Piezoelectric Micromachined Ultrasonic Transducer-Integrated Helmholtz Resonator with Microliter-Sized Volume-Tunable Cavity.

In this study, a piezoelectric micromachined ultrasonic transducer (PMUT) is integrated with a microliter-sized volume-tunable Helmholtz resonator. The passive Helmholtz resonator is constructed using an SU8 photolithography-defined square opening plate as the neck portion, a 3D-printed hollow structure with a threaded insert nut, and a precision set screw to form the volume-controllable cavity of the Helmholtz resonator. The fabricated piezoelectric films acted as ultrasonic actuators attached to the surface of the neck SU8 plate. Experimental results show that the sound pressure level (SPL) and operation bandwidth could be effectively tuned, and a 200% SPL increase and twofold bandwidth enhancement are achieved when setting the cavity length to 0.75 mm compared with the open-cavity case. A modified Helmholtz resonator model is proposed to explain the experimental results. The adjusting factors of the effective mass and viscous damper are created to modify the existing parameters in the conventional Helmholtz resonator model. The relationship between the adjusting factors and cavity length can be described well using a two-term power series curve. This modified Helmholtz resonator model not only provides insight into this active-type Helmholtz resonator operation but also provides a useful estimation for its optimal design and fabrication.

Piezoelectric Micromachined Ultrasonic Transducers with a Cost-Effective Bottom-Up Fabrication Scheme for Millimeter-Scale Range Finding.

This study proposes a novel piezoelectric micromachined ultrasonic transducer (PMUT), fabricated on a metal foil. Using a bottom-up, cost-effective micromachining technique, the PMUTs made of electrodes, a piezoelectric film, or electrode-sandwiched structures with versatile patterns were implemented on a large-area foil thinner rather than regular paper. The proposed microfabrication facilitated the PMUT to be able to generate ultrasonic waves with fundamental and harmonic resonances. The fourth-order resonances of the fabricated PMUT functionally operated at an ultrasonic spectrum of approximately 30 kHz as an ultrasonic emitter. The developed PMUT was paired with a microelectromechanical system (MEMS) microphone module for range-finding applications in the range of several tens of millimeters. A signal-processing scheme was developed to extract the representative pattern from the acquired signals that were emitted and received. The pattern enabled finding the distance between the PMUT and the microphone using time-of-flight and strength-variation technology. The developed PMUT-microphone pair demonstrated its range-finding performance, displaying an error of less than 0.7% using the time-of-flight method.

An Out-of-Plane Operated Soft Engine Driving Stretchable Zone Plate for Adjusting Focal Point of an Ultrasonic Beam.

This paper presents a soft engine which performs up-and-down motion with four planar film-structured ionic polymer-metal composites (IPMC) actuators. This soft engine assembled with a stretchable Fresnel zone plate is capable of tuning the focus of ultrasonic beam. Instead of conventional clamps, we employ 3D printed frame pairs with magnets and a conductive gold cloth to provide an alternative solution for securing the IPMC actuators during assembly. The design and analysis of the zone plate are carefully performed. The zone plate allows the plane ultrasonic wave to be effectively focused. The motion of IPMC actuators stretch the metal-foil-made zone plate to tune the focal range of the ultrasonic beam. The zone plate, 3D frames and IPMC actuators were fabricated, assembled and tested. The stiffness normal to the stretchable zone plate with varied designs was investigated and the seven-zone design was selected for our experimental study. The force responsible for clamping the IPMC actuators, controlled by the magnetic attraction between the fabricated frames, was also examined. The driving voltage, current and resulting displacement of IPMC actuation were characterized. The developed soft engine stretching the zone plate to tune the focal point of the ultrasonic beam up to 10% was successfully demonstrated.

[Health Care-seeking Behaviors in Mosuo and Pumi People in Yunnan Ninglang].

