Terahertz Nanoprobing of Semiconductor Surface Dynamics.

Most semiconductors have surface dynamics radically different from its bulk counterpart due to surface defect, doping level, and symmetry breaking. Because of the technical challenge of direct observation of the surface carrier dynamics, however, experimental studies have been allowed in severely shrunk structures including nanowires, thin films, or quantum wells where the surface-to-volume ratio is very high. Here, we develop a new type of terahertz (THz) nanoprobing system to investigate the surface dynamics of bulk semiconductors, using metallic nanogap accompanying strong THz field confinement. We observed that carrier lifetimes of InP and GaAs dramatically decrease close to the limit of THz time resolution (∼1 ps) as the gap size decreases down to nanoscale and that they return to their original values once the nanogap patterns are removed. Our THz nanoprobing system will open up pathways toward direct and nondestructive measurements of surface dynamics of bulk semiconductors.

Promiscuous methionyl-tRNA synthetase mediates adaptive mistranslation to protect cells against oxidative stress.

Aminoacyl-tRNA synthetases (ARSs) acylate transfer (t)RNAs with amino acids. Charging tRNAs with the right amino acids is the first step in translation; therefore, the accurate and error-free functioning of ARSs is an essential prerequisite for translational fidelity. A recent study found that methionine (Met) can be incorporated into non-Met residues of proteins through methionylation of non-cognate tRNAs under conditions of oxidative stress. However, it was not understood how this mis-methionylation is achieved. Here, we report that methionyl-tRNA synthetase (MRS) is phosphorylated at Ser209 and Ser825 by extracellular signal-related kinase (ERK1/2) under conditions of stress caused by reactive oxygen species (ROS), and that this phosphorylated MRS shows increased affinity for non-cognate tRNAs with lower affinity for tRNA(Met), leading to an increase in Met residues in cellular proteins. The expression of a mutant MRS containing the substitutions S209D and S825D, mimicking dual phosphorylation, reduced ROS levels and cell death. This controlled inaccuracy of MRS seems to serve as a defense mechanism against ROS-mediated damage at the cost of translational fidelity.

Nanoscale Single-Element Color Filters.

Visible-light filters constructed from nanostructured materials typically consist of a metallic grating and rely on the excitation of surface plasmon polaritons (SPPs). In order to operate at full efficiency, the number of grating elements needs to be maximized such that light can couple more efficiently to the SPPs through improved diffraction. Such conditions impose a limitation on the compactness of the filter since a larger number of grating elements represents a larger effective size. For emerging applications involving nanoscale transmitters or receivers, a device that can filter localized excitations is highly anticipated but is challenging to realize through grating-type filters. In this work, we present the design of an optical filter operating with a single element, marking a departure from diffractive plasmonic coupling. Our device consists of a ZnO nanorod enclosed by two layers of Ag film. For diffraction-limited light focused on the nanorod, narrow passbands can be realized and tuned via variation of the nanorod diameter across the visible spectrum. The spectral and spatial filtering originates from scattering cancellation localized at the nanorod due to the cavity and nanorod exhibiting opposite effective dipole moments. This ability to realize high-performance optical filtering at the ultimate size introduces intriguing possibilities for nanoscale near-field communication or ultrahigh resolution imaging pixels.

Optical field enhancement of nanometer-sized gaps at near-infrared frequencies.

We report near-field and far-field measurements of transmission through nanometer-sized gaps at near-infrared frequencies with varying the gap size from 1 nm to 10 nm. In the far-field measurements, we excluded direct transmission on the metal film surface via interferometric method. Kirchhoff integral formalism was used to relate the far-field intensity to the electric field at the nanogaps. In near-field measurements, field enhancement factors of the nanogaps were quantified by measuring transmission of the nanogaps using near-field scanning optical microscopy. All the measurements produce similar field enhancements of about ten, which we put in the context of comparing with the giant field enhancements in the terahertz regime.

Quantum dots-nanogap metamaterials fabrication by self-assembly lithography and photoluminescence studies.

