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Lung injury is a significant complication associated with cholestasis/cirrhosis. This problem significantly increases the risk of cirrhosis-related morbidity and mortality. Hence, finding effective therapeutic options in this field has significant clinical value. Severe inflammation and oxidative stress are involved in the mechanism of cirrhosis-induced lung injury. Taurine (TAU) is an abundant amino acid with substantial anti-inflammatory and antioxidative properties. The current study was designed to evaluate the role of TAU in cholestasis-related lung injury. For this purpose, bile duct ligated (BDL) rats were treated with TAU (0.5 and 1% w: v in drinking water). Significant increases in the broncho-alveolar lavage fluid (BALF) level of inflammatory cells (lymphocytes, neutrophils, basophils, monocytes, and eosinophils), increased IgG, and TNF-α were detected in the BDL animals (14 and 28 days after the BDL surgery). Alveolar congestion, hemorrhage, and fibrosis were the dominant pulmonary histopathological changes in the BDL group. Significant increases in the pulmonary tissue biomarkers of oxidative stress, including reactive oxygen species formation, lipid peroxidation, increased oxidized glutathione levels, and decreased reduced glutathione, were also detected in the BDL rats. Moreover, significant myeloperoxidase activity and nitric oxide levels were seen in the lung of BDL rats. It was found that TAU significantly blunted inflammation, alleviated oxidative stress, and mitigated lung histopathological changes in BDL animals. These data suggest TAU as a potential protective agent against cholestasis/cirrhosis-related lung injury.

Heat transfer enhancement is an important issue because of environmental effects and also cost reduction in any thermal installation. A combined propeller-type turbulator and Al2O3 nanofluid are considered for heat transfer enhancement in a horizontal circular tube. Three-dimensional governing equations using the two-phase mixture model with SST k–e turbulent model are numerically solved to predict the behavior of different thermo-fluid parameters in a horizontal circular tube. In addition to studying the effects of these, both means on the heat transfer enhancement, an important discussion on their simultaneous effects are also presented. The effects of turbulator on the generation of swirl flow and also on the turbulent kinetic energy are shown and discussed for different nanoparticle volume fractions and different nanoparticle mean diameters. On one hand, the effect of inserting a turbulator on the thermal performance significantly dominates the effect of using a nanofluid. For instance, at the Z/D = 13.5, using combined nanofluid and turbulator the heat transfer coefficient 2.68 times augments while using only a turbulator it is 2.53 times enhanced. On the other hand, turbulator generates a radial gradient on the momentum forces. The latter significantly deteriorates the uniformity of the nanoparticles concentration. A higher nanoparticle concentration at the near-wall region where the sedimentation problem is taken placed is seen. Thus, it is recommended that nanofluid is not a suitable choice for simultaneous consideration with a propeller-type turbulator in such an application particularly when considering its physicochemical stability drawback. However, further experimental investigations must be carried out to verify such a conclusion and recommendation. It should be mentioned that agglomeration and sedimentation of nanoparticles on the wall surface have not been considered on the modeling of nanofluid physical properties.

Background: Digital image analysis (DIA), used to extract information from pathology slides, provides better precision and no limitation regarding different interpretations by observers. Objectives: The present study aimed at evaluating the accuracy of DIA in the interpretation of borderline (2+) human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) slides of invasive ductal carcinoma of the breast. Methods: Sixty pathology samples with invasive ductal carcinoma of the breast were extracted based on HER2 (2+) and their fluorescence in situ hybridization (FISH), and chromogenic in situ hybridization (CISH) responses (as reference standard). The slides were digitized and, then, two pathologists examined the slides and documented diagnosis. DIA was performed by a free web application. Results: Totally, 307 digital images with 298 megabytes volume were extracted. The accuracy, sensitivity, and specificity values of DIA were 86 %, 46.1 %, and 97.8 %, respectively, with 8 false-negative cases. There was moderate agreement between the pathologist 1 (kappa = 0.42) and pathologist 2 (kappa = 0.41) with DIA. Conclusions: DIA had good accuracy and could be used for the interpretation of borderline HER2 IHC method in invasive ductal carcinoma.

