Mexenone protects mice from LPS-induced sepsis by EC barrier stabilization.

Blood vessels permit the selective passage of molecules and immune cells between tissues and circulation. Uncontrolled inflammatory responses from an infection can increase vascular permeability and edema, which can occasionally lead to fatal organ failure. We identified mexenone as a vascular permeability blocker by testing 2,910 compounds in the Clinically Applied Compound Library using the lipopolysaccharide (LPS)-induced vascular permeability assay. Mexenone suppressed the LPS-induced downregulation of junctional proteins and phosphorylation of VE-cadherin in Bovine Aortic Endothelial Cells (BAECs). The injection of mexenone 1 hr before LPS administration completely blocked LPS-induced lung vascular permeability and acute lung injury in mice after 18hr. Our results suggest that mexenone-induced endothelial cell (EC) barrier stabilization could be effective in treating sepsis patients.

Phospholipase C-ß1 potentiates glucose-stimulated insulin secretion.

PLC-ß exerts biologic influences through GPCR. GPCRs are involved in regulating glucose-stimulated insulin secretion (GSIS). Previous studies have suggested that PLC-ßs might play an important role in pancreatic ß cells. However, because of a lack of the specific inhibitors of PLC-ß isozymes and appropriate genetic models, the in vivo function of specific PLC-ß isozymes in pancreatic ß cells and their physiologic relevance in the regulation of insulin secretion have not been studied so far. The present study showed that PLC-ß1 was crucial for ß-cell function by generation of each PLC-ß conditional knockout mouse. Mice lacking PLC-ß1 in ß cells exhibited a marked defect in GSIS, leading to glucose intolerance. In ex vivo studies, the secreted insulin level and Ca2+ response in Plcb1f/f; pancreas/duodenum homeobox protein 1 (Pdx1)-Cre recombinase-estrogen receptor T2 (CreERt2) islets was lower than those in the Plcb1f/f islets under the high-glucose condition. PLC-ß1 led to potentiate insulin secretion via stimulation of particular Gq-protein-coupled receptors. Plcb1f/f; Pdx1-CreERt2 mice fed a high-fat diet developed more severe glucose intolerance because of a defect in insulin secretion. The present study identified PLC-ß1 as an important molecule that regulates ß cell insulin secretion and can be considered a candidate for therapeutic intervention in diabetes mellitus.-Hwang, H.-J., Yang, Y. R., Kim, H. Y., Choi, Y., Park, K.-S., Lee, H., Ma, J. S., Yamamoto, M., Kim, J., Chae, Y. C., Choi, J. H., Cocco, L., Berggren, P.-O., Jang, H.-J., Suh, P.-G. Phospholipase Cß1 potentiates glucose-stimulated insulin secretion.

Zafirlukast promotes insulin secretion by increasing calcium influx through L-type calcium channels.

The zafirlukast has been reported to be anti-inflammatory and widely used to alleviate the symptoms of asthma. However, its influence on insulin secretion in pancreatic ß-cells has not been investigated. Herein, we examined the effects of zafirlukast on insulin secretion and the potential underlying mechanisms. Among the cysteinyl leukotriene receptor 1 antagonists, zafirlukast, pranlukast, and montelukast, only zafirlukast enhanced insulin secretion in a concentration-dependent manner in both low and high glucose conditions and elevated the level of [Ca2+ ]i , further activating Ca2+ /calmodulin-dependent protein kinase II (CaMKII), protein kinase B (AKT), and extracellular signal-regulated kinase (ERK) signaling. These effects were nearly abolished by the L-type Ca2+ channel antagonist nifedipine, while treatment with thapsigargin, a sarco/endoplasmic reticulum Ca2+ ATPase inhibitor, did not have the same effect, suggesting that zafirlukast primarily induces the entry of extracellular Ca2+ rather than intracellular Ca2+ from the endoplasmic reticulum. Zafirlukast treatment resulting in a significant drop in glucose levels and increased insulin secretion in C57BL/6J mice. These findings will contribute to an improved understanding of the side effects of zafirlukast and potential candidate for a therapeutic intervention in diabetes.

Increasing the storage density of a page-based holographic data storage system by image upscaling using the PSF of the Nyquist aperture.

We introduce an image upscaling method that reduces bit errors caused by Nyquist apertures. Nyquist apertures used for higher storage densities generate optical aberrations and degrade the quality of the image that is recorded on the medium. Here, to correct the bit errors caused by the Nyquist aperture, an image upscaling method is used to restore the degraded image in the enhanced spatial frequency domain using its point spread function (PSF) as a restoration filter. The proposed method reduces the bit error rate (BER) significantly and hence allows higher storage densities.

Upscaling image resolution of compact imaging systems using wavefront coding and a property of the point-spread function.