We present a new and versatile technique of self-assembly lithography to fabricate a large scale Cadmium selenide quantum dots-silver nanogap metamaterials. After optical and electron microscopic characterizations of the metamaterials, we performed spatially resolved photoluminescence transmission measurements. We obtained highly quenched photoluminescence spectra compared to those from bare quantum dots film. We then quantified the quenching in terms of an average photoluminescence enhancement factor. A finite difference time domain simulation was performed to understand the role of an electric field enhancement in the nanogap over this quenching. Finally, we interpreted the mechanism of the photoluminescence quenching and proposed fabrication method of new metamaterials using our technique.

Selective electric and magnetic sensitivity of aperture probes.

We report the effect of geometrical factors governing the polarization profiles of near-field scanning optical microscope (NSOM) probes. The most important physical parameter controlling the selective electric or magnetic field sensitivity is found to be the width of the metal rim surrounding aperture. Probes with metal rim width w < λ/2 selectively senses the optical electric field, while those with w > λ/2 selectively senses the optical magnetic field. Intensity variation of optical Hertz standing wave formed upon reflection at oblique incidence shows a phase difference of π/2 between electric and magnetic probes: an analogue of the classical Wiener's experiment. Our work paves way towards electromagnetic engineering of nanostructures.

Electromagnetic Saturation of Angstrom-Sized Quantum Barriers at Terahertz Frequencies.

Metal-graphene-metal hybrid structures allow angstrom-scale van der Waals gaps, across which electron tunneling occurs. We squeeze terahertz electromagnetic waves through these λ/10 000 000 gaps, accompanied by giant field enhancements. Unprecedented transmission reduction of 97% is achieved with the transient voltage across the gap saturating at 5 V. Electron tunneling facilitated by the transient electric field strongly modifies the gap index, starting a self-limiting process related to the barrier height. Our work enables greater interplay between classical optics and quantum tunneling, and provides optical indices to the van der Waals gaps.

Screening of quinoline, 1,3-benzoxazine, and 1,3-oxazine-based small molecules against isolated methionyl-tRNA synthetase and A549 and HCT116 cancer cells including an in silico binding mode analysis.

Elevated activity of methionyl-tRNA synthetase (MRS) in many cancers renders it a possible drug target in this disease area, as well as in a series of parasitic diseases. In the present work, we report the synthesis and in vitro screening of a library of 1,3-oxazines, benzoxazines and quinoline scaffolds against human MRS. Among the compounds tested, 2-(2-butyl-4-chloro-1-(4-phenoxybenzyl)-1H-imidazol-5-yl)-5-(4-methoxyphenyl)-1-oxa-3-azaspiro[5.5]undecane (compound 21) and 2-(2-butyl-4-chloro-1-(4-nitrobenzyl)-1H-imidazol-5-yl)-2,4-dihydro-1H-benzo[d][1,3]oxazine (compound 8) were found to be potent inhibitors of MRS. Additionally, these compounds significantly suppressed the proliferation of A549 and HCT116 cells with IC50 values of 28.4, 17.7, 41.9, and 19.8 µM respectively. Molecular docking studies suggested that the ligand binding orientation overlaps with the original positions of both methionine and adenosine of MRS. This suggests the binding of compound 21 against MRS, which might lead the inhibitory activity towards cancer cells.

Secreted human glycyl-tRNA synthetase implicated in defense against ERK-activated tumorigenesis.

Although adaptive systems of immunity against tumor initiation and destruction are well investigated, less understood is the role, if any, of endogenous factors that have conventional functions. Here we show that glycyl-tRNA synthetase (GRS), an essential component of the translation apparatus, circulates in serum and can be secreted from macrophages in response to Fas ligand that is released from tumor cells. Through cadherin (CDH)6 (K-cadherin), GRS bound to different ERK-activated tumor cells, and released phosphatase 2A (PP2A) from CDH6. The activated PP2A then suppressed ERK signaling through dephosphorylation of ERK and induced apoptosis. These activities were inhibited by blocking GRS with a soluble fragment of CDH6. With in vivo administration of GRS, growth of tumors with a high level of CDH6 and ERK activation were strongly suppressed. Our results implicate a conventional cytoplasmic enzyme in translation as an intrinsic component of the defense against ERK-activated tumor formation.

Dual role of methionyl-tRNA synthetase in the regulation of translation and tumor suppressor activity of aminoacyl-tRNA synthetase-interacting multifunctional protein-3.