Cardiac fibrosis describes the inappropriate proliferation of cardiac fibroblasts (CFs), leading to accumulation of extracellular matrix (ECM) proteins in the cardiac muscle, which is found in many pathophysiological heart conditions. A range of molecular components and cellular pathways, have been implicated in its pathogenesis. In this review, we focus on the TGF-β and WNT signaling pathways, and their mutual interaction, which have emerged as important factors involved in cardiac pathophysiology. The molecular and cellular processes involved in the initiation and progression of cardiac fibrosis are summarized. We focus on TGF-β and WNT signaling in cardiac fibrosis, ECM production, and myofibroblast transformation. Non-coding RNAs (ncRNAs) are one of the main players in the regulation of multiple pathways and cellular processes. MicroRNAs, long non-coding RNAs, and circular long non-coding RNAs can all interact with the TGF-β/WNT signaling axis to affect cardiac fibrosis. A better understanding of these processes may lead to new approaches for diagnosis and treatment of many cardiac conditions.

Imaging technologies that simultaneously provide anatomical, functional, and molecular information are emerging as an attractive choice for disease screening and management. Since the 1980s, transrectal ultrasound (TRUS) has been routinely used to visualize prostatic anatomy and guide needle biopsy, despite limited specificity. Photoacoustic imaging (PAI) provides functional and molecular information at ultrasonic resolution based on optical absorption. Combining the strengths of TRUS and PAI approaches, we report the development and bench-to-bedside translation of an integrated TRUS and photoacoustic (TRUSPA) device. TRUSPA uses a miniaturized capacitive micromachined ultrasonic transducer array for simultaneous imaging of anatomical and molecular optical contrasts [intrinsic: hemoglobin; extrinsic: intravenous indocyanine green (ICG)] of the human prostate. Hemoglobin absorption mapped vascularity of the prostate and surroundings, whereas ICG absorption enhanced the intraprostatic photoacoustic contrast. Future work using the TRUSPA device for biomarker-specific molecular imaging may enable a fundamentally new approach to prostate cancer diagnosis, prognostication, and therapeutic monitoring.

Focused ultrasound has been shown to be effective at stimulating neurons in many animal models, both in vivo and ex vivo. Ultrasonic neuromodulation is the only noninvasive method of stimulation that could reach deep in the brain with high spatial-temporal resolution, and thus has potential for use in clinical applications and basic studies of the nervous system. Understanding the physical mechanism by which energy in a high acoustic frequency wave is delivered to stimulate neurons will be important to optimize this technology. We imaged the isolated salamander retina of either sex during ultrasonic stimuli that drive ganglion cell activity and observed micron scale displacements, consistent with radiation force, the nonlinear delivery of momentum by a propagating wave. We recorded ganglion cell spiking activity and changed the acoustic carrier frequency across a broad range (0.5–43 MHz), finding that increased stimulation occurs at higher acoustic frequencies, ruling out cavitation as an alternative possible mechanism. A quantitative radiation force model can explain retinal responses and could potentially explain previous in vivo results in the mouse, suggesting a new hypothesis to be tested in vivo. Finally, we found that neural activity was strongly modulated by the distance between the transducer and the electrode array showing the influence of standing waves on the response. We conclude that radiation force is the dominant physical mechanism underlying ultrasonic neurostimulation in the ex vivo retina and propose that the control of standing waves is a new potential method to modulate these effects. SIGNIFICANCE STATEMENT Ultrasonic neurostimulation is a promising noninvasive technology that has potential for both basic research and clinical applications. The mechanisms of ultrasonic neurostimulation are unknown, making it difficult to optimize in any given application. We studied the physical mechanism by which ultrasound is converted into an effective energy form to cause neurostimulation in the retina and find that ultrasound acts via radiation force leading to a mechanical displacement of tissue. We further show that standing waves have a strong modulatory effect on activity. Our quantitative model by which ultrasound generates radiation force and leads to neural activity will be important in optimizing ultrasonic neurostimulation across a wide range of applications.

