Analysis of optical propagation characteristics of the ultra-long period grating using RCWA.

There have been significant research and analyses on the diffraction efficiency and characteristics of spectral grating with a wavelength-scale period. However, thus far an analysis on a diffraction grating with an ultra-long pitch over several hundred times of the wavelength (>100µm) and a very deep groove over dozens of micrometers has not been performed. We analyzed the diffraction efficiency of these gratings by using the rigorous coupled-wave analysis (RCWA) method and confirmed that the RCWA analytic results correspond well to the actual experimental results on the wide-angle beam-spreading phenomenon. In addition, because a long-period grating with a deep groove results in a small diffraction angle with relatively uniform efficiency, it is possible to convert a point-like distribution to a linear distribution for a short working distance and a discrete distribution for a very long working distance. We believe that a wide-angle line laser with a long grating period can be used in various applications, such as level detectors, precision measurements, multi-point light detecting and ranging (LiDAR) light sources, and security systems.

Design of Piezoelectric Acoustic Transducers for Underwater Applications.

Interest in underwater transducers has persisted since the mid-1900s. Underwater transducers are designed in various shapes using various materials depending on the purpose of use, such as to achieve high power, improve broadband, and enhance beam steering. Therefore, in this study, an analysis is conducted according to the structural shape of the transducer, exterior material, and active material. By classifying transducers by structure, the transducer design trends and possible design issues can be identified. Researchers have constantly attempted new methods to improve the performance of transducers. In addition, a methodology to overcome this problem is presented. Finally, this review covers old and new research, and will serve as a reference for designers of underwater transducer.

Proteomic Analysis Reveals a Critical Role of the Glycosyl Hydrolase 17 Protein in Panax ginseng Leaves under Salt Stress.

Ginseng, an important crop in East Asia, exhibits multiple medicinal and nutritional benefits because of the presence of ginsenosides. On the other hand, the ginseng yield is severely affected by abiotic stressors, particularly salinity, which reduces yield and quality. Therefore, efforts are needed to improve the ginseng yield during salinity stress, but salinity stress-induced changes in ginseng are poorly understood, particularly at the proteome-wide level. In this study, we report the comparative proteome profiles of ginseng leaves at four different time points (mock, 24, 72, and 96 h) using a label-free quantitative proteome approach. Of the 2484 proteins identified, 468 were salt-responsive. In particular, glycosyl hydrolase 17 (PgGH17), catalase-peroxidase 2, voltage-gated potassium channel subunit beta-2, fructose-1,6-bisphosphatase class 1, and chlorophyll a-b binding protein accumulated in ginseng leaves in response to salt stress. The heterologous expression of PgGH17 in Arabidopsis thaliana improved the salt tolerance of transgenic lines without compromising plant growth. Overall, this study uncovers the salt-induced changes in ginseng leaves at the proteome level and highlights the critical role of PgGH17 in salt stress tolerance in ginseng.

USP13 regulates HMGB1 stability and secretion through its deubiquitinase activity.

BACKGROUND: High mobility group box 1 (HMGB1) is a damage-associated molecular pattern (DAMP) molecule that plays a central role in innate immunity. HMGB1 acts as a late mediator of inflammation when actively secreted in response to inflammatory stimuli. Several post-translational modifications (PTMs), including acetylation, phosphorylation, and oxidation, are involved in HMGB1 secretion. However, the E3 ligases of HMGB1 and the mechanism by which DUBs regulate HMGB1 deubiquitination are not well known. METHODS: LC-MS/MS, proximity ligation assay, immunoprecipitation were used to identify ubiquitin-specific protease 13 (USP13) as a binding partner of HMGB1 and to investigate ubiquitination of HMGB1. USP13 domain mutant was constructed for domain study and Spautin-1 was treated for inhibition of USP13. Confocal microscopy image showed localization of HMGB1 by USP13 overexpression. The data were analyzed using one-way analysis of variance with Tukey's honestly significant difference post-hoc test for multiple comparisons or a two-tailed Student's t-test. RESULTS: We identified ubiquitin-specific protease 13 (USP13) as a novel binding partner of HMGB1 and demonstrated that USP13 plays a role in stabilizing HMGB1 from ubiquitin-mediated degradation. USP13 overexpression increased nucleocytoplasmic translocation of HMGB1 and promoted its secretion, which was inhibited by treatment with Spautin-1, a selective inhibitor of USP13. CONCLUSION: Taken together, we suggest that USP13 is a novel deubiquitinase of HMGB1 that regulates the stability and secretion of HMGB1.