Objective To investigate the health care-seeking behaviors of Mosuo and Pumi people.Methods The subjects were enrolled by using the multi-stage stratified random sampling method and surveyed by the self-designed questionnaire.Results To tally 1669 subjects including 1121 Mosuo people and 548 Pumi people completed the survey.When Mosuo and Pumi people suffer from ailments,they preferred to buy drugs in drugstores(47.3% for Mosuo and 46.9% for Pumi),followed by visiting a local township hospital(27.0% for Mosuo and 24.3% for Pumi).When they suffered from severe diseases,they preferred to visit the county/city/state hospital(93.4% for Mosuo and 91.1% for Pumi).The mental disease were mainly treated in the county/city/state hospitals(49.3% for Mosuo and 52.7% for Pumi);notably,39.3% of the Mosuo respondents and 31.5% of the Pumi respondents skipped this question.Conclusion Health education,including awareness-raising activities on mental health,should be enhanced in Mosuo and Pumi people to further improve their health care-seeking behaviors.

Investigation on the Mechanical and Electrical Behavior of a Tuning Fork-Shaped Ionic Polymer Metal Composite Actuator with a Continuous Water Supply Mechanism.

This paper presents an innovative tuning fork-shaped ionic polymer metal composite (IPMC) actuator. With an integrated soft strain gauge and water supply mechanism (WSM), the surface strain of the actuator can be sensed in situ, and providing a continuous water supply maintains the water content inside the IPMC for long-term operation in air. The actuator was fabricated using a micromachining technique and plated with a nickel electrode. The device performance was experimentally characterized and compared with an actuator without a WSM. A large displacement of 1.5 mm was achieved for a 6 mm-long prong with 7-V dc actuation applied for 30 s. The measured current was analyzed using an electrochemical model. The results revealed that the faradaic current plays a crucial role during operation, particularly after 10 s. The measured strain confirms both the bending and axial strain generation during the open-and-close motion of the actuator prongs. Most of the water loss during device operation was due to evaporation rather than hydrolysis. The constructed WSM effectively maintained the water content inside the IPMC for long-term continuous operation.

Hypouricaemic action of mangiferin results from metabolite norathyriol via inhibiting xanthine oxidase activity.

Context Mangiferin has been reported to possess a potential hypouricaemic effect. However, the pharmacokinetic studies in rats showed that its oral bioavailability was only 1.2%, suggesting that mangiferin metabolites might exert the action. Objective The hypouricaemic effect and the xanthine oxidase inhibition of mangiferin and norathyriol, a mangiferin metabolite, were investigated. Inhibition of norathyriol analogues (compounds 3-9) toward xanthine oxidase was also evaluated. Materials and methods For a dose-dependent study, mangiferin (1.5-6.0 mg/kg) and norathyriol (0.92-3.7 mg/kg) were administered intragastrically to mice twice daily for five times. For a time-course study, mice received mangiferin and norathyriol both at a single dose of 7.1 µmol/kg. In vitro, inhibition of test compounds (2.4-2.4 mM) against xanthine oxidase activity was evaluated by the spectrophotometrical method. The inhibition type was identified from Lineweaver-Burk plots. Results Norathyriol (0.92, 1.85 and 3.7 mg/kg) dose dependently decreased the serum urate levels by 27.0, 33.6 and 37.4%, respectively. The action was more potent than that of mangiferin at the low dose, but was equivalent at the higher doses. Additionally, the hypouricaemic action of them exhibited a time dependence. In vitro, norathyriol markedly inhibited the xanthine oxidase activities, with the IC50 value of 44.6 µM, but mangiferin did not. The kinetic studies showed that norathyriol was an uncompetitive inhibitor by Lineweaver-Burk plots. The structure-activity relationships exhibited that three hydroxyl groups in norathyriol at the C-1, C-3 and C-6 positions were essential for maintaining xanthine oxidase inhibition. Discussion and conclusion Norathyriol was responsible for the hypouricaemic effect of mangiferin via inhibiting xanthine oxidase activity.

Upregulation of OX40 ligand on monocytes contributes to early virological control in patients with chronic hepatitis C.

