiency of the excavator with LS control is 18.3%, and with DDH (decentralized hydraulics) is 71.3 % for a selected typical working cycle.
A New Approach to Sizing Low Pressure Systems
Authors: Keller Nathan , Ivantysynova Monika
Published: December 2017

Closed-circuit hydraulic systems, like hydrostatic transmissions and Displacement Controlled (DC) architecture systems, require an integrated low-pressure system. These low-pressure systems provide several important functions to the hydraulic system. They prevent cavitation, provide cooling flow through the cooler, replenish the hydraulic system with cool oil, assist in the oil filtration process, provide pressure to the hydraulic unit control systems and, in the case of DC systems with differential cylinders, balance the unequal cylinder flow. Traditionally, the sizing of low-pressure systems is accomplished using a static sizing approach. In this approach, a constant efficiency of the hydraulic units is assumed, and the system is operating at a maximum power condition. The result is often an oversized charge pump and accumulator, if one is present. A dynamic sizing method has been developed using MATLAB/Simulink® with high fidelity empirical loss models for hydraulic displacement machines. Using realistic duty cycles for hydraulic systems and measured data, the low-pressure system can be accurately sized. Dynamically sizing low-pressure systems reduce parasitic losses on the prime mover because of smaller pump sizes, thus freeing power to be used elsewhere. Another concept presented in this work is the possibility of isolating the hydraulic unit control pressure supply and the low-pressure system. Realistic examples have been simulated to demonstrate the power savings of dynamically sizing low-pressure systems.
A Path Toward Effective Piston/Cylinder Interface Scaling Approach
Authors: Shang L. , Ivantysynova M.
Published: December 2017

Scaling three main lubricating interfaces (piston/cylinder interface, cylinder block/valve plate interface, and slipper/swash plate interface) of swash plate type axial piston machine while remaining the pump performance is a rewarding but challenging task. Instead of designing a new unit for the desired displacement, scaling a well-designed existing unit to the desired size requires much less computational and experimental cost. However, scaling all the components linearly is far from enough to remain the original sized unit’s performance due to the unscalable fluid properties and material properties. This paper proposes a novel scaling method for the piston/cylinder interface which is able to achieve the baseline performance at some of the operating conditions, and closing the gap between the scaled unit performance and the baseline performance at the rest of the operating conditions.

The authors use a special in-house developed simulation tool to study the design parameters of the piston/cylinder interface impacts on the performance in terms of leakage flow rate, and the energy dissipation. This in-house developed tool is able to model the lubricating fluid film behavior considering the complex fluid and structure interaction, the macro and micro motion of the piston, the three-dimensional fluid heat-transfer, the three-dimensional solid part heat-transfer, and the solid part deformation due to both the pressure and the thermal load.

This paper includes a brief introduction of the simulation tool, the results of the design parameters investigation, the proposed scaling method, and the simulation results comparison between the baseline unit and the scaled unit using the proposed method.
Low-Friction Antagonist Hydraulic Transmission Using Long-Stroke Rolling Diaphragm Cylinders
Authors: Hashemi Saeed , Sobojinski Steven , Durfee William K.
Published: December 2017

Hydraulic cylinders are the most common actuators for small, passive hydraulic systems. Friction and leakage of the actuators are the most crucial factors for force and volume efficiency. Development of a frictionless and leak-free cylinder would enable implementation of a passive human body controlled device. Due to the limitation of short stroke length in commercial rolling diaphragm (RD) cylinders, a novel fabric-elastomer long-stroke rolling diaphragm (LSRD) cylinder was developed, evaluated, and compared to the commercial rolling diaphragm, O-ring, and gap seal cylinders. The LSRD cylinder has low friction, zero leakage, and can operate at up to 700 kPa (100 psi). The performance of the LSRD cylinders was evaluated using an antagonist hydraulic transmission benchtop device.

Axial motion of the LSRD cylinders was converted to a rotary motion on the input and output shafts using timing belts and pulleys. Two LSRD cylinders were engaged on each shaft and two lever arms were used to control the transmission device. A rotation of 90 degrees was achieved using LSRD cylinders with 1.5-inch stroke length.

Friction, stiffness, tracking, impulse response, and step response tests were performed at 70, 170, and 275 kPa (10, 25, and 40 psi) preload pressures to evaluate the transmission device and LSRD cylinder dynamic performance. The results demonstrated that at least 275 kPa preload pressure is needed to have a satisfactory performance.