Increasing the transmission efficiency of transcranial ultrasound using a dual-mode conversion technique based on Lamb waves.

Transcranial focused ultrasound (FUS) is a noninvasive treatment for brain tumors and neuromodulation. Based on normal incidence, conventional FUS techniques use a focused or an array of ultrasonic transducers to overcome the attenuation and absorption of ultrasound in the skull; however, this remains the main limitation of using FUS. A dual-mode conversion technique based on Lamb waves is proposed to achieve high transmission efficiency. This concept was validated using the finite element analysis (FEA) and experiments based on changes in the incident angle. Aluminum, plexiglass, and a human skull were used as materials with different attenuations. The transmission loss was calculated for each material, and the results were compared with the reflectance function of the Lamb waves. Oblique incidence based on dual-mode conversion exhibited a better transmission efficiency than that of a normal incidence for all of the specimens. The total transmission losses for the materials were 13.7, 15.46, and 3.91 dB less than those associated with the normal incidence. A wedge transducer was designed and fabricated to implement the proposed method. The results demonstrated the potential applicability of the dual-mode conversion technique for the human skull.

Design and Analysis of an Active Reflection Controller That Can Reduce Acoustic Signal Refer to the Angle of Incidence.

Techniques for reducing the reflection of acoustic signals have recently been actively studied. Most methods for reducing acoustic signals were studied using the normal-incidence wave reduction technique. Although the technique of canceling an object from the normal incidence wave is essential, research on reducing acoustic signals according to the angle of incidence is required for practical applications. In this study, we designed, fabricated, and experimented with an active reflection controller that can reduce acoustic signals according to the angle of incidence. The controller consists of a transmitter on one layer, a receiver sensor on two layers, and an acoustic window on three layers. To reduce the reflected signal, a combination of the time delay and phase was applied to the controller to minimize the acoustic signal by up to -23 dB at an angle of 10°. A controller array simulation was performed based on the results of a controlled experiment. In conclusion, our proposed controller can reduce acoustic signals according to the angle of incidence, which makes it suitable for many applications.

Desorption technologies for remediation of cesium-contaminated soils: a short review.

This review summarizes the mechanisms for desorbing and extracting cesium (Cs+) from clay minerals and soil. Most techniques use ion exchange with acids, cations, polymers, and surfactants. Some improve desorption of Cs+ from clay minerals, while surfactants and polymers expand the interlayer. Mixtures of acids/polymers, acids/surfactants, cations/polymers, and cations/surfactants are therefore more effective agents for desorption of Cs+ from clay minerals. Hydrothermal treatment plays a role similar to that of polymers and surfactants in expanding the interlayer of clay minerals. The primary desorption mechanism expands the interlayer and desorbs Cs+, but multiple sequential extractions based on these techniques can more effectively desorb Cs+ from clay minerals and field-contaminated soils. Desorption techniques for Cs+ based on multiple sequential extractions can reportedly achieve an efficiency greater than 90%, and such approaches are likely to be important technologies for remediation of Cs+-contaminated soils and industrial accident sites, as well as the dismantling of nuclear power plants.

Inflachromene inhibits autophagy through modulation of Beclin 1 activity.