Dysfunctional hepatitis C virus (HCV) specific CD4(+) T cells are known to contribute to inadequate adaptive immunity in chronic hepatitis C (CHC), although the underlying mechanisms remain largely undefined. In this study, OX40 ligand (OX40L) expression was investigated in 41 treatment-naïve CHC patients, 20 sustained virological responders and 36 healthy subjects. We observed that OX40L expression was significantly upregulated in peripheral monocytes in CHC patients compared with sustained virological responders and healthy subjects. OX40L upregulation correlated significantly with plasma viral load rather than serum alanine aminotransaminase levels. Furthermore, longitudinal analyses indicated that upregulated OX40L expression on monocytes is closely associated with rapid or early virological responses in patients receiving pegylated IFN-α/ribavirin treatment. In vitro, HCV core antigen strongly stimulated monocyte expression of OX40L and blockade of TLR2 signaling significantly downregulated OX40L expression. More importantly, elevated OX40L expression was also shown to be closely associated with elevation of the HCV-specific CD4(+) T-cell response and in vitro blockade of OX40L expressed on monocytes led to impaired CD4(+) T-cell function. These findings, therefore, implicate OX40L expression can be used as a marker to evaluate antiviral treatment efficacy and extend the notion that enhancement of OX40L expression could be a good way for immunotherapy in CHC patients.

Fabrication and characterization of a micromachined swirl-shaped ionic polymer metal composite actuator with electrodes exhibiting asymmetric resistance.

This paper presents a swirl-shaped microfeatured ionic polymer-metal composite (IPMC) actuator. A novel micromachining process was developed to fabricate an array of IPMC actuators on a glass substrate and to ensure that no shortcircuits occur between the electrodes of the actuator. We demonstrated a microfluidic scheme in which surface tension was used to construct swirl-shaped planar IPMC devices of microfeature size and investigated the flow velocity of Nafion solutions, which formed the backbone polymer of the actuator, within the microchannel. The unique fabrication process yielded top and bottom electrodes that exhibited asymmetric surface resistance. A tool for measuring surface resistance was developed and used to characterize the resistances of the electrodes for the fabricated IPMC device. The actuator, which featured asymmetric electrode resistance, caused a nonzero-bias current when the device was driven using a zero-bias square wave, and we propose a circuit model to describe this phenomenon. Moreover, we discovered and characterized a bending and rotating motion when the IPMC actuator was driven using a square wave. We observed a strain rate of 14.6% and a displacement of 700 µm in the direction perpendicular to the electrode surfaces during 4.5-V actuation.

Study on the combination of virtual machine tools and wearable vibration devices for operators experiencing cutting forces in the milling process.

The primary goal of this study is to develop a wearable system for providing CNC machine operators with visual and tactile perception of triaxial cutting forces, thereby assisting operators in industrial environments to enhance work efficiency and prevent mechanical failures. To achieve this goal, we successfully integrated a virtual machining tool simulator with the remote-control wearable system (RCWS). Using the 'King Path' milling parameters, we employed the simulation software developed by the AIM-HI team to calculate static and dynamic cutting forces, converting this data into vibrational commands for the RCWS to generate corresponding tactile feedback. Furthermore, we conducted extensive experiments, testing various data conversion methods, including three sampling techniques and two data compression strategies, aiming to provide accurate tactile feedback related to cutting forces under different operating conditions.

Simple-structured capillary-force-dominated tunable-focus liquid lens based on the higher-order-harmonic resonance of a piezoelectric ring transducer.

This paper proposes a tunable-focus liquid lens implemented with a simple cylindrical container structure and liquid as the lens material. The cylindrical container was constructed using a Pb [Zr(0.52)Ti(0.48)]O(3) (PZT) ring transducer and a polydimethylsiloxane membrane that was attached to a flat side of the transducer. The free surface of the liquid in the cylindrical container can be driven as a static-like convex lens with different curvatures because the higher-order harmonic resonance of the PZT transducer was electrically controlled. Based on a capillary-force-dominant design, the activated liquid lens maintained surface curvature in an arbitrary orientation without a gravitational effect. Profiles of the liquid lenses were characterized with the driving voltages of the transducer ranging from 12 to 60 V peak-to-peak (Vpp) at a resonant frequency of 460 kHz. The temperature effects on the lenses caused by the continuous operation of the transducer were measured. Images showed the various curvatures of the lenses with a range of actuation voltages. A change in focal length of eight times (5.72 to 46.03 cm) was demonstrated within the 10 Vpp variation of the driving voltage. For the characterized liquid lenses, the distortion was less than 2%, and the modulation transfer function reached 63 line pairs per mm (lp/mm) using ZEMAX analysis.

