Hepatitis B Virus X Protein Impairs Hepatic Insulin Signaling Through Degradation of IRS1 and Induction of SOCS3

Hepatitis B virus (HBV) is a major cause of chronic liver diseases, and frequently results in hepatitis, cirrhosis, and ultimately hepatocellular carcinoma. The role of HCV in associations with insulin signaling has been elucidated. However, the pathogenesis of HBV-associated insulin signaling remains to be clearly characterized. Therefore, we have attempted to determine the mechanisms underlying the HBV-associated impairment of insulin signaling.The expressions of insulin signaling components were investigated in HBx-transgenic mice, HBx-constitutive expressing cells, and transiently HBx-transfected cells. Protein and gene expression was examined by Western blot, immunohistochemistry, RT-PCR, and promoter assay. Protein-protein interaction was detected by coimmunoprecipitation.HBx induced a reduction in the expression of IRS1, and a potent proteasomal inhibitor blocked the downregulation of IRS1. Additionally, HBx enhanced the expression of SOCS3 and induced IRS1 ubiquitination. Also, C/EBPalpha and STAT3 were involved in the HBx-induced expression of SOCS3. HBx interfered with insulin signaling activation and recovered the insulin-mediated downregulation of gluconeogenic genes.These results provide direct experimental evidences for the contribution of HBx in the impairment of insulin signaling

Non-linear dynamic analysis of reinforced concrete bridge columns under vehicle impact loadings

A 3D nonlinear impact analysis was performed for reinforced concrete bridge columns under truck impact loadings. Three different boundary conditions were considered to investigate the effect of superstructures on the integral column during impact. Fixed bottom conditions and restraints in the loading direction at the top of the column (Model I) showed the largest damaged area. The dominant failure mode of the column was shear. However, Model II, which is equivalent to Model I with the top released, showed less damage, and the dominant failure modes were flexure rather than shear. In Model III, in which the effect of featured the superstructure was considered, the shear and flexural damage to the column were reduced due to the movement of the superstructures

The Evolutionarily Conserved LIM Homeodomain Protein LIM-4/LHX6 Specifies the Terminal Identity of a Cholinergic and Peptidergic C. elegans Sensory/Inter/Motor Neuron-Type

The expression of specific transcription factors determines the differentiated features of postmitotic neurons. However, the mechanism by which specific molecules determine neuronal cell fate and the extent to which the functions of transcription factors are conserved in evolution are not fully understood. In C. elegans, the cholinergic and peptidergic SMB sensory/inter/motor neurons innervate muscle quadrants in the head and control the amplitude of sinusoidal movement. Here we show that the LIM homeobox protein LIM-4 determines neuronal characteristics of the SMB neurons. In lim-4 mutant animals, expression of terminal differentiation genes, such as the cholinergic gene battery and the flp-12 neuropeptide gene, is completely abolished and thus the function of the SMB neurons is compromised. LIM-4 activity promotes SMB identity by directly regulating the expression of the SMB marker genes via a distinct cis-regulatory motif. Two human LIM-4 orthologs, LHX6 and LHX8, functionally substitute for LIM-4 in C. elegans. Furthermore, C. elegans LIM-4 or human LHX6 can induce cholinergic and peptidergic characteristics in the human neuronal cell lines. Our results indicate that the evolutionarily conserved LIM-4/LHX6 homeodomain proteins function in generation of precise neuronal subtypes

Fragility of Bridge Columns under Vehicle Impact Using Risk Analysis

In this study, risk analysis was conducted to evaluate the vulnerability of bridge columns to vehicle impact. A three-step risk analysis procedure was used. The first step involved a Preliminary Risk Analysis (PRA), which was an initial screening step to determine whether a bridge column requires second-step analysis or not. The second step was a Simplified Risk Analysis (SRA), which involved determining the level of risk (low, moderate, or high) for a bridge column. The third step comprised a Detailed Risk Analysis (DRA). Computer simulation was based on the results of SRA. In this study, the risk level of 8,267 bridges in South Korea was evaluated, and a resulting total of 58 bridge columns in the Risk Level High (RLH) category were selected as a result of SRA. These bridge columns were classified into five types based on their slenderness ratio. Using these five types of bridge column, DRA was conducted. As expected, larger deformations of the bridge column were observed if the vehicle velocity and slenderness ratio were both increased. Using the bridge columns in the categories of response high and response moderate under vehicle impact, fragility curves were proposed using statistical data of material strength and the few results of the numerical analysis