Autophagy is a central intracellular catabolic mechanism that mediates the degradation of cytoplasmic proteins and organelles, and regulation of autophagy is essential for homeostasis. HMGB1 is an important sepsis mediator when secreted and also functions as an inducer of autophagy by binding to Beclin 1. In this study, we studied the effect of inflachromene (ICM), a novel HMGB1 secretion inhibitor, on autophagy. ICM inhibited autophagy by inhibiting nucleocytoplasmic translocation of HMGB1 and by increasing Beclin 1 ubiquitylation for degradation by enhancing the interaction between Beclin 1 and E3 ubiquitin ligase RNF216. These data suggest that ICM could be used as a potential autophagy suppressor.

Lobar evenness of deposition/retention in rat lungs of inhaled silver nanoparticles: an approach for reducing animal use while maximizing endpoints.

BACKGROUND: Information on particle deposition, retention and clearance are important for the evaluation of the risk of inhaled nanomaterials to human health. Recent revised OECD inhalation toxicity test guidelines require to evaluate the lung burden of nanomaterials after rodent subacute and subchronic inhalation exposure (OECD 412, OECD 413). These revised test guidelines require additional post-exposure observation (PEO) periods that include lung burden measurements that can inform on lung clearance behavior and translocation. The latter being particularly relevant when the testing chemical is a solid poorly soluble nanomaterial. Therefore, in the spirit of 3 R's, we investigated whether measurement of retained lung burden of inhaled nanoparticles (NPs) in individual lung lobes is sufficient to determine retained lung burden in the total lung. If it is possible to use only one lobe, it will reduce animal use and maximize the number of endpoints evaluated. RESULTS: To achieve these goals, rats were exposed nose-only for 1 or 5 days (6 h/day) to an aerosol of 20 nm well-dispersed silver nanoparticles (AgNPs), which is the desired particle diameter resulting in maximum deposition in the pulmonary region when inhaled as singlets. After exposure, the five lung lobes were separated and silver concentration was measured using inductively coupled plasma-mass spectrophotometer (ICP-MS). The results showed that the retention of deposited silver nanoparticle in the different lung lobes did not show any statistically significant difference among lung lobes in terms of silver mass per gram lung lobe. This novel finding of evenness of retention/deposition of inhaled 20 nm NPs in rats for all five lobes in terms of mass per unit tissue weight contrasts with earlier studies reporting greater apical lobe deposition of inhaled micro-particles in rodents. The difference is most likely due to preferred and efficient deposition of inhaled NPs by diffusion vs. additional deposition by sedimentation and impaction for micron-sized particles. CONCLUSION: AgNPs following acute inhalation by rats are evenly retained in each lung lobe in terms of mass per unit lung tissue weight. Accordingly, we suggest sampling any of the rat lung lobes for lung burden analysis can be used to determine deposited or retained total lung burden after short-term inhalation of NPs and using the other lobes for collecting and analyzing bronchoalveolar lavage fluid (BALF) and for histopathological analysis. Therefore, by combining lung burden measurement, histopathological tissue preparation, and BALF assay in the same rat will reduce the number of animals used and maximize the number of endpoints measured.

Comparison between Resonance and Non-Resonance Type Piezoelectric Acoustic Absorbers.

In this study, piezoelectric acoustic absorbers employing two receivers and one transmitter with a feedback controller were evaluated. Based on the target and resonance frequencies of the system, resonance and non-resonance models were designed and fabricated. With a lateral size less than half the wavelength, the model had stacked structures of lossy acoustic windows, polyvinylidene difluoride, and lead zirconate titanate-5A. The structures of both models were identical, except that the resonance model had steel backing material to adjust the center frequency. Both models were analyzed in the frequency and time domains, and the effectiveness of the absorbers was compared at the target and off-target frequencies. Both models were fabricated and acoustically and electrically characterized. Their reflection reduction ratios were evaluated in the quasi-continuous-wave and time-transient modes.

Single-Shot Waterless Low-Profile Photoacoustic System: Near-Field Volumetric Imaging In Vivo for Blood Vessels Based on Capacitive Micromachined Ultrasonic Transducer (CMUT).