A spherically-shaped PZT thin film ultrasonic transducer with an acoustic impedance gradient matching layer based on a micromachined periodically structured flexible substrate.

This paper presents the microfabrication of an acoustic impedance gradient matching layer on a spherically-shaped piezoelectric ultrasonic transducer. The acoustic matching layer can be designed to achieve higher acoustic energy transmission and operating bandwidth. Also included in this paper are a theoretical analysis of the device design and a micromachining technique to produce the novel transducer. Based on a design of a lead titanium zirconium (PZT) micropillar array, the constructed gradient acoustic matching layer has much better acoustic transmission efficiency within a 20-50 MHz operation range compared to a matching layer with a conventional quarter-wavelength thickness Parylene deposition. To construct the transducer, periodic microcavities are built on a flexible copper sheet, and then the sheet forms a designed curvature with a ball shaping. After PZT slurry deposition, the constructed PZT micropillar array is released onto a curved thin PZT layer. Following Parylene conformal coating on the processed PZT micropillars, the PZT micropillars and the surrounding Parylene comprise a matching layer with gradient acoustic impedance. By using the proposed technique, the fabricated transducer achieves a center frequency of 26 MHz and a -6 dB bandwidth of approximately 65%.

Micromachined optical fiber enclosed 4-electrode IPMC actuator with multidirectional control ability for biomedical application.

The present paper examined a novel micromachined column structured Ion Polymer Metal Composite (IPMC) actuator with multidirectional control capability. The developed 4-electrode transducer enclosed a section of optical fiber, thereby allowing electronic directional control of conducted laser light. The fabricated device with IPMC actuator dimensions of 5 mm x 2 mm x 1 mm reached a maximum displacement of 400 µm when a square wave of 9 V was applied to the top-bottom electrode pair. Displacements in different directions and moving angles were characterized with side-side and top-right electrode pairs connected to the actuating signals. Furthermore, the generating moment per volt per second by the transducer was analyzed. The maximum value of approximately 200 µN*m/V/s was displayed when the device actuated with the side-side electrode pair. Controlling the developed IPMC actuator moved the laser beam in multiple directions. This device could be promising for biomedical applications such as microendoscopic ocular surgery.

Electroactive polymer-based inner vessel-wall pressure transducer capable of integration with a PTA balloon catheter for examining blood vessel health.

This study presents a state-of-the-art soft and biocompatible transducer capable of detecting vessel inner-wall pressure for biomedical applications. The device includes a 3D electroactive polymer core element encapsulated by polydimethylsiloxane with an ellipsoidal structure. The device produces a voltage output when its sensing mechanism experiences different pressures, resulting in deformation at different orientations. Thus, it can be employed to detect the pressure exerted by inner vessel walls of different stiffness values. The output voltage is induced by the strain experienced by the sensing mechanism of the device without the need for any external electrical power source. The core element, which is made of an ionic polymer-metal composite, possesses a unique hollow design; this allows a catheter to pass through, and the core element can be anchored at an arbitrary position on the catheter. We also demonstrate that the fabricated device can be integrated with a medically used percutaneous transluminal angioplasty balloon catheter to form a smart sensing module. This module can detect different levels of fat accumulation around the inner wall of a blood vessel phantom. Evaluating vessel blockage and stiffness using the signals acquired from the developed device is discussed.

Flexible meniscus/biconvex lens system with fluidic-controlled tunable-focus applications.

Controlled injection of fluid into a flexible lens chamber has previously produced tunable spherical lenses with spherical aberration problems. This paper presents a novel fluidic-controlled meniscus/biconvex lens system with relatively low distortion. The lens fabrication method is described and manufactured lenses are characterized for different processing parameters. Images captured through one of our lenses for a range of different pressures are presented. A change in focal length of five times (19.1-80.8 cm) is demonstrated. The focal length shows a quadratic relation to the applied pressure (0-5 kPa). For the simple prototype lens, distortion is less than 5% and relative illumination is above 0.74 by ZEMAX analysis.