The passive antagonist hydraulic transmission can be used in applications such as wearable robots and telepresence devices.
Interaction Analysis Between a Hydraulic Load Simulator and a Pneumatic Positioning System
Authors: Ledezma Job A. , De Negri Victor J. , Barasuol Victor
Published: December 2017

Pneumatic positioning systems (PPS) are widely used in fields were mechatronics applications exist. In order to improve the performance and robustness, either by designing new controllers or studying other characteristics of PPSs under different load conditions, a test bench with a load simulator is required. Hydraulic load simulators (HLS) are one of the most significant applications of hydraulic force control systems. The HLS aims to control the forces according to static and dynamic requirements. Typically, a force control system interacts with the external environment such that a good performance and robustness are not easily achieved. Different approaches are being discussed in the literature consisting on increasing the system compliance. System compliance can be controlled or modified in active or passive ways. Active compliance is obtained by force-based feedback control, allowing more flexibility to perform tasks where compliance is required. On the other hand, passive compliance is typically obtained by introducing mechanical elastic components between the actuator and the environment. In this paper, the influence of PPS compliance in the force controlled tuning of HLS is discussed. Because HLS is applying a controlled force against to a very compliant system like a pneumatic system, stable force responses could be expected. However, the dynamic interaction between the HLS with the PPS effected the force responses. This paper focuses in analyzing these effects, highlighting the design of PI and QFT controllers for force control based on these characteristics. Both of Systems are analyzed mathematically via simulation.
PA5470 Counteracts Antimicrobial Effect of Azithromycin by Releasing Stalled Ribosome in Pseudomonas aeruginosa
Authors: Shi Jing , Liu Yiwei , Zhang Yueying , Jin Yongxin , Bai Fang , Cheng Zhihui , Jin Shouguang , Wu Weihui
Published: December 2017

Pseudomonas aeruginosa
causes various acute and chronic infections in humans. Treatment with azithromycin (AZM) has been shown to benefit patients with chronic
P. aeruginosa
infections. By binding to the exit tunnel of the 50S ribosome, AZM causes ribosome stalling and depletion of the intracellular tRNA pool. It has been shown that AZM is able to kill stationary-phase
P. aeruginosa
cells and repress quorum sensing-regulated virulence factors as well as swarming motility. In
P. aeruginosa
, the PA5470 gene encodes a putative peptide chain release factor whose expression is highly induced by macrolide antibiotics. However, its function remains unknown. Here, we found that overexpression of PA5470 increased bacterial tolerance against AZM and alleviated the repression of swarming motility. Ribosome pulldown assays revealed that PA5470 contributes to the release of ribosome stalled by AZM. We further demonstrate that overexpression of PA5470 counteracts AZM-mediated repression of the translation of the quorum sensing regulator RhlR. Overall, our results revealed a novel role of PA5470 in the bacterial response to AZM.
Epidemiology of Carbapenem-Resistant Enterobacteriaceae Infections: Report from the China CRE Network
Authors: Zhang Yawei , Wang Qi , Yin Yuyao , Chen Hongbin , Jin Longyang , Gu Bing , Xie Liangyi , Yang Chunxia , Ma Xiaobo , Li Huayin , Li Wei , Zhang Xiaoqian , Liao Kang , Man Sijin , Wang Shifu , Wen Hainan , Li Binbin , Guo Zhusheng , Tian Jinjing , Pei Fengyan , Liu Li , Zhang Lijun , Zou Cuimei , Hu Tongping , Cai Jun , Yang Hong , Huang Jiaming , Jia Xianghong , Huang Wenhui , Cao Bin , Wang Hui
Published: December 2017