Intensive research on photoacoustics (PA) for imaging of the living human body, including the skin, vessels, and tumors, has recently been conducted. We propose a PA measurement system based on a capacitive micromachined ultrasonic transducer (CMUT) with waterless coupling, short measurement time (<1 s), backward light irradiation, and a low-profile ultrasonic receiver unit (<1 cm). We fabricate a 64-element CMUT ring array with 6.2 mm diameter and 10.4 MHz center frequency in air, and 100% yield and uniform element response. To validate the PA tissue characterization, we employ pencil lead and red ink as solid and liquid models, respectively, and a living body to target moles and vessels. The system implements a near-field imaging system consisting of a 6 mm polydimethylsiloxane (PDMS) matching layer between the object and CMUT, which has a 3.7 MHz center frequency in PDMS. Experiments were performed in a waterless contact on the PDMS and the laser was irradiated with a 1 cm diameter. The experimental results show the feasibility of this near-field PA imaging system for position and depth detection of skin, mole, vessel cells, etc. Therefore, a system applicable to a low-profile compact biomedical device is presented.

Multipoint-Detection Strain Sensor with a Single Electrode Using Optical Ultrasound Generated by Carbon Nanotubes.

With the development of wearable devices, strain sensors have attracted large interest for the detection of human motion, movement, and breathing. Various strain sensors consisting of stretchable conductive materials have been investigated based on resistance and capacitance differences according to the strain. However, this method requires multiple electrodes for multipoint detection. We propose a strain sensor capable of multipoint detection with a single electrode, based on the ultrasound pulse-echo method. It consists of several transmitters of carbon nanotubes (CNTs) and a single polyvinylidene fluoride receiver. The strain sensor was fabricated using CNTs embedded in stretchable polydimethylsiloxane. The received data are characterized by the different times of transmission from the CNTs of each point depending on the strain, i.e., the sensor can detect the positions of the CNTs. This study demonstrates the application of the multipoint strain sensor with a single electrode for measurements up to a strain of 30% (interval of 1%). We considered the optical and acoustic energy losses in the sensor design. In addition, to evaluate the utility of the sensor, finger bending with three-point CNTs and flexible phantom bending with six-point CNTs for the identification of an S-curve having mixed expansion and compression components were carried out.

N-linked glycosylation plays a crucial role in the secretion of HMGB1.

HMGB1 protein is a delayed mediator of sepsis that is secreted to the extracellular milieu in response to various stimulants, inducing a pro-inflammatory response. HMGB1 is devoid of an endoplasmic reticulum (ER)-targeting signal peptide; hence, the mechanism of extracellular secretion is not completely understood, although HMGB1 is secreted after being subjected to post-translational modifications. Here, we identified the role of N-glycosylation of HMGB1 in extracellular secretion. We found two consensus (N37 and N134) and one non-consensus (N135) residues that were N-glycosylated in HMGB1 by performing liquid chromatography tandem mass spectrometry (LC-MS/MS) and analyzing for N-glycan composition and structure. Inhibition of N-glycosylation with tunicamycin resulted in a molecular shift of HMGB1 as assessed by gel electrophoresis. Non-glycosylated double mutant (N→Q) HMGB1 proteins (HMGB1(N37Q/N134Q) and HMGB1(N37Q/N135Q)) showed localization to the nuclei, strong binding to DNA, weak binding to the nuclear export protein CRM1 and rapid degradation by ubiquitylation. These mutant proteins had reduced secretion even after acetylation, phosphorylation, oxidation and exposure to pro-inflammatory stimuli. Taken together, we propose that HMGB1 is N-glycosylated, and that this is important for its DNA interaction and is a prerequisite for its nucleocytoplasmic transport and extracellular secretion.

Frequency-Based Analysis of Gramicidin A Nanopores Enabling Detection of Small Molecules with Picomolar Sensitivity.