Hydrothermally synthesized PZT film grown in highly concentrated KOH solution with large electromechanical coupling coefficient for resonator.

This paper presents a study of lead zirconate titanate (PZT) films hydrothermally grown on a dome-shaped titanium diaphragm. Few articles in the literature address the implementation of hydrothermal PZT films on curved-diaphragm substrates for resonators. In this study, a 50-µm-thick titanium sheet is embossed using balls of designed dimensions to shape a dome-shaped cavity array. Through single-process hydrothermal synthesis, PZT films are grown on both sides of the processed titanium diaphragm with good adhesion and uniformity. The hydrothermal synthesis process involves a high concentration of potassium hydroxide solution and excess amounts of lead acetate and zirconium oxychloride octahydrate. Varied deposition times and temperatures of PZT films are investigated. The grown films are characterized by X-ray diffraction and scanning electron microscopy. The 10-µm-thick PZT dome-shaped resonators with 60- and 20-µm-thick supporting layers are implemented and further tested. Results for both resonators indicate that large electromechanical coupling coefficients and a series resonance of 95 MHz from 14 MHz can be attained. The device is connected to a complementary metal-oxide-semiconductor integrated circuit for analysis of oscillator applications. The oscillator reaches a Q value of 6300 in air. The resonator exhibits a better sensing stability when loaded with water when compared with air.

Overview of the improvement of the ring-stage survival assay-a novel phenotypic assay for the detection of artemisinin-resistant Plasmodium falciparum.

Artemisinin resistance in Plasmodium falciparum threatens the remarkable efficacy of artemisinin-based combination therapies worldwide. Thus, greater insight into the resistance mechanism using monitoring tools is essential. The ring-stage survival assay is used for phenotyping artemisinin-resistance or decreased artemisinin sensitivity. Here, we review the progress of this measurement assay and explore its limitations and potential applications.

A self-strain feedback tuning-fork-shaped ionic polymer metal composite clamping actuator with soft matter elasticity-detecting capability for biomedical applications.

This paper presents a smart tuning-fork-shaped ionic polymer metal composite (IPMC) clamping actuator for biomedical applications. The two fingers of the actuator, which perform the clamping motion, can be electrically controlled through a unique electrode design on the IPMC material. The generated displacement or strain of the fingers can be sensed using an integrated soft strain-gage sensor. The IPMC actuator and associated soft strain gage were fabricated using a micromachining technique. A 13.5×4×2 mm(3) actuator was shaped from Nafion solution and a selectively grown metal electrode formed the active region. The strain gage consisted of patterned copper foil and polyethylene as a substrate. The relationship between the strain gage voltage output and the displacement at the front end of the actuator's fingers was characterized. The equivalent Young's modulus, 13.65 MPa, of the soft-strain-gage-integrated IPMC finger was analyzed. The produced clamping force exhibited a linear increasing rate of 1.07 mN/s, based on a dc driving voltage of 7 V. Using the developed actuator to clamp soft matter and simultaneously acquire its Young's modulus was achieved. This demonstrated the feasibility of the palpation function and the potential use of the actuator in minimally invasive surgery.

Fabrication of piezoelectric components for a tunable and efficient device for DNA delivery into mammalian cells.

We fabricated three piezoelectric components (PZT) that can produce ultrasonic waves with various generated power in order to improve the delivery of DNA molecule and polymer/DNA complexes into cells. Two cationic polymers (PEI and PDMAEMA) were interacted with DNA to form nano-scaled DNA/polymer complexes with/without the help of PZT devices. The application of PZT devices under optimal conditions helped to avoid cytotoxicity and greatly increased the transfection (DNA delivery) efficiency of these complexes in mammalian cells. The cytotoxicity and transfection efficiency were found to be correlated with the PZT-generated power, waveforms and duration of ultrasonic treatment. There was no observable cytotoxicity in our experimental models and, a maximum transfection efficiency 700% greater than that of polymer/DNA complexes without applying ultrasound was achieved. The transfection efficiency of plain polymer/DNA complexes (without PZT treatment) corresponded to a 630-fold increase in comparison to the naked DNA. The waveforms of generated ultrasound greatly influenced the transfection efficiency, while cytotoxicity was not significantly affected. This means that, for optimal DNA delivery, duration of the peak voltage (Vmax/Div) also plays a role. In addition, the generated waves from PZT do not cause dissociation of polymer/DNA complexes or a change in the particle sizes of these complexes. In conclusion, these results suggest that the operation of PZT devices can be a tunable/safe way to greatly improve DNA delivery for gene therapy.