A New Approach to Power Efficiency Improvement of Ultrasonic Transmitters via a Dynamic Bias Technique

To obtain a high-quality signal from an ultrasound system through the transmitter, it is necessary to achieve an appropriate operating point of the power amplifier in the ultrasonic transmitter by applying high static bias voltage. However, the power amplifier needs to be operated at low bias voltage, because a power amplifier operating at high bias voltage may consume a large amount of power and increase the temperature of the active devices, worsening the signal characteristics of the ultrasound systems. Therefore, we propose a new method of increasing the bias voltage for a specific period to solve this problem by reducing the output signal distortion of the power amplifier and decreasing the load on the active device. To compare the performance of the proposed method, we measured and compared the signals of the amplifier with the proposed technique and the amplifier only. Notably, improvement was achieved with 11.1% of the power added efficiency and 3.23% of the total harmonic distortion (THD). Additionally, the echo signal generated by the ultrasonic transducer was improved by 2.73 dB of amplitude and 0.028% of THD under the conditions of an input signal of 10 mW. Therefore, the proposed method could be useful for improving ultrasonic transmitter performance using the developed technique

Targeting of Secretory Proteins as a Therapeutic Strategy for Treatment of Nonalcoholic Steatohepatitis (NASH)

Nonalcoholic steatohepatitis (NASH) is defined as a progressive form of nonalcoholic fatty liver disease (NAFLD) and is a common chronic liver disease that causes significant worldwide morbidity and mortality, and has no approved pharmacotherapy. Nevertheless, growing understanding of the molecular mechanisms underlying the development and progression of NASH has suggested multiple potential therapeutic targets and strategies to treat this disease. Here, we review this progress, with emphasis on the functional role of secretory proteins in the development and progression of NASH, in addition to the change of expression of various secretory proteins in mouse NASH models and human NASH subjects. We also highlight secretory protein-based therapeutic approaches that influence obesity-associated insulin resistance, liver steatosis, inflammation, and fibrosis, as well as the gut–liver and adipose–liver axes in the treatment of NASH

High-efficiency high-voltage class F amplifier for high-frequency wireless ultrasound systems.

This paper presents a novel amplifier that satisfies both low distortion and high efficiency for high-frequency wireless ultrasound systems with limited battery life and size. While increasing the amplifier efficiency helps to address the problems for wireless ultrasound systems, it can cause signal distortion owing to harmonic components. Therefore, a new type of class F amplifier is designed to achieve high efficiency and low distortion. In the amplifier, the resonant circuit at each stage controls the harmonic components to reduce distortion and improve efficiency. Transformers with a large shunt resistor are also helpful to reduce the remaining noise in the input signal. The proposed class F amplifier is tested using simulations, and the voltage and current waveforms are analyzed to achieve correct operation with adequate efficiency and distortion. The measured performance of the class F amplifier has a gain of 23.2 dB and a power added efficiency (PAE) of 88.9% at 25 MHz. The measured DC current is 121 mA with a variance of less than 1% when the PA is operating. We measured the received echo signal through the pulse-echo response using a 25-MHz transducer owing to the compatibility of the designed class F amplifier with high- frequency transducers. The measured total harmonic distortion (THD) of the echo signal was obtained as 4.5% with a slightly low ring-down. The results show that the low THD and high PAE of the new high-efficiency and high-voltage amplifier may increase battery life and reduce the cooling fan size, thus providing a suitable environment for high-frequency wireless ultrasound systems

Novel Bandwidth Expander Supported Power Amplifier for Wideband Ultrasound Transducer Devices

Ultrasound transducer devices have their own frequency ranges, depending on the applications and specifications, due to penetration depth, sensitivity, and image resolution. For imaging applications, in particular, the transducer devices are preferable to have a wide bandwidth due to the specific information generated by the tissue or blood vessel structures. To support these ultrasound transducer devices, ultrasound power amplifier hardware with a wide bandwidth can improve the transducer performance. Therefore, we developed a new bandwidth expander circuit using specially designed switching architectures to increase the power amplifier bandwidth. The measured bandwidth of the power amplifier with the help of the bandwidth expander circuit increased by 56.9%. In addition, the measured echo bandwidths of the 15-, 20-, and 25-MHz transducer devices were increased by 8.1%, 6.0%, and 9.8%, respectively, with the help of the designed bandwidth expander circuit. Therefore, the designed architecture could help an ultrasound system hardware with a wider bandwidth, thus supporting the use of different frequency ultrasound transducer devices with a single developed ultrasound system