Methods to detect low concentrations of small molecules are useful for a wide range of analytical problems including the development of clinical assays, the study of complex biological systems, and the detection of biological warfare agents. This paper describes a semisynthetic ion channel platform capable of detecting small molecule analytes with picomolar sensitivity. Our methodology exploits the transient nature of ion channels formed from gramicidin A (gA) nanopores and the frequency of observed single channel events as a function of concentration of free gA molecules that reversibly dimerize in a bilayer membrane. We initially use a protein (here, a monoclonal antibody) to sequester the ion channel activity of a C-terminally modified gA derivative. When a small molecule analyte is introduced to the electrical recording medium, it competitively binds to the protein and liberates the gA derivative, restoring its single ion channel activity. We found that monitoring the frequency of gA channel events makes it possible to detect picomolar concentrations of small molecule in solution. In part, due to the digital on/off nature of frequency-based analysis, this approach is 103 times more sensitive than measuring macroscopic membrane ion flux through gA channels as a basis for detection. This novel methodology, therefore, significantly improves the limit of detection of nanopore-based sensors for small molecule analytes, which has the potential for incorporation into miniaturized and low cost devices that could complement current established assays.

A natural compound, aristoyagonine, is identified as a potent bromodomain inhibitor by mid-throughput screening.

Bromodomain-containing protein 4 (Brd4) is known to play a key role in tumorigenesis. It binds acetylated histones to regulate the expression of numerous genes. Because of the importance of brd4 in tumorigenesis, much research has been undertaken to develop brd4 inhibitors with therapeutic potential. As a result, various scaffolds for bromodomain inhibitors have been identified. To discover new scaffolds, we performed mid-throughput screening using two different enzyme assays, alpha-screen and ELISA. We found a novel bromodomain inhibitor with a unique scaffold, aristoyagonine. This natural compound showed inhibitory activity in vitro and tumor growth inhibition in a Ty82-xenograft mouse model. In addition, we tested Brd4 inhibitors in gastric cancer cell lines, and found that aristoyagonine exerted cytotoxicity not only in I-BET-762-sensitive cancer cells, but also in I-BET-762-resistant cancer cells. This is the first paper to describe a natural compound as a Brd4 bromodomain inhibitor.

Hydrophobic Nanoparticles Reduce the ß-Sheet Content of SEVI Amyloid Fibrils and Inhibit SEVI-Enhanced HIV Infectivity.

Semen-derived enhancer of virus infection (SEVI) fibrils are naturally abundant amyloid aggregates found in semen that facilitate viral attachment and internalization of human immunodeficiency virus (HIV) in cells, thereby increasing the probability of infection. Mature SEVI fibrils are composed of aggregated peptides exhibiting high ß-sheet secondary structural characteristics. Herein, we show that polymers containing hydrophobic side chains can interact with SEVI and reduce its ß-sheet content by ∼45% compared with the ß-sheet content of SEVI in the presence of polymers with hydrophilic side chains, as estimated by polarization modulation-infrared reflectance absorption spectroscopy measurements. A nanoparticle (NP) formulation of this hydrophobic polymer reduced SEVI-mediated HIV infection in TMZ-bl cells by 60% compared with the control treatment. Although these NPs lacked specific amyloid-targeting groups, thus requiring high concentrations to observe biological activity, the use of hydrophobic interactions to alter the secondary structure of amyloids represents a useful approach to neutralizing the SEVI function. These results could, therefore, have general implications in the design of novel materials that can modify the activity of amyloids associated with a variety of other neurological and systemic diseases.

Effects of Lipid Tethering in Extremophile-Inspired Membranes on H(+)/OH(-) Flux at Room Temperature.

This work explores the proton/hydroxide permeability (PH+/OH-) of membranes that were made of synthetic extremophile-inspired phospholipids with systematically varied structural elements. A fluorescence-based permeability assay was optimized to determine the effects on the PH+/OH- through liposome membranes with variations in the following lipid attributes: transmembrane tethering, tether length, and the presence of isoprenoid methyl groups on one or both lipid tails. All permeability assays were performed in the presence of a low concentration of valinomycin (10 nM) to prevent buildup of a membrane potential without artificially increasing the measured PH+/OH-. Surprisingly, the presence of a transmembrane tether did not impact PH+/OH- at room temperature. Among tethered lipid monolayers, PH+/OH- increased with increasing tether length if the number of carbons in the untethered acyl tail was constant. Untethered lipids with two isoprenoid methyl tails led to lower PH+/OH- values than lipids with only one or no isoprenoid tails. Molecular dynamics simulations revealed a strong positive correlation between the probability of observing water molecules in the hydrophobic core of these lipid membranes and their proton permeability. We propose that water penetration as revealed by molecular dynamics may provide a general strategy for predicting proton permeability through various lipid membranes without the need for experimentation.