Myeloid-derived suppressor cells are associated with viral persistence and downregulation of TCR ζ chain expression on CD8(+) T cells in chronic hepatitis C patients.

Myeloid-derived suppressor cells (MDSCs) play an important role in impairing the function of T cells. We characterized MDSCs in two chronic hepatitis C (CHC) cohorts: a cross-sectional group that included 61 treatment-naive patients with CHC, 14 rapid virologic response (RVR) cases and 22 early virologic response (EVR) cases; and a longitudinal group of 13 cases of RVR and 10 cases of EVR after pegylated-interferon-α/ribavirin treatment for genotype 1b HCV infection. Liver samples from 32 CHC patients and six healthy controls were subjected to immunohistochemical analysis. MDSCs frequency in treatment-naive CHC was significantly higher than in RVR, EVR, or healthy subjects and was positively correlated with HCV RNA. Patients infected with HCV genotype 2a had a significantly higher frequency of MDSCs than those infected with genotype 1b. Decreased T cell receptor (TCR) ζ expression on CD8(+) T cells was significantly associated with an increased frequency of MDSCs in treatment-naive CHC patients and was restored by L-arginine treatment in vitro. Increased numbers of liver arginase-1(+) cells were closely associated with the histological activity index in CHC. The TCR ζ chain was significantly downregulated on hepatic CD8(+) T cells in CHC. During antiviral follow up, MDSCs frequency in peripheral blood mononuclear cells was directly correlated with the HCV RNA load in the plasma and inversely correlated with TCR ζ chain expression in CD8(+) T cells in both RVR and EVR cases. Notably, the RVR group had a higher frequency of MDSCs at baseline than the EVR group. Collectively, this study provides evidence that MDSCs might be associated with HCV persistence and downregulation of CD8 ζ chain expression.

Risk factors for liver-related mortality in chronic hepatitis C patients: a deceased case-living control study.

AIM: To investigate the risk factors for liver-related mortality in chronic hepatitis C (CHC) patients. METHODS: All deceased CHC inpatient data were collected from the Beijing 302 Hospital clinical database, which includes more than 8250 CHC inpatients during the period from 2002 to 2012. The controls were matched to cases by age (± 2 years), sex and date of hospital admission (within the same year). Potential risk factors were included for the evaluation, and odds ratios (OR) and 95%CI were estimated using univariate (unadjusted) and multivariate (adjusted OR, AOR) conditional logistic regression. All statistical tests were two-sided. P values < 0.05 were considered statistically significant. RESULTS: Based on examinations of 144 CHC-related deceased cases and 576 controls, we found that antiviral therapy with interferon-α was associated with a 47% decrease in the risk of hepatic mortality (AOR = 0.53, 95%CI: 0.28-0.99, P = 0.048). Additionally, the initial diagnostic stage of the disease (AOR = 2.89, 95%CI: 1.83-4.56 and P < 0.001 for liver cirrhosis/AOR = 8.82, 95%CI: 3.99-19.53 and P < 0.001 for HCC compared with CHC), diabetes (AOR = 2.35, 95%CI: 1.40-3.95, P = 0.001), hypertension (AOR = 1.76, 95%CI: 1.09-2.82, P = 0.020), alcohol consumption (AOR = 1.73, 95%CI: 1.03-2.81, P = 0.037) and HBsAg positivity (AOR = 22.28, 95%CI: 5.58-89.07, P < 0.001) were associated with a significant increase in the risk of liver-related mortality in CHC patients. CONCLUSION: This study indicates that interferon-α treatment, the stage at the initial diagnosis of the disease and comorbidities are all independent risk factors for liver-related mortality in CHC patients.