Carbapenem-resistant
Enterobacteriaceae
(CRE) infection is highly endemic in China, but estimates of the infection burden are lacking. We established the incidence of CRE infection from a multicenter study that covered 25 tertiary hospitals in 14 provinces. CRE cases defined as carbapenem-nonsusceptible
Citrobacter freundii
,
Escherichia coli
,
Enterobacter cloacae
, or
Klebsiella pneumoniae
infections during January to December 2015 were collected and reviewed from medical records. Antimicrobial susceptibility testing and carbapenemase gene identification were performed. Among 664 CRE cases, most were caused by
K. pneumoniae
(73.9%), followed by
E. coli
(16.6%) and
E. cloacae
(7.1%). The overall CRE infection incidence per 10,000 discharges was 4.0 and differed significantly by region, with the highest in Jiangsu (14.97) and the lowest in Qinghai (0.34). Underlying comorbidities were found in 83.8% of patients; the median patient age was 62 years (range, 45 to 74 years), and 450 (67.8%) patients were male. Lower respiratory tract infections (65.4%) were the most common, followed by urinary tract infection (16.6%), intra-abdominal infection (7.7%), and bacteremia (7.7%). The overall hospital mortality rate was 33.5%. All isolates showed nonsusceptibility to carbapenems and cephalosporins. The susceptibility rate of polymyxin B was >90%. Tigecycline demonstrated a higher susceptibility rate against
E. coli
than against
K. pneumoniae
(90.9% versus 40.2%). Of 155 clinical isolates analyzed, 89% produced carbapenemases, with a majority of isolates producing KPC (50%) or NDM (33.5%)-type beta-lactamases among
K. pneumoniae
and
E. coli
. The incidence of CRE infection in China was 4.0 per 10,000 discharges. The patient-based disease burden in tertiary hospitals in China is severe, suggesting an urgent need to enhance infection control.
Novel Treatment of Staphylococcus aureus Device-Related Infections Using Fibrinolytic Agents
Authors: Hogan S. , O'Gara J. P. , O'Neill E.
Published: December 2017

Staphylococcal infections involving biofilms represent a significant challenge in the treatment of patients with device-related infections.
Staphylococcus aureus
biofilms have been shown to be SaeRS regulated and dependent on the coagulase-catalyzed conversion of fibrinogen into fibrin on surfaces coated with human plasma. Here we investigated the treatment of staphylococcal biofilm device-related infections by digesting the fibrin biofilm matrix with and without existing antimicrobials. The fibrinolytic agents plasmin, streptokinase, and nattokinase, and TrypLE, a recombinant trypsin-like protease, were used to digest and treat
S. aureus
biofilms grown
in vitro
using
in vivo
-like static biofilm assays with and without antimicrobials. Cytotoxicity, the potential to induce a cytokine response in whole human blood, and the risk of induction of tolerance to fibrinolytic agents were investigated. A rat model of intravascular catheter infection was established to investigate the efficacy of selected fibrinolytic agents
in vivo
. Under biomimetic conditions, the fibrinolytic agents effectively dispersed established
S. aureus
biofilms and, in combination with common antistaphylococcal antimicrobials, effectively killed bacterial cells being released from the biofilm. These fibrinolytic agents were not cytotoxic and did not affect the host immune response. The rat model of infection successfully demonstrated the activity of the selected fibrinolytic agents alone and in combination with antimicrobials on established biofilms
in vivo
. TrypLE and nattokinase most successfully removed adherent cells from plasma-coated surfaces and significantly improved the efficacy of existing antimicrobials against
S. aureus
biofilms
in vitro
and
in vivo
. These biofilm dispersal agents represent a viable future treatment option for
S. aureus
device-related infections.
Mutations in Genes Encoding Penicillin-Binding Proteins and Efflux Pumps Play a Role in β-Lactam Resistance in Helicobacter cinaedi
Authors: Rimbara Emiko , Mori Shigetarou , Kim Hyun , Suzuki Masato , Shibayama Keigo
Published: December 2017

β-Lactams are often used to treat
Helicobacter cinaedi
infections; however, the mechanism underlying β-lactam resistance is unknown. In this study, we investigated β-lactam resistance in an
H. cinaedi
strain, MRY12-0051 (MICs of amoxicillin [AMX] and ceftriaxone [CRO], 32 and 128 μg/ml; obtained from human feces). Based on a comparative whole-genome analysis of MRY12-0051 and the CRO-susceptible
H. cinaedi
strain MRY08-1234 (MICs of AMX and CRO, 1 and 4 μg/ml; obtained from human blood), we identified five mutations in genes encoding penicillin-binding proteins (PBPs), including two in
pbpA
, one in
pbp2
, and two in
ftsI
. Transformation and penicillin binding assays indicated that CRO resistance was mainly associated with mutations in
pbpA
; mutations in
ftsI
also led to increased resistance to AMX. Knocking out
cmeB
and
cmeD
, which encode resistance-nodulation-division-type efflux pump components, in
H. cinaedi
type strain CCUG18818 (AMX MIC, 4 to 8 μg/ml) resulted in 8- and 64-fold decreases, respectively, in the AMX MIC. Hence, MICs of AMX in
H. cinaedi
become similar to those of
Helicobacter pylori
isolates in the absence of
cmeD
. In conclusion, the difference in susceptibility to β-lactams between
H. pylori
and
H. cinaedi
is explained by differences in efflux pump components. Mutations in
pbpA
are the primary determinant of high resistance to β-lactams in
H. cinaedi
.
Role of
smeU1VWU2X
Operon in Alleviation of Oxidative Stresses and Occurrence of Sulfamethoxazole-Trimethoprim-Resistant Mutants in Stenotrophomonas maltophilia
Authors: Wu Chao-Jung , Chiu Tsu-Ting , Lin Yi-Tsung , Huang Yi-Wei , Li Li-Hua , Yang Tsuey-Ching
Published: December 2017