Mammalian methionyl-tRNA synthetase (MRS) plays an essential role in initiating translation by transferring Met to initiator tRNA (tRNA(i)(Met)). MRS also provides a cytosolic anchoring site for aminoacyl-tRNA synthetase-interacting multifunctional protein-3 (AIMP3)/p18, a potent tumor suppressor that is translocated to the nucleus for DNA repair upon DNA damage. However, the mechanism by which this enzyme mediates these two seemingly unrelated functions is unknown. Here we demonstrate that AIMP3 is released from MRS by UV irradiation-induced stress. Dissociation was induced by phosphorylation of MRS at Ser662 by general control nonrepressed-2 (GCN2) following UV irradiation. Substitution of Ser662 to Asp (S662D) induced a conformational change in MRS and significantly reduced its interaction with AIMP3. This mutant possessed significantly reduced MRS catalytic activity because of loss of tRNA(Met) binding, resulting in down-regulation of global translation. According to the Met incorporation assay using stable HeLa cells expressing MRS S662A or eukaryotic initiation factor-2 subunit-α (eIF2α) S51A, inactivation of GCN2-induced phosphorylation at eIF2α or MRS augmented the role of the other, suggesting a cross-talk between MRS and eIF2α for efficient translational inhibition. This work reveals a unique mode of regulation of global translation as mediated by aminoacyl-tRNA synthetase, specifically MRS, which we herein identified as a previously unidentified GCN2 substrate. In addition, our research suggests a dual role for MRS: (i) as a coregulator with eIF2α for GCN2-mediated translational inhibition; and (ii) as a coupler of translational inhibition and DNA repair following DNA damage by releasing bound tumor suppressor AIMP3 for its nuclear translocation.

Convergent evolution of two different random RNAs for specific interaction with methionyl-tRNA synthetase.

Aminoacyl-tRNA synthetases (ARSs) recognize a specific sequence or structural characteristics of their cognate tRNAs. To contribute to the understanding how these recognition sites were selected, we generated two different RNA libraries containing either 42mer or 70mer random sequence and used them to select RNA aptamers that specifically bound to methionyl-tRNA synthetase (MRS) of Mycobacterium tuberculosis. The aptamer pools selected from the two RNA libraries showed strong binding affinity and selectivity to M. tuberculosis MRS compared to that of the homologous Escherichia coli MRS. The RNA aptamers selected from the two completely unrelated RNA pools shared the octamer sequence including CAU and the anticodon sequence of tRNA(Met). The secondary structure prediction suggested that the octamer motif in the selected aptamers would form a loop similar to the anticodon loop of tRNA(Met). The results suggest that the RNA loop containing CAU triplet could selected as a major recognition site for MRS during evolution more or less regarding, and also showed that species-specific ARS inhibitors can be obtained by in vitro evolution.

Blockade of IL-6 secretion pathway by the sesquiterpenoid atractylenolide III.

Atractylenolide III (1) is the major bioactive component of Atractylodes lancea. The aim of this study was to analyze the effect on the regulation of interleukin (IL)-6 secretion pathway caused by 1. This sesquiterpenoid inhibited the secretion and expression of IL-6 in phorbol 12-myristate 13-acetate- and calcium ionophore A23187-stimulated human mast cells (HMC)-1. In addition, 1 inhibited histamine release in stimulated HMC-1 cells. In stimulated HMC-1 cells, 1 suppressed activation of p38 mitogen-activated protein kinase, C-Jun-N-terminal protein kinase, and nuclear factor-κB. In addition, 1 suppressed the activation of caspase-1 and the expression of receptor interacting protein-2. These results provide new insights that atractylenolide III (1) may control immunological reactions by regulating the cellular functions of IL-6 in mast cells.

Single-particle characterization of indoor aerosol particles collected at an underground shopping area in Seoul, Korea.