Capacitive micromachined ultrasonic transducers (CMUTs) with substrate-embedded springs offer highly efficient output pressure performance over conventional CMUTs, owing to their nonflexural parallel plate movement. The embedded silicon springs support thick Si piston plates, creating a large nonflexural average volume displacement efficiency in the operating frequency range from 1&ndash, 3 MHz. Static and dynamic volume displacements of the nonflexural parallel plates were examined using white light interferometry and laser Doppler vibrometry. In addition, an output pressure measurement in immersion was performed using a hydrophone. The device showed a maximum transmission efficiency of 21 kPa/V, and an average volume displacement efficiency of 1.1 nm/V at 1.85 MHz with a low DC bias voltage of 55 V. The device element outperformed the lead zirconate titanate (PZT) ceramic HD3203, in the maximum transmission efficiency or the average volume displacement efficiency by 1.35 times. Furthermore, its average volume displacement efficiency reached almost 80% of the ideal state-of-the-art single-crystal relaxor ferroelectric materials PMN-0.33PT. Additionally, we confirmed that high-efficiency output pressure could be generated from the CMUT device, by quantitatively comparing the hydrophone measurement of a commercial PZT transducer.

Touchscreen sensors are widely used in many devices such as smart phones, tablets, laptops, etc. There are many different types of modalities that enable sensing the touch. The dominant technologies on the market are the capacitive, resistive, acoustic or ultrasound, and optical touch systems. None of these technologies are perfect and each has some advantages and disadvantages. Capacitive touch technologies are the most common in the industry. However, hardware complexity, high manufacturing cost, and high power consumption have impeded their feasibility for certain applications such as larger screens. Acoustic/ultrasound technologies due to their simplicity, ease of manufacturing, and low cost have been identified as suitable alternatives for a wide spectrum of applications. However, lack of robustness and multi-touch capability have made them fall short as competitive technologies. We present design, analysis, and implementation of an ultrasonic touchscreen system that utilizes interaction of transient Lamb waves with objects in contact with the screen. It attempts to improve on the existing ultrasound technologies, with the potential of addressing some of the weaknesses of the dominant technologies, such as the capacitive or resistive ones. Compared with the existing ultrasonic and acoustic modalities, among other advantages, it provides the capability of detecting several simultaneous touch points and also a more robust performance.

Image-guided high intensity focused ultrasound (HIFU) is widely used not only for non-invasive therapy but also as a precise approach for cardiac tissue ablation. However, most HIFU systems use piezoelectric transducers, which are typically bulky due to active cooling, and separate imaging and HIFU transducers, and therefore impractical for catheter-based applications. Taking advantage of a single 2-D capacitive micromachined ultrasonic transducer (CMUT) array, we developed a percutaneous cardiac catheter that can switch between ultrasound imaging mode and HIFU ablation mode.

We developed a fully-populated 2-D capacitive micromachined ultrasonic transducer (CMUT) array for high intensity focused ultrasound (HIFU) treatment. The 2-D CMUT array, which consists of 20 × 20 square CMUT elements with an element-to-element pitch of 1 mm, was designed and fabricated using the thick-buried-oxide (BOX) fabrication process. It was then assembled on a custom interface board that can provide various array configurations depending on the desired applications. In this study, the interface board groups the CMUT array elements into eight channels, based on the phase delay from the element to the targeted focal point at a 20-mm distance from the array surface, which corresponds to an F-number of 1. An 8-channel phase generating system supplies continuous waves with eight different phases to the eight channels of the CMUT array through bias-tees and amplifiers. This array aperture, grouped into eight channels, gives a focusing gain of 6.09 according to field simulation using Field II. Assuming a...