Overexpression of resistance-nodulation-division (RND)-type efflux pumps is an important mechanism for bacteria to combat antimicrobials. RND efflux pumps are also critical for bacterial physiology, such as oxidative stress tolerance.
Stenotrophomonas maltophilia
, a multidrug-resistant opportunistic pathogen, harbors eight RND-type efflux pump operons. Of these, the
smeU1VWU2X
operon is unique for its possession of two additional genes,
smeU1
and
smeU2
, which encode proteins of the short-chain dehydrogenase/reductase (SDR) family. Overexpression of the SmeVWX pump is known to contribute to the acquired resistance to chloramphenicol, quinolone, and tetracycline; however, SmeU1 and SmeU2 are little involved in this phenotype. In the study described in this article, we further linked the
smeU1VWU2X
operon to oxidative stress alleviation and sulfamethoxazole-trimethoprim (SXT)-resistant mutant occurrence. The
smeU1VWU2X
operon was inducibly expressed upon challenge with menadione (MD), plumbagin (PL), and hydrogen peroxide (H
2
O
2
), as verified by the use of the chromosomal
smeU1VWU2X-xylE
transcriptional fusion construct and quantitative real-time PCR (qRT-PCR). The MD-mediated
smeU1VWU2X
upexpression was totally dependent on SoxR and partially relied on SmeRv but was less relevant to OxyR. SmeRv, but not SoxR and OxyR, played a regulatory role in the H
2
O
2
-mediated
smeU1VWU2X
upexpression. The significance of
smeU1VWU2X
upexpression was investigated with respect to oxidative stress alleviation and SXT-resistant mutant occurrence. Overexpression of the
smeU1VWU2X
operon contributed to the alleviation of MD-mediated oxidative stress. Of the encoded proteins, the SmeVWX pump and SmeU2, rather than SmeU1, participated in MD tolerance. Furthermore, we also demonstrated that the MD-mediated expression of the
smeU1VWU2X
operon decreased the SXT resistance frequency when
S. maltophilia
was grown in a reactive oxygen species (ROS)-rich environment.
In Vitro
,
In Silico
, and
In Vivo
Analyses of Novel Aromatic Amidines against Trypanosoma cruzi
Authors: Santos Camila C. , Lionel Jéssica R. , Peres Raiza B. , Batista Marcos M. , da Silva Patrícia B. , de Oliveira Gabriel M. , da Silva Cristiane F. , Batista Denise G. J. , Souza Sandra Maria O. , Andrade Carolina H. , Neves Bruno J. , Braga Rodolpho C. , Patrick Donald A. , Bakunova Svetlana M. , Tidwell Richard R. , Soeiro Maria de Nazaré C.
Published: December 2017

Five bis-arylimidamides were assayed as anti-
Trypanosoma cruzi
agents by
in vitro
,
in silico
, and
in vivo
approaches. None were considered to be pan-assay interference compounds. They had a favorable pharmacokinetic landscape and were active against trypomastigotes and intracellular forms, and in combination with benznidazole, they gave no interaction. The most selective agent (28SMB032) tested
in vivo
led to a 40% reduction in parasitemia (0.1 mg/kg of body weight/5 days intraperitoneally) but without mortality protection.
In silico
target fishing suggested DNA as the main target, but ultrastructural data did not match.
Extreme Drug Tolerance of Mycobacterium tuberculosis in Caseum
Authors: Sarathy Jansy P. , Via Laura E. , Weiner Danielle , Blanc Landry , Boshoff Helena , Eugenin Eliseo A. , Barry Clifton E. , Dartois Véronique A.
Published: December 2017