UNLABELLED: In this study, single-particle characterization of aerosol particles collected at an underground shopping area was performed for the first time. A quantitative single-particle analytical technique, low-Z particle electron probe X-ray microanalysis, was used to characterize a total of 7900 individual particles for eight sets of aerosol samples collected at an underground shopping area in Seoul, Korea. Based on secondary electron images and X-ray spectral data of individual particles, fourteen particle types were identified, in which primary soil-derived particles were the most abundant, followed by carbonaceous, Fe-containing, secondary soil-derived, and secondary sea-salt particles. Carbonaceous particles exist in three types: organic carbon, carbon-rich, and CNO-rich. A significant number of textile particles with chemical composition C, N, and O were encountered in some of the aerosol samples, which were from the textile shops and/or from clothes of passersby. Primary soil-derived particles showed seasonal variation, with peak values in spring samples, reflecting higher air exchange between indoor and outdoor environments in the spring. Secondary soil-derived, secondary sea-salt, and ammonium sulfate particles were frequently encountered in winter samples. Fe-containing particles, contributed from a nearby subway station, were in the range of about 19% relative abundances for all samples. PRACTICAL IMPLICATIONS: In underground shopping areas, particulate matters can be a considerable health hazard to the workers, shoppers, passersby, and shop-keepers as they spend their considerable time in this closed microenvironment. However, no study on the characteristics of indoor aerosols in an underground shopping area has been reported to our knowledge. This work provides detailed information on characteristics of underground shopping area aerosols on a single particle level.

The regulatory mechanism of ß-eudesmol is through the suppression of caspase-1 activation in mast cell-mediated inflammatory response.

ß-Eudesmol is sesquiterpenoid alcohol which contains the rhizome of Atractylodes lancea. Although it has multiple pharmacological effects, the anti-inflammatory effect of ß-eudesmol and its molecular mechanisms are poorly elucidated. In this study, we investigated the regulatory mechanism of ß-eudesmol on mast cell-mediated inflammatory response. The results indicated that ß-eudesmol inhibited the production and expression of interleukin (IL)-6 on phorbol 12-myristate 13-acetate and calcium ionophore A23187-stimulated human mast cell (HMC). In activated HMC-1 cells, ß-eudesmol suppressed activation of p38 mitogen-activated protein kinase (MAPKs) and nuclear factor-κB. In addition, ß-eudesmol suppressed the activation of caspase-1 and expression of receptor-interacting protein-2. These results provide new insights into the pharmacological actions of ß-eudesmol as a potential molecule for use in therapy in mast cell-mediated inflammatory diseases.

Inhibitory effects of the transgenic Panax ginsengs on phorbol ester plus A23187-induced IL-6 production and cyclooxygenase-2 via suppression of NF-κB and MAPKs in HMC-1.

Our previous studies have that demonstrated the overexpression of the squalene synthase gene enhances the biosynthesis of triterpene and phytosterol in Panax ginseng. The total ginsenoside contents in adventitious roots of transgenic P. ginseng were about 1.6-3-fold higher than those in the wild-type. In the present work, we have evaluated the anti-inflammatory effects of two types of transgenic P. ginseng (BS and SS) and the wild-type P. ginseng (GS) in a stimulated human mast cell line 1 (HMC-1). GS, BS, and SS inhibited not only the production of interleukin 6 (IL-6), but also the expression of cyclooxygenase-2 in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 (PMACI)-stimulated HMC-1. Additionally, GS, BS, and SS suppressed the expression of the nuclear transcription factor κB and mitogen-activated protein kinases induced by PMACI. The anti-inflammatory effects of BS and SS were higher than that of GS. These results provide new insights into the pharmacological actions of transgenic P. ginseng as a potential molecule for use in therapy in mast cell-mediated inflammatory diseases.

Libanoridin inhibits the mast cell-mediated allergic inflammatory reaction.

BACKGROUND AND AIM: Corydalis heterocarpa is a biennial herb in South Korea, with spikes of yellow flowers. It has been used for as a folk medicine to cure travail and spasm. However, studies on this herb and its secondary metabolites have rarely been reported. In the present study, we isolated secondary metabolite libanlibanoridin from Corydalis heterocarpa. We have also examined the effect of libanoridin on the inflammatory cytokines production in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore, A2318 stimulated human mast cell line, HMC-1. PMA plus A23187 significantly increased interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha production compared to media control (P < 0.05). RESULTS: We report that treatment with libanlibanoridin can inhibit PMA plus A23187-induced IL-1beta, IL-6, IL-8, and TNF-alpha production in a concentration-dependent manner with IC50 of 0.002, 1.38, 1.48, and 0.36 mug/ml, respectively. Maximal inhibition rates of IL-1beta, IL-6, IL-8, and TNF-alpha production by libanlibanoridin were about 117.5%, 86.22%, 86.41%, and 90.74%, respectively. libanoridin inhibits the mRNA expression of IL-1beta, IL-6, IL-8, and TNF-alpha. libanoridin also inhibits the expression of cyclooxygenase-2. CONCLUSION: These results indicate that libanlibanoridin may be helpful in regulating mast cell-mediated allergic inflammatory response.