We propose an image-resolution upscaling method for compact imaging systems. The image resolution is calculated using the resolving power of the optics and the pixel size of a digital image sensor. The resolution limit of the compact imaging system comes from its size and the number of allowed lenses. To upscale the image resolution but maintain the small size, we apply wavefront coding and image restoration. Conventional image restoration could not enhance the image resolution of the sensor. Here, we use the upscaled image of a wavefront-coded optical system and apply an image-restoration algorithm using a more precisely calculated point-spread function (PSF) as the deconvolution filter. An example of a wavefront-coded optical system with a 5-megapixel image sensor is given. The final image had a resolution equivalent to that of a 10-megapixel image using only four plastic lenses. Moreover, image degradation caused by hand motion could also be reduced using the proposed method.

A study on the realization of high resolution solid immersion lens-based near-field imaging optics by use of an annular aperture.

We report on the realization of solid immersion lens (SIL)-based near-field (NF) optics with an annular aperture, which is targeted to achieve high optical resolution. A numerical aperture (NA) = 1.84 hemisphere SIL-optics with an annular aperture achieves higher optical resolution than the conventional NA = 2.0 SIL-optics. The designed aperture is fabricated by photo-lithography and dry-etching technique. Experimental verification of the designed optics was performed through beam spot profile measurement under NF imaging conditions. A 15% smaller full-width-at-half-maximum spot diameter is obtained by the aperture. We verified that this method gives an improvement of the resolution in the optical imaging systems requiring higher resolution.

Multiple excitation of localized surface plasmon to create a 10 nm x 10 nm strong optical spot using an Au nanoparticle array-based ridge waveguide.

We present a description of a multiple excitation of localized surface plasmons (LSPs) from an Au nanoparticle (NP) array-based ridge waveguide to create a small optical spot size with an extremely strong intensity. Using a numerical finite-difference time-domain method, we find that the optical intensity of the ridge waveguide with an Au NP array is about 700% higher than that of a simple ridge waveguide. Moreover, the spacing between the NPs plays an important role in the multiple excitation of LSPs. The spot size, calculated at FWHM, is 10 nm x 10 nm at a distance of 5 nm from the exit plane.

Cover-layer-protected solid immersion lens-based near-field recording with an annular aperture.

Currently, data recording density in cover-layer-protected near-field-recording (NFR) and multiple-recording layered NFR optical data storage technology is limited by the difficulty in obtaining high-refractive-index cover layer materials. In addition, with the exception of improved resolution, the higher the numerical aperture (NA), the poorer the optical characteristics. However, in this study, we present novel cover-layer-protected solid immersion lens (SIL)-based NFR optics that provide superior optical performance with higher recording density, greatly enhanced focal depth, and less sensitivity to near-field air-gap-distance variation by modulating the amplitude and phase in the entrance pupil using annular pupil zones. Using an annular aperture consisting of three concentric annular zones to effect amplitude and phase modulation, the 1.45 NA cover-layer-protected SIL-based NFR optics achieved a data recording density as high as that of conventional 1.80 NA SIL-based NFR optics. These 1.45 NA optics yielded a full-width at half-maximum (FWHM) spot size of 0.315 lambda, a focal depth of 0.82 lambda, a focused beam spot sensitivity to air-gap-distance within the near-field region of 0.04 lambda, and a sidelobe intensity lower than 7%. In comparison with conventional 1.80 NA SIL-based NFR optics, the annular aperture optics achieved 3.5 times longer focal depth and much lower focused beam spot sensitivity to air-gap distance while maintaining the same high resolution. The introduction of this novel specially designed NFR optics could greatly improve data capacity in multiple-recording layered NFR.

Feasibility study of the application of radially polarized illumination to solid immersion lens-based near-field optics.

We analyzed the behavior of the electric field in a focal plane consisting of a solid immersion lens (SIL), an air gap, and a measurement sample for radially polarized illumination in SIL-based near-field optics with an annular aperture. The analysis was based on the Debye diffraction integral and multiple beam interference. For SIL-based near-field optics whose NA is higher than unity, radially polarized light generates a smaller beam spot on the bottom surface of a SIL than circularly polarized light; however, the beam spot on the measurement sample is broadened with a more dominant transverse electric field. By introducing an annular aperture technique, it is possible to decrease the effects of the transverse electric field, and therefore the size of the beam spot on the measurement sample can be small. This analysis could have various applications in near-field optical storage, near-field microscopy, lithography at ultrahigh resolution, and other applications that use SILs for high resolution.

Effects of motion of an imaging system and optical image stabilizer on the modulation transfer function.

This paper analyzes the effects due to the angular motion of a small-sized imaging system equipped with an optical image stabilizer (OIS) on image quality. Accurate lens moving distances for the OIS required to compensate the ray distortion induced by the angular motion are determined. To calculate the associated modulation transfer function, the integrated and the compensated point spread functions are defined. Finally, the deterioration of the image resolution due to angular motion and the restorative performance of the OIS are analyzed by isolating seven types of angular motion.