Effect of alcohol consumption on peripheral blood Alu methylation in Korean men.

Alcohol use disorders (AUD) are defined as alcohol abuse and alcohol dependence, which create a substantial public health problem worldwide. To date, no therapeutic can effectively solve these problems. They are complex diseases characterized by both genetic and environmental factors. DNA methylation can act as a downstream effector of environmental signals and account for multi-factorial nature of the disease. Global DNA methylation of peripheral blood cells has recently been proposed as a potential biomarker for disease risk. Alu elements host one-quarter of CpG dinucelotides in the genome to function as proxies for global DNA methylation. In this study, we evaluated the Alu methylation in the peripheral blood DNA of healthy volunteers and AUD patients using the pyrosequencing technology. The Alu methylation level is significantly higher in AUD compared to healthy controls (23.4 ± 1.6 versus 22.1 ± 1.0, t = 7.83, p < 0.0001). Moreover, significant correlation was found between Alu methylation and alcohol use disorders identification test score (r = 0.250, p < 0.0001), alcohol problem (r = 0.294, p < 0.0001), and life position (r = -0.205, p = 0.0005). Overall, these novel findings indicate that alcohol-related increase in Alu methylation might play a complex role in the etiology and pathogenesis of AUD. Further studies are required to elucidate the mechanisms underlying this relationship.

Polycyclic aromatic hydrocarbons are associated with insulin receptor substrate 2 methylation in adipose tissues of Korean women.

Polycyclic aromatic hydrocarbons (PAHs) are highly lipid soluble and are an increasing concern for general populations given their various adverse health effects, including obesity-related metabolic dysfunction. DNA methylation can act as a downstream effector for the biological effects of environmental exposures, but whether PAHs influence DNA methylation is unclear. To test for possible adverse effects of PAHs on adipose tissue (AT), we determined the promoter methylation status of 12 genes involved in glucose and lipid metabolism (CS, GLUT4, IR, IRS1, IRS2, LIPIN1, MCAD, PCK1, PCK2, PPARGC1Β, SDHA, and SREBP1) in visceral AT of Korean women by using methylation-specific PCR (MSP). IRS2 methylation alone was significantly associated with concentrations of individual PAH chemicals. When the PAH summary measure was used, the odds ratios of IRS2 hypermethylation across quartile of the PAH summary measure were 1, 1.7, 2.0, and 11.2 (95% confidence interval: 1.5-84.0) after adjusting for age and BMI (P trend=0.02). The strength of association between PAH summary measure and IRS2 hypermethylation was as similar as that of BMI. Collectively, these results suggested that lipophilic PAHs might be contributing factors to the pathogenesis of insulin resistance through methylation-mediated suppression of the IRS2 gene. However, further studies with large sample size are needed to confirm our findings.

Resonance Raman spectra of carotenoid molecules: influence of methyl substitutions.

We report here the resonance Raman spectra and the quantum chemical calculations of the Raman spectra for ß-carotene and 13,13'-diphenyl-ß-carotene. The first aim of this approach was to test the robustness of the method used for modeling ß-carotene, and assess whether it could accurately predict the vibrational properties of derivatives in which conjugated substituents had been introduced. DFT calculations, using the B3LYP functional in combination with the 6-311G(d,p) basis set, were able to accurately predict the influence of two phenyl substituents connected to the ß-carotene molecule, although these deeply perturb the vibrational modes. This experimentally validated modeling technique leads to a fine understanding of the origin of the carotenoid resonance Raman bands, which are widely used for assessing the properties of these molecules, and in particular in complex media, such as binding sites provided by biological macromolecules.