Touchscreen sensors are widely used in many devices such as smart phones, tablets, and laptops with diverse applications. We present the design, analysis, and implementation of an ultrasonic touchscreen system that utilizes the interaction of transient Lamb waves with objects in contact with the screen. It attempts to improve on the existing ultrasound technologies, with the potential of addressing some of the weaknesses of the dominant technologies, such as the capacitive or resistive ones. Compared with the existing ultrasonic and acoustic modalities, among other advantages, it provides the capability of detecting several simultaneous touch points and also a more robust performance. The localization algorithm, given the hardware design, can detect several touch points with a very limited number of measurements (one or two). This in turn can significantly reduce the manufacturing cost.

High-intensity focused ultrasound (HIFU) has been used as noninvasive treatment for various diseases. For these therapeutic applications, capacitive micromachined ultrasonic transducers (CMUTs) have advantages that make them potentially preferred transducers over traditional piezoelectric transducers. In this paper, we present the design and the fabrication process of an $8 \times 8$ -mm $^{2}~32 \times 32$ -element 2-D CMUT array for HIFU applications. To reduce the system complexity for addressing the 1024 transducer elements, we propose to group the CMUT array elements into eight HIFU channels based on the phase delay from the CMUT element to the targeted focal point. Designed to focus at an 8-mm depth with a 5-MHz exciting frequency, this grouping scheme was realized using a custom application-specific integrated circuit. With a 40-V dc bias and a 60-V peak-to-peak ac excitation, the surface pressure was measured 1.2 MPa peak-to-peak and stayed stable for a long enough time to create a lesion. With this dc and ac voltage combination, the measured peak-to-peak output pressure at the focus was 8.5 MPa, which is expected to generate a lesion in a minute according to the temperature simulation. The following ex vivo tissue experiments successfully demonstrated its capability to make lesions in both bovine muscle and liver tissue.

Real-time volumetric ultrasound imaging systems require transmit and receive circuitry to generate ultrasound beams and process received echo signals. The complexity of building such a system is high due to requirement of the front-end electronics needing to be very close to the transducer. A large number of elements also need to be interfaced to the back-end system and image processing of a large dataset could affect the imaging volume rate. In this work, we present a 3-D imaging system using capacitive micromachined ultrasonic transducer (CMUT) technology that addresses many of the challenges in building such a system. We demonstrate two approaches in integrating the transducer and the front-end electronics. The transducer is a 5-MHz CMUT array with an 8 mm × 8 mm aperture size. The aperture consists of 1024 elements (32 × 32) with an element pitch of 250 μm. An integrated circuit (IC) consists of a transmit beamformer and receive circuitry to improve the noise performance of the overall system. The assembly was interfaced with an FPGA and a back-end system (comprising of a data acquisition system and PC). The FPGA provided the digital I/O signals for the IC and the back-end system was used to process the received RF echo data (from the IC) and reconstruct the volume image using a phased array imaging approach. Imaging experiments were performed using wire and spring targets, a ventricle model and a human prostrate. Real-time volumetric images were captured at 5 volumes per second and are presented in this paper.

Synthetic phased array (SPA) beamforming with Hadamard coding and aperture weighting is an optimal option for real-time volumetric imaging with a ring array, a particularly attractive geometry in intracardiac and intravascular applications. However, the imaging frame rate of this method is limited by the immense computational load required in synthetic beamforming. For fast imaging with a ring array, we developed graphics processing unit (GPU)-based, real-time image reconstruction software that exploits massive data-level parallelism in beamforming operations. The GPU-based software reconstructs and displays three cross-sectional images at 45 frames per second (fps). This frame rate is 4.5 times higher than that for our previously-developed multi-core CPU-based software. In an alternative imaging mode, it shows one B-mode image rotating about the axis and its maximum intensity projection, processed at a rate of 104 fps . This paper describes the image reconstruction procedure on the GPU platform and presents the experimental images obtained using this software.