Tuberculosis (TB) recently became the leading infectious cause of death in adults, while attempts to shorten therapy have largely failed. Dormancy, persistence, and drug tolerance are among the factors driving the long therapy duration. Assays to measure
in situ
drug susceptibility of
Mycobacterium tuberculosis
bacteria in pulmonary lesions are needed if we are to discover new fast-acting regimens and address the global TB threat. Here we take a first step toward this goal and describe an
ex vivo
assay developed to measure the cidal activity of anti-TB drugs against
M. tuberculosis
bacilli present in cavity caseum obtained from rabbits with active TB. We show that caseum
M. tuberculosis
bacilli are largely nonreplicating, maintain viability over the course of the assay, and exhibit extreme tolerance to many first- and second-line TB drugs. Among the drugs tested, only the rifamycins fully sterilized caseum. A similar trend of phenotypic drug resistance was observed in the hypoxia- and starvation-induced nonreplicating models, but with notable qualitative and quantitative differences: (i) caseum
M. tuberculosis
exhibits higher drug tolerance than nonreplicating
M. tuberculosis
in the Wayne and Loebel models, and (ii) pyrazinamide is cidal in caseum but has no detectable activity in these classic nonreplicating assays. Thus,
ex vivo
caseum constitutes a unique tool to evaluate drug potency against slowly replicating or nonreplicating bacilli in their native caseous environment. Intracaseum cidal concentrations can now be related to the concentrations achieved in the necrotic foci of granulomas and cavities to establish correlations between clinical outcome and lesion-centered pharmacokinetics-pharmacodynamics (PK-PD) parameters.
Proinflammatory Role of Monocyte-Derived CX3CR1
int
Macrophages in Helicobacter hepaticus-Induced Colitis
Authors: Bain Calum C. , Oliphant Christopher J. , Thomson Carolyn A. , Kullberg Marika C. , Mowat Allan M.
Published: December 2017

Cells of the monocyte/macrophage lineage play important roles in the pathogenesis of inflammatory bowel diseases, but they are also present in the normal healthy intestine, where they are critical for maintaining homeostasis. It has been unclear whether the proinflammatory roles of intestinal macrophages reflect altered behavior of the existing resident cells, or whether they involve recruitment of a distinct cell type. Here, we have explored these ideas using the model of colitis induced by
Helicobacter hepaticus
in the context of neutralization or deletion of interleukin-10 (IL-10). Granulocytes and monocytes made up most of the inflammatory myeloid infiltrates found in the colon of
H. hepaticus
-infected colitic mice, rising to a peak within 2 weeks of
H. hepaticus
inoculation but taking several months to resolve completely. The inflammatory response was dependent on the combined presence of
H. hepaticus
and absence of IL-10 and was accompanied by increased production of inflammatory mediators such as IL-1β, tumor necrosis factor alpha (TNF-α), IL-6, and IL-23p19 by infiltrating myeloid cells, mostly relatively immature cells of the macrophage lineage that express intermediate levels of CX3CR1. In contrast, the population of mature CX3CR1
hi
macrophages did not expand as markedly during colitis, and these cells made little contribution to inflammatory mediator production. Taking into account their numerical dominance in the myeloid compartment, we conclude that newly recruited monocytes are the main source of proinflammatory mediators in colitis induced in the absence of IL-10 signaling and that altered behavior of mature macrophages is not a major component of this pathology.
Novel Mechanism behind the Immunopathogenesis of Vulvovaginal Candidiasis: “Neutrophil Anergy”
Authors: Yano Junko , Peters Brian M. , Noverr Mairi C. , Fidel Paul L.
Published: December 2017

For over 3 decades, investigators have studied the pathogenesis of vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC) through clinical studies and animal models. While there was considerable consensus that susceptibility was not associated with any apparent deficiencies in adaptive immunity, protective immune mechanisms and the role of innate immunity remained elusive. It was not until an innovative live-challenge design was conducted in women that a fuller understanding of the natural history of infection/disease was achieved. These studies revealed that symptomatic infection is associated with recruitment of polymorphonuclear neutrophils (PMNs) into the vaginal lumen. Subsequent studies in the established mouse model demonstrated that infiltrating PMNs were incapable of reducing the fungal burden, which supported the hypothesis that VVC/RVVC was an immunopathology, whereby
Candida
and the host response drive symptomatic disease. Further studies in mice revealed the requirement for
C. albicans
hyphae and identified pattern recognition receptors (PRRs) and proinflammatory mediators responsible for the PMN response, all of which are critical pieces of the immunopathogenesis. However, a mechanism explaining PMN dysfunction at the vaginal mucosa remained an enigma. Ultimately, by employing mouse strains resistant or susceptible to chronic VVC, it was determined that heparan sulfate (HS) in the vaginal environment of susceptible mice serves as a competitive ligand for Mac-1 on PMNs, which effectively renders the PMNs incapable of binding to
Candida
to initiate killing. Hence, the outcome of symptomatic VVC/RVVC is postulated to be dependent on a PMN-mediated immunopathogenic response involving HS that effectively places the neutrophils in a state of functional anergy.