Shear Stress-Dependent Targeting Efficiency Using Self-Assembled Gelatin-Oleic Nanoparticles in a Biomimetic Microfluidic System.

Cellular properties and microenvironments, as well as the characteristics of nanoparticles (NPs), affect the cellular uptake and cytotoxic effects of drug-loaded NPs. Since there is fluid flow in the human blood system, fluid flow also affects the drug delivery efficiency of NPs. This study aimed to evaluate the cellular behaviors of drug-loaded soft NPs on A549 cancer cells under different levels of shear stress (0.5, 5, and 50 dynes/cm2) in the biomimetic microfluidic system. The soft self-assembled NPs were formed by the gelatin-oleic conjugate (GOC). The poorly water-soluble coumarin-6 or paclitaxel (PTX) were used as model markers for encapsulation within self-assembled NPs (C-GONs or PTX-GONs, respectively). The cellular uptake of C-GONs was found to be improved with shear-stress dependence. The inhibitory concentration (IC50) of PTX-GONs at 0.5, 5, and 50 dynes/cm2 was 0.106 µg/mL, 0.108 µg/mL, and 0.091 µg/mL, respectively, as compared to 0.138 µg/mL in a static condition. The cell killing efficiency of PTX-GONs was increased in the highest shear stress of 50 dynes/cm2 in the static condition, and other levels of shear stress in dynamic conditions.

Terahertz-driven polymerization of resists in nanoantennas.

Plasmon-mediated polymerization has been intensively studied for various applications including nanolithography, near-field mapping, and selective functionalization. However, these studies have been limited from the near-infrared to the ultraviolet regime. Here, we report a resist polymerization using intense terahertz pulses and various nanoantennas. The resist is polymerized near the nanoantennas, where giant field enhancement occurs. We experimentally show that the physical origin of the cross-linking is a terahertz electron emission from the nanoantenna, rather than multiphoton absorption. Our work extends nano-photochemistry into the terahertz frequencies.

Magnetic Nature of Light Transmission through a 5-nm Gap.

Slot antennas have been exploited as important building blocks of optical magnetism because their radiations are invoked by the magnetic fields along the axes, as vectorial Babinet principle predicts. However, optical magnetism of a few-nanometer-width slit, for which fascinating applications are found due to the colossal field enhancement but Babinet principle fails due to the nonnegligible thickness, has not been investigated. In this paper, we demonstrated that the magnetic field plays a dominant role in light transmission through a 5-nm slit on a 150-nm-thick gold film. The 5-nm slit was fabricated by atomic layer lithography, and the transmission was investigated for various incident angles by experiment and simulation at 785-nm wavelength. We found that, due to the deep subwavelength gap width, the transmission has the same incident angle dependence as the tangential magnetic field on the metal surface and this magnetic nature of a nanogap holds up to ~100-nm width. Our analysis establishes conditions for nanogap optical magnetism and suggests new possibilities in realizing magnetic-field-driven optical nonlinearities.

Terahertz rectification in ring-shaped quantum barriers.

Tunneling is the most fundamental quantum mechanical phenomenon with wide-ranging applications. Matter waves such as electrons in solids can tunnel through a one-dimensional potential barrier, e.g. an insulating layer sandwiched between conductors. A general approach to control tunneling currents is to apply voltage across the barrier. Here, we form closed loops of tunneling barriers exposed to external optical control to manipulate ultrafast tunneling electrons. Eddy currents induced by incoming electromagnetic pulses project upon the ring, spatiotemporally changing the local potential. The total tunneling current which is determined by the sum of contributions from all the parts along the perimeter is critically dependent upon the symmetry of the loop and the polarization of the incident fields, enabling full-wave rectification of terahertz pulses. By introducing global geometry and local operation to current-driven circuitry, our work provides a novel platform for ultrafast optoelectronics, macroscopic quantum phenomena, energy harvesting, and multi-functional quantum devices.